Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative, antiangiogenic, antiproliferative, and pro-apoptotic properties.Methods: In this study, we investigated the interaction of some natural compounds with SENP1 to inhibit its activity. We also screened the ZINC database including natural compounds. Molecular docking was performed, and toxicity of compounds was determined; then, molecular dynamics simulation (MDS) and essential dynamics (ED) were performed on natural compounds with higher free binding energies and minimal side effects. By searching in a large library, virtual screening of the ZINC database was performed using LibDock and CDOCKER, and the final top 20 compounds were allowed for docking against SENP1. According to the docking study, the top three leading molecules were selected and further analyzed by MDS and ED.Results: The results suggest that resveratrol (from the selected compounds) and ZINC33916875 (from the ZINC database) could be more promising SENP1 inhibitory ligands.Discussion: Because these compounds can inhibit SENP1 activity, then they can be novel candidates for cancer treatment. However, wet laboratory experiments are needed to validate their efficacy as SENP1 inhibitors. Cancer is one of the leading causes of mortality worldwide. Chemotherapy and radiotherapy have been reported to be considerable in cancer therapy, but these treatments have side effects. Then, anticancer drugs based on medicinal plants have been paid attention to because of their lowest side effects. The beneficial effects of herbal medications were shown on immunological regulation, survival, and quality of life in cancer patients, alone or using a combination of herbal medications with diverse mechanisms in clinical trial-based studies .in vitro and in vivo growth of colon cancer cells  and MMP9 expression. This introduces SENP1 in the progression of prostate cancer and suggests SENP1 as a prognostic marker and a therapeutic target for prostate cancer metastasis patients  is located at 12q13.11 in humans. SENP1 prefers small ubiquitin-like modifier (SUMO1) over SUMO2/3 for deSUMOylation . Decreaser cells . Prostater cells . SENP1 rpatients . Moreoveigration .vs. human hepatocellular carcinoma (HCC) metastasis. Data represented SENP1 knockdown leads to the inhibition of HGF-induced proliferation and migration at the same time  with the SENP1 protein which act as compounds for molecular dynamics simulation (MDS) and were selected based on higher docking free energy and the lowest toxicity. Moreover, we carried out virtual screening of the ZINC database, and the selected compounds with high docking free energy and the lowest toxicity were applied for MDS.To survey 28 natural compounds, we selected a suitable protein structure based on the resolution and amino acids of the binding site. Initially, the SENP1 protein and natural compounds were prepared using Molegro Virtual Docker and the SENP1 active site was determined. Then, molecular docking was carried out between SENP1 and the compounds. The compounds were also evaluated by Lipinski’s rule of five, and ADMET and TOPCAT modes. Then, the selected compounds underwent MDS and essential dynamic analysis, as shown in http://www.uniprot.org/) (https://www.rcsb.org) (http://zinc.docking.org/) (http://pubchem.ncbi.nlm.nih.gov) (Protein information was extracted from the UniProt database (ot.org/) , and thecsb.org) . Referring.org/)  and PubCnih.gov) , naturalMolecular docking of SENP1 was performed with natural compounds including apigenin, aspirin, berberine, catechin, curcumin, cinnamic acid, ethyl gallate, ferulic acid, kaempferol, naringin, naringenin, quercetin, resveratrol, rutin, rusmarinic acid, silybin, silymarin, senegenin, sulforaphane, tangeretin, tannic acid, triptolide, ugonin, urolithin A, urolithin M5, ursolic acid, usnic acid, ugonin, veatric acid, and momordin IC using AutoDock software . The bin5 energy evaluations with the maximum of 27,000 generation numbers were performed in this simulation. The population size was fixed at 150 in each run, mutation rate at 0.02, and crossover rate at 0.80. For the ligands, the torsions were defined using the “Ligand torsions” menu option of AutoDock4. Other parameters were set to default amounts  points at the center and with the grid resolution of 0.375 Å to cover the SENP1-binding site. Docking was performed with a genetic algorithm. Then, 25×10 amounts . DiscoveAfter molecular docking, it is necessary to investigate the toxicity effects of these compounds. When a chemical compound is used as an oral drug, it first enters the stomach. The drug must be resistant to the vicinity of gastric acid and must be able to enter intestinal cells after passing through the stomach. The drug must be able to enter the bloodstream through the intestinal wall and go through the blood vessels to the liver. In the liver, the drug must show resistance to metabolism, until it eventually enters the bloodstream and reaches the target. It is observed that a drug whose computational and laboratory effects were verified on the target protein may not be suitable for using as an oral drug because this complex route may cause changes in its pharmacological properties. On the other hand, about 20 years ago, before the introduction of computational methods, about 50% of potential therapeutic compounds failed before entering the clinical stage. Therefore, a successful drug is not necessarily the best inhibitor of its purpose. It needs to meet the necessary criteria such as absorption, distribution, metabolism, excretion, and toxicity (as indicated by ADMET) and TOPKAT that is based on QSAR and QSTR models.The human body is constantly exposed to multiple compounds over time. During development, several defense barriers have been created to inactivate them, including the family of cytochrome P450 isoenzymes (CYP) present in the liver, the active return of drug compounds using permeability glycoprotein (P-gp), the blood–brain barrier, and the glomerular filtration assembly in kidneys. Because the range of chemical compounds is so wide, it is almost impossible to examine each of them in the laboratory. However, further investigation can be assisted by the QSAR and QSTR methods. The basis of these methods is based on the principle that compounds with similar structures will have similar functions .in vitro for a period of 2 years on mice and rats. The TOPKAT model is a tool for using these data as training series and using QSTR methods and finding similar structures in the newly introduced structure to predict the toxic properties of new compounds.As explained, the ADMET method is based on a training series, so its operation is dependent on an experimental database. However, in the TOPCAT method, the effects of different chemical compounds at different concentrations were measured 3. SPC/E water molecules were added to solvate the system. Solvation was performed with 1 nm of the distance between the cage edges and the protein periphery. Then, system neutralization was accomplished by the addition of seven chloride ions. To inhibit the instability of the MDS, the solvated system was subjected to 1,000-cycle minimization. Before MDS, the temperature of the crystal structure reached 300 K and was balanced during 100 ps at the conditions of constant volume and temperature (NVT). Then, the system was changed to a constant pressure and temperature (NPT) and was balanced for 100 ps. The non-bonded cut-off was fixed at 10 Å, and the non-bonded pair list was updated every five steps. MDS was performed via the particle mesh Ewald (PME) parallel version in GROMACS. The LINKS mode was used to impose all hydrogen bonds and motion equation integration .The GROMACS 4.6.5 package was run on a great-performance Linux cluster to distinguish the behavior of ligands with GROMOS53a6 force field . The PROegration , and stregration . We perfTo count the binding energy of biomolecular complexes, MM-PBSA was extensively utilized and its combination with the MDS is an effective manner to study biomolecular interactions. Other uses of g_mmpbsa include the better potency to differentiate inactive and active lead molecules, rescoring of docked assemblies, and decomposing of the total counted binding energy into portions per residue . The MM-g_mindist built-in functions of the GROMACS package, respectively. Interactions between SENP1 and ligands were portrayed in Discovery Studio , root-mean-square fluctuation (RMSF), hydrogen bond (Hb), radius of gyration (Rg), solvent-accessible surface area (SASA), dictionary of the secondary structure of protein (DSSP), and minimum distance (mindist) using g_rmsd, g_rmsf, g_hbond, g_gyrate, g_sasa, do_dssp, and y Studio .Essential dynamics, known as the principal component analysis (PCA), can show the collective atomic motion of compound–SENP1 complexes by the GROMACS tool. PCA was computed using g_covar and g_anaeig built-in functions of the GROMACS package. PCA is a standard protocol for the characterization of eigenvectors and the projection across the first PC1 and PC2 .For virtual screening, A total of 20 compounds obtained from the virtual screening of 84,000 natural compounds of the ZINC database, according to CDOCKER energy, were docked with SENP1 using AutoDock.4, according to molecular docking instructions (section 2.1 of the present study). Toxicity of the 20 compounds was measured by Lipinski’s law, and ADMET and TOPCAT criteria. Then, the desired compounds in terms of binding energy of AutoDock.4, CDOCKER energy, ADMET, and TOPCAT were extracted. Finally, three compounds were selected and applied for further studies with molecular dynamics.Here, molecular dynamics was performed for 100 ns for further investigation of selected compounds , according to the Molecular Dynamics Instruction (section 2.2 of the present study). We also applied PCA to these compounds (according to section 2.4 of the present study).We performed flexible docking using AutoDock.4 so that the optimal ligand geometry was defined in docking. Furthermore, the present molecular docking studies could contribute to further development and understanding of SENP1 inhibitors for the prevention of cancer. The compounds are presented according to their binding energy in 2. All compounds could be localized in the mitochondria except cinnamic acid, which could be localized in the plasma membrane.Drug-likeness is a qualitative meaning used in the design of a drug, indicating how a substance is “drug-like”. The drug-likeness properties of these compounds were gained using Lipinski’s rule of five, ADMETSAR, and TOPCAT. All of the compounds obeyed Lipinski’s rule of five. The results of the drug-likeness by ADMET and TOPKAT are presented in Another indicator that was evaluated at this stage was the ability to bind and suppress glycoproteins that are actively involved in the removal of xenobiotics from the cell. The ideal drug-like compounds are compounds that do not bind to glycoproteins and, therefore, do not leave the cell. In this case, five compounds were neither substrates for glycoproteins nor inhibitors. The point to be considered is that from these selected compounds, ideal compounds are neither glycoprotein substrates nor inhibitors. Because these glycoproteins play other roles that by inhibiting them, these roles can be inhibited and the normal function of the cell is likely disturbed.Tetrahymena pyriformis toxicity (TPT) was high for all compounds, and honey bee toxicity (HBT) was high for all compounds except berberine. Moreover, all the compounds represented weak inhibition potential of the human ether-a-go-go-related gene (hERG), whose expression plays a significant