We found that the 13 core pyroptosis genes exerted opposite prognostic effects in different cancer types, which were subgrouped as pyroptosis positively related cancer and pyroptosis negatively related cancer. Subsequently, π signature was identified separately from the hub genes in pyroptosis positively related cancer and pyroptosis negatively related cancer subtypes. It was shown that π signature was well correlated with patient survival, pathological stages, tumor lymphocyte infiltration, and immunotherapy response. π signature was also applied as a predictive tool for chemotherapy drug responses and used as an independent factor for patient overall survival prediction. In short, this elaborated genetic signature could help us understand the oncogenic mechanism and pave the way for further therapeutic strategies based on pyroptosis.Despite mounting evidence linking pyroptotic cell death to tumor growth, the clinical significance and disease mechanism of pyroptosis in cancer remain uncertain. In this study, we established a unique gene signature ( Many oncogenic or tumor suppressor molecules in these pathways have been identified and are being applied as drug targets in cancer therapeutics , 2. Pyroroptosis , 9. In troptosis , 11. In roptosis –15, can Pyroptosis is a ubiquitous biological process involved in many different cell types responding to different PAMPs or DAMPs , 17. ExtThere is no conclusive evidence that pyroptosis induction improves cancer prognosis, and the precise roles of pyroptosis and the genetic background required for antitumor immunity remain unknown. To conquer this ambiguity, we analyzed several public tumor databases and developed integrated prediction models for different pyroptosis-related cancer subtypes with elaborated gene signatures.To evaluate the predictive or prognostic values of pyroptosis-related molecules in cancer, we defined 13 core genes that are directly involved in pyroptosis signaling  (Tables π” signature (onset syllable of pyroptosis) and quantified as π score (PP score for PPRC and PN score for PNRC). High and low π score patients were grouped (P < 0.0001) in PPRC patients   Tables -6. We pe) Tables -8. There grouped , and KM patients -C. Receipatients . The arepatients . Similarpatients -H, and Apatients . We furt cohorts . By comp of them . These rπ signature. Besides, π score in PPRC and PNRC were significantly higher in more advanced pathological stages , tumor protein P53 (TP53), or ATRX chromatin remodeler (ATRX) mutation in GBMLGG exhibited lower PN score, SET domain containing 2 (SETD2) mutation in KIRC and Kirsten rat sarcoma oncogene homolog (KRAS) or TP53 mutation in PAAD-exhibited higher PN scores, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) or glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) mutation in PPRC patients exhibited higher PP scores    , indicatelation) .π score in different cancer subtypes. As we did in π score (stable patients), and those drugs in the right column could be potentially applied to patients with a high π score (progressive patients)  . In summπ signature could be used as an independent prognostic parameter for OS prediction, univariate Cox regression analysis was conducted, and the PP score or PN score, as well as other clinicopathologic parameters such as age and tumor stage, were independent prognostic factors affecting the OS of cancer patients in both PPRC and PNRC , and the PP score and PN score together were termed π score. The optimal cutoff values for π score were determined by the R package “survminer.” In addition, the R package “survivalROC” was used to develop time-dependent ROC curves with AUC values in order to assess the predictive efficacy of the signature genes.Univariate Cox regression analysis and the Cox proportional hazard model were adopted for the construction of the optimal gene set from hub genes using R packages “survival” and “glmnet” . The linπ score and tumor stages and pathology M, and pathology N stages was investigated using Student's t-test, with a P value < 0.05 considered statistically significant.The tumor stages, pathology M (distant organ metastasis), and pathology N (lymph node metastasis) stage information were obtained alongside the transcriptome data in the TCGA database. The tumor stages of GBM and LGG were not accessible, so we considered GBM patients as III/IV stages and LGG patients as I/II stages. The association between the pyroptosis score or XCELL was used to estimate the immune cell composition of patients with each cancer type . The immπ signature and drug sensitivity. Signaling pathways targeted by the top 20 correlated drugs were analyzed in different cancer subtypes.Chemotherapy responses for each patient were predicted based on two public pharmacogenomics databases: Genomics of Drug Sensitivity in Cancer (GDSC) and the Broad Institute's Cancer Therapeutics Response Portal (CTRP). The drug sensitivities of each sample were estimated using the R package “oncoPredict” which enabled the generation of anticipated drug response models that could be used as a virtual screen for patient drug response . Then, uπ signature, as well as clinical characteristics considering age and tumor stages were selected to construct two visualized prognostic nomogram models. For patients from various cancer subtypes, the R packages “rms” and “survival” were used to predict the probability of 1-, 3-, and 5-year overall survival. The predictability of the nomogram models was assessed using a bootstrap approach with 1,000 resamplings to measure discrimination and calibration. Discrimination was accessed via the C-index, which is used to evaluate the predictive value of a nomogram. When the C-index is closer to 1, it implies a more accurate predictive ability of the nomogram. The calibration curves evaluated the consistency between the nomogram's predicted and actual survival probabilities.Univariable Cox regression analysis was performed to select independent clinicopathologically prognostic factors for OS prediction, and as a result, cancer type, https://www.r-project.org/) and GraphPad Prism 8.0 software. We used the D'Agostino and Pearson test to test data for normality. Student's t test or Kruskal–Wallis one-way ANOVA were used to determine the relationship between the pyroptosis score or π score and tumor stages, gene mutations, and the TIDE score, with a P value of 0.05 considered statistically significant.  The Pearson correlation method was used for correlation analysis. The Kaplan–Meier method was used to calculate the survival probability in terms of OS, and the log-rank test was used to examine intergroup differences. Univariate, multivariate analyses, and lasso regression were performed through a Cox proportional hazard model, and P value < 0.05 was considered as the statistical significance.Data were analyzed using R 3.5.2 (


Assessed by TA-cloning, the variant promoted the skipping of exon 18 and a premature stop codon (p.Asn511*), resulting in a predicted truncated protein. This variant, that is lacking the forkhead-box DNA-binding domain and nuclear localization signal 2, may disrupt the protein function and thus cause FOXP1 syndrome-related symptoms. Our study extends the phenotypic and allelic spectra of the FOXP1 syndrome.FOXP1 syndrome is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and language delay, with or without autistic features. Several splicing variants have been reported for this condition, but most of them lack functional evidence, and the actual effects of the sequence changes are still unknown. In this study, a  FOXP1 gene, which is located on chromosome 3p13 and spans 21 exons. Variants in FOXP1 are associated with the FOXP1 syndrome (MIM #613670) featured by global developmental delay, intellectual disability, language delay, with or without autistic features , including 49 gross deletions/insertions, 46 missense/nonsense, 31 indels, and 11 splicing variants. Although all of the splicing variants are predicted to affect RNA splicing and produce abnormal transcripts, most predictions have not been confirmed by published transcriptional studies. Therefore, the actual effects of mRNA changes in individuals remain unknown. Hence, caution should be exercised in interpreting these variants, and further functional studies are needed. Herein, one de novo FOXP1 variant (c.1652 + 5 G>A) was identified in a patient presenting global developmental delay, mild intellectual disability, speech delay, and autistic features. Assessed by an RNA analysis, we demonstrated that this variant promoted the skipping of exon 18 and a premature stop codon (p.Asn511*), and was scored as a pathogenic according to the ACMG guidelines. Our study extends the phenotypic and allelic spectra of the FOXP1 syndrome.Foxp1 (forkhead-box protein P1) is a member of the FOX transcription factor family, characterized by the presence of a specific DNA-binding domain known as the forkhead-box (FOX). It contains four main functional domains: an N-terminal glutamine rich region, a zinc finger domain, a leucine zipper domain, and a C-terminal FOX domain . The Foxfeatures . Althougfeatures , currentfeatures . Thus faPeripheral blood samples from the patient, his sister, and parents were obtained by venipuncture and collected into a tube containing anethylenediaminetetraacetic acid dipotassium salt (EDTA-K2) . This study was approved by the Ethics Committee of Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China (No. IRB-20200216-SC).DNA and total RNA were extracted with the QIAamp® DNA Blood Mini Kit  and TaKaRaMiniBEST Universal RNA Extraction Kit , respectively, according to the manufacturer’s instructions. Complementary DNA (cDNA) was synthesized using the PrimeScript 1st strand cDNA Synthesis Kit .Genotypes and CNVs were detected by the Affymetrix CytoScan™ HD array  in accordance with the manufacturer’s instructions. Data were visualized and analyzed with the Chromosome Analysis Suite software  based on hg19 assembly. Gains ≥500 kb and losses ≥200 kb, containing a minimum of 50 markers in the region were considered as significant.The genomic DNA samples were captured by Agilent SureSelect Human All Exon V6  and sequenced on an Illumina NovaSeq platform. BAM alignment file and variant calling were performed using bwa-mem and GATK Haplotype Caller (3.X) from the Sentieon implementation (version sentieon-genomics-201808.03) with the GRCh37/hg19 human genome as a reference. The average sequencing coverage was 120-fold with >92% of the region-of-interest covered at least 20-fold. Variants were filtered through 1000 Genomes, ESP6500, gnomAD databases, and further annotated by AilisNGS® internal pipeline using databases such as ClinVar, the Online Mendelian Inheritance in Man database (OMIM), HGMD, and Ailife internal variant/gene/disease databases.The fragments containing the variant were amplified using primers IN18-F (5′-GTGCGTCATAATCTTAGTCTTCACA-3′) and IN18-R (5′-AAAACAGGAGGGATGAAATGC-3′) for gDNA, and F (5′-CCCATTTCGTCAGCAGATATTGC-3′) and R (5′-GTACAGGATGCACGGCTTG-3′) for cDNA. The PCR reactions were performed in 50 μl of the total reaction volume containing 50 ng of gDNA or cDNA using 2×GoldStar Best MasterMix  at an annealing temperature of 60°C. TA cloning was performed on purified cDNA PCR products using the HieffCloneTM Zero TOPO-TA Cloning Kit . Sanger sequencing was conducted on an ABI 3500xL Dx Genetic Analyzer .The PubMed, OMIM, HGMD, ClinVar, and gnomAD (v2.1.1) databases and the professional version of the Human Splicing Finder