role in the repolarization of the cardiac action potential  was high for all compounds except berberine. otential .vs. Carc (v3.1) test. Cinnamic acid was also carcinogenic only in the FDA Carcinogenicity Male Rat Single vs. Mult (v3.1), FDA Carcinogenicity Male Mouse Single vs. Mult (v3.1), and FDA Carcinogenicity Female Mouse Non vs. Carc (v3.1) tests. Ferulic acid was also carcinogenic only in the FDA Carcinogenicity Male Rat Non vs. Carc (v3.1), the FDA Carcinogenicity Male Rat Single vs. Mult (v3.1), and FDA Carcinogenicity Female Mouse Single vs. Mult (v3.1) tests.On the other hand, to evaluate the toxicity of the identified compounds based on the QSTR model, TOPKAT  was applied. This model is based on repetitive statistical methods with high credit ratings and highly developed. In this model, the toxic effects of these compounds based on their chemical structure were predicted. The TOPCAT results showed all compounds are safe for the AMES mutagenicity except cinnamic acid. In addition, in all the National Toxicology Program (NTP) carcinogenicity tests, berberine was carcinogenic. Berberine and aspirin were also carcinogenic only in the NTP Carcinogenicity Call  (v3.2) test, cinnamic acid was carcinogenic only in the NTP Carcinogenicity Call  (v3.2) test, and ferulic acid was carcinogenic only in the NTP Carcinogenicity Call  (v3.2) test, while resveratrol was not carcinogenic in any test. The Food and Drug Administration (FDA) carcinogenicity tests emphasize the contact frequency, and long-term effects faced the compounds under investigation. Berberine was not carcinogenic in any FDA carcinogenicity test. Resveratrol and aspirin were carcinogenic only in the FDA Carcinogenicity Male Rat Non vs. MLD/NON (v5.1) test. Through the Ocular Irritancy SEV vs. MOD (v5.1) test, aspirin, berberine, and ferulic acid cannot cause ocular irritation and through the Ocular Irritancy MLD vs. NON (v5.1) test, only aspirin and ferulic acid do not cause ocular irritation. In the aerobic biodegradability test, berberine, cinnamic acid, and ferulic acid were biodegradable, which means these compounds can be biodegraded by air. We concluded using TOPCAT and ADMET properties, resveratrol and aspirin have the lowest carcinogeneses and toxicity properties. These five compounds showed most favorable factors, for example, lower carcinogenicity and mutagenicity, crossing the blood–brain barrier and intestinal wall, penetration to CaCO2, no inhibition of CYP enzymes and glycoprotein, and aerobic biodegradability.Developmental toxicity potential indicates mutagenic characteristics during development that can restrict their use in pregnancy; non compounds were mutagenic except for berberine. The skin irritation test (v6.1) showed only berberine cannot irritate the skin. Skin sensitization examination revealed berberine, resveratrol, and aspirin do not cause skin allergies in the Sensitization NEG v SENS (v6.1) test, and all compounds cause skin allergies through the Skin sensitization MLD/MOD v SEV (v6.1) test. The ocular irritancy test also showed only resveratrol and aspirin cannot cause ocular irritation through the Ocular irritancy SEV/MOD The simulation of physical interactions and moves of molecules and atomic systems by the computer simulation method known as MDS was carried out. Affinity and binding mechanisms of compounds to the SENP1 at an atomistic scale were applied to explore binding free energy prediction. Since aspirin, berberine, cinnamic acid, ferulic acid, and resveratrol had high binding energy and lowest toxicity, they were selected for further steps.Analogical analysis of structural aberrations in free-SENP1 and ligand–SENP1 complexes such as RMSD, RMSF, H-bond, Rg, SASA, DSSP, and mindist was calculated.The average binding energy for different ligands was computed, which includes 35.791 for aspirin, −3.918 for berberine, 197.111 for cinnamic acid, 441.350 for ferulic acid, −82.829 for resveratrol, and −455.685 kcal/mol for momordin.The behavior of the ligands during simulation was evaluated through the RMSD . RMSD waRMSF of the compound–SENP1 complexes and free-SENP1 amino acids are shown in Rg is an indicator of the level of structure compaction, i.e., the polypeptide is unfolded or folded . The Rg Furthermore, hydrogen bonding is a factor that plays a major role in maintaining the protein stable conformation . To realWe also computed the intramolecular hydrogen bond with 174, 179, 173, 161, 171, and 168 hydrogen bonds for aspirin, berberine, cinnamic Acid, ferulic acid, resveratrol, momordin, and free-SENP1, respectively, as shown in 2, the average SASA for berberine, cinnamic acid, and ferulic acid was found to be 70 nm2, and the average SASA for momordin was 72 nm2, as shown in The estimation of SASA provides information about the conformational changes in protein upon ligand binding . The aveThe purpose of this analysis is measuring the changes in the secondary structure of SENP1 upon binding to our compounds as a function of time. We observed the lowest of alterations in the resveratrol complex including an increase in the α-helix and 3-helix, and a decrease in bend. Most of the alterations are seen in ferulic acid, as shown in The distance between SENP1 and ligands was obtained using the embedded packages within GROMACS. The distance between aspirin, berberine, cinnamic acid, ferulic acid, resveratrol, and momordin were 0.43, 0.26, 0.22, 0.37, 0.22, and 0.21 nm, respectively, as shown in After docking and MDS, the interaction between ligands and SENP1 was visualized and analyzed using Discovery Studio, as shown in In this step, we used essential dynamics analysis to obtain the dynamics of various compound complexes. The projection of trajectories of compound–SENP1 complexes during essential dynamics in the phase space along the first two principal components (PC1 and PC2) at 300 K is plotted in For virtual screening, in the first stage, the LibDock module from Discovery Studio was used, in which the resulting compounds were sorted according to the LibDock score, and these compounds with a LibDock score greater than or equal to those of momordin were selected. A total of 787 compounds were docked through CDOCKER. Then, the compounds were selected based on CDOCKER energy. A total of 20 compounds were selected to be docked with AutoDock, as shown in The compounds ZINC33916875, ZINC85902334, and ZINC79204151 had higher binding energy and lowest toxicity than the others.Interactions between SENP1 protein and compounds ZINC79204151, ZINC85902334, and ZINC33916875 with Discovery Studio are plotted, as shown in The toxicity of all 20 compounds was measured by ADMET and TOPCAT criteria, as shown in 2. All compounds could be localized in the mitochondria.AMES carcinogenicity was safe for these three compounds, and they were neither a carcinogen nor a mutagen. They can cross the blood–brain barrier and the intestinal wall except ZINC79204151 that cannot cross the blood–brain barrier. Only ZINC33916875 was permeable to CaCOOther indicators that were evaluated at this stage show the ability to bind and suppress glycoproteins which are actively involved in the removal of xenobiotics from the cell. The ideal drug-like compounds are compounds that do not bind to glycoproteins and therefore do not leave the cell. In this case, all compounds were neither substrates for glycoproteins nor inhibitors. The point to be considered is that from these selected compounds, ideal compounds are neither glycoprotein substrates nor inhibitors. All compounds were substrates of P-gp. ZINC79204151 was not an inhibitor of P-gp. However, ZINC33916875 and ZINC85902334 were inhibitors of P-gp. Another indicator that has been measured was the possibility of metabolizing by cytochrome 450 and inhibiting this complex of metabolic proteins. The compound which cannot be metabolized can accumulate in the body and lead to unwanted side effects. ZINC79204151 was neither a substrate nor an inhibitor of CYP450. However, ZINC33916875 and ZINC85902334 were CYP3A4 substrates. Similarly, ZINC85902334 was an inhibitor of CYP3A4.Tetrahymena pyriformis toxicity (TPT) was high for all compounds, and honey bee toxicity (HBT) was low for ZINC85902334 and ZINC79204151. In addition, these compounds represented weak inhibition potential of the human ether-a-go-go-related gene (hERG), whose expression plays a significant role in the repolarization of the cardiac action potential (Fish toxicity (FHMT) was high for all compounds, otential .vs. Mult (v3.1) test. ZINC85902334 was carcinogenic in FDA Carcinogenicity Male Rat Non vs. Carc (v3.1), FDA Carcinogenicity Male Mouse Single vs. Mult (v3.1), and FDA Carcinogenicity Female Mouse Single vs. Mult (v3.1) tests.The TOPCAT results showed all compounds are safe for the AMES mutagenicity test. Similarly, in all NTP carcinogenicity tests, ZINC85902334 was not carcinogenic. ZINC33916875 was only carcinogenic in the NTP Carcinogenicity Call  (v3.2) test, and ZINC79204151 was only carcinogenic in NTP Carcinogenicity Call  (v3.2) and NTP Carcinogenicity Call  (v3.2) tests. ZINC79204151 was only carcinogenic in the FDA Carcinogenicity Female Rat Single vs. MLD/NON (v5.1) test. In the Ocular Irritancy SEV vs. MOD (v5.1) test, ZINC85902334 can cause ocular irritation and in the Ocular Irritancy MLD vs. NON (v5.1) test, only ZINC33916875 can cause ocular irritation. We concluded using TOPCAT and ADMET properties, ZINC85902334 and ZINC33916875 have the lowest toxicity because these two compounds demonstrated more favorable factors, especially less carcinogenicity.Developmental toxicity potential indicates mutagenic characteristics during development that can restrict their use in the pregnancy. All compounds were safe except ZINC85902334. The skin irritation test (v6.1) showed only ZINC79204151 can irritate the skin. Skin sensitization examination revealed three compounds do not cause skin allergies in the Sensitization NEG v SENS (v6.1) test, and only ZINC79204151 through the Skin Sensitization MLD/MOD v SEV (v6.1) test do not cause skin allergies. The ocular irritancy test also showed every three compounds can cause ocular irritation in the Ocular Irritancy SEV/MOD The binding energies of ZINC79204151, ZINC85902334, and ZINC33916875 with SENP1 during molecular dynamics were also calculated with MM-PBSA to be −140.4 kcal/mol for ZINC33916875, −7.173 kcal/mol for ZINC79204151, and −84.852 kcal/mol for ZINC85902334. The RMSD was plotted to evaluate the stability of the compound complex with SENP1, as shown in Study of the Rg also showed ZINC33916875 with an Rg of 1.84 nm, ZINC85902334 with an Rg of 1.84 nm, and ZINC79204151 with an Rg of 1.83 nm do not have a significant effect on protein folding, as shown in The distance between SENP1 and ligands was obtained using the embedded packages within GROMACS. The distance between ZINC79204151, ZINC85902334, and ZINC33916875, and momordin was 0.25, 0.21, 0.26, and 0.21 nm, respectively, as shown in In the molecular dynamics simulation, ZINC85902334 and momordin formed more hydrogen bonds. ZINC85902334 and ZINC33916875 bind to SENP1 with a higher number of van der Waals bonds. ZINC79204151, ZINC85902334, and ZINC33916875 bind to amino acids of the active site of SENP1, while momordin had no connection with the active site of SENP1, as shown in The projection of trajectories of these compounds during the essential dynamics in the phase space along the first two principal components (PC1 and PC2) at 300 K is plotted in in silico screening. We also represented gallic acid can potentially inhibit SENP1 for cancer treatment (During the past decades, cancer has been the primary reason for death worldwide. SENP1 is a main protease in deSUMOylation. The list of SUMOylated proteins is increasing and includes proteins located in the most of the microcellular sections that are involved in cell cycle regulation, transcription, survival, and proteins involved in the cell death. The experimental results have shown the SENP1 protein is involved in cancer . Qiao etreatment , bethanireatment , and betreatment . This stIn this study, first, we examined 28 compounds for SENP1 inhibition. Among them, aspirin, berberine, cinnamic acid, ferulic acid, and resveratrol showed high docking binding energy and lowest toxicity, and then, they were selected for MDS. The MDS results demonstrated tesveratrol constitute a stable complex with SENP1, high free energy, more hydrogen bonds, more stable RMSD plot, stable Rg and SASA plots, and lower distance with SENP1. Resveratrol is a popular polyphenolic molecule that is present in various foods, such as fruits, vegetables, and chocolate. In addition, resveratrol is a popular part of grapes and wines . It has In the following section, because the compounds from the first section were not sufficient for conclusion, we studied 84,000 library of the ZINC database through molecular docking by LibDock and CDOCKER modules. Then, 20 selected compounds docked with AutoDock.4 and, at the end, compounds with higher docking binding energy and the lowest toxicity were applied to MDS. MDS of the final three compounds showed ZINC85902334 is more stable than the other two compounds, with high hydrogen bonds, strong interactions with SENP1, low RMSD, high binding energy, and lower distance with SENP1 . TherefoAccording to our results and other results, we hope these compounds, especially resveratrol and ZINC85902334, can effectively treat various and complex diseases, especially cancer, and these compounds can be examined to treat other diseases with the overexpression of SENP1. We screened a library of the ZINC database and measured a big scale of natural compounds for SENP1 inhibition. In addition, in the best scenario, as a result of further investigations, side effects of the compounds can be reduced and the cost of anticancer drugs can be reduced. These compounds could be new leads for treatment of diverse cancer cell lines. To choose molecules with therapeutic potential, computational tools such as ADME/Tox properties, ligand-based virtual screening, and molecular dynamics  have the


ATP1A1, LRRC4C, SPCS2, XRRA1, CELF4, NTM, TMEM45B, ATE1, and FGFR2, were associated with udder traits, while the ENSCHIG00000017110, SLC9A8, GLRB, GRIA2, GASK1B, and ENSCHIG00000026285 genes were associated with litter size. These SNPs and candidate genes can provide useful biological information for improvement of the reproductive traits of goats.Reproductive traits are the basic economic traits of goats and important indicators in goat breeding. In this study, Dazu black goats , an important Chinese local goat breed with excellent reproductive performance, were used to screen for important variation loci and genes of reproductive traits. Through genome-wide association studies (GWAS), 18 SNPs were found to be associated with kidding traits , and 10 SNPs were associated with udder traits . After gene annotation of the associated SNPs and in combination with relevant references, the candidate genes, namely  Goats are one of the most important livestock in China, and the goat industry plays an important role in improving the national economy. According to the report of the Ministry of Agriculture, there are nearly 120,000 Dazu black goats (DBGs) in southwest China. It is an important local goat breed in Chongqing and has been widely farmed because of its excellent reproductive performance. The birth rates of twins, triplets, and quadruplets can reach 47.27, 40.02, and 10.29%, respectively, in this breed [FecB gene has been identified as a high-breeding gene for sheep, goats still do not have a recognized candidate gene with a strong correlation with kidding traits. So, to understand the genetic basis of litter size traits, many molecular biology and genetic studies have been carried out to detect chromosome regions, candidate genes, and genetic markers associated with reproductive performance in goats [Reproductive characteristics are important economic traits in the goat industry, and improving the kidding traits of goats is particularly important for increasing the economic benefits of the goat industry. Litter size is a very important economic trait, and is affected by many factors, including ovarian follicular development, ovulation, fertilization rate, embryonic development, and embryo implantation , and litin goats ,6,7. Genin goats . Previouin goats , horn stin goats , body coin goats , and milin goats .MARF1, SYCP2, TMEM200C, SF1, ADCY1, and BMP5 genes. Xu et al. [BMPR1B, FBN1, MMP2, GRIA2, SMAD1, and CTNNB1 genes were associated with litter size. To study the genomic regions related to the teat and udder structure of Canadian Angus dairy cows, Devani et al. [Many candidate genes and genetic markers are associated with reproductive traits in mammals. Islam et al.  found seu et al.  conductei et al.  conductei et al.  conducteTo better understand the genomic regions and biological pathways affecting the reproductive traits of DBGs, we performed a genome-wide association analysis of seven reproductive traits. The SNPs and candidate genes identified in this study can provide useful biological information for improvement of the reproductive traits of goats.The Chongqing Key Laboratory of Forage and Herbivore approved this experiment. All goat experiments followed the Institutional Animal Care and Use Committee of Southwest University regulations (IACUC-20230306-16), and no animals were anesthetized or euthanized during this study.(1)Udder depth (UD) is the vertical distance from the root of the left udder to the top of the teat.(2)Teat diameter (TD) is the teat diameter of the left udder.(3)Teat length (TL) is the teat length of the left udder.(4)Supernumerary teats (SNTs) were observed and recorded with the naked eye.In this study, a total of 150 female DBGs aged 3–5 years and weighing 35–40 kg were selected from Tengda Animal Husbandry Co., Ltd. . We also collected data on litter size (LS) and used Microsoft Excel to calculate the average litter size (ALS), average litter size in the first three parity (ALS3), and average litter size in the first six parity (ALS6), and the udder traits of 80 does in constant lactation period were measured:The genome data used in this study were generated as part of a previous whole-genome resequencing study, where the sequencing of each sample was performed on the DNBSEQ-T7 platform  . The avep < 1 × 10−6. Phenotype quality control criteria: delete individuals with phenotypic deletion [kγk is the marker effect to be tested; ξ~N  is the polygenic effect; e~N  is the residual effect; and K is the kinship matrix inferred from the SNPs.Standard quality control of genotypes and phenotypes is needed in GWAS to eliminate the influence of abnormal genotypes and phenotypes on the results of the analysis. The genotype QC process removes individuals or loci that meet the following criteria: (1) deletion rate > 10%; (2) minor allele frequency (MAF) < 1%; and (3) Hardy–Weinberg equilibrium (HWE) with deletion . Since Gdeletion  to inferdeletion  and is wp-value corrected using Bonferroni was 6.01 × 10−8. Significant SNPs were visualized as a Manhattan map and quantile–quantile (QQ) map in R (v4.0.4) [Then, we used GEEMA to obtain significant SNPs, and the (v4.0.4) .http://www.openbioinformatics.org/annovar/, accessed on 14 September 2023) [Candidate genes were identified according to their physical positions and functions based on the ARS1 reference genome assembly, and the significant SNPs were annotated to the corresponding genes using ANNOVAR  measured in this study are presented in p-value distribution of reproduction traits found in the GWAS. Most of the SNPs did not deviate from the expected p-value, and only a few SNPs in ALS6 and TL showed a certain degree of deviation. After screening for and obtaining the adjusted phenotype, GWAS was performed on the identified SNPs. TBC1D22A and TAFA5, near the locus. ALS6 identified 16 important SNPs, and among them, eight significant differences were identified on chromosome 17, most of which were annotated to the GLRB gene. Additionally, one locus was identified on each of the chromosomes 6, 11, 13, 19, 27, and 28. UD identified a locus on chromosome 3 and annotated two genes ATP1A and ENSCHIG00000022779 near the locus. TD identified one locus on chromosomes 15 and 18, and annotated the LRRC4C and ENSCHIG00000000547 genes near it, respectively. TL identified one locus on chromosome 24 and 29 respectively, and two loci on chromosome 15. The loci on chromosome 15 were annotated to the XRRA1, NTM, and TMEM45B genes, while the locus on chromosome 24 was annotated to the ENSCHIG00000022267 and CELF4 genes. The locus on chromosome 29 was annotated to the SPCS2 gene. SNT identified one locus each on chromosomes 18, 23, and 26. The locus of chromosome 18 was annotated to the CD83 and ENSCHIG00000008871 genes, while the locus of chromosome 23 was annotated to the ATE1 and FGFR2 genes. The locus of chromosome 26 was annotated to the BICRA gene.The QQ plot in A total of 217 different GO entries were enriched in the selected reproduction-related candidate genes. ALS6 alone was enriched to 77 strips, while SNT, TD, UD, and TL were enriched to 63, 52, 17, and 8 strips, respectively. A large number of items were enriched in molecular functions and biological processes . The topKEGG analysis revealed a total of 40 significantly enriched pathways . UD enriLRP1B and GLRB, related to litter size. In addition, they also analyzed the effect of copy number variation (CNV) on the litter size of DBGs and found that the new CNV of the CBLB gene was significantly related to the litter size of DBGs [As litter size is an important limiting factor affecting the reproductive efficiency of goats, the identification and use of goat molecular markers to increase litter size can effectively accelerate the development of the goat breeding industry. In the study of E et al. , genome- of DBGs . Wang et of DBGs  divided GLRB gene. This gene is consistent with the candidate gene obtained by E et al. [TBC1D22A and TAFA5 genes annotated by the SNP did not correlate with goat reproductive performance. However, as a member of the TAFA family, TAFA5 can encode small secretory proteins in the central nervous system and has been shown to increase expression in human malignant tumors [TAFA5 was mainly expressed in the central nervous system, is co-located with vasopressin and oxytocin in neurons, and may be involved in the regulation of homeostasis.According to the National Animal and Poultry Genetic Resources Variety list 2021 Edition), there are eight goat breeds with an average kidding rate of more than 200%, one of which is DBG. The reproductive period of female DBGs is mostly between 5 and 7 years, while some high-yielding does can even reach eight years. The results of this study showed that a total of 1, 0, and 17 SNPs were associated with ALS, ALS3, and ALS6, respectively. These SNPs are mainly concentrated on chromosome 17, of which six SNPs are located within the  Edition,t tumors  and Bundt tumors  examinedNDST3, GLRB, and TRAM1L1 have been associated with reproductive traits of livestock. One study investigated the role of heparan sulfate polysaccharide (HSPG) in regulating uterine receptivity by targeting NDST3 deletion in mice. Results showed that although reproductive tract development