system (HSF_Pro) were used to evaluate the pathogenicity of the variants. The mutated protein was predicted by MutPred2.The patient was a 29 year old male, the second-born child of non-consanguineous Chinese parents. He had one older unaffected sister and there was no family history of the disease . He presFMR1 screening (data not shown). Whole exome sequencing (WES) was performed on the patient, which revealed a splice-site variant in intron 18 of the FOXP1 gene (NM_032682: c.1652 + 5 G>A) in heterozygosis. Sanger sequencing confirmed the presence of the FOXP1 variant in the patient. It was neither detected in the samples of his parents nor his sister, indicating that the inheritance status was de novo . In comparison, another splicing variant c.1653–2A>T  and three β strands (β1-β3) . The preFOXP1. We hypothesized that it was caused by other genes, but no associated pathogenic variations were observed. Moreover, this symptom was verbally described by the patient’s father but he could not provide any test report. Consequently, it is hard for us to determine the cause without detailed clinical manifestations. Whether this variant might contribute to hemolytic anemia remains an open question; further studies are needed to investigate the effect of FOXP1 on the hematologic system.By comparison, all C-terminally truncating variants  and splicing variants  present mild to severe developmental delay involving intellectual disability, delayed speech and language development, and motor delay . Other cde novo variant in the FOXP1 gene (c.1652 + 5 G>A) was identified in an adult patient with the FOXP1 syndrome. It was proved to alter splicing and produce an aberrant transcript (p.Asn511*), which may disrupt the protein function and thus cause FOXP1 syndrome-related symptoms. Our study extends the phenotypic and allelic spectra of the FOXP1 syndrome.In summary, a splicing


Motivation:Brucella, the causative agent of brucellosis, is a global zoonotic pathogen that threatens both veterinary and human health. The main sources of brucellosis are farm animals. Importantly, the bacteria can be used for biological warfare purposes, requiring source tracking and routine surveillance in an integrated manner. Additionally, brucellosis is classified among group B infectious diseases in China and has been reported in 31 Chinese provinces to varying degrees in urban areas. From a national biosecurity perspective, research on brucellosis surveillance has garnered considerable attention and requires an integrated platform to provide researchers with easy access to genomic analysis and provide policymakers with an improved understanding of both reported patients and detected cases for the purpose of precision public health interventions.Results: For the first time in China, we have developed a comprehensive information platform for Brucella based on dynamic visualization of the incidence (reported patients) and prevalence (detected cases) of brucellosis in mainland China. Especially, our study establishes a knowledge graph for the literature sources of Brucella data so that it can be expanded, queried, and analyzed. When similar “epidemiological comprehensive platforms” are established in the distant future, we can use knowledge graph to share its information. Additionally, we propose a software package for genomic sequence analysis. This platform provides a specialized, dynamic, and visual point-and-click interface for studying brucellosis in mainland China and improving the exploration of Brucella in the fields of bioinformatics and disease prevention for both human and veterinary medicine. Brucella, a Gram-negative bacterium that does not form spores and is generally non-motile. Brucellosis is often linked to animal reservoirs and has significant zoonotic potential. Brucella spp. Could infect humans through animals via different routes of contact , the annotation of genomes by Prokka (version 1.14.5), the identification of single nucleotide polymorphisms by Snippy (version 4.6.0), the location the antimicrobial resistance genes by ABRicate (version 1.0.0), and the construction of an evolutionary tree with FastTree (version 2.1.9); this combination provides users with a specialized software package to compute and analyse Brucella-related data with a point-and-click interface (1) The software package is based on a combination of multiple visualized genome sequence analytic software programs for nterface .2) There is a visual interface for the incidence (reported disease cases) and the prevalence (detected cases) of brucellosis in China, that presents the spatiotemporal distribution of brucellosis incidence and the aggregation of each region using a map based on the years and hosts and incorporates the dynamic evolution and chronological prevalence of brucellosis in humans and animals through previous data collected from the literature; this allows the analysis of an epidemic situation of human and animal brucellosis in dynamic time .To address these existing limitations, we developed a comprehensive information platform for Brucella, which consists of an “Overview” and three functional modules.Brucella, which shows the prevalence distribution of human brucellosis and animal brucellosis in various provinces of China. The “Software” module has five software programs for Brucella genome analysis and is detailed in Brucella Prevalence” module visualizes and presents the brucellosis prevalence in mainland China using previous data collection based on the literature and is detailed in The “Overview” introduces our work regarding Brucella genome while also visualizing the incidence and prevalence of brucellosis in mainland China in an intuitive and interactive format. Moreover, this platform could provide high-performance computational extensions for future therapeutic research on brucellosis and may have advantages for brucellosis source tracking in the future.Overall, this platform integrates professional analytic software to provide easy, efficient, and rapid data analysis operations for the Brucella was developed on the Linux server (CentOS 7.5.1804), which employs MySQL (version 8.0.20) as the database server. The back and front ends of the website are based on the Django framework (version 3.1.1) and bootstrap framework (version 4.4.1), respectively. We deployed the website  and the number of cases .Brucella prevalence data were collected from the College of Animal Sciences, Zhejiang University  Genomic assembly: Shovill (version 1.1.0) is a pipeline for the assembly of bacterial isolate genomes from Illumina paired-end reads, which is detailed in section 4.1.1.2) Genome annotation: Prokka (version 1.14.5) is used to provide genome annotation services, which are detailed in section 4.1.2.3) Identification of single nucleotide polymorphisms: Snippy (version 4.6.0) is used for SNP identification, which is described in detail in section 4.1.3.4) Scanning for antimicrobial resistant genes: ABRicate (version 1.0.0) is used to scan the antimicrobial resistant genes, which is detailed in section 4.1.4.5) Evolutionary tree construction: FastTree (version 2.1.9) is used to provide the phylogenetic tree construction service, which is detailed in section 4.1.5.With respect to the study of Brucella , we chos Shovill , Prokka  Shovill , Snippy  Shovill , ABRicat Shovill  and Fast Shovill .1) GenomThe workflow for brucellosis incidence development can be referred on Here, Brucella incidence in China can be then realized by the Z-test =−Under the assumption that local Moran’s I follows the normal distribution, it can be considered statistically significant when  outlier . Figure  outlier .Investigating the prevalence of brucellosis can provide scientific data for the prevention of susceptible populations and serve as a reference to monitor epidemic prevention and the decontamination of breeding sites for brucellosis.Brucella is described on Brucella data is met ” and “Reverse reads (R2)” entries. For example, users should upload the sequence files obtained by paired-end sequencing onto “Forward reads (R1)” and “Reverse reads (R2)”.For another 5 parameters, including “Trim reads”, “Contig name format”, “Depth”, “Minimum contig length”, and “Minimum contig coverage”, if users click the sample file option “Use Test Data and Preset Parameters”, they can use the default parameters.https://github.com/Rainbow-24/Brucella-supplementary. Each file has a common prefix, listed within After users complete the parameter setting and click the “Submit” button, the system will generate 5 files in the specified output directory, which are shown in Prokka can help users quickly annotate the genomes of bacteria, archaea and viruses for further analysis or viewing in the genome browser and produce standards-compliant output files , which iProkka shows 15 parameters. Among them, users must input “Contigs to annotate” and “Kingdom (--kingdom)” entries. For example, users should upload the FASTA genome sequence file onto the “Contigs to annotate” and select the species type for “Kingdom (--kingdom)”.For another 13 parameters, including “Locus tag prefix (--locustag)”, “Locus tag counter increment (--increment)”, “GFF version (--gffver)”, “Force GenBank/ENA/DDJB compliance (--compliant)”, “Add ; features for each “CDS” feature (--addgenes)”, “Minimum contig size (--mincontiglen)”, “Sequencing centre ID (--centre)”, “Genus name (--genus)”, “Species name (--species)”, “Strain name (--strain)”, “Plasmid name or identifier (--plasmid)”, “Use genus-specific BLAST database (--usegenus)”, and “Optional FASTA file of trusted proteins to first annotate from (--proteins)”, users can select the default parameters by clicking the sample file option Use Test (--Data and Parters)”.https://github.com/Rainbow-24/Brucella-supplementary. Each file has a common prefix, listed within After users complete the parameter setting and click the “Submit” button, the system will generate 12 files in the specified output directory, which are shown in Snippy can help users find SNPs between a reference genome and NGS sequence reads. Snippy will use as many CPUs as researcher can give it on a single computer (tested to 64 cores), and it is designed with speed in mind, and produces a consistent set of output files, including a core SNP alignment, in a single folder (and ultimately a phylogenomic tree) , which iSnippy shows that users need to input 5 parameters. Among them, users need mandatory to input “Upload fasta contigs. (--ctgs)” and “Using a fasta/embl/genbank file as the reference sequence (--reference)” entries. For example, users should upload the FASTA genome sequence file onto the “Upload fasta contigs. (--ctgs)” and a reference sequence onto the “Using a file as the reference sequence (--reference)”.For another 3 parameters, such as “Single-end reads, Paired-end reads, Contigs”, “Minimum mapping quality”, “Minimum coverage”, if users click the sample file option “Use Test Data and Preset Parameters”, they can use default parameters.https://github.com/Rainbow-24/Brucella-supplementary. Each file has a common prefix, listed within After users complete the parameter setting and click the “Submit” button, the system will generate 16 files in the specified output directory, which are in E. coli .ABRicate, which comes bundled with multiple databases , can help users mass screen contigs for antimicrobial resistance or virulence genes , as descABRicate shows 5 parameters. Among them, users must input “Input file ” and “Database to use - default is ‘resfinder'” entries. For example, users should upload the genome sequence file of antimicrobial resistant genes into the “Input file ” and select the database for “Database to use - default is “resfinder”.For another 3 parameters, such as “Suppress header“, “Minimum DNA %identity (0–100)“, “Minimum DNA %coverage (0–100)“, if users click the sample file option “Use Test Data and Preset Parameters“, they can use default parameters.https://github.com/Rainbow-24/Brucella-supplementary. It contains multiple columns, listed within After users complete the parameter setting and click the “Submit“ button, the system will generate a tap-separated in the specified output directory, which is in FastTree can help users infer approximate maximum-likelihood phylogenetic trees from the alignments of nucleotide or protein sequences to further estimate their reliability , which iFastTree shows 6 parameters. Among them, users must input “FASTA file“ and “Protein or nucleotide alignment“ entries. For example, users should upload a multiple sequence alignment file onto the “FASTA file” and select the sequence alignment type for “Protein or nucleotide alignment”.For another 4 parameters, including “Aligned sequences file (FASTA or Phylip format)”, “Allow spaces and other restricted characters (but not ') in sequence and quote names in the output tree”, “Set starting tree”, and “Nucleotide evolution model”, if users click the sample file option “Use Test Data and Preset Parameters”, they can use the default parameters.https://github.com/Rainbow-24/Brucella-supplementary.After users complete the parameter setting and click the “Submit” button, the system will generate a Tree file in Newick format in the specified output directory, which is shown in The brucellosis incidence visualization module can show users the statistical information for brucellosis in China. After clicking the “Brucellosis Incidence” link on the homepage , the disWhen users select the time and host, Brucella visualization module can show the trend, confidence interval, and statistical information for brucellosis in China. After clicking the “Brucella Prevalence” link on the homepage  in China or elsewhere in the world that provides a framework to query the trend and predicted direction of the incidence of infectious diseases.Brucella-related genomic analysis and to dynamically visualize the incidence (reported patients) and prevalence (detected cases) of brucellosis in mainland China.Therefore, we developed this platform to integrate five commonly used genomic applications for convenient Brucella data so that it can be expanded, queried and analyzed. When similar “epidemiological comprehensive platforms” are established in the distant future, we can use knowledge graph to share its information.Especially, our study establishes a knowledge graph for the literature sources of Importantly, the current incidence dataset (the reported cases) and the prevalence dataset, (the detected positive cases) have generally good agreement for the different geographic regions .Brucella could offer an essential toolkit for primary genomic analysis and, more importantly, establish a framework to understand the burden of brucellosis regarding humans vs animals in a dynamic way, over a long period of time (1953–2018), for 31 different geographic locations.Moreover, the newly developed, national-scale database for However, the current platform can only provide a reference for the genomic analysis process and cannot be fully embedded into all aspects of the bioinformatics analysis process; data on the incidence and prevalence of brucellosis are relatively fixed and do not allow for real-time updates of relevant data.For these reasons, we will apply more sophisticated bioinformatics applications  to bruce


The produced CoMoP nanosheets are also characterized by very small Tafel slopes, 54.9 and 69.7 mV dec−1 for OER and HER, respectively. When used as both cathode and anode electrocatalyst in the overall water splitting reaction, CoMoP-based cells require just 1.56 V to reach 10 mA cm−2 in alkaline media. This outstanding performance is attributed to the proper composition, weak crystallinity and two-dimensional nanosheet structure of the electrocatalyst.The development of high-performance and cost-effective earth-abundant transition metal-based electrocatalysts is of major interest for several key energy technologies, including water splitting. Herein, we report the synthesis of ultrathin CoMoP nanosheets through a simple ion etching and phosphorization method. The obtained catalyst exhibits outstanding electrocatalytic activity and stability towards oxygen and hydrogen evolution reactions (OER and HER), with overpotentials down to 273 and 89 mV at 10 mA cm The mate peaks ,48,49. F33.0 eV) f [50,51,2 catalyst were also evaluated in the same cell and reaction conditions. The LSV polarization curves displayed the CoMoP to be characterized by an outstanding OER activity, with an overpotential of only 273 mV at a current density of 10 mA cm−2 , CoP (71.5 dec−1) and RuO2 (86.4 mV dec−1), which indicates CoMoP to have associated a faster OER reaction kinetics [The OER activity of CoMoP was evaluated at room temperature using a three-electrode system in a 1.0 M KOH alkaline solution. As a reference, Mo–CoP, CoP and a commercial RuO mA cm−2 . This ovkinetics ,54.2 were estimated according to the double-layer capacitance (Cdl) determined via CV in the non-faradaic region at different scan rates, 20, 40, 60, 80 and 100 mV·s−1 (dl (12.6 mF cm−2) than Mo–CoP (8.7 mF cm−2), CoP (4.9 mF cm−2) and RuO2 (2.3 mF cm−2). This result indicates that CoMoP offers a higher density of accessible electrochemical active sites, which we relate to the proper composition and nanosheet structure of CoMoP.The electrochemical active areas (ECSA) of CoMoP, Mo–CoP NCs, CoP and RuO0 mV·s−1 c. CoMoP ct) and a solution resistance (Rs) during the OER process was used to fit the Nyquist plots displayed in ct (17.99 Ω), well below that of Mo–CoP (Rct = 27.90 Ω), CoP (Rct = 36.70 Ω) and RuO2 (45.47). These results reveal the CoMoP nanosheets to enable a faster charge transfer at the electrode/electrolyte interfaces, thus accelerating the OER electrocatalytic kinetics.The charge transport/transfer ability of the electrocatalysts was evaluated by electrochemical impedance spectroscopy (EIS). An equivalent circuit model including a charge transfer resistance  and well below that of Mo–CoP (154 mV), CoP (165 mV) and most previously reported phosphide-based HER electrocatalysts (−1) was also much lower than those of Mo–CoP (83.7 mV dec−1), CoP (113.4 mV dec−1) and close to that of Pt/C (56.1 mV dec−1)  b, which V dec−1) c, showinV dec−1) e. The mo−2, which is significantly below that of a cell containing Pt/C and RuO2 electrodes (1.61 V). More importantly, after 40 h of continuous operation at 100 mA cm−2, the CoMoP-based cell still maintained an outstanding performance, with just a 14.8% loss at high current density (Due to the excellent OER and HER performances demonstrated by CoMoP, a two-electrode configuration electrolyzer with CoMoP both as the positive and negative electrodes was constructed and tested for OWS in 1.0 M KOH solution a. As sho density c. Thus,  density . Besides−2 for HER and OER, respectively. Furthermore, CoMoP electrocatalysts also showed excellent long-term stabilities in alkaline electrolytes, with a minor current density decrease after 100 h continuous operation. When used for OWS, a cell voltage of only 1.56 V was needed to reach a current density of 10 mA cm−2. This work provides a suitable strategy to synthesize high-performance Co–Mo–P electrocatalysts with abundant exposed active sites and effective avenues for charge and electrolyte transport, and it can be employed to further tune the structure and composition of other 2D nanostructures with optimized performance towards OWS and other electrocatalytic reactions.In conclusion, ultrathin CoMoP nanosheets were engineered using the Co–MOF ZIF-67 as a self-sacrificial template and ammonium molybdate as a shape-defining agent and Mo source. CoMoP nanosheets exhibited outstanding performance towards HER and OER in alkaline media, which we associate with the proper transport properties and electronic energy levels provided by their composition and their porous nanosheet structure. In particular, CoMoP presented low overpotentials of 89 and 273 mV at a current density of 10 mA cm


To synthesize the details of the exercises prescribed for the improvement of muscle mass/muscle strength/physical performance among sarcopenic older adults.Frequency, intensity, duration, type, mode, and progression while prescribing resistance, aerobic, balance, and flexibility exercises for sarcopenic older adults were identified and reported.A multicomponent exercise program targeting muscle strength, aerobic, balance, and flexibility are recommended and tailored as per the existing fitness level and targeted outcomes for sarcopenic older adults.The online version contains supplementary material available at 10.1007/s41999-022-00693-7. To synthesize the details of the exercises/exercise program prescribed for the improvement of muscle mass/muscle strength/physical performance among sarcopenic older adults.A systematic literature search was conducted in five electronic databases and the details of exercises such as single component or multicomponent exercise program, frequency/week, intensity, duration of the exercise program, type of exercises, progression, adverse events reported, outcome measures used, and whether technology or other educational aids were used to deliver the program were extracted.A total of 10,045 records were identified and 27 records were included. Resistance exercises were included in all the studies, with the frequency ranging from 1 to 5/week, intensity ranging from 20 to 80% of 1 repetition maximum (RM), or 6–14 points on ratings of perceived exertion (RPE), and duration per session ranging from 20 to 75 min. The intensity of aerobic exercises ranged from 50 to 70% of heart rate max or a level of 7–17 in RPE with a duration ranging from 6 to 30 min per session for 2–5 days/week. For balance exercises, the intensity was mentioned as the level of effort 3 on a scale of 10, and the time duration per session ranged from 5 to 30 min for a frequency of 2/3 per week.This review synthesized the components of exercise prescription for sarcopenic older adults which would help practitioners and researchers in selecting the frequency, intensity, duration, type, mode, and progression while prescribing exercises.The online version contains supplementary material available at 10.1007/s41999-022-00693-7. Sarcopenia among older adults is a disorder that causes a gradual loss of skeletal muscle mass, strength, and deterioration in physical performance –3. The pSarcopenia is concerning as it leads to negative health outcomes in older people, such as falls, frailty, physical restrictions, activity limitations, lower quality of life, and an increased risk of premature death –11. The The studies were included if they met the criteria: (a) original study, (b) on older adults, (c) including those diagnosed with sarcopenia, (d) with study design such as pilot study, randomized controlled trial, pre–post intervention trial, or longitudinal studies, (e) single-component or multicomponent exercise-based intervention. The studies were excluded if they failed to meet the inclusion criteria and/or: (a) full text was not available, (b) language was