and ovarian function appear to be normal in knockout dams, they remained infertile due to implantation defects [NDST3 can promote the synthesis of heparan sulfate (HS) and assist in embryo implantation [SLC9A8 is one of the regulatory genes of the sodium/proton reverse transporter (NHE) protein [TRAM1L1 has been associated with fecundity in Holstein cows using GWAS [GLRB was shown to be located in the acrosome region of spermatozoa [GLRB is related to the litter size of DBG [GRIA2 is part of the secretion mechanism of gonadotropin-releasing hormone (GnRH) [GLRB and GRIA2 genes were related to the hind leg hair traits of southern Chinese goats. In another study, Mahmoudi et al. [In this study, the significant SNPs associated with ALS6 were annotated to 14 genes. Among them, five genes including  defects . Palleriantation . In addi protein . The NHE protein . TRAM1L1ing GWAS , while Grmatozoa . Previoue of DBG . Finallye (GnRH) , which ae (GnRH) ,33,34. Te (GnRH) , throughi et al.  performeIn female mammals, the mammary gland changes dynamically throughout the reproductive cycle, which can be divided into five stages: embryo, prepuberty, puberty, pregnancy, lactation, and degeneration. This developmental process is mainly regulated by hormones, growth factors, and cytokines. Jena et al.  recordedDue to the limited number of teats, most does struggle to feed multiple kids. Therefore, teat number is an important consideration in goat breeding, playing a key role in the healthy growth of kids. In addition, supernumerary teats greatly affect the efficiency of machine milking, but Hardwick et al.  showed tATP1A1, LRRC4C, XRRA1, TMRM45B, BICRA, and CD83, etc.) were annotated. Liu et al. [ATP1A1 of Holstein cows (n = 320) and found that ATP1A1 was associated with somatic cell score and 305d milk yield, which played a role in mastitis. The candidate genes that may affect SNT are BICRA, CD83, ATE1, and FGFR2. In previous studies, Scott et al. [BICRA led to a unique neurodevelopmental disorder. CD83 is a member of the Ig superfamily. Expressed in the form of membrane binding or soluble, it can be detected in a variety of activated immune cells. It is reported that CD83 participates in the regulation and balance of the immune system and can be used as an immunomodulator with therapeutic potential [CD83 promoted the growth and proliferation of ovarian cancer cells. In previous studies, FGFR2 has mainly been related to breast cancer. Bao et al. [GH overexpression may promote breast proliferation through FGF7 and FGFR2, and FGFR2 was expressed in endometrial epithelium and trophoblastic epithelium [FGFR2 in the mammary gland of a mouse model and found that FGF/FGFR2 drives the development of breast cancer, and inhibiting FGFR2 and blocking immune checkpoints can reduce the number of cancer cells [FGFR2 plays a crucial role in normal uterine development and normal uterine function in mice after birth. Arginyltransferase 1 (ATE1) is an evolutionarily conserved eukaryotic protein located in the cytoplasm and nucleus. It can regulate metabolism and apoptosis, resulting in decreased intercellular contact and chromosome aberration [DBGs not only maintain high reproductive performance, but also ensure a high survival rate of young kids, which is strongly related to the udder function of does, in theory. In this study, the udder traits of 80 lactating does were selected for GWAS. In this GWAS, 1, 2, 4, and 3 important SNPs were detected in UD, TD, TL, and SNT, respectively, and a total of 15 candidate genes (u et al.  analyzedt et al.  found thotential . In addio et al.  showed tithelium . Lei et er cells . Additioer cells  found therration .The studies mentioned above have made different efforts in exploring the factors affecting reproductive traits in goats, but there are differences in the results of the studies, and these differing findings suggest that reproductive traits in goats are influenced by complex genetic mechanisms. Subsequent studies will explore the function of this candidate gene and the mechanism of its effect on reproductive traits.ATP1A1, BICRA, CD83, ATE1, NDST3, GLRB, GRIA2, and GASK1B may be involved in the regulation of reproductive traits in DBGs. The significant SNPs and genes identified in this study will aid in the molecular-based breeding of goats to improve reproductive performance.In this study, the genome and reproductive phenotypic data of 150 DBGs were collected and combined with GWAS. Results revealed that the genes


Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated.The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein–protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).PTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. For the characteristic Aβ and Tau pathology of AD, RAPGEF3 was associated significantly positively with AD and NF1 significantly negatively with AD. In addition, we also found ADCY5 and NF1 significant correlations with DM phenotypes. Other datasets verified that NF1, RAB14, ADCY5, and RAPGEF3 could be used as key markers of DM complicated with AD. Meanwhile, the immune cell infiltration score reflects the different cellular immune microenvironments of the two diseases.The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases. Type 2 diabetes mellitus (DM) is a complex disease characterized by insulin resistance, the neurodegenerative mechanisms are inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction . The priThe common transcriptional feature provided a novel and feasible scheme for the common pathogenesis of AD and DM at the genetic level. We analyzed the two gene expression matrix (GSE97760 and GSE95849). Comprehensive bioinformatics and enrichment analysis will determine common DEGs and their function on AD and DM. In addition, the PPI network was constructed with the STRING database and analyzed with Cytoscape software. ImmuCellAI is a reliable and efficient platform for immune infiltration analysis, successfully quantifying 24 immune cell subsets of AD and DM. Finally, we identified and validated 10 significant representative hub genes in AD and DM. In addition, we validated the transcription factors of these genes and their expression in the final analysis. Revealing the hub genes of AD and DM helps clarify the common mechanism between them. It provides a new means for exploring the molecular biological mechanism of other multiple diseases.n = 9) and healthy controls (n = 10) (n = 6) and healthy female controls (n = 6) from the peripheral blood mononuclear cells  . GSE9584ar cells .p < 0.05 and |logFC| ≥ 1 were identified as DEGs. The Funrich was used to obtain the common DEGs between AD and DM.The GEO query package reads matrix data in Rstudio. Remove probe sets without gene symbols and take their maximum values for genes with multiple probe sets. Only the genes value with p < 0.05 was considered significant.Gene ontology (GO) is a multifaceted annotation of the genome for biological processes, cellular components, and molecular functions . The Kyohttp://string-db.org) (version 11.5) constructed an interaction network between genes with a combined score of over 0.4 (https://clue.io/) database, DEGs were compared with a reference dataset, pert type selected for perturbation types, and trt cp selected for compounds. A connectivity score was obtained according to the enrichment of DEGs in the reference gene expression profile. A negative correlation analysis was performed to predict small molecule drugs capable of reversing the pathology of the disease , a widely used database for evaluating cell infiltration in the microenvironment  to evaluate and select hub genes. Subsequently, based on these hub genes, we constructed a co-expression network T-test, a p-value <0.05 was considered significant.iRegulon implements a genome-wide ranking and recovery approach to detect enriched transcription factor motifs and their optimal sets of direct targets . SubsequGO functions and KEGG Pathway enrichment analyses were performed to analyze the biological functions and pathways involved in the 339 common DEGs . GO analThe PPI network contains 233 nodes and 286 interaction pairs . DEGs weDetecting the microenvironment has a significant reference value for clinical treatment sensitivity and disease diagnosis . After sPTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, and RAB14) and three down-regulated genes  (ADCY5 and PRKACG) were almost involved in all top 10 KEGG Pathways  . Table 1 PRKACG) . Further PRKACG) . InteresPathways . Thus, nEEA1, LRRK2, NF1, PTGS2, RAB10, RAB14, and SOS1 were significantly positively associated with immune infiltration scores, and ADCY5, RAPGEF3 were significantly negatively associated with immune infiltration scores  networks, which have two hidden layers and five neurons in each hidden layer. For the obtained mlpcla model, the network structure of the model can be visualized using the plotnet  function. After running the program, the image shown in NF1, LRRK2, EEA1, etc. , we found that RAPGEF3 was significantly positively correlated with Aβ and Tau, while NF1 was significantly negatively correlated with Aβ and Tau. Besides, we also use the Attie lab diabetes database  and found that ADCY5 and SOS1 had a significant positive association with insulin and body weight, but significantly negatively associated with glucose; On the contrary, PTGS2, EEA1 were significantly and positively associated with glucose, but a significant negative association with insulin and body weight. Human Genetic Evidence Calculator , the query results showed ADCY5, NF1 significant associations with type 2 diabetes phenotypes  may regulate the expression of hub genes . Furtherub genes .There is growing evidence that both DM and AD diseases are involved in impaired glucose homeostasis and changes in brain function . CurrentPTGS2, RAB10, LRRK2, SOS1, EEA1, NF1, RAB14, ADCY5, RAPGEF3, and PRKACG. GO, and KEGG pathway enrichment disclosed that hub genes were significantly involved in inflammatory, immune, insulin regulation, and hormone metabolism pathways. These 10 genes may play an important role in AD and DM diseases, and play a regulatory role in the occurrence and development of the two diseases.In this study, we screened 10 hub genes from 339 overlapping DEGs, including Endocytosis is an active transport system, which involves the cell membrane of transport molecules entering and leaving the cell through the endocytosis transport system, and all components of the system form the endocytosis pathway . When thADCY5) can be used as an effector of neurotransmitters such as the D2 dopamine receptor, mu, δ opioid receptor, and mGluR3 glutamate receptor. It is preferentially expressed in the dorsal striatum and nucleus accumbens, and to a lesser extent in other regions of the brain, such as the prefrontal cortex and cerebellum  and prostaglandins (PGs) are involved in the pathogenesis of AD, COX-2 dysregulation influences abnormal cleavage of the β-amyloid precursor protein, aggregation, and deposition of β-amyloid plaques and the inclusion of phosphorylated tau in neurofibrillary tangles. The mechanisms of PTGS2 regulation of AD may include neuroinflammation, oxidative stress, synaptic plasticity, neurotoxicity, autophagy, and apoptosis   . Besidesed in AD .EEA1) was significantly increased in the human cerebrospinal fluid from AD patients compared with neurological controls, and EEA1 levels correspond to the increased total-tau levels , thereby effectively controlling the development of DM symptoms; Thirdly, the function of hub genes in disease needs further verification by corresponding biological models. Whether these genes have positive significance for clinical evaluation remains to be explored, which will be a challenge for our future work in AD and DM.However, we have to point out some limitations of this study. First of all, this is a microarray data analysis study, which theoretically belongs to the retrospective study, although this approach can speed up our work efficiency in discovering disease mechanisms, more external verification is needed to verify the key objects of our findings; Secondly, the development of DM into AD is a dynamic and slow process. In the future, we will study the gene matrix of DM complicated with AD, and look for the marker genes of this process  can be found in the article/X-fX and X-rL developed a major research plan. W-jX and XW analyzed the data. S-qC, Y-yB, and C-sL drew charts. M-nL and X-wY wrote manuscripts. L-lY and X-xW helped to collect data and references. JW and S-yZ implemented corrections in the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (no. 81973480) and the National Key Research and Development Program of China (no. 2019YFC1711500).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to investigate the outcomes of patients who received early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy due to esophageal cancer.A prospective randomized clinical trial was performed between March 2020 and June 2022. Patients who were scheduled for thoracoscopic and laparoscopic esophagectomy due to esophageal cancer were enrolled. Then, these patients were assigned to the control group  and study group . The outcomes, which included the length of hospital stay and medical expenses, and postoperative complications, which included pulmonary infection, atelectasis, respiratory dysfunction and anastomotic leakage, were compared between these two groups.P < 0.05). Moreover, there were statistically significantly fewer incidences of overall complications in study group, when compared to the control group .A total of 106 patients were enrolled for the present study, and 53 patients were assigned for the control and study groups. There were no statistically significant differences in gender, age, and location of the esophageal cancer between the two groups. Furthermore, the length of hospital stay was statistically significantly shorter and the medical expenses were lower during hospitalization in the study group, when compared to the control group (12.3 ± 1.2 vs. 18.8 ± 1.3 days, 5.5 ± 0.9 vs. 7.2 ± 1.2 Chinese Yuan, respectively; all, For patients with esophageal cancer, early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expense and incidence of postoperative complications. Esophageal cancer has been reported as the 7th most common malignancy in the world . The higIt has been reported that different strategies, including adequate pain control, respiratory muscle training, nebulizer treatment, fluid balance control, and corticosteroid administration, can be employed to decrease pulmonary secretions after esophagectomy, with variable efficacies –10. FurtThe present study conducted a randomized clinical trial, and compared the postoperative outcomes of patients with or without fiberoptic bronchoscopic sputum aspiration and lavage after minimally invasive thoracoscopic and laparoscopic esophagectomy, with the purpose of improving the recovery and prognosis of these patients.A prospective randomized clinical trial was performed at the Affiliated Hospital of Putian University, Putian, Fujian, China, between March 2020 and June 2022. The study protocol was approved by the hospital ethics committee. All study participants provided a signed informed consent.The participant inclusion criteria were, as follows: (1) patients between 44 and 76 years old; (2) esophageal cancer patients who were scheduled for thoracoscopic and laparoscopic esophagectomy; (3) patients with normal preoperative cardiopulmonary, hepatic and renal function evaluations. The exclusion criteria were, as follows: (1) patients with a previous history of psychiatric disorder, (2) patients with coagulation dysfunction, and (3) patients with previous thoracic surgical operations.The baseline characteristics, including the demographics, history of smoking, alcohol abuse, diabetes, chronic obstructive pulmonary disease (COPD), neoadjuvant therapy, and location and stage of the esophageal cancer, were recorded. The patients were randomized to the control and study groups using the random ball method. After the thoracoscopic and laparoscopic esophagectomy, patients in the control group received traditional treatment, while patients in the study group received fiberoptic bronchoscopic lavage and sputum aspiration, in addition to traditional treatment.The thoracoscopic and laparoscopic esophagectomy was performed according to the standard method . At postThe fiberoptic bronchoscopic sputum aspiration and lavage was performed according to the following steps: (1) the fiberoptic bronchoscope, adequate light source system, negative pressure suction, oxygen saturation monitor, oxygen supply, and cardiac monitor were prepared in advance; (2) the patient was laid flat, and high-flow oxygen (6–8 L/min) was provided for 20 min before the procedure; (3) the nasal cavity was cleaned, and topical 2% lidocaine was applied for local anesthesia; (4) a fiberoptic bronchoscope was inserted through one nostril, and high-flow oxygen was provided through the other nostril to maintain an oxygen saturation of > 90% throughout the procedure; (5) a bronchoscope was entered into the left and right bronchus, respectively, and the sputum was aspirated with a constant negative pressure of 150 mmHg ; (6) the fiberoptic bronchoscope was withdrawn. The whole procedure was performed for approximately 15 min. The procedure was terminated when the patient had bradycardia, hypotension, or an oxygen saturation of < 85%.The outcomes were the entire length of hospital stay and the medical expenses during hospitalization. Postoperative complications, including pneumonia, atelectasis, pulmonary dysfunction, vocal cord paralysis, and anastomotic leakage, were documented. Atelectasis was defined as the partial or complete collapse of one side, lobe, or segment of the lungs. Pulmonary dysfunction was defined as an arterial blood oxygen partial pressure of < 60 mmHg in the resting position in room air, with or without a carbon dioxide partial pressure of > 50 mmHg, after excluding interventricular shunt and reduced cardiac output. Vocal cord paralysis refers to the loss of adduction, abduction, and normal tone of the vocal cords, resulting in voice change, protective laryngeal sphincter adduction, or difficult breathing. It was diagnosed by the fiberoptic bronchoscopic examination in patients with clinical symptoms suspected to have vocal cord injury. Anastomotic leakage is defined as the formation of a fistula due to an unsealed or poorly healed anastomosis between the esophagus and stomach.t-test. Categorical data were presented in number with percentage, and compared by performing Chi-square analysis. All statistical analyses were performed using SPSS . A P-value of < 0.05 was considered statistically significant.Continuous data were presented as mean ± standard deviation, and compared using Student A total of 106 patients were enrolled and completed the study. Then, 53 patients were assigned to the control and study groups . Moreover, patients with vocal cord paralysis or COPD were further analyzed. It was found that the incidence of pneumonia was statistically and significantly lower in the study group, when compared to the control group  . FurtherThe limitations of the present study include the single-center nature of the study, and the small sample size. Furthermore, the performance of the fiberoptic bronchoscopy and sputum removal was influenced by the skill of the operator. The present study results need to be confirmed through future large-scale studies.In conclusion, early fiberoptic bronchoscopic sputum aspiration and lavage after thoraco-laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expenses and incidence of postoperative complications of patients with esophageal cancer. However, further studies are warranted.


Curcumin and artemisinin are commonly used in traditional East Asian medicine. In this study, we investigated the inhibitory effects of these active compounds on xanthine oxidase (XO) using allopurinol as a control. XO was purified from the serum of arthritis patients through ammonium sulfate precipitation (65%) and ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose. The specific activity of the purified enzyme was 32.5 U/mg protein, resulting in a 7-fold purification with a yield of 66.8%. Molecular docking analysis revealed that curcumin had the strongest interaction energy with XO, with a binding energy of −9.28 kcal/mol. The amino acid residues Thr1077, Gln762, Phe914, Ala1078, Val1011, Glu1194, and Ala1079 were located closer to the binding site of curcumin than artemisinin, which had a binding energy of −7.2 kcal/mol. In vitro inhibition assays were performed using nanocurcumin and artemisinin at concentrations of 5, 10, 15, 20, and 25 µg/mL. Curcumin inhibited enzyme activity by 67–91%, while artemisinin had a lower inhibition ratio, which ranged from 40–70% compared to allopurinol as a control. Xanthine oxidoreductase (XOR) is a widely studied enzyme found in various species ranging from bacteria to humans. Despite some variations in its structure and catalytic activity among different species, XOR can be categorized into two types: xanthine dehydrogenase XDH, EC 1.1.1.204) and xanthine oxidase  .1.1.204 . XOR hasThe molecular mechanisms involved in the regulation of inflammation, immunity, oxidative stress, and cell death play a crucial role in the development of chronic kidney diseases (CKD) and acute kidney injury (AKI) . CKD andThe utilization of natural compounds in drug products has been a common practice for the treatment of various diseases ,13. One According to studies, nanocurcumin has been shown to possess higher antioxidant, anti-inflammatory, antiproliferative, and neuroprotective properties compared to normal curcumin . NanocarArtemisinin (ARS) is a potent compound with a molecular weight of 282 derived from Artemisia annua L., a traditional Chinese medicinal plant. It was first discovered in 1972 by Chinese researchers. The chemical structure of artemisinin consists of a sesquiterpene lactone with peroxide bridges, which have been proven to exhibit superior antimalarial effects ,25. WhenIn this work, the serum of arthritis patients was used to obtain XO through an ion exchange chromatography process. The resulting purified enzyme displayed a specific activity of 32.5 U/mg protein, leading to a 7-fold purification and a yield of 66.8%. Molecular docking analysis revealed that nanocurcumin had a high interaction energy with XO  and was found to bind closer to specific amino-acid residues compared to artemisinin . In vitro inhibition assays using nanocurcumin and artemisinin indicated that curcumin showed a significant inhibition (67–91%), whereas artemisinin exhibited 40–70% compared to the control, allopurinol.The isolation of Xanthine oxidase (XO), which is a widely distributed enzyme found in various species, involves extracting the enzyme from diverse sources, such as bacteria, milk, and different animal organs. Subsequently, purification is carried out to obtain a purified form of the enzyme from the crude extract . ResearcIn a specific case, Buffalo liver xanthine oxidase (BLXO) was isolated to homogeneity using chromatography and acetone precipitation methods on Sephacryl S-300 and DEAE-cellulose columns. The specific activity of the purified