other than English, (c) was a single/multiple component intervention in which exercise was not a component, (d) studies providing no extractable data, and (e) patients had secondary sarcopenia due to conditions like COPD, cancer, kidney disease, stroke, Parkinson’s disease, and Alzheimer's disease.A systematic literature search was undertaken in December 2021 using the following electronic databases: PubMed, Scopus, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Relevant MeSH terms and Boolean phases were used for the search: “sarcopenia” OR “reduced skeletal muscle mass” OR “muscle mass loss” OR “muscle atrophy” AND “aged” OR “elderly” OR “older adults” OR “older people” AND “physical therapy” OR “rehabilitation programme” OR “therapeutic exercise”  AND “residential care facilities” OR “long-term care facilities” OR “old age homes” without time restrictions and no filters were applied. The complete search strategy for each database is shown in the supporting information (search strategy.pdf).Two reviewers, PK and GN, independently searched the literature. The identified studies were imported to Rayyan (Ref. # 366956) software. After resolving the duplicates, two reviewers (PK and GN) conducted title and abstract screening separately. If the study was deemed suitable, it progressed to the retrieval of the full text. If, after a review of the full text, the article was still considered suitable for the analysis, then it progressed to data extraction. Any conflict regarding the article selection was resolved by discussion with the third reviewer, SU. Full-text reading of the identified articles was done by PK, and relevant studies were included in this review matching our inclusion criteria. The data charting form was drafted by PK as per the American College of Sports Medicines’ (ACSM)  frequencA total of 10,045 studies were identified through database searches. After removing duplicate studies, the titles and abstracts of 5,372 studies were screened. A review of the titles and abstracts yielded 314 relevant studies for full-text screening. Finally, 27 studies met all inclusion criteria and included in this review. A Preferred Reporting Items for Systematic Review and Meta-analysis 2020 (PRISMA 2020) flowchart of the literature search is demonstrated in Fig. Nine studies used Asian Working Group for Sarcopenia 2014 (AWGS 2014) criteria –23, one n = 16), the exercise intervention was given as a single component with all studies using resistance exercise [n = 11) administered multicomponent exercise intervention [n = 4) [n = 3) [n = 1) [n = 2) [n = 1) [n = 25), a supervised exercise program [n = 1) an unsupervised exercise program [n = 1) an initial training was administered and then participants performed exercise unsupervised [Twenty-seven studies, which used exercise intervention in single- and multicomponent modes, were included in this review. Out of 27, in 16 studies  , 28, 41; [n = 3) , 30, 36, [n = 2) , 33; res [n = 1) . In 25 s program , 20–41, pervised .The details of the exercise program are summarized in Tables n = 9) used repetition maximum (RM) criteria [n = 10) used rating of perceived exertion (RPE) [n = 1) used OMNI-RES scale  [n = 4) [n = 10) that used RPE, it ranged from 6 to 14 points. The frequency/week of resistance training ranged from 1 to 5/week. Eight studies (n = 8) administered resistance training two/week [n = 14) three/week [n = 1) each one [n = 3) did not report the frequency of resistance training [n = 22), among which 9 (n = 9) [n = 2) [n = 10) [n = 1) [n = 5) [Of the 27 studies on resistance exercises, 9 studies  , 39, 41 n scale) , heart rn scale)  or coachn scale) , and maxn scale)  while fo [n = 4) , 22, 35 two/week , 33, 41,ree/week , 34–38, each one , respecttraining , 17, 39. (n = 9) , 40 repo[n = 10) , 38, 41  [n = 1)  reported [n = 5) , 35, 39 n = 7) [n = 2) [n = 2) [n = 3) [n = 1) [Seven studies (n = 7) , 36, 39  [n = 2) , 33 used [n = 3) , 24, 35 n = 9) [n = 1) reported the intensity of balance exercises [n = 2) included in this review mentioned the progression of the balance exercise on the bases of weeks and challenging exercise [n = 2) [Balance exercises were used as a component of the multicomponent program in nine studies (n = 9) , 39, 41 exercise , 28. Two [n = 2) , 33 ment [n = 2)  did not We have proposed the recommendation which the practitioner and researcher could use while prescribing exercise program for sarcopenic older adults in Table This rapid review intended to synthesize the details of the exercises/exercise program prescribed for the improvement of either muscle mass or muscle strength or physical performance among sarcopenic older adults residing in either long-term care setting or in the community. A total of 27 records were summarized with regard to the details of exercises such as a single-component or multicomponent exercise program, frequency/week, intensity, duration/session, total duration of the exercise program, type of exercises, progression, adverse events reported, outcome measures used, and whether technology or other educational aids were used to deliver the program. Also, the Consensus on Exercise Reporting Template (CERT)  was usedGiven that the studies did not use uniform diagnostic criteria for sarcopenia, the prevalence varied greatly from 10 to 30%  dependinEleven studies in this review used multicomponent exercise interventions for the management of sarcopenic older adults. Since there are no exercise recommendations or guidelines for the management of sarcopenia, most of the authors have followed the recommendations for physical frailty that report the beneficial effects of a multicomponent over a single-component intervention . Currentn = 7) included in this review are part of a multicomponent exercise intervention. The frequency of aerobic exercises for sarcopenia ranged from two to five times per week. The American College of Sports Medicine physical activity recommendation for older adults states 3–5 days per week of aerobic activity, and for older adults with knee OA, the most common recommendation that exists is to perform 3–5 days per week of cardiorespiratory training [Aerobic and endurance studies  reported the intensity of balance exercise, which is 3 on a rating of perceived exertion and this corresponds to the recommendations for frail older adults [The intensity of resistance exercises for sarcopenic older adults ranged from 20 to 79% of 1 RM or 6 to 14 RPE in the studies included in this review. For frail older adults as per the literature, the intensity varies from 40 to 80% 1RM or somewhat hard (12–14) RPE . The litr adults .The duration for resistance exercise ranged from a minimum of 20 min to a maximum of 75 min in the included studies. A study has mentioned that the duration for resistance exercise ranged from 10 min for frail and 20 min for pre-frail older adults . The durThe type and mode of exercise should be chosen based on the participant's level of fitness, as well as his or her interests and available resources for better compliance and for lowering the risk of injury , 52. Then = 1) [max with higher rating of perceived exertion. Mazzeo et al. [n = 2) included in this review have mentioned about the progression of balance exercise on the basis of weeks and challenging exercise. A similar recommendation by the US Department of Health and Human Services (2008) Physical Guidelines for Americans says progressively difficult postures gradually reduce the base of support and dynamic movements perturb the center of gravity and stress the postural muscle groups [The progression of resistance training reported in the studies included in this review suggests starting with a fewer number of sets, higher repetition with less intensity progression, to more sets with less number of repetitions. An author has recommended that clinicians should start their clients with higher repetitions, that is, 12–15, and at a lower intensity (55% of 1RM) and eventually progress to fewer repetitions of 4–6 at a greater intensity (> 80% of 1RM) . Aerobicn = 1)  in this o et al.  recommene groups .n = 4 were study protocols and n = 23 were completed studies. Of these 23 studies, n = 15 studies did not assess for any adverse events [n = 5 studies reported no adverse events [n = 3 studies reported adverse events because of exercise intervention [Among the included studies, e events , 33–41, e events , 28, 30,rvention , 26, 31.None of the studies in this review has reported a novel or a non-traditional exercise, except one study that incorporated a BFR program (blood flow restriction) , which wIn this paper, the researchers have synthesized the components of the exercises/exercise program prescribed for the improvement of muscle mass/muscle strength/physical performance among sarcopenic older adults.There are a few limitations to this review. First and foremost, this review has considered only the published articles available in electronic databases. Second, it considered only full-text articles as abstracts, and proceedings were excluded.This review has done a narrative summarization of the details of the exercise for sarcopenia. In the future a systematic review with a meta-analysis could be conducted to quantify the efficacy of the exercise program. Since there are more than two types of exercises to be compared for their effect, the authors would recommend performing a network meta-analysis. Also, studies published in non-electronic databases and on gray literature could be carried out as an update to this review.This review has synthesized the exercise components and has come up with the exercise recommendations that would benefit the interdisciplinary team to assess, design, and appraise safe and effective exercise programs for sarcopenic older adults. The exercises identified in this review are multicomponent and multimodal in nature, giving the practitioners and researchers the freedom to choose, as per the need and available resources. Also, strategies to improve and maintain adherence to exercise-based intervention have been identified, which need to be incorporated. Moreover, this review has summarized the exercises using the CERT checklist, making the recommendations replicable and transferrable across a variety of settings ; delivery methods , and personnels .This review would help practitioners and researchers in selecting the frequency, intensity, duration, type, mode, and progression while prescribing exercises for sarcopenic older adults. Also, this review may assist in identifying the variations in the components of exercise prescription for sarcopenic older adults as per the targeted outcome.Supplementary file1 (DOCX 201 kb)Supplementary file2 (PDF 69 kb)Below is the link to the electronic supplementary material.


Helicobacter pylori , Journal of Insect Science, Volume 19, Issue 6, November 2019, 17, https://doi.org/10.1093/jisesa/iez120This is a correction to: Daniela Alvarez, Kevin A Wilkinson, Michel Treilhou, Nathan Téné, Denis Castillo, Michel Sauvain, Prospecting Peptides Isolated From Black Soldier Fly (Diptera: Stratiomyidae) With Antimicrobial Activity Against 2.” There was a mistake in this calculation and the result should read “the surface area of the peptides should be about 3500 Å2.”In the originally published version of this manuscript, the second paragraph of the Discussion incorrectly states that “the surface area of the peptides should be about 8 ÅThis detail has been corrected only in this correction notice to preserve the published version of record.