enzyme, measured in units per milligram of protein, was determined to be 7.2 units/mg. This represents a significant increase in purity, with a 31.3-fold improvement compared to the initial crude extract .Molecular enzyme docking studies were conducted to investigate the interaction between xanthine oxidase and nanocurcumin, as well as artemisinin. The findings revealed that the binding energy of nanocurcumin was determined to be −9.28 kcal/mol, while artemisinin exhibited a binding energy of −7.2 kcal/mol. Based on these results, nanocurcumin exhibited the lowest S-value, indicating the strongest interaction with xanthine oxidase.The principle behind molecular docking is to predict the ability of a ligand (active compound) to bind to an enzyme (receptor) and form a stable complex. This technique offers several advantages in drug design, including a reduced time and cost compared to experimental methods .In a previous study by Sumirtanurdin et al., molecular docking was employed to investigate the interaction between ligands, such as curcumin and its derivatives (korkumod 23 and 24), and the target receptor Cyclin-Dependent Kinase 2 (CDK2). The binding energies were reported to be −7.80 kcal/mol, −9.15 kcal/mol, and −9.36 kcal/mol, respectively. These values indicate the strength of the interactions between the ligands and the CDK2 receptor .Furthermore, in another study , it was The S-value serves as an indicator of the ligand’s ability to interact with the protein receptor and its potential as a potent inhibitorThe impact of xanthine oxidase inhibition on uric acid production was investigated, and the active compounds exhibited inhibitory activity against xanthine oxidase at all tested concentrations. Xanthine oxidase inhibitors (XOIs) play a significant role in the treatment of hyperuricemia and gout by reducing the levels of circulating uric acid and alleviating vascular oxidative stress associated with elevated uric acid levels. The main function of XOIs is to inhibit the biosynthesis of uric acid from purine in the body. In addition to pharmaceutical XOIs, various herbs and their extracts have been traditionally used for the treatment of conditions caused by increased xanthine oxidase activity. These natural remedies have shown potential in modulating xanthine oxidase activity and may offer alternative options for managing hyperuricemia and related disorders . Turmeri6H3(OCH3)CH=CHCO]2CH2, while artesunate has a chemical formula of C19H28O8 and was in microsize. Additionally, we procured a range of high-quality chemicals for our study from reputable suppliers, in order to process the investigation. Here, Odium nitrate, DMSO, MTT stain, EDTA, RPMI 1640 media, RPMI media, trypsin, fetal bovine serum, ascorbic acid, sodium chloride, and sodium bicarbonate were obtained from Sigma-Aldrich . These chemicals are essential for various experimental procedures and analytical assays conducted during our research. Additionally, we sourced Tris-HCl, bovine serum albumin (BSA), Coomassie brilliant blue G-250, DEAE-cellulose, sodium chloride, aluminum chloride, hydrochloric acid, and rutin from BDH . These high-quality reagents were carefully selected to ensure accurate and reliable results for our study.Nanocurcumin and artesunate were obtained from Sigma-Aldrich with purities of 99% and 98%, respectively. Curcumin has a chemical formula of HOCCurcumin, which exhibited a higher impact compared to artesunate, was characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). TEM is a technique used to visualize and analyze the size, shape, distribution, and crystal structure of nanoparticles. In this study, TEM images were acquired using the EM 208S (Philips) device. To prepare the samples for TEM, a mixture of nanoparticles (NPs) and ethanol was placed onto a carbon-coated copper grid. The solution was then air-dried at room temperature. This sample preparation method allows for the visualization of the nanoparticles under TEM.TEM works by directing a beam of electrons through the sample, which interacts with the nanoparticles and produces an image that can be magnified and analyzed. By examining the TEM images, detailed information about the size, shape, and distribution of the nanoparticles can be obtained, providing insights into the physical characteristics of curcumin in this study. Additionally, XRD analysis can be performed to further investigate the crystal structure of curcumin and provide complementary information about its molecular arrangement.In X-ray diffraction (XRD), a beam of X-rays is directed at a sample, and the interaction of the X-rays with the atoms in the sample produces a diffraction pattern that can be detected and analyzed. The diffraction pattern provides valuable information about the crystal structure of the sample, including the lattice spacing, the orientation of crystal planes, and size and shape of the unit cell. The angle between the incident beam and the diffracted beam is known as the diffraction angle . In XRD, the diffraction angle is typically measured as 2θ, which is twice the angle between the incident and diffracted beams. By measuring the 2θ values for a series of diffraction peaks from a sample, it is possible to determine the crystal structure, lattice parameters, and other properties of the material.In our study, the XRD measurements were conducted using the X’Pert Pro MRD apparatus from PANalytical. This XRD instrument is capable of analyzing the diffraction pattern produced by the X-rays interacting with the curcumin sample. The obtained diffraction data can be further analyzed to gain insights into the crystal structure and other relevant characteristics of curcumin.Xanthine oxidase was extracted and purified from the serum of Iraqi patients suffering from arthritis using a two-step purification technique, as described by .In the first step, solid-phase ammonium sulfate was gently added to 50 mL of the crude enzyme to achieve a 65% saturation ratio. The mixture was then centrifuged for 20 min at 6000 rpm, and the resulting precipitate was dissolved in an appropriate amount of 0.05 M phosphate buffer. In the second step, the precipitate obtained from the previous step was dialyzed against the aforementioned buffer for 24 h under cooling conditions (4 °C), using a dialysis tube with a 3500 Mw cutoff. Enzyme activity and protein concentration were determined.In the third step, the enzyme solution obtained from the previous step was applied to a 3 × 25 cm DEAE-cellulose column, which had been pre-equilibrated with potassium phosphate buffer . The column was rinsed with the same buffer, and XO was subjected to a 0.1–1 M NaCl concentration gradient at a flow rate of 30 mL/h.The xanthine oxidase activity was determined using the method outlined in . The absThe protein-ligand binding affinity was assessed using the Molecules Operator Environment (MOE) software, following the procedure described in . The XanThe structures of the inhibitors were also optimized through energy minimization. The binding affinity was evaluated using a statistical value known as the S-value, which was calculated based on the identification of hydrogen bonds, salt bridges, solvation effects, and hydrophobic interactions .The XO-hindering activity under aerobic conditions was assessed using a modified version of the method described in . The reaThe XO protein was retrieved from the Protein Data Bank, and its structure was optimized by removing water molecules, adding hydrogen atoms, adding missing side chains, and minimizing its energy. The structures of the inhibitors were also optimized through energy minimization. The binding affinity was evaluated using a statistical value , which was estimated by identifying hydrogen bonds, salt bridges, solvation effects, and hydrophobic interactions. The XO was extracted and purified from the serum of Iraqi patients suffering from arthritis using a two-step purification technique. The impact of nanocurcumin and artesunate on enzyme activity was characterized via TEM and XRD techniques. Nanocurcumin and artemisinin were used in in vitro inhibitory experiments at doses of 5, 10, 15, 20, and 25 g/mL. The findings demonstrated that nanocurcumin had a larger effect than artesunate, using allopurinol as a control. This research paves the way for further studying nanosize natural materials and utilizing them in therapy applications.


Olive Europa) commonly called Zaitoon. The stem branches of Zaitoon were collected and then kept in water for 40–45 days at room temperature to extract the cellulose fibers. These cellulose fibers were then kept in the Soxhlet apparatus for washing in n-hexane for 72 h. The purified cellulose was divided into three parts: one part was subjected to thermal activation (TAC), the second was modified chemically (CMC) with Benzyl Chloride, while the last one remained un-functionalized (UFC). All the three forms of cellulose were characterized via FTIR and SEM, then utilized for the removal of Titan Yellow (TY) dye from aqueous media via adsorption process by varying the contact time, temperature, concentration of dye and type, and dose of adsorbent. The adsorption efficiencies of all adsorbents were compared under different experimental variables. Thermally activated cellulose showed the best results for the removal of TY compared with other materials. The calculated removal percentage of TY was found to be 97.69, 94.83, 94.83, and 98% under equilibrium conditions of contact time, temperature, adsorbent dose, and TY concentration. Similarly, the uptake capacities of TAC under optimal experimental conditions were found to be 19.56, 18.96, 18.52, and 18.75 mg/g. Thermodynamic studies of TAC, CMC, and UFC showed that the values of ΔG are negative, while those of ΔH and ΔS are positive in all cases and at all temperatures. This indicates that the TY elimination process is endothermic and spontaneous with an entropy-driven nature. The obtained results indicate that the as-fabricated low-cost biomaterials can effectively remove dyes from wastewater through physicochemical interactions. The removal process was influenced by the nature of the adsorbent and the operating variables.This research work focuses on the isolation and thermo-chemical modification of cellulose and its application as an adsorbent for the removal of organic pollutants. The used cellulose was collected from a locally available plant ( Biopolymers are one of nature’s numerous abundant resources. Cellulose, starch, protein, DNA, etc., are all examples of biopolymers that are generated by living organisms. Cellulose is an example of a semi crystalline polymer. The crystalline parts are the cellulose whiskers, which are used as reinforcing phases in synthetic and natural polymeric matrices due to their high aspect ratio and extensive contact area. The vast specific surface area, high mechanical quality, biocompatibility, and regenerative nature of these materials all contribute to their enduring appeal. The potential uses for these nanofibers in fields such as tissue engineering and nanoelectronics are vast . Cellulo−1 were assigned to the C-Cl functional groups for UFC, CMC, and TAC, respectively. The peaks at 1039, 1018, and 1025 cm−1 represented the strong stretching of C-OH functional group. The peak at 1233 cm−1, usually allocated in thermally functionalized (TAC) cellulose, manifested the strong stretching of the C-O-C functional group. In addition, the peaks at 1643 and 1623 cm−1 in UFC and TAC were ascribed to the weak C=C alkene, while the peaks at 2358 and 2353 cm−1 in UFC and CMC, respectively, corresponded to C-N functionality. The peak at 2875 cm−1 in TAC indicated weak C-H stretching. The peaks at 3336, 3329, and 3310 cm−1 were attributed to the strong OH stretching functionality, respectively, in UFC, CMC, and TAC. Overall, the FTIR analysis reflects some qualitative changes upon thermal/chemical modifications of the base material (UF).FTIR analysis of unmodified, thermally modified, and chemically modified cellulose  adsorbenSEM micrographs of cellulosic materials such as UFC, CMC, and TAC before adsorption of TY are shown in The amount of adsorbent used is a key factor regarding the efficiency of dye removal from contaminated water. Adsorption experiments were performed using 20 mL of a 100 mg/L TY solution and 0.1 g adsorbent doe at a stirring speed of 240 rpm and a temperature of 25 °C for a contact time in the range of 20–120 min with a 20 min interval, as shown in The removal of TY has been also investigated as a function of medium temperature  for different adsorbents TAC, CMC, and UFC using a fixed dose of each adsorbent (0.1 g) for 50 mg/L dye concentration at 30 min contact time. tq, and eq are the adsorption capacity (mg/g) at time’s interval at equilibrium, while k1 and k2 are the pseudo-first order rate constant (min−1) and pseudo-second order rate constant (g/mg/min), respectively. The values of rate constants (k1 and k2) were obtained from the linear plots of log (e − qtq) versus time for PFO and et/q versus time for PSO, respectively, as presented in 2 value of 0.964 compared with the PSO model, which presents best fitting of the experimental data with high R2 (0.996) and close matching the theoretical eq values with experimental eq, as shown in The adsorption kinetics provides insightful information about the mass transfer of adsorbate from liquid medium to the solid adsorbent surface. The kinetic studies of TY adsorption on TAC, CMC, and UFC were carried out using 50 mg/L TY solution (50 mL) at room temperature and 0.1 g of adsorbents. The obtained data were then fitted to pseudo-first order (PFO) and pseudo-second order (PSO) models (Equations (1) and (2)) :(1)logqeThe experimental adsorption data of TY onto different adsorbents TAC, CMC, and UFC were investigated by means of Langmuir, Freundlich, and Temkin isotherms (Equations (3)–(5)).e, qeC, mq, and LK are the equilibrium concentration of TY, equilibrium adsorption capacity, maximum adsorption capacity, and Langmuir constant, respectively. The linearized plot of eCe/q versus Ce , which is mathematically expressed as follows :(3)Ceqe=ersus Ce A–C provieq is the adsorption capacity (mg/g), FK is Freundlich adsorption capacity mg/g, and n is the intensity constant. The representative plots of the Freundlich isotherm model for the adsorption of TY dye on TAC, CMC, and UFC adsorbents are given in The Freundlich adsorption isotherm model describes the physical nature of adsorption as a multilayer phenomenon, which is mathematically expressed as:TmK and B are Temkin’s adsorption constants, with TmK relating to maximal binding energy (mg/L) and B relating to heat of adsorption. The slope and intercept of the linear plots of eq versus elog C are used to determine these values. The Temkin plots for the adsorption of TY dye on different adsorbents TAC, CMC, and UFC are shown in The Temkin adsorption model highlights the adsorption on relatively heterogeneous surfaces of adsorbent. It also gives information on adsorbate/adsorbent interactions and enthalpy of adsorption, which decreases with the progress of the adsorption process, as shown by following equation:2 values, i.e., 0.990 and 0.983 for Langmuir and Temkin, respectively, and the relatively lower value of R2 (0.818) for the Freundlich isotherm. Adsorption on the surface of TAC, CMC, and UFC manifests relatively heterogeneously, as shown by the Temkin isotherm, and most of the TY dye is removed dominantly through chemisorption mechanism, as indicated from the outcomes of the Langmuir isotherm. Based on kinetics and isothermal results, overall, it is demonstrated that the adsorption process is not purely chemical or physical, but that it can be of a physicochemical nature. These possible physicochemical interactions may include Vander Waals forces, hydrogen bonding, and electrostatic interactions between TY molecules and the surface of these adsorbents.The results of the above-mentioned isotherm models are presented in t is the amount adsorbed at time t (mg/g). Here, we have optimized both linear and nonlinear equations of the Elovich adsorption model. For the nonlinear model, a user define equation (tq = 1/B × (ln(A × B × t + 1)) was applied in which A and B represent α and β, respectively. For the linear equation, we fitted the data directly in origin through the help of Equation (7), and the results are presented in 2 values in the range of 0.85 and 0.96. The results are consistent with the reported literature [The simplified form of the Elovich equation (Equation (6)) was utilized to determine the chemisorptive nature of TY adsorption on the surface of cellulosic adsorbents such as TAC, CMC, and UFC .(6) qt=terature . Based oThe stability, reusability, and recycling performance of UFC, CMC, and TAC toward the removal of TY dye from water solution were also tested using similar experimental conditions, such as time = 30 min, temperature = 25 °C, and initial concentration of TY = 50 mg/L, and the results are presented in dK) or equilibrium distribution constant (eqK) by using Equation (8a) at different temperatures.dK or eqK is the measure of the affinity of an adsorbent/sorbent for a particular adsorbate, which is TY dye in this case. Quantitatively, it is simply the ratio of concentration of the TY (adsorbate) adsorbed onto the sorbent (adsorbedC) to the concentration of the adsorbate remaining un-adsorbed in the bulk of the solution (eC) at equilibrium. Similarly, using the values of eqK, the values of ΔG were estimated through Equation (8b) [A thermodynamics study of TY adsorption on TAC, CMC, and UFC was also investigated to calculate the change in entropy (ΔS), change in enthalpy (ΔH), and Gibbs free energy (ΔG) by using the following equations (Equations (8)–(10)) . First oion (8b) .K versus 1/T provides the values of ΔS and ΔH. Similarly, these values were also cross-checked using Equation (10).In this Equation (9) ΔH, R, ΔS, T, and K are the enthalpy change, universal gas constant, entropy change, temperature in Kelvin, and adsorption constant, respectively. The linearized plot of lnA concise comparison of the TY dye removal performances of the present materials  with the data of some of the selected materials, reported previously, is also presented in Olive Europa was collected from the valleys of district Malakand, Khyber Pakhtunkhwa, Pakistan, cleaned and washed with distilled water, dried in oven at a temperature of 50 °C for 2 h, and used for cellulose extraction as per the following procedure.The textile dye Titan Yellow (TY) and all required chemicals including Potassium Hydroxide, Sodium Hydroxide, Ethylene Diamine, Benzoyl Chloride, and Thionyl Chloride were purchased from Sigma Aldrich  in analytical grade and were used without further purification. The chemical structures of Titan Yellow dye is given in Olive Europa were soaked in 3 L of tap water for 45 days at room temperature; as a result of this, the fibers were clearly separated out from sticks. The extracted fiber was washed with distilled water followed by drying in an oven at 110 °C for 3 h. The dried fibers were subjected to Soxhlet extraction [The 3 cm long dried shot stems of traction  with n-htraction . The chemical activation of cellulose fibers was performed via benzoylation  to obtaimax) wavelength using a UV-Visible spectrophotometer . A similar set of experiments was carried out individually for three different kinds of adsorbents . Ultimately, the obtained results were compared for optimizing the best experimental conditions and adsorbent for TY uptake.A 1000 mg/L stock solution of aqueous TY was diluted to prepare the desired working concentrations of 50, 100, 150, 200, 250, and 300 mg/L. The comparative adsorption performance of unmodified, thermally modified, and chemically modified cellulosic adsorbents were investigated for TY uptake from aqueous solution by batch experiments. The influence of experimental variables was investigated using 20 mL of TY dye solution with different initial concentrations (50–300 mg/L), adsorbent amounts (0.1–0.6 g), and at room temperature. The kinetics of TY adsorption for different initial concentrations (50–300 mg/L) was performed using 0.1 g adsorbent (fixed amount) in 20 mL dye solution at neutral pH and room temperature for a contact time ranging from 20 to 120 min. The adsorption isotherm and thermodynamics studies were carried out using a fixed amount of adsorbent (0.1 g) in 20 mL of 50 mg/L TY solution at neutral pH for 30 min contact time at different working temperatures . Aliquots of dye solution were withdrawn at regular intervals for each experiment, filtered out, followed by measuring the absorbance of solution at 403 nm (λeq (mg/g) of TY and its removal capacity (%) were calculated using the following, Equations (11) and (12):C0 and Ce (mg/L) are initial and equilibrium concentrations of TY, respectively, V is the solution volume (L), and w is the adsorbent amount used (g).The adsorbed amount In summary, we have successfully applied well-known and abundantly available materials by employing inexpensive and easily accessible approaches to modify natural biopolymer to un-functionalized cellulose (UFC), thermally activated cellulose (TAC), and thermo-chemically modified cellulose (CMC). The as-obtained materials were employed for the removal of Titan Yellow dye from aqueous media through a batch adsorption process under various experimental conditions for each adsorbent such as contact time, temperature, concentration, and dosage used. Based on FTIR, SEM, and respective adsorptive results/performance of UFC, CMC, and TAC, it can be reflected that the chemical modification of cellulose via benzoylation reaction, resulted in the addition of some new functional groups onto the cellulose surface through a chemical reaction, which altered the FTIR peak positions, surface morphology, charge, and hydrophobicity of the original cellulose (UFC) as compared with those of the CMC. Similarly, thermo-modification of cellulose may also lead to the removal of hemicellulose and lignin components, resulting in an increase in crystallinity and surface area of the cellulose UFC. This process can also lead to the formation of some new possible surface functional groups, such as carboxyl and hydroxyl groups. These changes have not only altered the surface morphology/porosity and hydrophobicity, but also the dye removal performances. The adsorption rate and capacity of these materials were found to be appreciable, with TAC exhibiting the highest percentage of dye adsorption under present experimental conditions. The materials also showed promising potential for reusability, as observed through their slightly decreased efficiency over three consecutive cycles. Based on thermodynamics and kinetics results, it is supposed that TY can interact with cellulose-based materials through common physicochemical interactions such as Vander Waals forces, hydrogen bonding, and electrostatic interactions. The results obtained in this study suggest that the investigated materials exhibit promising potential for further exploration in the field of water treatment. It is suggested that these materials could be utilized for the removal of contaminants and pathogens from wastewater, providing an environmentally sustainable and economically feasible approach to water treatment.