The function of the integrin family of receptors as central mediators of cell-extracellular matrix (ECM) and cell–cell adhesion requires a remarkable convergence of interactions and influences. Integrins must be anchored to the cytoskeleton and bound to extracellular ligands in order to provide firm adhesion, with force transmission across this linkage conferring tissue integrity. Integrin affinity to ligands is highly regulated by cell signaling pathways, altering affinity constants by 1000-fold or more, via a series of long-range conformational transitions. In this review, we first summarize basic, well-known features of integrin conformational states and then focus on new information concerning the impact of mechanical forces on these states and interstate transitions. We also discuss how these effects may impact mechansensitive cell functions and identify unanswered questions for future studies. Over three decades after receiving its name, the integrin family of transmembrane adhesion receptors is now recognized as the core component of the most studied cellular mechanotransduction pathways to date ,2,3,4,5.Integrins are noncovalent heterodimers formed by an α and a β subunit. Both subunits consist of an extracellular globular ‘head’ with a rod-like ‘leg’, a membrane-spanning helix, and a short cytoplasmic tail A. The maMechanotransduction requires that integrins bear mechanical load. These are transmitted via noncovalent binding to extracellular ligands and cytoplasmic adapters that link the extracellular matrix and the contractile actin cytoskeleton. Force can originate either from intracellular contractile acto-myosin or from extracellular deformations but with similar consequences. Integrins respond to forces through changes in adhesion assembly, and in the organization and function of the entire structure, from extracellular matrix fibrils that require tension to assemble , to the Integrins exist in different types of adhesions that can be classified as nascent adhesions, focal complexes, and mature focal adhesions . During During the assembly of adhesions, from nascent to focal complexes and mature focal adhesions, integrins undergo dynamic transitions from the bent (inactive) to the extended (active) conformations ,36,38. THow these conformational transitions impact integrin functions as a structural linker, a mechanotransducer, and a signaling receptor is the subject of this review. We will focus on the current evidence supporting a role for integrin conformation in mechanotransduction by discussing how integrins change conformation under force and identifying prevailing hypotheses for future studies. We will start by focusing on how conformational changes of integrins are implicated in cell adhesiveness. Then, we will summarize the experimentally detected ranges of force on adhesion complexes and on single adhesion molecules and present the characteristics of integrin conformation and molecular rearrangements underlying its interconversion from inactive to active conformations. Lastly, we will identify important questions for future research needed to better understand integrin conformational dynamics in physiology and disease.1, β2, and β3 integrins, three main conformations have been visualized: bent-closed, extended-closed, and extended-open [Changes in integrin conformation tightly regulate its affinity for ligand binding, thus determining cellular adhesion to ligands in the ECM or on other cells. Electron microscopy and X-ray crystallography studies using ECM ligands or activating and inhibitory antibodies have shown that integrins adopt a range of conformations ,48,49,50ded-open ,52. For ded-open ,54,55.Attachment and spreading of cells on ligand-coated substrates to assess cell adhesiveness indicate a role for mechanics in these processes. Cells adhere and spread less well on soft substrates, which impacts a range of signaling and gene expression pathways, a process termed stiffness sensing . The difVβ3 mutants on elastic substrates of varying stiffness showed that these mutants shift cell traction and spreading towards lower stiffnesses [Studies of cell spreading in different mechanical environments have revealed that integrin conformational activation depends on ECM stiffness and cytoskeletal forces ,59. Analffnesses . CollectIIBβ3 integrins under various mechanical stimuli were found in conformational intermediates with ectodomain extensions and affinities for binding ECM ligands that are intermediate between those of the bent and extended conformations [This concept is valid also in other types of cell adhesiveness measurements. For example, measures of platelet aggregation have implicated force-dependent integrin conformations that are intermediate between bent and extended conformations . Using frmations . The conrmations . InteresTaken together, these studies on the relation between integrin conformation, adhesion dynamics, and cell adhesiveness revealed the existence of functionally important integrin conformations that are different from the well-known bent and extended conformations. These conformations are mechanosensitive and depend both structurally and functionally on force, further suggesting that they can underlie distinct signaling mechanisms.Force on integrin adhesions can be measured in bulk, for the whole adhesion or whole cell, or per molecule. Bulk measurements use deformable substrates, such as polymer films or gels, or cantilevers to determine traction stresses ,63,64,65Traction force microscopy with smooth muscle cells and mouse fibroblasts combined with estimates of numbers of engaged integrins have also suggested that the average force per integrin within focal adhesions is in the single pN range ,74. Thes2 and corresponds to forces between 1–25 nN [2 [Using elastic micropatterned substrates, stationary fibroblasts, and cardiac myocytes on elastic gels exert adhesion forces that positively correlate with the area of the adhesion, which varies between 2–5 μm 1–25 nN . The str25 nN [2 . Forces 25 nN [2 .It is generally considered that forces at a few pN are sufficient to regulate protein conformation and thus local molecular interactions . This seSingle molecule sensors have reported differences in the magnitude of force on adhesion molecules during the initial assembly, during the “sliding” towards the cell center, which involves disassembly at the rear and assembly at the front, and in mature adhesions . GeneralLβ2 integrin in living cells via its ligand ICAM-1 increases the lifetime of the ligand-bound state [Force strengthens integrin-mediated adhesions by promoting their growth, maturation, and recruitment of new cytoskeletal proteins that help resist the applied force. There is extensive evidence that force-dependent activation and stabilization of the talin-vinculin connection contributes to force-induced strengthening and maturation of adhesions ,76,77,78nd state ,81. Undend state , indicatvβ8 integrins with closed legs can bind ligands [1 integrins present on-rates for ligand binding up to ~20-fold higher than the extended-open conformation [Experiments and simulations on adhesion proteins that show affinity shifts have revealed that integrin catch bond behavior is coupled to long range conformational rearrangements of the receptor far from the binding site ,84,85. B ligands . Additioormation . These rormation . Taken tIn regard to ECM stiffness sensing, cells in or on soft ECM substrates not only spread less but also reduce their contractility and exert lower force on the matrix, compared to cells in or on stiff materials ,93. Accoα subunits have an α-A domain (I or inserted domain), consisting of approximately 200 amino acids, located between blades 2 and 3 of the β-propeller (gray domain in α-I domain) followed by the hybrid domain, the plexin-semaphorin-integrin domain (PSI), and four cysteine-rich epidermal growth factor (EGF) modules (I-EGF) 1-4 and β-T domains (α cytoplasmic domains show little homology. The transmembrane domains (TMD) of the α and β subunits  associate with each other, which helps stabilize the closed, low affinity conformation. During conformational activation from bent to extended conformations, the domains reorient and change relative positions  directly coordinates with the acidic sidechain shared by all integrin ligands [2+ ion that triggers activation of low-affinity integrins [2+ at the ADMIDAS, Mn2+ shifts integrin conformational equilibrium towards the open conformation [2+. SyMBS was found bound to the ion simultaneously with the AMIDAS in the ligated crystal structure of αVβ3 integrin. On the lower side of the β–propeller blades facing away from the ligand-binding surface, the last three or four blades of the β -propeller domain in the α subunit contain EF-hand domains that also bind Ca2+, to affect ligand binding allosterically [Before ligand binding, three metal ion binding sites in the β subunit β-I domain are typically occupied by Caand Mg2+ . The Mg2 ligands . The sitntegrins . By compormation . On the erically ,112.In the ligand binding interface of integrin, the forces between ions and the chains of the ligand can drive changes in the positions of the aminoacids of the β-I and β-propeller domains of integrin, resulting in increased ligand binding affinity. Conversely, the changes in positions of these aminoacids upon integrin activation change the distances between ions and ligand chains, thus increasing electrostatic interaction potentials and integrin affinity for ligand binding. Therefore, ligand binding affects integrin conformation and integrin conformation affects ligand binding, creating a reciprocal relationship between structure and ligand-bound state of integrin.Several studies have reported that force promotes integrin conformational activation by governing the transition from bent to extended conformations ,115,116.Xβ2 in different crystal lattices show that the β subunit appears to be more flexible than the α subunit [α subunits contain two regions of high flexibility: the linker between the β–propeller and thigh domain and the knee at the bend between the thigh and the calf-1 domain, which allows extension of this subunit by a hinging at the α knee, or “genu” [IIBβ3, the displacement of the α7-helix in the hybrid domain leads to a ~60° reorientation between the β-I and hybrid domain, and the α and β leg knees become separated by 70° due to the transmission through the firmly linked PSI domain in the upper β leg [The two main conformational rearrangements during integrin activation are hinging of the legs in the transition from bent to extended and swing out of the β subunit hybrid domain. SMD analysis and single-molecule experiments have indicated a role for mechanical force in hybrid domain swing-out and integrin extension ,117,118. subunit , α subunr “genu” . For ther “genu” . In the r “genu” ,124,125.er β leg .IIBβ3 and αvβ8 integrins, and of a β2 subunit fragment [5β1 and αXβ2 integrins [One hypothesis for how force induces these conformational changes is that force physically propagates from the ligand binding site and the intracellular β tail across the integrin structure, with sequential stretching and deformations of the interconnections between its rigid domains. In this case, rapid force transmission across the protein leads to rigid-body domain displacements without affecting secondary structures. Force, propagated along the linkers between domains, provides the energy for overcoming the barrier(s) between bent and extended conformations. This concept of rigid body-based structure, in which domains act as rigid units with articulation points located between them, was proposed from high-resolution reconstructions of αfragment ,127,128.ntegrins ,129. Thentegrins ,91; thusntegrins . A thirdntegrins . This fintegrins ,133. TheBoth closed and open conformations of integrin can bind ligands . Integri3 integrins , whether or how it applies to other integrins is uncertain, in particular, α-I domain containing integrins such as αXβ2, or α4β1, and α5β1. Truncated integrin α5β1 ectodomains do not undergo the large conformational change in the presence of the RGD peptide alone [1 integrins bind ligands with higher on-rates and higher ligand binding affinity than the extended-open conformation [4β1 was shown to be easier to activate, but its high-affinity conformation binds fibronectin ~100- to 1000-fold lower affinity than α5β1 [5β1 ectodomain may not reach a fully bent conformation [It is important to note that, although this pathway is generally shared across several βde alone . In thesormation ,91. α4β1han α5β1 . Moreoveormation . Thus, formation ,132. TheIt is also hypothesized that force from the actin cytoskeleton is exerted on extended-closed integrin, with the force parallel to the plasma membrane ,136. ThiTo summarize the above discussion, integrin conformational dynamics in which bent, low affinity conformations convert to extended, open, high affinity conformations are modulated by cytoplasmic adapter and ECM ligand binding, and then further modified by tension applied through this linkage. Accelerated conversion to or stabilization of high affinity conformations contributes to cellular mechanotransduction, such as stiffness sensing or responses to applied tension. However, major questions remain about the exact conformational paths that mediate these transitions, how forces are transmitted through the integrin structure, and how they impact these transitions. It is also unclear whether integrins under tension might access conformations that are rare in unloaded conditions.In the absence of experimental techniques to obtain dynamic, atomic-level insights into the integrin activation pathway particularly under tension, addressing these questions will remain limited to computational modeling based on Xray or cryo-EM structures of the unliganded closed-hinge and the ligand-bound open-hinge β3-integrin headpiece domains . MoleculLastly, how integrin conformational dynamics impact cell functions is a major unexplored area. Integrin-based adhesions of platelets and leukocytes are “off” in the vasculature and “on” when these cells are activated. Directional cell migration requires local control of integrin activation and adhesion strengthening at the cell front and deactivation and detachment at the rear . Indeed,


Most body composition measures were significantly (p < 0.05) related to performance in men and women but limited in master’s men; no relationships were seen in master’s women. “Fran” time was negatively correlated to NBLM and fat-free mass index in all percentile groups (ρ = -0.37 to -0.64) and bone mineral characteristics for >25th percentile (ρ = −0.41 to −0.63), and positively correlated to fat mass in 25–75th percentiles (ρ = 0.33–0.60). No other relationships were seen in ≤25th percentile. The influence of body composition on “Fran” time appears to vary by both competition class and percentile rank. Though training to increase lean mass always seems relevant, reducing body fat only appears relevant in mid-skilled trainees and when it is outside healthy parameters.This study examined relationships between body composition and high-intensity functional training (HIFT) workout performance. Fifty-seven men  and thirty-eight women  with HIFT experience (≥6 months) reported completing “Fran” (21-15-9 repetitions of barbell thrusters and pull-ups) in 4.78 ± 2.22 min and 6.05 ± 2.84 min, respectively, and volunteered to complete dual-energy X-ray absorptiometry assessments. Participants were grouped by competition class  and percentile rank in “Fran” . Two-way analyses of variance revealed expected differences ( High-intensity functional training (HIFT) variably programs multimodal, functional movements designed to be performed at a relatively high intensity (within the context of prescribed repetitions or durations) in an effort to promote general physical fitness across multiple physiological parameters . This mer = −0.67) and the CrossFit® Total (r = 0.77). r = -0.46 and r = 0.53, respectively) to a 15-min circuit of 19 wall balls and 19 calories on a rowing ergometer where the goal was to complete “as many repetitions as possible” (AMRAP), but not a modified version of “Fran” that replaced pull-ups with bar-facing burpees. Stronger correlations (r ≥ 0.56) were seen from several other performance measures collected in that study, with aerobic capacity being the best predictor (r = 0.68) of the 15-min circuit. In fact, the only other study to observe body composition as the best predictor of HIFT used the results of dual-energy X-ray absorptiometry (DXA) in relation to a scaled version of “Murph” , bone mineral content (BMC), and bone mineral density (BMD) are characteristics that support greater force and power expression . ConversTo examine differences in and relationships between body composition and HIFT performance across sex, skill level, and competition class, recreationally active adults with at least 6 months of HIFT experience were recruited for this study. During enrollment, participants were asked to provide their personal best time-to-completion for the benchmark workout “Fran.” This workout was selected because of its status as a benchmark workout that users may upload scores for on the most popular HIFT leaderboard . Additiof = 0.68, α = 0.05, β = 0.95). All participants had been regularly (≥2 sessions per week) and currently participating in HIFT for at least 6 months and were free of any injury or health condition  known to impact physical activity, as determined by health and physical activity questionnaire. The University’s Institutional Review Board approved all testing protocols and procedures for this study.Following a description of all study procedures, a convenience sample of ninety-five adults . Anthropometric measures were completed with participants standing barefoot, feet together, on the scale while wearing athletic clothing. Subsequently, participants were further assessed by DXA  performed by the same researcher using standardized positioning procedures. Participants were asked to remove any metal or jewelry prior to laying supine on the DXA table for an entire body scan in “standard” mode using the supplied algorithms. Quality assurance was assessed by daily calibrations performed prior to all scans using a calibration block provided by the manufacturer. In addition to total PBF (±0.1%), BMC (±0.01 kg), BMD (±0.01 g cmsquared) .2P: Partial eta squared) at the following levels: small effect (0.01–0.058), medium effect (0.059–0.137) and large effect (>0.138)  analyses of variance (ANOVA) were conducted on all transformed measures of body composition and “Fran” time. All significant main effects and interactions were further assessed using the Tukey’s Honest Significant Difference test. All between group differences were also evaluated using effect sizes (η(>0.138) . Spearma(>0.138) . All staThe results of each ANOVA are presented in p ≤ 0.008), total body mass , NBLM , FFMI , and BMC , as well as lower percent total body fat  and percentage gynoid fat , than women and master’s women. Men also possessed a higher BMI  and greater BMD  than women and master’s women, whereas BMI  and BMD  were only greater in master’s men compared to master’s women. Further, although men and master’s men completed “Fran” faster than their female counterparts , no differences in percentile rank were seen. No other differences were found between competition classes. Significant differences between competition classes are presented in Main effects for competition class were observed for all variables except fat mass and the percentage of android fat. Post hoc analysis indicated that men and master’s men possessed greater height  completed “Fran” faster than those within the 25th–75th percentiles  and below . Those ranking between the 25th–75th percentiles were also faster (p < 0.001) than those ranking below. Those from >75th percentile possessed lower fat percentage , less FM, and more NBLM than all other percentiles. Those ranking above the 75th percentile also possessed a greater FFMI than those below the 25th percentile. No other differences were seen between percentiles. The differences between percentiles for measures of body composition are illustrated in Significant main effects for percentile rank were observed for “Fran” performance, body fat percentage , FM, FFMI, and NBLM. Regardless of competition class, individuals from >75th percentile  bivariate and partial (controlling for competition class) correlations were found between “Fran” time and all measures of body composition, with differences in each’s ability to explain variance ranging between 5.0% and 34.6%. These relationships were altered when the analysis was repeated after splitting the sample by competition class. In men, all body composition measures except for height were related to “Fran” time, whereas significant (p < 0.05) relationships were limited to percent fat , FM, NBLM, and FFMI in women. Within the master’s class, fewer relationships were seen. Percent android and total fat, as well as FFMI, were the only measures related to “Fran” time in master’s men, and no significant relationships were seen in master’s women.Bivariate and partial correlations between “Fran” time and body composition measures are presented in p < 0.05) related to “Fran” time when controlling for the influence of percentile rank. The ability of each variable in explaining variance in “Fran” time ranged between 9.6% and 36.0%. When the analysis was repeated with the sample split by percentile rank groupings, different combinations of significant relationships were seen within each grouping. All variables except FM were related to “Fran” time for participants ranking between the 25th and 75th percentiles. Likewise, all body composition variables, except those relating to fat distribution , were related to “Fran” time in >75th percentile. In contrast, only NBLM and FFMI were related to “Fran” time in participants from <25th percentile. The effects of percentile rank on relationships between “Fran” time and measures of body composition are illustrated in Except for FM and percent android fat, all measures were again significantly p < 0.0 related This study aimed to assess the influence of competition class and percentile rank on relationships between body composition and HIFT performance using the benchmark workout “Fran.” Though nearly a handful of studies have reported relationships between various measures of body composition and one or more HIFT workouts , any conr = −0.598) (r = −0.608 to −0.822), upper-body strength endurance is clearly important. Indeed, an individual must have the capacity to complete a total of 45 pull-ups to finish “Fran.” While there is evidence of women being more resistant to upper-body fatigue than men  . Althougthan men , they hathan men . This isthan men . On averthan men . Being hthan men . Women othan men , an inapthan men . Women mthan men , but sinThe lack of differences between age groups, as well as the fewer significant relationships seen between body composition and “Fran time” in the master’s class, are most likely the consequence of reduced statistical power. There were nearly three times as many younger participants as those who were older than age 35 years. While this may be viewed as a limitation to this study, and potential source of type II error, these numbers are consistent with the ratios seen between master’s and younger athletes in Open and international competition . NeverthParticipants from >75th percentile possessed less fat mass and more NBLM than all other participants. Meanwhile, no differences were seen among the lower percentile groups or with any measure of bone health. The size, architecture, and quality of skeletal muscle reflect its ability to produce force . The masr = 0.673) with the 2K rowing time (Interquartile range = 7.3–7.7 min) . A leaner individual might use less energy when performing repeated movements at a given intensity, and assuming proper hydration and ventilation, thermoregulate better than someone with a higher body fat percentage during exercise . Togethe7.7 min) , anotherThe findings of this study indicate that the various sub-categories of body composition are all related to “Fran” performance, but their individual relevance is modulated by competition class and skill. Despite the compositional differences seen between men and women, relationships to performance were similar for each sex. The lack of age group differences within each sex, and significant relationships to performance in the master’s class, are contrary to this conclusion. However, this was likely because less participants qualified for the master’s class and thus, reduced statistical power. A more deliberate effort in recruiting sufficient participants within each competitive class will help to clarify this disagreement. Across percentile ranks, the higher-ranking participants (>75th percentile) possessed more NBLM and less body fat than all other participants, and those who possessed more lean mass  performed better. Although middle- (25th–75th percentiles) and lower-ranking (<25th percentile) participants possessed similar body composition, the relationships of each sub-category to performance were different. Moderate to high correlations with “Fran” time were noted for all sub-categories (except FM) in middle-ranking participants, whereas NBLM was the only sub-category associated with performance in the lower-ranking participants. Including assessments of muscular strength in the thruster exercise and maximal pull-up repetitions  would have helped to better explain the practical importance of NBLM to performance. These findings are also limited to self-reported “Fran” times. Future studies may want to confirm our findings by directly testing “Fran” or expand on them by including a greater variety of benchmark workouts. Nevertheless, this appears to be the first study to examine the influence of competition class and percentile rank on relationships between any physiological measure and HIFT performance.The findings of this study suggest that relationships between “Fran” time and body composition are important for both men and women. Striving for a healthy ratio of NBLM to fat mass appears to be related to a faster “Fran” time but men and women may accomplish this differently. In men, greater body mass and bone mineral content/density were relevant to performance, and these traits are typically enhanced when long-term training goals are to develop muscle size, strength, and power. In women, body and skeletal mass were not related to “Fran” time. Though the reasons for this are unknown, it may imply a greater reliance on movement efficiency rather than strength to complete workout tasks. Significant relationships were not found in master’s participants. Still, it may be prudent to assume that this was the consequence of reduced power. Master’s class adults should seek to model their training goals after their younger counterparts. When the analysis considered percentile rank, NBLM was related to performance in all participants, and the strength of this relationship increased in those who completed “Fran” in less time. By improving NBLM, strength is presumably increased, and this would reduce the relative intensity of the fixed loads prescribed for this workout. Meanwhile, attention to PBF and fat mass reduction only appears to be relevant for moderately ranked individuals. More skilled participants possessed the healthiest fat-to-lean mass ratio, and this seems to suggest that a threshold exists where continued focus on this goal has no additional benefit. In the lowest ranked participants, the only relationship observed was between NBLM and “Fran” time. This may reflect a need to improve strength, technique, pacing strategy, or possibly all three. Any concerted effort to reduce fat mass at this stage seems to be premature.


The samples could also form good adhesion to diverse substrates. This work opens a simple route for fabricating strong, tough, and adhesive hydrogels.Hydrogels with high mechanical strength, good crack resistance, and good adhesion are highly desirable in various areas, such as soft electronics and wound dressing. Yet, these properties are usually mutually exclusive, so achieving such hydrogels is difficult. Herein, we fabricate a series of strong, tough, and adhesive composite hydrogels from polyampholyte (PA) gel reinforced by nonwoven cellulose-based fiber fabric (CF) via a simple composite strategy. In this strategy, CF could form a good interface with the relatively tough PA gel matrix, providing high load-bearing capability and good crack resistance for the composite gels. The relatively soft, sticky PA gel matrix could also provide a large effective contact area to achieve good adhesion. The effect of CF content on the mechanical and adhesion properties of composite gels is systematically studied. The optimized composite gel possesses 35.2 MPa of Young’s modulus, 4.3 MPa of tensile strength, 8.1 kJ m Polymeric hydrogel is a three-dimensional hydrophilic network containing a lot of water ,2. The s−2) due to dynamic ionic bonds  is chosen as the matrix  but also good adhesion to diverse solid substrates. This study provides a simple but effective strategy to fabricate strong, tough, and adhesive hydrogel materials.In this work, we develop a series of strong, tough, and adhesive composite hydrogels from polyampholyte (PA) gel reinforced by nonwoven cellulose-based fiber fabric (CF) sheets via a simple composite strategy a. Due toe matrix b. After p-styrenesulfonate  was purchased from Macklin Biochemical Co., Ltd . 3-(methacryloylamino)propyl-trimethylammonium chloride  was purchased from J&K Chemical Ltd. N,N′-methylene-bis-acrylamide (MBAA) and α-ketoglutaric acid (α-keto) were purchased from Sinopharm Chemical Reagent Co., Ltd . Short cellulose-based fibers were laboratory-made from coniferous wood. The chemical structures of the monomers and cellulose molecule are shown in Sodium In order to achieve PA/CF composite hydrogels, a nonwoven cellulose-based fiber fabric (CF) sheet should be fabricated before integrating it with a pre-gel solution . First, α-keto) was prepared according to the literature , as illustrated in w = 10 mm) for the tests was determined based on width-dependent tensile data, as presented in −1. In order to prevent hydrogel dehydration, a humidifier was used during the tests. Young’s modulus, E, was calculated from the initial slope of the stress−strain curves at the stain within 10%. The work of tension of the samples during the tests, Wb, was calculated by integrating the area under the stress-strain curves as follows:σ and ε are the stress and strain, respectively, and Tensile tests of the samples were carried out on a tensile tester  with a 250 N load cell (standard: JIS-K6251-7). Before the tests, the samples were cut into a rectangle shape [length T. The samples were cut into a rectangular shape [l (40 mm) × w (20 mm) × t (≈1 mm)] with a 20 mm notch in the middle (standard: JIS-K6252 1/2), as illustrated in −1 until the crack advanced through the entire sample, while the tensile force was recorded. The tearing energy, T, was calculated as follows:Fave and t are the average tearing force to advance the crack and the sample thickness, respectively. Each sample was tested at least three times, the average value was calculated, and the standard derivation was obtained as the error bar.Trouser tearing tests of hydrogel samples were performed at room temperature to characterize the tearing energy, l (70 mm) × w (20 mm) × t (≈1 mm)], and the overlapping length, b, between the hydrogels and substrates was kept constant at 15 mm, as illustrated in −1. Adhesive strength, Fmax is the maximum force on the force-extension (F-Δ) curves. Each sample was tested at least three times, the average value was calculated, and the standard derivation was obtained as the error bar.The adhesive strength of the hydrogel samples to diverse substrates (including hydrogels themselves) was characterized by lap-shear tests (standard: ASTM F2255) at ambient temperature. The samples were cut into a rectangular shape [l (70 mm) × w (20 mm) × t (≈1 mm)], and the overlapping length, b, between the hydrogels and substrates was kept constant at 15 mm, as illustrated in −1. Photographs of the tests are shown in Γ, was calculated as follows:Fave is the average plateau force in the steady-state region on the force-extension (F-Δ) curves, and w is the sample width. Each sample was tested at least three times, the average value was calculated, and the standard derivation was obtained as the error bar.Interface toughness between the hydrogel samples was characterized by 90-degree peeling tests (standard: ASTM D2861) at ambient temperature. The samples were cut into a rectangular shape [ωw) of composite hydrogels was tested using an electronic moisture meter . The mode was set as automatic stop, and the temperature was set as 120 °C. ωw was calculated as follows:m0 and m1 are the weights of wet and dehydrated hydrogel samples, respectively. Each sample was tested at least three times, the average value was calculated, and the standard derivation was obtained as the error bar.Water content  network, which is copolymerized from sodium p-styrenesulfonate (NaSS) and 3-(methacryloylamino)propyl-trimethylammonium chloride (MPTC) with a small amount of chemical crosslinker  hydrogel as the matrix and nonwoven cellulose-based natural fiber fabric (CF) sheets as the reinforcement filler a. In detsslinker a-i,ii [1The design strategy and fabrication process of the composite hydrogels are given in T = 6.8 kJ m−2), which is 1.5 times that of the PA gel matrix 3N+ groups, and the peak at 3440 cm−1 are related to −NH− groups. On the spectrum of PA/CF composite gel, some characteristic peaks of these functional groups change in intensity or position, indicating the existence of some physical interactions between the two individual components. In detail, in PA/CF composite gel the characteristic peaks of −SO3– groups at 1034, 678, and 581 cm−1 become weaker compared to neat PA gel; their peaks at 1180 and 1123 cm−1 become a single broad peak. The peak of −SO3– groups at 581 cm−1 blueshifts to 607 cm−1 in PA/CF composite gel. Meanwhile, in PA/CF composite gel the peaks of −COO− groups at 1640 and 1428 cm−1 redshift compared to neat CF. This result tells that some ionic bonds were probably formed between −(CH3)3N+ groups in the PA network and −COO− groups in CF instead of some −(CH3)3N+•••−SO3− bonds. In addition, in PA/CF composite gel, the peak of −NH− groups at 3440 cm−1 becomes stronger and redshifts to 3419 cm−1, suggesting that hydrogen bonds were probably formed between −NH− groups in PA network and −OH or −COO− groups in CF. These possible ionic and hydrogen bonds existing between the hydrogel matrix and CF could provide good interfacial interactions, enabling significant mechanical improvements.In order to understand the mechanical enhancement, the chemical structures of the neat and composite gels were also investigated by FTIR spectra a. On theFracture surfaces of the hydrogel samples were further observed to understand the fracture behavior, and the corresponding SEM images are presented in ϕCF = 1.5–9.0 wt%) on the mechanical properties of PA/CF composite gels. Tensile tests were first carried out, and the data are presented in ϕCF (1.5–6.0 wt%), both Young’s modulus (E) and tensile fracture strength (σb) of the samples first increase gradually, and after ϕCF > 6.0 wt%, the increase becomes relatively slow. When ϕCF is only 3.0 wt%, the sample was reinforced clearly: E = 12.2 MPa and σb = 2.4 MPa, which are 7.6 and 1.3 times these of neat PA gel, respectively. When ϕCF = 9.0 wt%, the optimal E and σb of the sample reach 35.3 MPa and 4.3 MPa, which are 22.1 and 2.3 times these of neat PA gel, respectively. This enhancement should be due to the fact that the strong fibers with good interfacial interactions with the matrix could effectively transfer and disperse the loads widely, which could reduce rapid stress concentration, enabling high load-bearing performance. However, excessive CF introduction might weaken the interfacial interaction, decreasing the enhancement efficiency of the composite gel. The introduction of CF probably shortened the effective stretch length of polymer chains in the hydrogel network, decreasing the tensile strain and work of extension of the composite gels.Filler loading usually influences the mechanical reinforcement in composite gels . Next, wϕCF = 1.5–9.0 wt%) on the crack resistance  of PA/CF composite gels by tearing tests, and the data are shown in ϕCF (1.5–9.0 wt%), tearing energy (T) increases gradually. When ϕCF is only 3.0 wt%, the sample could be toughened effectively, and T reaches 6.0 kJ m−2, which is 1.3 times of neat PA gel. When ϕCF increases further to 9.0 wt%, the maximized T highly reaches 8.1 kJ m−2, which is 1.8 times of neat PA gel. As aforementioned, introducing the strong, high-aspect-ratio fibers into the relatively tough, sticky PA gel could enlarge the process zone  remarkably, allowing it to highly dissipate energy broadly when resisting a crack. With increasing ϕCF, the continuously increased T indicates that the energy dissipation of the hydrogel is still not saturated. However, when ϕCF > 9.0 wt%, the samples are difficult to fabricate successfully due to the high viscosity of the pre-solutions. It is worth noting that, despite mechanical enhancements, the composite gels still show increased water contents (ωw) compared to the neat PA gel  on adhesive strength (F-Δ) curves and the calculated F-Δ curves, we can find that each sample has a peak adhesive force before failure, in agreement with the literature [ϕCF could clearly influence the lap-shear adhesion behavior. In detail, with increasing ϕCF (1.5–6.0 wt%), ϕCF > 6.0 wt%, ϕCF is only 1.5 wt%, the sample achieved a much higher ϕCF = 6.0 wt%, the optimized sample possesses the highest As discussed above, filler loading could significantly influence the mechanical properties of the composite gels, which also probably results in different adhesion properties to diverse substrates. To clearly understand this point, here we systematically investigate the adhesion behaviors of the samples on different solid surfaces  by lap-shear tests and 90-degree peeling tests. The detailed data are presented in terature ,41,42. AϕCF on adhesive energy (Γ) of two pieces of composite gels by 90-degree peeling tests. F-Δ curves and the calculated Γ of the samples are given in F-Δ curves, it is seen that each sample shows a sawtooth-like plateau adhesive force before failure, which is also usually observed in previous studies [Γ than the neat PA gel, and the samples with different ϕCF show different enhancements. In detail, with increasing ϕCF (1.5–6.0 wt%), Γ of the samples increases, and after ϕCF > 6.0 wt%, it decreases but is still higher than that of neat PA gel. When ϕCF is only 1.5 wt%, the sample achieved a much higher Γ (543 J m−2), which is 1.6 times that of neat PA gel. The optimized sample with ϕCF = 6.0 wt% has the highest Γ (1400 J m−2), which is 4.2 times that of neat PA gel.We further evaluate the effect of  studies ,35,43. SΓ) of a hydrogel-solid bonding could be expressed as Γ = Γ0 + ΓD, where Γ0 is the intrinsic energy dissipation by the scission of a thin interfacial layer, and ΓD is the energy dissipation from the bulk of the samples. Usually, ΓD from the highly deformed bulk mainly contributes to the tough bonding. In our fabricated composite gels, varying ϕCF should mainly affect ΓD, enabling different enhancements described above. When keeping the same overlapping area (20 mm × 15 mm) of the samples, we can see that the maximum failure adhesive forces (Ff) for both tests are quite different. When ϕCF = 6.0 wt%, Ff for the lap-shear test highly reaches >280 N, but Ff for the 90-degree peeling test is relatively low (around 20 N), giving a high parallel/vertical adhesion force ratio  relatively soft, sticky gel matrix provided good contact between the components while strong fibers could bear the relatively higher load. (ii) The strong fibers could also enlarge the energy-dissipative area in the bulk. According to a recent adhesion theory , the totϕCF to a glass substrate by lap-shear tests, and the data are shown in ϕCF (1.5–6.0 wt%), and then decreases after ϕCF > 6.0 wt%. When ϕCF is only 1.5 wt%, ϕCF = 6.0 wt%) to diverse substrates  by lap-shear tests, as shown in Γ0). All of the above results demonstrate that high strength, high fracture toughness, and good adhesion could be achieved simultaneously in PA/CF composite hydrogels.Adhesion of the composite gels to diverse solid substrates is important for their practical applications. Here we first study the adhesion behavior of the composite gels with different dhesives ,44,45,46ϕCF, 1.5–9.0 wt%) on the mechanical and adhesion properties of composite gels was systematically studied. The results show that ϕCF could dramatically influence both the mechanical and adhesion properties. The optimized composite gel achieved 35.2 MPa of Young’s modulus, 4.3 MPa of tensile fracture strength, 8.1 kJ m−2 of tearing energy, 943 kPa of self-adhesive strength, and 1.4 kJ m−2 of self-adhesive energy, which is 22.1, 2.3, 1.8, 6.0, and 4.2 times those of neat PA gel, respectively. Additionally, the composite gels could also adhere well to diverse solid substrates . This work opens a simple yet effective pathway to achieve soft and wet materials with high strength, high toughness, and good adhesion.In summary, we have developed a series of strong, tough, and adhesive composite hydrogels from relatively tough, sticky polyampholyte (PA) gel reinforced by cellulose-based nonwoven fiber fabric (CF) via a composite strategy. In PA/CF composite gels, strong fibers in CF could interact with the relatively tough matrix well through possible ionic and hydrogen bonds, enabling effective stress transfer and dispersion (high strength) as well as wide energy dissipation (high toughness). Meanwhile, the soft, sticky matrix could also provide a large contact area to realize good adhesion. The effect of CF content (


Moreover, isotopic changes from the bone to gelatin during the processing were examined to evaluate the effectiveness of these factors as origin indicators. The results of the one-way analysis of variance (ANOVA) showed that the δ13C, δ15N, and δ2H of gelatin from different regions display significant differences, and using the linear discriminant analysis (LDA), the correct differentiation of origin reached 97.9%. Certain differences in stable isotope ratios were observed during the processing of bone to gelatin samples. Nonetheless, the fractionation effect caused by the processing of bone to gelatin samples was not sufficient to influence the identification of gelatin from different origins, which proves that δ13C, δ15N, and δ2H are effective origin indicators of gelatin. In conclusion, the stable isotope ratio analysis combined with the chemometric analysis can be used as a reliable tool for identifying gelatin traceability.Geographical traceability is crucial to the quality and safety control of gelatin. However, currently, methods for gelatin traceability have not been established anywhere in the world. This study aimed to investigate the possibility of differentiating the geographical origins of gelatin from different regions in China using stable isotope technology. To achieve this objective, 47 bovine stick bone samples from three different regions  in China were collected, and gelatin was extracted from these bones using the enzymatic method. The fingerprint characteristics of stable isotopes of δ Gelatin, a natural polymer extracted from the bones, skin, or connective tissue of animals, has been widely used in food, pharmaceuticals, cosmetics, and other industries due to its distinctive physicochemical property , 2. In rRecently, various methods, such as stable isotope ratio analysis , 5, mineMany studies on gelatin focused on species identification, and there are few related studies on traceability methods for gelatin are available at present. Jannat et al. successfully differentiated bovine, porcine, and fish sources of gelatin in commercially pure gelatin and gelatin-containing food and drug products using real-time polymerase chain reaction (PCR) and the analysis of mass spectrometry (MS)-based proteomic datasets . Sha et 13C, δ15N, and δ2H from bone raw materials to gelatin during processing were also investigated to evaluate their effectiveness as geographical origin indicators. The results of the present study will provide a new idea and strategy for the origin traceability of gelatin.Based on the aforementioned studies, stable isotope ratio analysis coupled with chemometric analysis was first used to trace the geographical origin of gelatin in this study. The key aim of this study was to explore the regional differences in stable isotopes in gelatin from China and develop a reliable identification method. In addition, changes in δA total of 47 bovine stick bone samples were sampled from three representative regions of China, including Mashan County of Guangxi Province (GX), Heze City of Shandong Province (SD), and Hulun Buir City of Inner Mongolia (NMG) . DefatteGelatin was extracted from defatted bovine granules using the enzymatic method , as show−1, and the measurement range varied between 800 and 200 cm−1.Ultraviolet spectra of gelatin samples were obtained using a Hitachi U-3900 spectrophotometer . Gelatin samples were dissolved in 0.5 M acetic acid to form a mixed solution at room temperature. The spectra were obtained at a resolution of 4 cm−1 and the measurement range varied between 400 and 4,000 cm−1. Automatic signals were collected in 32 scans at a resolution of 4 cm−1.The FTIR spectrum  of gelatin samples was recorded using the tablet method. Briefly, the bovine gelatin samples were mixed and ground with potassium bromide (KBr) in the ratio of 1:100 to make a tablet; the spectra were obtained at a resolution of 4 cm13C = −27.771 ± 0.043‰ VPDB, δ15N = 1.0 ± 0.2‰ air N2), USGS24 (δ13CVPDB = −16.05 ± 0.07‰), USGS42 , and USGS43 (δ2HVSMOW = −44.4 ± 2.0‰) were performed to calibrate the stable isotope data.Stable isotope ratios were determined using an Elemental Analyzer (EA)  connected to an Isotope Ratio Mass Spectrometer (IRMS) . IAEA-600  and nitrogen gas (N2) in an oxidation–reduction furnace at 980°C, and then, the gases were separated using the gas chromatography (GC) before being sent to the IRMS for analysis.For the δ2H analysis, appropriate amounts of gelatin samples were weighed into silver capsules and introduced into the EA using the autosampler. Hydrogen in the sample was converted into molecular hydrogen gas (H2) in a pyrolysis furnace at 1,380°C, and then, the gases were separated using the GC before being sent to the IRMS for analysis.For the δ13C/12C, 15N/14N, and 2H/1H) were expressed in δ notation in parts per thousands (‰) and were calculated using the following equation:Stable isotopic ratios  was performed to determine significant differences between the mean values of gelatin samples from different regions (p < 0.05)   . A paire < 0.01) , 29. The < 0.01) .The UV spectra of the gelatin sample (GS) and commercial gelatin (CG)  are depicted in −1  and the distribution characteristics of gelatin samples from the three different regions in China are given in 13C, δ15N, and δ2H in the three regions, the stable isotope ratios are significantly different (P < 0.05) in gelatin samples from the regions.Three stable isotope ratios  value in gelatin samples compared to GX (−12.27 ± 2.63‰) and SD (−13.27 ± 0.98‰). In a previous report, the δ13C values of milk samples from Inner Mongolia were also significantly lower than those from Tianjin, Hebei, and Jiangsu  have lower δ13C in their tissues than those fed C4 plants   . Thus, t15N in animal products is closely linked to the diet consumed by the animals and the regions of their habitat  are significantly lower than those in NMG (6.38 ± 0.91‰) and GX (6.52 ± 0.88‰). This may be due to the cattle from SD being mainly fed maize but the cattle from NMG and GX being mainly fed pasture. During the growing process, maize uses more chemical fertilizers, while pasture uses more organic fertilizers, which are then transferred to the cattle through feed. Compared to organic fertilizers, chemical fertilizers are depleted in δ15N . Combined with 13C, δ15N, and δ2H can be used as good indicators for gelatin origin traceability.In summary, differences were found in δ13C, δ15N, and δ2H were not sufficient to identify gelatin samples from different origins; thus, the combination of these three indicators was used to improve the rate of correct classification. As shown in As single indicators, δ13C, δ15N, and δ2H) could be used as effective origin indicators for gelatin traceability, and the classification model also shows high discriminant ability. Therefore, stable isotope ratio analysis coupled with chemometric analysis can be used as an effective method for gelatin traceability. Furthermore, the results of this study may provide technical support for the quality and safety control of gelatin.This study investigated the feasibility of using stable isotope ratio analysis combined with chemometric analysis to identify the origins of gelatin. The results show that stable isotopes (δThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.SL: methodology, investigation, validation, and writing. DJ: methodology, formal analysis, reviewing, and editing. JL: software and formal analysis. YM, JY, and LD: formal analysis support. YX: supervision, reviewing, and editing. YQ: supervision, funding acquisition, review, and editing. All authors contributed to the article and approved the submitted version.