Invar36 alloy is a low expansion alloy, and the triply periodic minimal surfaces (TPMS) structures have excellent lightweight, high energy absorption capacity and superior thermal and acoustic insulation properties. It is, however, difficult to manufacture by traditional processing methods. Laser powder bed fusion (LPBF) as a metal additive manufacturing technology, is extremely advantageous for forming complex lattice structures. In this study, five different TPMS cell structures, Gyroid (G), Diamond (D), Schwarz-P (P), Lidinoid (L), and Neovius (N) with Invar36 alloy as the material, were prepared using the LPBF process. The deformation behavior, mechanical properties, and energy absorption efficiency of these structures under different load directions were studied, and the effects and mechanisms of structure design, wall thickness, and load direction were further investigated. The results show that except for the P cell structure, which collapsed layer by layer, the other four TPMS cell structures all exhibited uniform plastic collapse. The G and D cell structures had excellent mechanical properties, and the energy absorption efficiency could reach more than 80%. In addition, it was found that the wall thickness could adjust the apparent density, relative platform stress, relative stiffness, energy absorption, energy absorption efficiency, and deformation behavior of the structure. Printed TPMS cell structures have better mechanical properties in the horizontal direction due to intrinsic printing process and structural design. Invar36  is a Fe-Ni alloy with a face-centered cubic lattice, renowned for its low expansion property below 250 °C (Curie temperature). The Invar36 alloy was initially discovered by French scientist Guillaume and earned him the Nobel Prize in Physics in 1920 [A lattice structure is a class of lightweight structures with special mechanical, acoustic, thermal, and other physical properties constructed from one or more structural units  optimally combined in a specific way  . The perTPMS is a kind of periodic smooth implicit surface with zero average curvature. Compared with other types of porous structures, TPMS has two significant advantages: (1) the overall TPMS porous structure can be precisely described using mathematical expressions, and basic properties, such as porosity and specific surface area, can be controlled directly using the function expression parameters; (2) the TPMS surface is extremely smooth without sharp turns or connection points of pillar-based lattice porous structures, and the overall structure is interconnected, which not only reduces stress concentration but also facilitates the removal of powder during the manufacturing process. Compared to solid alloys, TPMS structures have properties such as being lightweight and having high specific strength , and theThe traditional methods for preparing lattice structures mainly include investment casting, metal wire weaving, and wire cutting, but they have certain limitations: investment casting requires high fluidity of the metal liquid, and metal wire weaving and wire cutting require complex and delicate operations with low production efficiency and limited allowable structural complexity. There is, therefore, an urgent need to develop efficient, agile, and flexible manufacturing methods to prepare complex lattice structures .Additive manufacturing, also known as 3D printing, is an intelligent manufacturing technology that uses digital models as the basis for adding materials layer by layer to create three-dimensional solid structures ,19. LaseDue to the excellent damping performance of TPMS lattice structures ,26,27 anCurrently, there are few studies on Invar alloy lattice structures. In this study, we conducted a systematic investigation of Invar TPMS structures and their mechanical properties, and explored their potential applications for the first time. Five different Invar alloy lattice structures with three wall thicknesses were prepared using LPBF technology, and compression tests were conducted in different directions. The printing parameter was optimized to achieve an exceptionally high quality, and the performance, including platform stress, stiffness, energy absorption, and energy absorption efficiency, was quantitatively calculated and systematically analyzed, and the effects and mechanism of structure, wall thickness, and load direction on the performance were discussed. Possible practical applications were also proposed.3, and the powder flowability measured by a Hall flow meter is good. A total of 50 g of powder can pass through a standard funnel with a diameter of 2.5 mm in only 15.24 s. It is observed that the majority of the gas-atomized Invar36 alloy powders exhibited a regular spherical shape, with a few smaller irregularly shaped particles. Moreover, most of the powder particles have no satellite powders on their surface, and the particle size distribution is in accordance with the normal distribution, satisfying the requirements of LPBF. In this study, Invar36 alloy powder  was produced via gas atomization method. The particle size range is between 13 and 53 μm with a D50 value of 36.28 μm, as shown in A geometric model of TPMS was established using nTopology-4.1.3 software and STL files were exported for additive manufacturing. In this study, five types of TPMS cell structures with different unit structures were designed, namely Gyroid (G), Diamond (D), Schwarz-P (P), Lidinoid (L), and Neovius (N). Each structure was set with three wall thicknesses of 0.6 mm, 0.8 mm, and 1.0 mm, so that there were 15 different samples. The unit cell length of the designed cell structures in this study was 11 mm, and each lattice was composed of 2 × 2 × 2 unit cells. Therefore, the final model size was 22 mm × 22 mm × 22 mm, which satisfies the requirements of the ISO 13314:2011 standard  that theThe TPMS structure is manufactured using an EOS-M290 machine  and a 400 W single-mode fiber laser. Through a series of parameter optimization experiments, the molding process parameters of invar36 alloy powder were determined as follows: laser power of 150 W, scanning spacing of 70 μm, scanning speed of 800 mm/s, layer thickness of 30 μm, and laser beam diameter of 100 μm. Scan strategy is unidirectional scanning, with each layer rotating 67°. The process was carried out in an atmosphere filled with high-purity argon gas.The Archimedes method was used to determine the relative density of the samples, and quasi-static compression tests are conducted using an electronic universal testing machine . The top plate was moved downward at a constant displacement rate of 0.05 mm/s, and the maximum strain was set to 75% according to the ISO 13314:2011  standardX-axis at 50% strain.Finally, the compressive yield strength, the plateau stress between 20% and 40% strain, and the unit volume energy absorption at 50% strain were calculated according to the ISO 13314:2011 standard. The yield strength was determined as the 0.2% offset yield strength. The plateau stress was calculated as the average stress between 20% and 40% compressive strain. The unit volume energy absorption at 50% strain was calculated as the area enclosed by the stress–strain curve and the Since all the specimens were prepared under the same process parameters in the same batch, their quality parameters, such as density, microstructure, and roughness, should be almost the same. The parameters of the prepared TPMS-cellular structure samples are shown in The slope of the elastic section of the stress–strain curve, i.e., the structural stiffness, increases with an increase in wall thickness for the five types of TPMS structures (as shown in As shown in −3), and the D, N, and G-cell structures have higher specific stiffness values. There is a certain degree of anisotropy in the specific stiffness values of all cell structures in different directions, and the specific stiffness in the X direction is greater than that in the Z direction. The specific stiffness of the D and N-cell structures fluctuates significantly due to the influence of the structure’s wall thickness.As shown in The energy absorption capacity of the cellular structure is an important performance indicator for its applications. The energy absorption capacity of the cellular structure can be determined by numerically integrating the stress–strain curve under compression, which is denoted as the volumetric energy absorption (Wv) :Wv=∫0εσεSEA) is the energy absorbed per unit mass of the material [SEA can be defined as:Specific energy absorption .In the equation, The energy absorption of TPMS-cellular structures at 50% strain is shown in In order to further illustrate the energy absorption capabilities of different structures, the energy absorption efficiency curves for each structure are shown in η is the energy absorption efficiency of the material, ε is the strain at a specific moment during compression, and mσ is the stress corresponding to a specific ε. It can be seen that the energy absorption efficiency first decreases and then increases, and after a period of stability or fluctuation the curve shows an overall downward trend. Except for the P-cellular structure and the 0.6 mm wall thickness N-cellular structure, the energy absorption efficiency curves of all the structures are relatively stable, and the rapid decline in the later stage of the curve is mainly due to the rapid increase in the stress–strain curve during the densification stage. The energy absorption efficiency of all wall thicknesses of the D-cellular structure is mostly above 75% during the compression deformation process because the stress–strain curves of all wall thicknesses of the D-cellular structure have a longer plateau period. The energy absorption efficiency curve of the P-cellular structure is similar to that of the 0.6 mm wall thickness N-cellular structure, and the corresponding energy absorption efficiency curve fluctuates more due to the obvious shake in its stress–strain curve compared to the stress–strain curves of other structures. At the strain corresponding to the trough position of the stress–strain curve, the energy absorption efficiency of the P-cellular structure and the 0.6 mm N-cellular structure exceeds 1. At this point, the energy absorption of the lattice structure  may exceed the ideal energy absorption value  as shown in The mechanical properties of lattice structures depend on their topology, relative density, and base material. Compared to pillar-based lattice structures, TPMS structures have higher self-supporting capabilities. In addition, pillar-based lattice structures tend to have severe stress concentration at the pillar nodes. In contrast, TPMS surfaces have a more uniform stress distribution and higher stiffness . TherefoThe five TPMS structures designed in this study exhibit significantly different mechanical properties. As shown in At the same wall thickness, the L-cell structure has a higher plateau stress and stronger energy absorption capacity than the other structures, but its relative stiffness and resistance to deformation are weaker. Moreover, the energy absorption efficiency of the L-cell structure is not stable during the entire deformation process, and it drops sharply after a strain greater than 30%, which is mainly due to the relatively high relative density of the L-cell structure, short platform period, and too rapid densification process  and the X-Z plane (Z direction) to determine the grain morphology and orientation characteristics of the samples. As shown in X-axis than that on the Z-axis.In addition, there is a correlation between the anisotropy of performance and the internal stresses caused by non-equilibrium solidification . Figure Due to the unique structural characteristics, TPMS unit cell structures have a wide range of applications in fields such as acoustics, optics, thermodynamics, and mechanics. However, when TPMS unit cell structures made of materials such as 316L and Ti6Al4V bear large loads, they tend to undergo layer collapse and shear failure, resulting in unstable energy absorption efficiency and other unstable behaviors ,29. In tThe TPMS cell structures made of Invar36 alloy with high toughness and low coefficient of thermal expansion, coupled with the excellent characteristics of lattice structures, achieve a large range of uniform deformation and outstanding damping and energy absorption properties;The five structural designs exhibit unique mechanical properties. The D-cell structure has the best overall performance. If considering structure lightweighting, the G-cell structure is more suitable because it has a 20% lower mass compared to the D-cell structure with the same wall thickness. The P-cell structure shows non-uniform deformation characteristics and a lower stress plateau and relative density. The L-cell structure has a high relative density, high strength, and a short stress plateau period. The failure mode of the N-cell structure can be altered with a change in wall thickness;The wall thickness can adjust the apparent density, stress plateau ratio, specific stiffness, energy absorption, energy absorption efficiency, and deformation mechanism of the structure. When the wall thickness is increased from 0.6 mm to 1.0 mm, the stiffness and stress plateau of the D, G, P, L, and N-cell structures increase by 74.37%, 42.33%, 97.03%, 69.84%, and 33.86%, respectively, and the stress plateau ratio increases by 104.14%, 89.60%, 209.48%, 128.57%, and 128.87%, respectively. The failure mode of the N-cell structure changes from the stretching dominant mode at 0.6 mm to the bending dominant mode at 0.8 mm and 1.0 mm;The performance of the TPMS structure in the horizontal direction is better than that in the vertical direction, which may be related to the anisotropy of the texture obtained after LPBF processing of the samples. The deformation of grains is more uniform and the yield strength is higher in the horizontal direction.In this article, five types of Invar36 alloy TPMS cell structures with three different wall thicknesses were prepared using the LPBF process, and microstructural characterization and compression tests were performed to investigate the deformation behavior, mechanical properties, and energy absorption performance under different loading directions. We also explored the effects and mechanisms of structural design, wall thickness, and loading direction. The following conclusions can be drawn from this study: