Trypanosomes are single-celled eukaryotes that rely heavily on post-transcriptional mechanisms to regulate gene expression. RNA-binding proteins play essential roles in regulating the fate, abundance and translation of messenger RNAs (mRNAs). Among these, zinc finger proteins of the cysteine3histidine (CCCH) class have been shown to be key players in cellular processes as diverse as differentiation, regulation of the cell cycle and translation. ZC3H41 is an essential zinc finger protein that has been described as a component of spliced leader RNA granules and nutritional stress granules, but its role in RNA metabolism is unknown.Trypanosoma brucei cells, and also to identify the cohort of mRNAs associated with the ZC3H41/Z41AP complex. Levels of 5S ribosomal RNA (rRNA) species in ZC3H41- and Z41AP-depleted cells were assessed by quantitative reverse transcription-polymerase chain reaction. Surface sensing of translation assays were used to monitor global translation.Cell cycle analysis in ZC3H41- and Z41AP-depleted cells was carried out using 4′,6-diamidino-2-phenylindole staining, microscopic examination and flow cytometry. The identification of ZC3H41 protein partners was done using tandem affinity purification and mass spectrometry. Next-generation sequencing was used to evaluate the effect of ZC3H41 depletion on the transcriptome of procyclic We showed that depletion of the zinc finger protein ZC3H41 resulted in marked cell cycle defects and abnormal cell morphologies. ZC3H41 was found associated with an essential protein, which we named Z41AP, forming a stable heterodimer, and also with proteins of the poly(A)-binding protein 1 complex. The identification of mRNAs associated with the ZC3H41/Z41AP complex revealed that it is primarily composed of ribosomal protein mRNAs, and that binding to target transcripts is diminished upon nutritional stress. In addition, we observed that mRNAs encoding several proteins involved in the maturation of 5S rRNA are also associated with the ZC3H41/Z41AP complex. Finally, we showed that depletion of either ZC3H41 or Z41AP led to the accumulation of 5S rRNA precursors and a decrease of protein translation.We propose that ZC3H41 and Z41AP play important roles in controlling the fate of ribosomal components in response to environmental cues.The online version contains supplementary material available at 10.1186/s13071-023-05728-x. RNA transcription, processing, modification, translation and turnover constitute a central part of cell physiology . RNA metTrypanosoma brucei is the organism of choice for functional analyses in trypanosomatids, and is responsible for human and animal trypanosomiasis in sub-Saharan Africa. Trypanosomes alternate between insect (tsetse fly) and mammalian hosts, including humans, and undergo profound changes in their transcriptomes and proteomes in order to adapt to the contrasting environments they face in their life cycle ATP  and 10 units of PNK (Promega), incubated for 20 min at 37 ºC in a Thermomixer at 800 r.p.m., washed thrice in PNK buffer lacking DTT, and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis for PhosphorImager analysis and immunoblot.The method described in  was follFor transcriptome analyses of ZC3H41-depleted trypanosomes, RNAi was induced for 2 days, and total RNA was obtained using the RNeasy Mini Kit (Qiagen). mRNA libraries were obtained using the TruSeq Stranded mRNA sample preparation protocol (Illumina). Biological triplicates were processed in parallel with a high-throughput sequencing (RNA-seq) of control procyclic 449 cells described in  [Gene Exhttps://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and mapped to the T. brucei 11 megabase chromosomes  using the align module of the Subread package  with thM values method [2 in edgeR. For coverage plots, regions of interest were binned and counted  using the countReadsPerBin module of deepTools API  with pas method  and trann 3.5.0; ), and coT. brucei 11 megabase chromosomes  using option –f 0.5.RIP-seq data were analyzed using either edgeR as above, comparing input RNA with immunoprecipitated RNA samples, or peak calling with MACS2 . In theGene ontology analysis was performed in TriTrypDB  using geAATP11 mRNA (Tb927.4.4730) as a reference. All quantitative reverse transcription–polymerase chain reaction (RT-PCR) experiments were performed with at least three biological replicates. Oligodeoxynucleotide pairs used are listed in Additional file PCR conditions, calculations and small-scale RNA immunoprecipitations were done as described  using AA7 trypanosomes were deposited in 24-well plates, incubated in the presence of 10 µg/ml puromycin for 30 min at 28 ºC, washed in serum-free medium at the same temperature and subjected to immunoblot analysis as described above. Two controls were included: cells not treated with puromycin, and cells incubated for 30 min with 50 µg/ml of cycloheximide prior to the addition of puromycin. Puromycinilated peptides were detected with an anti-puromycin antibody  in an Odyssey Imaging System, and quantified using Image Studio . DRBD3, which is stable over the course of the experiment [The surface sensing of translation assay  was usedperiment , was useTo gain more insight into the function of ZC3H41, depletion in vivo using RNAi was used. We first generated a trypanosome procyclic cell line that expressed a TAP-tagged version from the endogenous locus. TAP-ZC3H41 was detected as a single band of the expected size in western blot analysis of total cell extracts  after 2 days of tetracycline induction, and compared to that of control cells. Differential abundance analyses were carried out with edgeR using cutoffs of 1 for |log2| fold change (i.e. ± twofold linear fold change) and 0.01 for false discovery rate (FDR). A volcano plot for the differentially expressed genes in ZC3H41-silenced genes is shown in Fig. r = 0.559 vs 0.242; Additional file NT8 and AATP6 mRNAs in the PuREBP1-TAP dataset, which are known components of the PuREBP1/2 complex [We showed above that ZC3H41 and Z41AP are bona fide RNA-binding proteins. To identify the cohort of mRNAs bound to the ZC3H41/Z41AP complex, we performed TAP followed by high-throughput sequencing (RIP-seq) using Z41AP as bait. Z41AP-TAP purification, generation of RNA-seq libraries and Illumina sequencing were done in parallel with a RIP-seq of another RNA-binding protein complex, PuREBP1/2 , and thu complex , we consr = 0.968) between TAP-ZC3H41 and TAP-Z41AP quantitative RT-PCR enrichment values  in TAP-ZC3H41 or TAP-Z41AP purifications than in PuREBP1-TAP samples  in all tested ZC3H41/Z41AP-associated mRNAs upon nutritional stress , the ZCinfantum . However. brucei .T. brucei ribosome [T. brucei showed that tethering of ZC3H41 or Z41AP to a reporter gene did not result in apparent changes in gene expression [Depletion of ZC3H41 led to minimal changes in the transcriptome, suggesting that the main role of this protein is unrelated to mRNA turnover. RIP-seq of ZC3H41/Z41AP complexes, on the other hand, revealed that they are mainly associated with ribosomal protein mRNAs, as 72 of the 104 top-ranked bound transcripts encode ribosomal proteins. Excluding paralogs, 46 of the 77 protein components of the ribosome , 72 are ribosome ), which pression .T. brucei PABP1 complex is specialized in the regulation of a small subgroup of mRNAs probably encoding ribosomal proteins [L. infantum [T. brucei [As mentioned above, ZC3H41 and Z41AP associate with PABP1 complexes together with the RNA-binding protein RBP23 and the translation factor eIF4E4 . It has proteins , in lineinfantum  and eIF4. brucei . Moreove. brucei , and we . brucei , it is t. brucei . Phospho. brucei . TherefoT. brucei . b TAP-ZC3H41 localization was analyzed by immunofluorescence using an anti-protein A antiserum. c Representative flow cytometry plots are shown for uninduced or ZC3H41-depleted cell lines stained with propidium iodide.Additional file 3: Figure S2. RNA interference of ZC3H41 using a different double-stranded RNA. Cells expressing TAP-ZC3H41 were transfected with a different tetracycline-inducible RNAi plasmid. a Growth curve of uninduced or RNAi-induced trypanosomes. b ZC3H41-depleted cells were mounted in mounting medium containing DAPI and analyzed for the appearance of zoids and 'nozzled cells'.Additional file 4: Table S2. List of proteins associated with ZC3H41.Additional file 5: Figure S3. Protein abundances of ZC3H41 and Z41AP. Data from deep proteome surveys carried out in bloodstream and procyclic trypanosomes were plotted according to protein intensity-based absolute quantification (iBAQ) values or protein abundance rank positions. a Components of the PABP1 complex. bTrypanosoma brucei zinc finger proteins of the CCCH class.Additional file 6: Table S3. Effect of ZC3H41 depletion on the transcriptome of procyclic Trypanosoma brucei.Additional file 7: Table S4. Raw read counts mapped to transcripts upon depletion of ZC3H41 in procyclic Trypanosoma brucei.Additional file 8: Figure S4. Additional information related to ZC3H41/Z41AP RIP-seq. a Correlation analysis between the percentages of immunoprecipitated target mRNAs and MACS2 score or edgeR fold change values. b RIP followed by quantitative RT-PCR to confirm association of the indicated transcripts with ZC3H41/Z41AP. c Effect of ZC3H41 depletion on NRBD2, P0 and S9 protein levels.Additional file 9: Table S5. Transcripts associated with the ZC3H41/Z41AP complex.Additional file 10:Table S6. Protein abundances of zinc finger proteins of the CCCH family in Trypanosoma brucei.


Drosophila and by HRas, NRas, and KRas in mammals. In the past dozen years, multiple reports have characterized both inhibitory and activating ubiquitination events regulating Ras proteins. Inhibitory Ras ubiquitination mediated by Rabex-5 or Lztr1 is highly conserved between flies and mammals. Activating ubiquitination events at K117 and K147 have been reported in mammalian HRas, NRas, and KRas, but it is unclear if these activating roles of K117 and K147 are conserved in flies. Addressing a potential conserved role for these lysines in Drosophila Ras activation requires phenotypes strong enough to assess suppression. Therefore, we utilized oncogenic Ras, RasG12V, which biases Ras to the GTP-loaded active conformation. We created double mutants RasG12V,K117R and RasG12V,K147R and triple mutant RasG12V,K117R,K147R to prevent lysine-specific post-translational modification of K117, K147, or both, respectively. We compared their phenotypes to RasG12V in the wing to reveal the roles of these lysines. Although RasG12V,K147R did not show compelling or quantifiable differences from RasG12V, RasG12V,K117R showed visible and quantifiable suppression compared to RasG12V, and triple mutant RasG12V,K117R,K147R showed dramatic suppression compared to RasG12V and increased suppression compared to RasG12V,K117R. These data are consistent with highly conserved roles for K117 and K147 in Ras activation from flies to mammals.Ras signaling plays an important role in growth, proliferation, and developmental patterning. Maintaining appropriate levels of Ras signaling is important to establish patterning in development and to prevent diseases such as cancer in mature organisms. The Ras protein is represented by Ras85D in  Drosophila . The E3 ubiquitin ligase Rabex-5 inhibits Drosophila Ras and mammalian HRas and NRas by promoting their mono- and di-ubiquitination  as we did previously with UAS RasG12V . The plasmids were sent to BestGene for injection and generation of transgenic lines at the attp40 locus. Lines were balanced with second chromosome balancers, and then each individual balanced line was allowed to homozygose. Homozygous lines were then maintained as true-breeding homozygous stocks. BestGene confirmed insertion at attp40, and we sequenced genomic DNA to confirm the sequence of each insert. Importantly, G12V,K117RUAS Ras, G12V,K147RUAS Ras, and G12V,K117R,K147RUAS Ras differ in sequence from G12VUAS Ras only at K117 and/or K147. These transgenes are listed in Drosophila medium as in our previous work  in the G12V background to assess the contribution of K117 and K147 to Ras activation: double mutants RasG12V, K117R and RasG12V,K147R and triple mutant RasG12V,K117R,K147R. All transgenes carry the same tags and were inserted at the same attp40 location in the genome to rule out position insertion effects. If neither K117 nor K147 contributes to Ras activation, these double and triple mutants will phenocopy RasG12V. If only 1 lysine contributes to Ras activation, then that specific double mutant should show phenotypic suppression compared to a RasG12V control and will phenocopy the suppression seen in the triple mutant. If both K117 and K147 contribute to Ras activation, then the triple mutant should show suppression compared to a RasG12V control and greater suppression than that shown by each individual double mutant.To address conservation of the role of K117 and K147 between mammalian Ras isoforms and eviously . The G12c765-gal4, which drives expression generally across the wing . We performed categorical analysis  (apterous gene including in the third instar dorsal wing, tarsal segment 4, brain, thorax, and elsewhere (While e thorax , in the ng flies  comparedng flies . These p7R,K147R . To high7R,K147R  typicallanalysis  and ANOVanalysis  both of enotypes  to RasG1rom 21°C  not seenrom 21°C . These bG12V,K117R,K147R would show suppressed phenotypes compared to RasG12V and greater suppression than either RasG12V,K117R or RasG12V,K147R alone. Taken together, the different degrees of suppression of RasG12V phenotypes in G12V,K117R and RasG12V,K117R,K147R are consistent with both lysines K117 and K147 playing a role in the status of Ras activation in Drosophila as seen in mammals. Arginine substitution preserves the positive charge of lysine while preventing modifications such as ubiquitination and acetylation. It is formally possible these substitution mutants are inactivating by affecting Ras structure or its ability to adopt an active conformation, and we have not ruled out such structural defects from K117R and K147R mutants in Drosophila Ras. However, work in mammalian systems showed that K147R in mammalian KRas maintained an active conformation capable of binding the RBD (G12V,K117R,K147R showed suppressed phenotypes compared to RasG12V, it exhibited clear Ras gain-of-function wing (As noted earlier, if both K117 and K147 contribute to Ras activation, then triple mutant Ras the RBD , thus exion wing  and 2 anion wing  phenotypG12V,K117R and RasG12V,K147R transgenes would be useful tools in future work to identify and evaluate these E3 enzymes and explore their role in development and disease.An alternate explanation for the activating role of K117 and K147 is modification at these sites. K117 is a site of activating ubiquitination in mammals, and K147 undergoes both activating ubiquitination and activating acetylation events (jkad201_Supplementary_DataClick here for additional data file.


Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the Editorial Office to multiple concerns within the paper. Various images seem to appear in papers by other, unrelated authors. The Figure 2C control and miR-NC panels and 5C control panel seem to appear in Figure 3B from Feng et al. 2017 (doi: 10.1042/BSR20170019), Figure 3B from Guan et al. 2018 (doi: 10.1111/jcmm.13620) and in Figures 3A, 3C and 7D from Li et al. 2017 (doi: 10.18632/oncotarget.22133). The GAPDH Western Blots from Figure 1D also seem to appear as the Figure 1D GAPDH blots from Yin et al. 2018 (doi: 10.1111/jcmm.13888). Multiple duplications have also been identified within the paper by both the Reader and the Editorial Office between features of the Figures 3 and 6 panels, which include the following:Figure 3A, 48h/control and 48h/miR-NC panelsFigure 3A 0h/miR-mimics and Figure 6A 24h/siRNA-NC panelsFigure 6A 48h/control and 48h/siRNA/NCFigure 3A 48h/control and Figure 6 48h/controlFigure 3A 48h/miR-NC and Figure 6 48h/siRNA-NCThis article is being retracted from It has also been noted that the middle scatter plot graphs of Figures 2E and 5E (the FITC miRNA-NC and FITC siRNA-NC plots respectively) seem to share heavily similar features. It has also been noted that the Figure 6E E-cadherin and Vimentin blots seem to be duplicates after a 180-degree rotation. The authors are unable to correct the article and wish to retract the article. The Editor-in-Chief and Editorial Board agree with the retraction.


The presence of pharmaceutical compounds in wastewater due to an increase in industrialization and urbanization is a serious health concern. The demand for diverse types of pharmaceutical compounds is expected to grow as there is continuous improvement in the global human health standards. Discharge of domestic pharmaceutical personal care products and hospital waste has aggravated the burden on wastewater management. Further, the pharmaceutical water is toxic not only to the aquatic organism but also to terrestrial animals coming in contact directly or indirectly. The pharmaceutical wastes can be removed by adsorption and/or degradation approach. Nanoparticles (NPs), such as 2D layers materials, metal-organic frameworks (MOFs), and carbonaceous nanomaterials are proven to be more efficient for adsorption and/or degradation of pharmaceutical waste. In addition, inclusion of NPs to form various composites leads to improvement in the waste treatment efficacy to a greater extent. Overall, carbonaceous nanocomposites have advantage in the form of being produced from renewable resources and the nanocomposite material is biodegradable either completely or to a great extent. A comprehensive literature survey on the recent advancement of pharmaceutical wastewater is the focus of the present article.  The advantage of using bismuth and graphitic carbon nitride (Energy band gap = 2.7) eV in photo-heterostructures is their visible light-tuneable energy bandgap, low toxicity, cost-effectiveness, and high storage stability. Various types of graphene-based composites have been used for the treatment of antibiotic contaminant water. TiO2–ZnO/CS–Gr nanocomposite has been used to achieve the light-mediated degradation of tetracycline [The demand for food, and medicines is continuously increasing due to rapid increase in the global population . Every cnanorods , nanoflonanorods , and nannanorods  have sucnanorods . The adsnanorods . Nano-phnanorods . The benacycline ,19.2O3-TiO2 nanocomposite on exposure to sunlight [2O4@UiO-66 nanocomposite has been used for the photo-catalytic degradation of metronidazole antibiotic [3N4, metal oxide nanorods, nanoflowers, and nano-leaves) have been reviewed which are widely used in the manufacturing of visible light-assisted photocatalyst and nano adsorbents due to its high carrier mobilities, good thermal conductivity, mechanical flexibility, and high visible light absorption capacity. The novelty of this work is focused on the comparative discussion about the photocatalytic and adsorption capacity of the three most explored carbonaceous nanomaterials, metal organic frameworks (MOF’s) and 2D layer nanomaterials. It also highlights all the difficulties in handling, creating, and implementing nanocarriers for contaminated water treatment. This review article provides crucial information to address the pressing issue of pharmaceutical contamination.Nanocomposites have earlier been reported for the removal of more than one type of pharmaceutical molecules from wastewater. In such a study, maltodextrin/reduced graphene and maltodextrin/reduced graphene/copper oxide have been used for the adsorption-based removal of amoxicillin antibiotic as well as the anti-inflammatory and painkiller drug diclofenac . The degsunlight . ZnFe2O4tibiotic . The nantibiotic . In thistibiotic ,13. Simi2.2.1.3N4) is studied widely due to suitable band energy, better stability, and high surface area [3N4 [3N4 for the treatment of pharmaceutical waste through better photocatalytic activity [3N4 composite for diclofenac treatment [3N4 and AgI NPs, respectively.Recently, attention has been focused on employing nanotechnology-based employing carbon nanocomposites because of low fabrication cost, high surface area, and environmental stability . Due to ace area . Poor abrea [3N4 . It has activity . Zhang ereatment . The deg2O4/g-C3N4-Nvac) that uses nickel cobaltate NPs embedded in nitrogen-defects containing graphitic carbon nitride nanosheets. The defects were responsible for the activation of key species peroxymonosulfate, •SO4− based oxidation and Z-scheme-charge-transfer thus leading to better tetracycline degradation in case of the composite than NiCo2O4/g-C3N4 and g-C3N4 [6+/Mo5+ oxidation-reductioncycle and PMS activation mediated degradation of tetracycline hydrochloride have been reported using MoO3/Bi2O3/g-C3N4 composites [Jiang et al. have developed a Z-scheme photocatalyst  > g-C3N4@ PDA + BiOBr (47%) > BiOBr (42%) > g-C3N4 (30%). The increased efficiency of the composite was attributed to the better electron transfer ability of polydopamine between g-C3N4 and BiOBr. It was established that h+ and •O2− were the main reactive species responsible for oxidizing sulfmethoxazole.Guo et al.  reported3N4/NiO/ZnO/Fe3O4 has been used for the degradation of esomeprazole [2O2, as well as a Fenton-related process, were mainly responsible for the degradation of esomeprazole. Zhang et al. prepared a Fe3O4/CdS/g-C3N4 photocatalyst using the mono-dispersion approach with 81% degradation efficiency for ciprofloxacin [3N4 broadens the optical response spectrum of CdS. With the aid of simulated solar light, the ternary catalyst CuO/CuFe2O4/g-C3N4, decomposed 99% of tetracycline hydrochloride and removed 74% of the chemical oxygen requirement. Both the values are reportedly greater than those of either CuO/CuFe2O4 and pure g-C3N4 [2O4 and pure g-C3N4. The enhanced reaction sites are provided by g-C3N4 substrate and inhibition of recombination of photo-excited electrons and holes is due to the synergetic effect of individual moieties in composite. •O2−, h+, and •OH were the oxidative components involved in the breakdown. Hydrothermal approach is successfully used to fabricate Fe3O4/CeO2/g-C3N4 composites for the photocatalytic degradation of tetracycline hydrochloride [3N4 decreased the release of Fe from the catalyst surface and ensures proper interaction of tetracycline hydrochloride with •OH. The experiment to capture active species demonstrated that •OH was the main reactive species to carry out the photocatalytic degradation of the antibiotic molecule. Fe3O4/g-C3N4/MoO3 nanocomposite displayed 94% degradation efficiency for tetracycline degradation under visible light irradiation [•O2− generation and synergetic effect of components to form Z-scheme structure leading to separation of e/h+ pairs.Quaternary nanohybrid photocatalyst of composition g-Ceprazole . Esomeprfloxacin . The sepe g-C3N4 . With thchloride . The comadiation . Nanocom3N4/NaBiO3 nanocomposites produced through the hydrothermal method have been reported for the degradation of tetracycline [•O2− and •OH, which reduced tetracycline to 87% of its original strength. The ternary photocatalyst BiOI/g-C3N4/CeO2 prepared by calcination and hydrothermal treatment has been used for the degradation of tetracycline under visible-light irradiation [3N4/CeO2. The photocatalytic activity was reported in order BiOI/g-C3N4/CeO2> BiOI/g-C3N4> BiOI > CeO2> g-C3N4. The nanocomposite possessed approximately 13 and 34 times higher degradation rate and rate constant as compared to g-C3N4, respectively. The better separation of produced electron-hole and dual charge transfer process between different components at ternary heterojunction were the main reasons behind the improved photocatalytic activity. Akbarzadeh et al. reported g-C3N4/Ag/AgCl/BiVO4-based composite for the photocatalytic degradation of ibuprofen. The hydrothermal method was used for the fabrication of g-C3N4/Ag/AgCl/BiVO4 composites and maximum 94.7% ibuprofen degradation was observed within 60 min of light exposure [+) were the major reactive species causing the photocatalytic effect. The composite has shown better photocatalytic activity than BiVO4, Ag/AgCl/BiVO4, and g-C3N4/BiVO4 due to higher absorption of visible light and availability of electron-hole pairs generated along the heterojunction for a longer time. A similar mechanism was followed in the case of g-C3N4/Ag/AgCl/BiVO4-induced photocatalytic degradation of tetracycline. Nanocomposite has shown the best photocatalytic activity as compared to individual components and it was found to decrease in order g-C3N4/Ag/AgCl/BiVO4, Ag/AgCl/BiVO4, g-C3N4/BiVO4, BiVO4, g-C3N4. Kang et al. reported g-C3N4/Na-BiVO4 heterojunction as a catalyst for tetracycline degradation on visible light exposure in the presence of peroxymonosulfate [4. The increased tetracycline degradation over the composite is attributed to the creation of Z-scheme heterojunctions, and oxygen vacancies brought on by Na+ which make it easier for electron–hole couples to move apart and form free radicals as shown in g-Cacycline . The Z-sadiation . Tetracyexposure . Photogeosulfate . About 93PO4/C3N4 heterojunction has been used for the decomposition of ibuprofen under sunlight. The protection of Ag3PO4 and the effective separation of electron–hole pairs by AgSCN and C3N4 components in the composite has resulted in its better degradation efficiency. The composite followed Z-mechanism and has 1.5–3.3 times higher catalytic activity than AgSCN/Ag3PO4, and Ag3PO4 [2(OH)2CO3/g-C3N4 heterojunction (Cu/CN) has been used for the degradation of tetracycline [3N4 and Cu2(OH)2CO3 components. During solar light stimulation, type II heterojunction transfer pathway increased the membrane oxidation thus producing many active species that leads to tetracycline degradation.AgSCN/Agd Ag3PO4 . Celluloacycline . The Cu/3O4/rGO for the degradation of carbamazepine  is one more carbonaceous substance that is frequently used as a design template and support for many hybrid composites. The addition of GO to composite materials makes an excellent photo catalyst because it activates the fabricated composite under sunlight and maintains effective charge carrier separation because of its large surface area . These cmazepine . The int2O3/2D g-C3N4 nanosheet has been fabricated using hydrothermal process for the tetracycline and ciprofloxacin treatment [3N4 nanosheets, respectively. Su et al. fabricated Fe3O4@SiO2@BiFeO3/rGO composite using a hydrothermal technique which shows 95.6% and 98.2% ciprofloxacin and tetracycline hydrochloride degradation, respectively [3O4/ZnO/SnO2 nanocomposite has been reported for azithromycin degradation with a maximum of 90% efficiency on exposure to UV-C [Composite comprising 2D rGO nanosheet/3D Fereatment . The disectively . rGO has to UV-C . Azithro•O2− and H2O2 through a single electron, respectively, which resulted in direct oxidation and indirect photo-Fenton-like reaction of tetracycline. With the increase in the amount of N-CQDs in composite, the photocatalytic performance is greatly improved.Carbon quantum dots (CQDs) have been regarded as remarkable candidate for interfacial modulation because of their inherent up-conversion photoluminescence, superior electron-transfer capabilities, and favorable biocompatibility ,55. As a3N4 nanosheets (uCN) composite has mediated the transfer of electrons between BiOCOOH and uCN to fasten photocatalytic degradation of sulfathiazole. The composite containing 50 wt% uCN leads to complete degradation after 90 min of LED lamp exposure due to quick transfer and separation of photo-generated charges. The degradation efficiency was reported to be 97.35% ± 1.57 after five cycles of reuse [3O4/BiOBr/CQDs composite. The composite has been used for the photo-catalytic degradation of carbamazepine. The photocatalytic effect was mainly caused by Z-scheme structures formation, photoluminescence of CQDs, the synergetic effect of CQDs and Fe3O4 and generation of •O2−, h+, and •OH [Likewise, CQDs included in the CQDs/BiOCOOH/ultrathin g-C and •OH . Table 12.2.Adsorption offers greater benefits in terms of pollutant treatment strategies when compared to photo degradation and other membrane-based technologies, because it is an efficient, straightforward, ecologically beneficial, and simple procedure . The eff3O4 has been fabricated for phenazopyridine residue removal from waste-water samples [rGO-Fe samples . The mag3O4@SiO2-Chitosan/GO nanocomposite is explored for tetracycline elimination [NPs can be functionalized using enzyme to increase their adsorption efficiency. Chitosan-graphene oxide (CsGOn) composite functionalized with horseradish peroxidase (HRP) has been used for the removal of ofloxacin ,68. HRP mination . The gre3O4@ polyethyleneimine (PEI)-rGO nanocomposite synthesized using a self-assemble method has been documented for adsorption of polar non-steroidal anti-inflammatory medicines; ketoprofen, naproxen, diclofenac, and ibuprofen. This composite involved the synergetic effect of both PEI and rGO which demonstrated greater extraction efficiency as compared to individual components, Fe3O4@ PEI, Fe3O4-rGO, and Fe3O4@PEI-GO. The adsorption mechanism displayed the potential of Fe3O4@PEI-rGO as a polar and π-π type adsorbent [3O4@ graphene nanoplatelets composite prepared by solid-phase fabrication has been reported for the removal of these non-steroidal anti-inflammatory drugs. H-bonding, hydrophobic, π–π electrostatic, and n–π electron acceptor–donor interaction were responsible for adsorption of drugs on the surface of nanocomposite [Fedsorbent . Similaromposite .2/graphene nanocomposite [2 nanorods has modified adsorption efficiency as it avoided stacking too many graphene sheets together throughout the adsorption process and gave additional chances to tetracycline molecules for contacting the adsorbents. The primary adsorption mechanism involved complex formation by Mn(IV) and π-π interactions involving benzene ring of graphene sheets with tetracycline. Nanocomposite containing 40% MnO2/graphene has shown 198 mg g−1 adsorption capacity that was better than free treated graphene sheets with 170 mg g−1 capacity. A triple-network composite hydrogels with composition carbon nanotubes/L-cysteine@graphene oxide/sodium alginate (CNTs/L-cys@GO/SA) has been reported to remove ciprofloxacin antibiotic from aqueous contaminated samples [Tetracycline elimination rate of 99.4% is observed by using MnOomposite . The inc samples . The int3O4-g-CN@PEI-β-CD nanocomposite removes tetracycline with an efficiency of 833.33 mg/g. Larger surface area, more porosity, and presence of function groups that form nanocomposite–drug complex were main factors responsible for tetracycline adsorption [The ability of graphitic carbon nitride material to selectively interact with the various type of pollutant has been extended to remove pharmaceutical molecules from contaminated waste. It offers other advantages like being a nonmetallic environmentally safe material with tuneable thermal, chemical, and physical properties ,76. Fe3Osorption .3O4 (AC-Fe3O4) nanocomposite with magnetic properties has been fabricated for the removal of promazine which is a phenothiazine antipsychotic drug. Nanocomposites possess high adsorption efficiency, quick adsorption, and simple magnetic separation. Complete drug removal with 101.01 mg/g adsorption capacity was achieved within 6 min [The activated carbon (AC) at the microscale is frequently utilized as a sorbent to remove various contaminants because of its unique structure and strong adsorption ability . AC madein 6 min . Yeast-ein 6 min . Nanocomin 6 min . MaximumSpherical fullerene is one of the members of the carbon nanomaterials family that has zero-dimensional structure with exceptional electron withdrawing capabilities . These n3.3.1.+) generation by nanocomposite were mainly responsible for the ciprofloxacin photodegradation.Functionalization of metal/metal oxide nanocomposite for wastewater remediation is well documented. Functionalized metal/metal oxide nanocomposite has been reported to contain high photocatalytic activity, low band gap, better separation of charge carriers, and recovery of the catalyst. The details about metal and metal oxide-based nanocomposite for remediation of pharmaceutical wastewater are tabulated in 2CO3/Ag2O for the photocatalytic degradation of ibuprofen. The presence of Ag2CO3 and Ag2O heterostructure over the ZnO surface led to 99% degradation of Ibuprofen that is 10-fold better degradation than the pure ZnO [2 nanocomposites under UV irradiation, diclofenac photocatalytic degradation of the drug is increased as reported [2 nanocomposites to commercial TiO2, nano TiO2, and CeO2 revealed that these materials have increased activity. Until to the fifth cycle, the Ce@TiO2 nanocomposite remained stable. Payan et al. produced Cu-TiO2@functionalized single-walled carbon nanotubes for the catalytic degradation of sulfamethazine within 135 min [2 particles are reported to be distributed uniformly that help to uniformly capture light induced electrons and reduction of electron–hole recombination.A simple two-step synthesis approach has been used to fabricate ZnO/Agpure ZnO . By emplreported . After b 135 min . On the + was the primary oxidizing species in charge of the 81% degradation of diclofenac by PPy-ZnO in just 60 min [3O4/Bi2S3/BiOBr nanocomposites prepared using Fe3O4 nanosphere, Bi2S3 nanorod, and BiOBr nanosheet demonstrated excellent photo catalytic performance for the removal of diclofenac and ibuprofen with removal efficiencies of 93.81% and 96.78%, respectively [+ and e− played the most important roles in the diclofenac and ibuprofen photo degradation as per active species trapping experiment. BiOBr/Fe3O4@SiO2 nanocomposite prepared via the solvothermal method has been reported for the photocatalytic degradation of ibuprofen [−CB-mediated processes and direct-hole oxidation. The magnetic property was useful in photocatalyst recycling and approximately 80% of the photocatalytic activity was maintained even after five consecutive cycles.Polypyrrole (PPy)-ZnO composite fabricated using polymerization technique has been used for the diclofenac degradation. PPy-ZnO has demonstrated a higher photocatalytic rate constant which is about twice as compared to ZnO. The ht 60 min . Fe3O4/Bectively . The solbuprofen . The nan2@ ZnFe2O4/Pd nanocomposite. The nanocomposite has been used in batch and continuous systems to carry out diclofenac degradation using sunlight [2O4 and TiO2@ZnFe2O4 owing to its magnetically properties nanocomposite was recycled up to five cycles of usage, although the maximum photo catalytic activity was dropped from 86.1% in the first cycle to 71.38% in the final cycle. p-type nanoanatase TiO2/Zinc ferrite NPs based photocatalyst has been used for the degradation of anti-inflammatory drug, etodolac [Model pharmaceutical pollutant has been used to study photocatalytic removal using TiOsunlight . Pd coatetodolac .2O4 nanocomposite has been reported for photocatalyic degradation of carbamazepine [2O2. Overall, •O2− and •SO4− were the main species involved in the photocatalytic process. Sodium dodecyl sulfate (SDS)/BiOBr-magnetic bentonite (MB) nanocomposites has been used for the catalytic degradation of tetracycline and ciprofloxacin [3O4, and the addition of bentonite, which created a platform for dispersing the growth of BiOBr. Overall, these factors were responsible for the improved photocatalytic efficacy of SDS/BiOBr-MB 2·2 H2O) showed the highest rate of tetracycline degradation (87%). The main active groups involved in tetracycline degradation are h+ and •O2−. The Z-scheme transfer route as a means of enhancing photocatalytic activity is considered. Fe3O4@ SiO2@ Bi2O2CO3-sepiolite nanocomposite has been reported for ciprofloxacin and tetracycline hydrochloride photodegradation with 92% and 100%, respectively [To create the Feh system . During ectively . Sepioli4.4.1.MOFs have a spatial topology with a periodic porous structure and are often created by the self-assembly of organic ligand, metal ions, or clusters of metal ion. Ultra-high porosity, large surface area, tuneable structure, and ease of preparation are some of the amazing characteristics of MOFs . These f2-MIL-53(Fe) composite has also been used to adsorb chlortetracycline and tetracycline hydrochloride [2-MIL-53(Fe), the π-π interaction and hydrogen bonding between amino functional groups of composites with hydroxyl functional groups on tetracycline hydrochloride/chlortetracycline hydrochloride were collectively accountable for the increased adsorption capacity.Adsorption is a highly competitive technology to remove pharmaceutical waste from aqueous solutions due to its cost-effective nature, ease of use, and lack of chances of secondary contamination. MIL-101(Cr) with sodium alginate (MIL-101(Cr)/SA) and MIL-101(Cr) with chitosan (MIL-101(Cr)/CS) composite prepared by combining MIL-101(Cr) with SA and CS has been used as an adsorbent for adsorption of ibuprofen and ketoprofen . The comchloride . The imp3O4@SiO2-chitosan/GO [2-MIL-101(Cr) [2/g), which raised their maximum adsorption effectiveness to 99.02%. MrGO/ZIF composite is created for the adsorption of methamphetamine by attaching ZIF-67 on magnetic substrates [2/GO nanocomposite have shown five times better tetracycline hydrochloride adsorption than that of UiO-66 [The addition of graphene oxide (GO) to MOF adsorbents produced more functional substances with wide pore structure in order to increase the adsorption efficiency. Hence, highly porous MOF composites are shaped by fusing GO with MIL-101(Cr) . The lintosan/GO , ZIF-8 [tosan/GO , NH2-MIL-101(Cr) , MIL-101-101(Cr) , and UiO-101(Cr) . Further-101(Cr) . GNP/UiObstrates . Some ofbstrates . In addibstrates . It is ff UiO-66 . It has The metal doping of MOFs changes the electronegativity of the composite surface which ultimately alters the electrostatic interactions between the nanocomposite and pharmaceuticals. Jin et al.  reported2O/CuO@C were reported for the adsorption of ciprofloxacin and tetracycline [n–π interactions for higher adsorption efficiency than individual components.Porous carbon materials can be functionalized to acquire essential properties including structural stability, porosity, and functional groups so that they can be used as excellent adsorbents. MnO@C nanocomposite produced by pyrolysis of metals or metal oxides self-supported on porous carbon was used for the adsorption of antibiotic pollutants including tetracycline, ciprofloxacin, diclofenac, and chloramphenicol in aqueous medium . Adsorptacycline . Nanocom3O4/HKUST-1 copper-based MOF composite as an efficient and recyclable adsorbent for the removal of ciprofloxacin and norfloxacin types of fluoroquinolone antibiotics [3O4/HKUST-1 included π–π interactions, hydrophobic interactions, electrostatic interactions, and hydrogen bonding. Fe3O4/HKUST-1 was effectively regenerated and found reusable up to more than 10 times. Naeimi and Faghihian prepared MIL-53(Fe)/Fe3O4 composite for the removal of 322 mg/g doxycycline from aqueous solutions [3O4@MIL-68 (Al) has maximum 248.05 mg/g adsorption efficiency [3O4, has been reported for the adsorptive removal of ciprofloxacin [3O4@MIL-100(Fe) and Fe3O4@MOF-235(Fe) is scrutinized for ciprofloxacin removal [3O4@MIL-100 (Fe) composition has a comparatively higher 322.58 mg/g adsorption capacity. The adsorption occurred in the form of a monolayer over the nanocomposite surface. The presence of Fe3O4NPs was mainly responsible for better adsorption capacity due to an increase in the number of accessible sorption sites as compared to bare MOFs.The interference observed during the practical application in term of recovery and regeneration of the adsorbent after use is difficult to manage at large scale. One way to accomplish the goal of recovering and reusing the adsorbent is by combining magnetic materials with MOFs. Based on this concept, Wu et al. developed a Feibiotics . Due to olutions . The supficiency . The adsfloxacin . Tempera removal . However2@Fe3O4, which was produced through the self-assembly of ZIF-8 with SiO2@Fe3O4 [2/g, it demonstrated a greater adsorption capacity of 96.84 mg/g. After five cycles, nanocomposite could be efficiently regenerated with over 90% efficiency. Additionally, a dual MOFs-based smart platform produced using ZIF-8 and 2D amino-functionalized Al-MOF (NH2-MIL-53(Al)) nanoplates for the adsorption and detection of doxycycline, tetracycline, oxytetracycline, and chlortetracycline [2 group on surface of NH2-MIL-53(Al) displayed significant affinity toward these drugs due to hydrogen-bond formation, π−π stacking and chemisorption.Zeolite imidazolate framework-8 (ZIF-8) containing MOFs are known for their exceptional chemical stability, porosity, thermal/water stability, and active sites endowed for various types of chemical and physical interactions with pharmaceutical molecules in aqueous phase . CeftaziO2@Fe3O4 . Due to acycline . In part4.2.Adsorption and degradation processes for pharmaceutical waste are the main water clean-up techniques. The adsorption process could only reduce the concentration of pharmaceutical waste, but it could not get rid of this pharmaceutical waste . Antibio3/UiO-66-NH2 binary p–nheterojunction has been reported for the degradation of norfloxacin by designing and evolving competent heterogeneous catalyst for harvesting solar energy [3/UiO-66-NH2 and norfloxacin, (iii) greater ability to respond to solar light than a photocatalyst in its purest state and (iv) unlocking new surface pores to capture the suitable adsorbates. Hydrothermal approach has been used to synthesize the double Z-scheme CuWO4/Bi2S3/ZIF67 ternary heterostructure for the degradation of metronidazole and cephalexin under visible light illumination [4/Bi2S3 and pristine ZIF67, the photoactivity of the former showed a notable improvement. Based on the dual Z-scheme structure, the augmentation of CuWO4/Bi2S3/ZIF67 photoactivity is attributed to the higher surface area, photo-stability, and suppression of bandgap in addition to better charge separation. Metronidazole and cephalexin, the ternary heterostructure had maximum degradation efficiencies of 95.6% and 90.1%, respectively. The ternary heterostructure showed remarkable chemical stability and reusability after six cycles. The trapping experiments are used to investigate the governing active species and the results showed that the main oxidants are hydroxyl free radicals. Bi2O2CO3/porous g-C3N4 Z-scheme heterojunction is created by Wang et al. to remove sulfamethazine [2O2CO3 NPs evenly disperse across surface, edge, and interlayer in g-C3N4 nanosheet. The mechanism analysis showed that Bi2O2CO3/g-C3N4 composites specifically encouraged molecular oxygen activation into singlet oxygen (1O2). This may be attributed to Bi-N bonds at the interface and the development of Z-scheme system which speeded up the oxidation of •O2− by holes. The composites outperformed the pristine g-C3N4 in the elimination of sulfamethazine after 90 min of visible light illumination and helped to selectively generate (1O2) in a targeted manner during molecular oxygen activation.CoTiOr energy . The invmination . Compariethazine . The amo•O2−) and hydroxyl radicals (•OH) are shown to be the predominant active species in the photocatalytic degradation of sulfamethoxazole as per the radical capture studies. Phenyl nitrification, isoxazole ring hydroxylation, and S-N bond cleavage are all components of the sulfamethoxazole degradation pathway. Ag2S NPs are coupled with MOFs material (MIL-53(Fe)) using an easy solvothermal method for tetracycline degradation to create Ag2S/MIL-53(Fe) heterojunction hybrids [2O2 which further improved the catalytic activity.For the photocatalytic elimination of sulfamethoxazole, an in-situ growing approach is used to generate a visible light responsive composite photocatalyst AgI/UiO-66 composite . As comp hybrids . Nano co2-based catalysts upon using a molybdenum disulfide/ZIF-8 composite photocatalyst have been reported for ciprofloxacin and tetracycline hydrochloride degradation [A series of mesoporous composites of UiO-67/CdS/rGO-x has been fabricated by incorporating visible-light responsive CdS NPs into MOF and encapsulating them in excellent conductor rGO thin sheets. In this composite, the simultaneous utilization of sunlight-harvesting and electron-relay-penetration is exploited . It led radation . Nanocom1O2was observed that ultimately indicated the involvement of type II photosensitization reaction. The degradation of diclofenac is facilitated by both the energy transfer from TCPP to triplet oxygen and the electron transport from TCPP to Zr clusters. A dual-function platform with CuBi2O4@ZIF-8 composites has been documented to carry out sensing and degradation of tetracycline [2O4.MOFs can have structural defects and combining different capabilities because of heterogeneity as they are solid-state crystals. By carefully managing the structural heterogeneity and defects through defect engineering, it is possible to manipulate the desired characteristics of MOFs, such as the production of mesopores, reduction of network rigidity/density, enhancement of active sites, development of novel functionalities, and mechanical properties. In continuation to this aspect, Gao et al. reported the use of defect-engineered MOFs with multi-functionalities for the degradation of diclofenac . The levacycline . Nanocom0.5 could attain 87.7% tetracycline photodegradation within 60 min. Type II heterojunction formation between ZnO and ZIF-9 is primarily responsible for the higher photocatalytic activity because it increases the conductance of light generated electrons to make it easier to separate charges from holes. Li et al. reported ZIF-8@TiO2NPs containing composite for the catalytic degradation of tetracycline [2 micron composite, reducing the charge carrier’s recombination rate, visible light absorption and narrow band gap are prominent factors for enhancing the catalytic ability of the composite photocatalyst.The extraordinary function that the heterostructure plays in charge separation made the development of heterostructures in photocatalysts an efficient way to increase their catalytic activity. Regarding this, a simple so no crystallization method is successful in producing a new type II photocatalyst ZnO/ZIF-9 heterojunction . ZnO/ZIFacycline . MOF wit2 composite with magnetic properties has been prepared to photodegrade tetracycline to take the advantage of easy separation of catalyst [2 added to the composite has a significant effect on the catalytic process, which could be enhanced by light exposure to produce significant amounts of the radicals •O2− and •OH. The composite has high reusability as it is easy to recover the composite from tetracycline solution using a magnet. Using Fe3O4 as a metal precursor, Fe3O4@MIL-100(Fe) was created through microwave in 30 min and used to treat diclofenac sodium in water samples [2O2-assisted Fe3O4@MIL-100(Fe) photocatalytic process 99.4% diclofenac sodium degradation was achieved. The diclofenac sodium degradation process followed Fenton-like reaction. Rasheed et al. combined MIL-100(Fe) with Fe3O4 and carbon aerogel to form a nanocomposite for the removal of tetracycline hydrochloride [3O4/CA nanocomposite that was higher than observed in case of individual components. The performance of MIL-100(Fe)@Fe3O4 increased 1.6 times by coupling carbon aerogel with it. This significantly speeded up the transfer of light produced charge carriers. Further, MIL-88A (Fe) particles were immobilized onto the porous block substrate and then calcined to produce the supported MIL-88A derivative Fe3O4@ porous block substrate catalyst to remove tetracycline hydrochloride [2O/Fe3O4/MIL-101(Fe) nanocomposite degraded the antibiotic ciprofloxacin in an aqueous solution when exposed to visible light [–/h+ recombination suppression, and production of hydroxyl and superoxide radicals. After five cycles, the ciprofloxacin degradation efficiency dropped by just 6%, which demonstrated the outstanding cyclability of Cu2O/Fe3O4/MIL-101(Fe) nanocomposites. Bagherzadeh et al. reported the best performance of MIL/CoFe2O4/(3%)GO as compared to MIL-101(Fe), CoFe2O4, novel binary (MIL-101(Fe)/CoFe2O4, MIL-101(Fe)/GO and CoFe2O4/GO) for visible light photocatalytic and photo-Fenton-like degradation of tetracycline hydrochloride [2O4/(3%)GO significantly boosted the absorption of visible light. A magnetic photocatalyst Fe3O4@MIL-53(Fe) is fabricated via calcination treatment of pristine MIL-53(Fe) under visible light and composite demonstrated 99% photocatalytic removal of ibuprofen in the presence of H2O2 after 60 min [+, •OH, e−, and •O2− played crucial roles. g-C3N4@CoFe2O4/Fe2O3 composite is fabricated by taking advantage of the Z-scheme heterojunction upon combining g-C3N4 and MOF-derived CoFe2O4/Fe2O3 [2O4/Fe2O3 doping significantly improved the adsorption capacity of g-C3N4 to absorb visible light and decrease its band gap. As a high-efficient mediator, the generated hybrid photocatalysts were used to activate persulfate for the degradation of emerging pharmaceutical pollutants upon exposure to visible light. After 80 min, tetracycline (99.7%), sulamethoxazole (94.8%), diclofenac (97.0%), ibuprofen (96.1%), and ofloxacin (96.5%) all could be removed. The magnetic Fe3O4@MIL-100(Fe) hybrid composites can encourage photo-Fenton-like process which has been further exploited for levofloxacin degradation [3O4: MIL-100(Fe) mass ratio of 1:4 has a greater degrading efficiency (up to 93.4%) as compared to Fe3O4, MIL-100(Fe) and the other produced composites. This increased catalytic activity is attributed to the synergistic interaction between Fe3O4 and MIL-100(Fe) which favored both the effective reduction of Fe3+ to Fe2+ in the photo-Fenton reaction and the speedy separation of the hole-electron pair from MIL-100(Fe). Based on free radical quenching, electron paramagnetic resonance, and mass spectrometry research, a preliminary hypothesis is made on the potential degradation mechanism and intermediates of levofloxacin in the photo-Fenton reaction.MIL-101(Fe)/TiOcatalyst . Under s samples . Under vchloride . The comchloride . Maximumle light . The cipchloride . Besidesr 60 min . In the O4/Fe2O3 . A smallradation . The com5.As potential adsorbents and photocatalyst for the efficient treatment of several environmental pollutants, functionalized two-dimensional 2D NPs/nanocomposites possess distinctive properties. The different parameters about other 2D-based nanocomposite as photocatalyst for remediation of pharmaceutical wastewater are in 5.1.2has been reported to cause low quantum yield and poor photocatalytic efficiency [2 with MXenes resulted into semiconductor heterojunctions with reduced band gap and an effective photocatalysis [3C2Tx MXene. The presence of {0 0 1} facets of TiO2 inserted into Ti3C2Tx sheets was primarily responsible for the better photocatalytic activity of pure MXene. The superior photocatalytic activity was attributed to Schottky junctions and the additional e− and h+ produced by {0 0 1} facets of TiO2. Because of free radicals •OH, •O2– and the strong oxidation ability of 001-T/MX photocatalyst to breakdown carbamazepine into CO2 and H2O toward the end of the process are possible carbamazepine photocatalytic degradation mechanism. Despite good catalytic activity, the poor stability of MXenes makes them less useful. On the other hand, polymeric carbon nitride (C3N4) has good solubility being a metal-free photocatalyst, but it has disadvantages in the form of low conductivity and severe charge recombination. Keeping this in mind, delaminated-Ti3C2Tx/alkalized-C3N4 (TC-aCN), a strong heterostructure photocatalyst made by Yi et al., was embedded into alkalized C3N4 in a few layers without being oxidized [3N4 and Ti3C and holes generated in the in the VB of C3N4 on visible light exposure were mainly responsible for the catalytic breakdown of tetracycline hydrochloride. The photocatalyst demonstrated exceptional stability and reusability up to four cycles. In another study, g-C3N4/Ti3C2/TNTAs has been used as a visible-light-driven catalyst for the 85% degradation of tetracycline hydrochloride. g-C3N4 and Ti3C2 mixture had uniformly covered the TiO2 nanotube arrays that led to increase in surface area, better light absorption, and charge carrier migration. Hydroxylation, dimethyl amino loss, aromatic ring, double bond oxidation, and carboatomic ring cleavage were identified as five steps of the degradation process [Several studies reported MXene as a photocatalyst for the removal of hazardous pollutants from air and water . MXenes ficiency . The comatalysis . Shahzadatalysis . The nanoxidized . The com process .2/g-C3N4. The nanocomposite demonstrated higher photocatalytic degradation of tetracycline and ciprofloxacin compared to TiO2/graphene, g-C3N4, and conventionalTiO2/g-C3N4. Better photocatalytic activity was attributed to improved visible light adsorption, carrier separation, and generation of •OH and •O2– free radicals [A single step in-situ calcination process has been reported to prepare MXene-derived TiOradicals .2WO6/Nb2CTx nanosheets [2CTx nanosheets significantly increased the separation of carriers and transfer of electrons from conduction band of Bi2WO6 to Nb2CTx. The created at the Bi2WO6/Nb2CTx interface act as Schottky junction to prevent recombination of photogenerated electron-hole pairs. Bi2WO6/Nb2CTx hybrid nanosheet photocatalysts have shown superior photodegradation efficiency for tetracycline hydrochloride as compared to Bi2WO6.Simple hydrothermal procedure has been used to produce Binosheets . Nb2CTx 3C2-based MXene (nZVI@Ti3C2) nanosheets has been used for the treatment of ranitidine [2O2 dependent oxidation of ranitidine. Ti3C-based MXene prevented the agglomeration of and promoted the electron transmission between the magnetic NPs. Ranitidine molecules are primarily broken down by hydroxyl radical (•OH) attacks, particularly those that targeted surface-bound •OHads  has a van der Waals heterojunction and 2D atomic crystal structure like graphene and hence, is referred as ‘white graphene.’ It is made up of an equal amount of nitrogen and boron atoms . h-BN ar2MoO6 heterojunction with good photocatalytic activity using a workable solvothermal method [2MoO6. The addition of h-BN boosted the photocatalytic ability through better absorb of light. Nanocomposites having 50 wt% h-BN/Bi2MoO6 had better degradation with maximum 99.19%, 95.28%, and 91.04% efficiency in case of tetracycline, oxytetracycline, respectively. h+ and •O2– were mainly responsible for photocatalytic activity. h-BN prevented photogenerated electron-hole pairs from recombining. TiO2-BN nanocomposites prepared and their potential as attractive photocatalysts for the treatment of ibuprofen in water is explored under visible light [2-BN composites appeared to have shorter band gaps as compared to pure TiO2 nanoscale fibers as per UV-vis absorption spectra. Higher photocurrents are reported for the TiO2-BN nanocomposites than for pure TiO2 which suggested that negative charge on the BN nanosheets encouraged the charge separation by transporting the holes to the TiO2 surface. The maximum photocatalytic activity for the treatment of ibuprofen under visible light is demonstrated by TiO2-10 wt% BN and kinetic rate constant is almost 10 times more for TiO2-10 wt% BN than pure TiO2 [•SO2−, •OH and •O2–. Cai et al. produced MoSe2/ZnO/p-BN photocatalyst for the degradation of ofloxacin (OFL). Nanocomposite with 30 wt % of produced maximum 92.2% ofloxacin degradation under visible light irradiation. Synergetic effect of tight adsorption of ofloxacin by p-BN and better visible light absorption by flower-shape MoSe2 was responsible for improved catalytic activity. Active species quenching tests revealed that the degradation of antibiotic was largely mediated by e−, •O2−, h+, and •OH [3N4 (BNRU) nanocomposite has been produced for the ciprofloxacin, ofloxacin, enrofloxacin, norfloxacin, and lomefloxacin with 100%, 94.4%, 87.7%, 100%, and 94.6% efficiencies, respectively. BNRU had a 1.7-fold greater carrier density as compared to ultrathin g-C3N4. Synergistic effects of defect engineering and quantum dots loading were mainly responsible for better antibiotic degradation activity of BNRU [Du et al. developed an ultrathin h-BN/Bil method . The surle light . The TiOure TiO2 . The add and •OH . Boron n of BNRU .5.3.2WS4/g-C3N4 heterojunction to form 2D nanocomposite. The Cu2WS4/YC/g-C3N4 has been used for the degrading tetracycline under visible light [2WS4 has a strong photo-catalytic activity and ease of crystal surface modulation. YC sphere acted as electron bridge which helped to prevent rapid electron recombination and significantly increased the ability to absorb visible light. The nanocomposite exhibited better catalytic activity than individual pure components. O2−, h+ and •OH all have a significant impact on the degradation of tetracycline. An immobilized Z-scheme CdS/Au/TiO2 nanobelts composite photocatalyst made of CdS, Au, and TiO2 nanobelts were produced to augment the norfloxacin degradation activity on exposure to solar light [2 NBs offered more absorption and reaction sites for the special designs and Au served as the electron transfer mediator, boosted the interfacial charge transfer and effective separation of electrons and holes. CdS/Au/TiO2 nanobelts showed the highest rate of degradation after being exposed to light for 60 min. The other photocatalysts degrade in the following order: CdS/Au/TiO2 NBs (64.67%) > CdS/TiO2 NBs (55.94%) > Au/TiO2 NBs (50.60%) > TiO2 NBs (42.04%). This trend is ascribed to increased light absorption and the separation of photogenerated electrons and holes result in mentioned composite. Superoxide radicals (•O2−) shown to be the most active species throughout the photocatalysis process in the radical trapping tests. Cu2WS4/NiTiO3 (CWS/NTO) composite prepared using an easy electrospinning/calcination approach along with hydrothermal procedure has been documented to show improved abilities to separate photo-generated charge carriers, endowing these composites with good and enduring photocatalytic performance for tetracycline. The degradation rate for pure NTO and CWS is just 21.5% and 43.9%, respectively within 60 min. The degradation efficiency for tetracycline exhibited a substantial improvement after the formation of CWS/NTO heterojunction under the same conditions, with degradation efficiency 88.6%, CWS/NTO composites (x = 0.5). Free radical species •O2− and h+ were mainly responsible for the degradation of tetracycline degradation are [2S4/MoO3 is fabricated using hydrothermal method tailed by the impregnation for the efficient degradation of paracetamol as compared to pure MoO3 and ZnIn2S4 [2S4/MoO3 has prolonged electron-hole pairs separation and the better visible light absorption owing to the direct Z-scheme system. Ganguly et al. reported ternary metal chalcogenide heterostructure nanocomposites photo-catalyst of titania via hybrid nanoarchitectures of AgInS2 with TiO2 using a modified sol-gel technique [2 loading exhibited more than 95% sunlight assisted degradation of doxycycline in 3 h. Recent studies on boron nitride (BN) have shown that it is an effective adsorbent for organic pollutants and heavy metal ions [3O4@Ti3C2 [3O4@Ti3C2. Maximum 97% adsorption was achieved. Hydrogen bonding between -O, -F, and -OH functional groups on the MXene Ti3C2and aromatic ring/phenolic hydroxyl groups of 17-ethinylestradiol were mainly responsible for adsorption.Metal chalcogenides due to their easy availability in a range of chemical composition, variable bandgap, light tuneable optical, electrical, and catalytic properties are in focus for treatment of pharmaceutical contaminant in water . Hence, le light . Cu2WS4 ar light . The CdStion are . Z-schem ZnIn2S4 . The comechnique . In comptal ions . The lowtal ions . FurtherO4@Ti3C2 . The quaWorldwide nanotechnology market was approximately 7.73 billion in 2022 which is expected to grow up to more than $114 billion by 2030 . Further6.Advancements in medical research have resulted in the modernization of healthcare facilities, subsequently leading to a higher level of production and usage of pharmaceuticals to sustain better quality of life . 26% of The presence of pharmaceutical compounds has been reported in more than 1,052 sites of 258 rivers in more than half of the world’s countries. Water pollution by pharmaceutical products is a serious health concern. Pharmaceutical pollutant has been reported to induce severe genotoxic response upon long-term exposure to human. Sub-Saharan Africa, south Asia, and South America were the most contaminated areas with under developed and developing countries were having highest amount of pharmaceutical contaminant ,209. IncAmong the various types of pharmaceutical wastewater treatment methods, the microorganism-based method is cost-effective and produces sludge with low toxicity to environment. However, sometimes microorganism may covert less toxic pharma waste to more toxic components. The conventional treatment methods suffer from high capital investment and require regular input to maintain efficiency. Microbial treatment methods are cost effective; generate less toxic secondary sludge and are eco-friendly . AdsorptMembrane-based technologies are the most efficient available and reliable method to filter water for drinking purposes. This method is expensive and wastes more water than it filters. We still lack another reliable method that can work at large scale making it the most used method . NanomatGreen synthesis of NPs gives better stability products however, green synthesis suffers from few drawbacks that needs to be sorted out before making it is a method of choice for large scale production ,216. Hen7.The elevated concentration of pharmaceuticals in water have posed an alarming situation for human health and environmental sustainability. This review discusses the current developments in the adsorptive and photocatalytic techniques being used to remove pharmaceutical pollutants using nanocomposites decorated with diverse types of nanomaterials. This has enhanced the effectiveness of photocatalysis and adsorption process. In-depth review is conducted on the nanocomposites that contain metal organic frameworks, carbonaceous material, metal/metal oxide and 2D materials such as MXenes, boron nitride, and metal chalcogenides. Introduction of carbonaceous QDs to the photocatalyst formulation can enhance the photodegradation rate to almost double as a result of increasing the light absorption efficiency. The degradation rate of hybrid materials can be significantly improved by using metal oxides nanomaterials. Metal oxide NPs are non-biodegradable material and can be replaced with biodegradable carbonaceous materials. Carbonaceous materials  forms hybrid material with NPs to improve the absorption efficiency up to 10 folds due to their better surface area and active functional groups. The interaction of pharmaceuticals with nanocomposites is due to coordination with unsaturated sites, π-π stacking, hydrogen, and electrostatic bond formation. Various variables involved in enhancing the photocatalytic degradation of pharmaceutical water include pH, Fenton reagent, catalyst dose, ultra violet/visible light exposure, oxidation-reduction potential, number of free radicals, and charge carrier recombination rate. This review provides critical information regarding the creation of functionalized nanocomposite materials to obtain complete or near to complete pharmaceutical waste degradation.


BACH2) gene encodes a transcription factor that acts on the differentiation and formation of B and T lymphocytes. BACH2 is also involved in the suppression of apoptosis and inflammation in pancreatic beta-cells, indicating a role for it in the development of T1DM. Therefore, the aim of this study was to evaluate the association of the BACH2 rs11755527 single nucleotide polymorphism (SNP) with T1DM. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by a complex interaction between environmental and genetic risk factors. BTB domain and CNC homolog 2 (BACH2 rs11755527 (C/G) SNP was genotyped using real-time PCR with TaqMan MGB probes. This case-control study comprised 475 patients with T1DM and 598 nondiabetic individuals. The HLA DR/DQ genotypes of high-risk for T1DM. Although, well-known high-risk T1DM HLA DR/DQ genotypes were associated with T1DM in our population [OR= 7.42 (95% CI 3.34 – 17.0)], this association was not influenced by the rs11755527 SNP. Genotype distributions of rs11755527 SNP were in accordance with frequencies predicted by the Hardy–Weinberg equilibrium in case and control groups and were similar between groups (P = 0.729). The minor allele frequency was 43.6% in cases and 42.5% in controls (P = 0.604). Moreover, the G allele frequency did not differ between groups when considering different inheritance models and adjusting for age, gender, body mass index, and  The BACH2 rs11755527 SNP seems not to be associated with T1DM in a Brazilian population. HLA DR/DQ locus has the greatest impact on susceptibility, accounting for up to 30-50% of the genetic variance of T1DM  could be useful to help improve prediction of the disease (HLA SNPs associated with T1DM may help disease prediction (Type 1 diabetes mellitus (T1DM) affects 10-15% of patients with diabetes mellitus (DM) and is caused by autoimmune destruction of pancreatic beta-cells, making patients dependent of insulin for life . This di disease ,5. Conseediction .loci associated with T1DM , incl T cells -10.BACH2 inhibition aggravated cytokine-induced apoptosis of pancreatic beta-cells through activation of the JNK1/BIM pathway, whereas opposite effects were observed after BACH2 overexpression. Hence, SNPs in the BACH2 gene might contribute to development of T1DM since this gene is related to T cell control and B cell differentiation, modulating the balance between tolerance and immunity, and also plays an anti-apoptotic role in beta-cells . Real-Time PCR reactions were run in 384-well plates, using 2 ng of DNA, TaqMan Genotyping Buffer 1x (Thermo Fisher Scientific) and TaqMan SNP Genotyping Assay 1x, in a final volume of 5 mL. Next, plates were placed in the ViiA7 Real-Time PCR System (Thermo Fisher Scientific) and heated for 10 min at 95º C, followed by 50 cycles of 95º C for 15 sec and 63º C for 90 sec. Ten percent of samples were amplified twice in order to check the quality of Real-Time PCR reactions, confirming their genotypes.A standardized salting-out technique was used to extract total DNA from peripheral blood leukocytes. The SNP rs11755527 (C/G) in the HLA DR/DQ genotypes may affect the association between non-HLA SNPs and T1DM  were genotyped using Custom TaqMan Genotyping Assays 20x (Thermo Fisher Scientific), as previously reported , intermediate-risk genotype (DR3/DRx), and high-risk genotypes (DR4/DQ8 or DR3/DR4-DQ8 or DR3/DR3)  ,23. Thesenotypes .2tests. Genotype and allele frequencies were compared between case and control groups with c2 tests. Moreover, genotypes were also compared between groups under different inheritance models  (2 tests. Bonferroni’s correction was used to account for multiple comparisons.Deviations of genotype frequencies from the Hardy–Weinberg equilibrium (HWE) were calculated using cdditive) ,26. LaboBACH2 genotypes on T1DM susceptibility, both for genotype frequencies and the different inheritance models, and adjusting for covariates. Interactions between BACH2 and high-risk T1DM HLA DR/DQ genotypes were investigated using generalized linear model – GLM (binary logistic model) analysis, adjusting for age, gender, and BMI. The power calculation was performed using the WinPepi program (v. 11.65). The study has a power of 80% (a = 0.05) to detect an OR ≥ 1.4 (for the recessive model of inheritance). All analyses were performed using SPSS 18.0 software , and P values < 0.05 were considered significant.Logistic regression analyses were used to estimate the odds ratio (OR) with 95% CI and P values for the effects of HLA DR/DQ genotypes  were higher in T1DM patients than in controls (P ≤ 0.0001). BMI values and the percentage of males were higher in control subjects compared to T1DM patients (P ≤ 0.006). Additionally, mean age at T1DM diagnosis was 17.7 ± 10.1 years, 46.7% of the cases had diabetic retinopathy (DR), and 28.8% had diabetes kidney disease (DKD) (The main characteristics of the subjects in case and control groups are shown in se (DKD) .BACH2 gene in case and control groups. Genotype distributions of the rs11755527 SNP were in accordance with the frequencies estimated by the HWE in both samples (P ≥ 0.05). The frequency of the G minor allele of the BACH2 rs11755527 SNP was 43.6% in white individuals and 37.0% in black individuals (P = 0.081). Therefore, black and white individuals were analyzed together. Genotype frequencies did not differ between patients with T1DM and nondiabetic subjects  (P > 0.05) (subjects  and thisenotypes . In the  > 0.05) .HLA DR/DQ genotypes  were associated with risk for T1DM [OR = 7.42 (95% CI 3.34 – 17.0)] in our population. However, the BACH2 rs1175527 SNP did not influence this association , adjusting for age, gender and BMI.According to previous studies by our group ,24,27, hvs. 9.3 ± 2.2 %; P = 0.004) after Bonferroni’s correction. The other characteristics described in Clinical and laboratory characteristics usually associated with T1DM were compared between patients broken down by the presence of the rs11755527 C/G + G/G genotypes (dominant model) . HbA1c lBACH2 is also important for regulation of apoptosis and inflammation in pancreatic beta-cells, suggesting an important role for this gene in development of T1DM (BACH2 gene and T1DM. Our results suggest that this SNP is not associated with T1DM risk in our population.BACH2 has been shown to play a key role in autoimmunity [reviewed in ]. BACH2  of T1DM . We therBACH2 among the major candidate genes for T1DM (BACH2 rs11755527 SNP and T1DM (P = 4.7 x 10-12)  . In the x 10-12)  and the vs. our sample of a mixed ethnicity population). Wegner and cols. ], consistent with the role of BACH2 in B cell differentiation.immunity -10,34,35t manner ,10. Jin t manner  demonstrBACH2 dysregulation is directly involved in T1DM pathogenesis since inhibition of this gene caused cytokine-induced apoptosis of human and rodent beta-cells through activation of the JNK1/BIM pathway and anti-apoptotic members of the BCL-2 family, whereas BACH2 overexpression protected these cells against apoptosis  to detect an OR ≥ 1.4 for T1DM risk, we cannot rule out the possibility that the BACH2 rs11755527G allele could be associated with T1DM at lower ORs. Despite these limitations, taking into account that frequencies of the BACH2 rs11755527G SNP are very similar between case and control groups, it seems improbable that this variant could play a major role in T1DM pathogenesis in our population. Therefore, the lack of association of the rs11755527G SNP with T1DM in our population could be explained by differences between studies in terms of the ethnicities and the genetic and environmental backgrounds of the populations studied. Our study is the first to analyze this SNP in a South American population of mixed ethnicity while previous studies mostly included North American and European populations.This study has some limitations. We cannot exclude the occurrence of population stratification bias, even though the number of black subjects was similar in case and control samples, and frequencies of the BACH2 rs11755527 SNP is not associated with T1DM in our Southern Brazilian population. Additional studies with larger sample sizes are needed to better elucidate the effects of BACH2 SNP in the pathogenesis of T1DM in different ethnicities.In conclusion, data reported here suggest that the


Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear.The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western blotting and IHC staining. The role of SEC23A in ER stress resistance was explored by functional experiments in vitro and vivo. The occupation of STAT3 on the SEC23A promoter region was verified by luciferase reporter plasmids and CHIP assay. The interaction between SEC23A and ANXA2 was identified by Co-IP and mass spectrometry analysis.We demonstrated that SEC23A was upregulated in gastric cancer and predicted poor prognosis in patients with gastric cancer. Mechanistically, SEC23A was transcriptional upregulated by ER stress-induced pY705-STAT3. Highly expressed SEC23A promoted autophagy by regulating the cellular localization of ANXA2. The SEC23A-ANXA2-autophay axis, in turn, protected gastric cancer cells from ER stress-induced apoptosis. Furthermore, we identified SEC23A attenuated 5-FU therapeutic effectiveness in gastric cancer cells through autophagy-mediated ER stress relief.We reveal an ER stress-SEC23A-autophagy negative feedback loop that enhances the ability of gastric cancer cells to resist the adverse survival environments. These results identify SEC23A as a promising molecular target for potential therapeutic intervention and prognostic prediction in patients with gastric cancer.The online version contains supplementary material available at 10.1186/s13046-023-02807-w. Gastric cancer (GC) is the fifth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide , 2. It iEndoplasmic reticulum (ER) stress caused by intrinsic and extrinsic variables and adverse survival environments, such as increased metabolic demand, reactive oxygen species (ROS) overproduction, and cytotoxic medicines, which tumor cells frequently encounter, affects the function and survival of tumor cells . The unfMacroautophagy/autophagy is a highly conserved cellular process that is rigorously governed by a series of signaling pathways . AutophaSec23 homolog A (SEC23A) is a core component of coat protein complex II (COPII), which helps transport proteins and lipids from the endoplasmic reticulum to the Golgi apparatus . FunctioIn the present study, we reported that SEC23A is highly expressed in GC cells under ER stress, which is important for ER stress relief and avoidance of ER stress-induced apoptosis via the autophagy induction. ER stress, SEC23A and autophagy form a negative feedback loop that maintain GC cells survival advantage during ER stress. The ER stress-induced activation of SEC23A transcription requires activation of the JAK2–STAT3  signaling pathway to phosphorylate STAT3 at Tyr705, which binds to the SEC23A promoter region more frequently during ER stress. In addition, we demonstrated that SEC23A facilitates Annexin A2 (ANXA2) plasma membrane trafficking, resulting in increased autophagic flux in GC cells. Moreover, SEC23A suppression significantly enhanced 5-fluorouracil (5-FU) efficacy for GC cells in vitro and in vivo by inhibiting autophagy and relieving ER stress. Due to its cytoprotective function during ER stress, SEC23A may represent a promising molecular target whose inhibition could be used to inhibit GC development and improve chemotherapeutic efficacy.A total of 82 paired GC and adjacent normal tissues were obtained at the First Affiliated Hospital of Nanjing Medical University for comparisons of SEC23A expression between paired tumor and paratumor tissues. Of these, 30 pairs of tissues were used for immunohistochemical staining, 12 pairs for western blotting, and 82 pairs were used for qRT-PCR. None of these patients have received chemotherapy or radiotherapy. The research has been endorsed by the Medical Ethics Committee of the First Affiliated Hospital of Nanjing Medical University.2 and operating at 37 °C.MKN45 and HGC27 human GC cell lines were purchased from Cell Bank of the Chinese Academy of Sciences  and were cultured in RPMI-1640  supplemented with 10% fetal bovine serum (FBS)  in an incubator supplemented with 5% COTo establish stable SEC23A-knockdown and SEC23A-overexpressing GC cells, lentivirus vectors containing short-hairpin RNA (shRNA) sequences against SEC23A (shSEC23A-1 and shSEC23A-2), SEC23A sequence plasmid (oeSEC23A) and their control vectors (shNC and vector) were obtained from GEMA .For the silencing of STAT3, ATF6, ATF4, CHOP, XBP1 and CREB3L2, MKN45 and HGC27 cells were transiently transfected with small interfering RNAs (siRNAs)  targeting these mRNAs and their negative controls by using the Lipofectamine 3000 Reagent  according to the protocol.All the sequences are listed in Supplementary Table STotal RNA was extracted from cultured cells as described in a previous study . The cDNThe primers used for qPCR were listed in Supplementary Table SCell protein was extracted with RIPA Lysis Buffer  and the concentration was detected by Enhanced BCA Protein Assay Kit . Western blotting was performed as described previously . The resThe antibodies were used for western blotting are listed in Supplementary Table S6 shNC and shSEC23A MKN45 cells were diluted with PBS to 100 µl and then injected into the axilla of the forelimbs of 4- to 5-week-old nude mice. 12 days after inoculation, mice were intraperitoneally injected with drugs respectively  every four days. The tumor volume was monitored every 2 days postinjection and calculated with the following formula: V = p /6 (Length × Width2). At the 4th week postinoculation, animals were sacrificed and tumors were collected and weighed.The animal procedures were approved by the Committee on the Ethics of Animal Experiments of Nanjing Medical University. All the mice were purchased from the Animal Center of Nanjing Medical University. For the subcutaneous tumor formation models, five mice per group, 2 × 10Expression differences and survival analyses of SEC23A in TCGA dataset were obtained from GEPIA2 database. Survival analyses in GEO dataset and 82 GC patients from our center, univariate and multivariate Cox regression analysis, GSEA, and Spearman correlation analysis were performed with RStudio (1.4.1717).p < 0.05 were considered statistically significant. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.All experiments were preformed three times independently and the results are reported as mean ± SD.Comparisons of SEC23A expression between paired tumor and paratumor tissues were performed by paired Student’s t-test. The relationship between SEC23A expression and clinicopathological characteristics was analyzed with chi-square test. Differences between experimental and control groups were analyzed with unpaired Student’s t-test for parametric tests and Wilcoxon signed-rank test for nonparametric tests. Values of According to the TCGA and GTEx datasets, we found that SEC23A was highly expressed in GC tissue Fig. A. In add2O2, to mimic the ER stressors that GC cells typically encounter  qRT-PCR (left) and western blotting (right) analysis of SEC23A expression in HGC27 cells under concentration gradient treatments of DTT for 12 h. (B) qRT-PCR (left) and western blotting (right) analysis of SEC23A expression in HGC27 cells under concentration gradient treatments of TM for 12 h. (C) qRT-PCR (upper) and western blotting (lower) analysis of SEC23A expression in HGC27 cells under concentration gradient treatments of H2O2 for 24 h. (D) qRT-PCR (upper) and western blotting (lower) analysis of SEC23A expression in HGC27 cells under concentration gradient treatments of 5-FU for 24 h. (E) Representative images of immunofluorescence co-staining SEC23A, BiP and cytokeratin in 15 GC paratumor tissues. (F) Fluorescence intensity quantitative analysis of SEC23A expression in BiP+ and BiP- areas of human GC paratumor tissues (n = 15). (G) Correlation between SEC23A and BiP fluorescent intensity in BiP+ areas of 15 paired GC and adjacent normal tissues. (n= 30). (H) Representative images of SEC23A and BiP western blotting results in 30 paired GC and adjacent normal tissues. (I) Quantitative analysis of SEC23A and BiP western blotting results in 30 paired GC and adjacent normal tissues. (J) Correlation between SEC23A and BiP protein expression in 30 paired GC and adjacent normal tissues. (n = 60). (K and L) Knockdown and overexpression efficiencies were verified in MKN45 and HGC27 cells by qRT-PCR (K) and western blotting (L) assays. (M and N) Western blotting assays to analysis the expression of BiP in the condition of SEC23A knockdown (M) or overexpression (N). Figure S2. Additional results of Figure. (A-E) Western blotting to analysis SEC23A expression changes in MKN45 and HGC27 cells under TM treatment  after knockdown ATF4 (A), ATF6 (B), XBP1 (C), CHOP (D) and CREB3L2 (E) respectively. Figure S3. Additional results of Figure 4. (A) CCK 8 assays in MKN45 cells and HGC27 cells when SEC23A was overexpressed under concentration gradient TM treatments for 12 h. (B) Quantification of colony formation assays to determine cell survival in SEC23A overexpressed MKN45 and HGC27 cells treated with indicated doses of TM for 12 h. (C and D) Representative images of colony formation assays and flow cytometry in TM  treated MKN45 and HGC27 cells with SEC23A knockdown, overexpression and corresponding control. (E) Quantification of flow cytometry to analysis cell apoptosis in SEC23A overexpressed MKN45 and HGC27 cells treated with indicated doses of TM for 12 h. (F) Western blotting against c-PARP performed on SEC23A silenced MKN45 and HGC27 cells under 12 h TM treatment with indicated doses. (G and H) Western blotting against c-caspase3 (G) and c-PARP (H) performed on SEC23A overexpressed MKN45 and HGC27 cells under 12 h TM treatment with indicated doses. Figure S4. Additional results of Figure 5. (A) Representative immunofluorescence images of the mCherry-EGFP-LC3B transfected MKN45 and HGC27 cells with SEC23A overexpression and corresponding controls. (B) Quantification of the mCherry-EGFP-LC3B transfected MKN45 and HGC27 cells with SEC23A overexpression and corresponding controls. Figure S5. Additional results of Figure 6. (A) Co-IP assay using anti-SEC23A and anti-ANXA2 antibody to detect the binding of SEC23A and ANXA2 in HGC27 cells. (B) Western blotting assay to detect the expression of ANXA2 in MAN45 and HGC27 cells in the condition of SEC23A knockdown or expression. (C and D) Immunofluorescence images (C) and quantitation (D) to detect the cell membrane localization of ANXA2 in shNC and shSEC23A-1 HGC27 cells. (E) Western blotting analysis to detect the subcellular expression of ANXA2 in shNC and shSEC23A-1 HGC27 cells. (F) IP assay using anti-ANXA2 antibody to detect the content of TFEB bound to ANXA2 in shNC and shSEC23A-1 HGC27 cells. (G and H) Immunofluorescence quantitation (G) and images (H) to detect the co-localization of ANXA2 and ATG16L1 in shNC and shSEC23A-1 HGC27 cells. (I) CCK8 assays in MKN45 and HGC27 cells with indicated experimental settings. (J) Western blotting analysis to detect the expression of LC3B-I, LC3B-II, p62, BiP, c-caspase3 in HGC27 cells with indicated experimental settings. (K) Western blotting analysis to detect the expression of c-PARP in MKN45 and HGC27 cells with indicated experimental settings. Figure S6. Additional results of Figure 8. (A) Representative images of flow cytometry of the indicated groups. (B) CCK8 assays of three groups  in MKN45 cells and HGC27 cells under concentration gradient 5-FU for 12 h. (C) Flow cytometry quantification of the indicated groups in MKN45 and HGC27 cells with or without 4 µM 5-FU treatments for 12 h. (D) Colony formation assays quantification of the indicated groups in MKN45 and HGC27 cells with or without 4 µM 5-FU treatments for 12 h. (E) Western blotting against c-caspase3 and BiP in the indicated groups in MKN45 and HGC27 cells with or without 4 µM 5-FU treatments for 12 h. (F) Representative images of Colony formation assays of the indicated groups. (G) Western blotting against c-PARP in the indicated groups in MKN45 and HGC27 cells with or without 4 µM 5-FU treatments for 12 h.Additional file 3. Supplemental Methods.Additional file 4. Additional file 5.


The skin, the outermost layer of the human body, is exposed to various external stimuli that cause inflammatory skin reactions. These external stimulants trigger external epithelial cell damage and the release of intracellular substances. Following cellular damage or death, intracellular molecules are released that enhance tissue inflammation. As an important substance released from damaged cells, the S100 protein is a low-molecular-weight acidic protein with two calcium-binding sites and EF-hand motif domains. S100 proteins are widely present in systemic organs and interact with other proteins. Recent studies revealed the involvement of S100 in cutaneous inflammatory disorders, psoriasis, and atopic dermatitis. This review provides detailed information on the interactions among various S100 proteins in inflammatory diseases. The skin is the human body’s outermost layer organ; thus, it is exposed to a variety of external stimuli associated with inflammatory reactions ,2,3. TheAs an important substance released from damaged cells, the S100 protein is a low-molecular-weight acidic protein abundant in nervous system tissues. This protein family was first discovered by Moore  and has More than 20 types of S100 proteins have been recognized to date , and thePsoriasis is a chronic cutaneous inflammatory disease characterized by deregulation of the cutaneous immune system . Scaly eThe primary components of the skin barrier are intercellular lipids in the stratum corneum, including ceramides ,19 Figu. PatientChronic skin inflammation in AD is significantly affected by skin barrier dysfunction . IL-33 aIn the following sections, we describe the actions of S100 proteins in psoriasis and AD in detail. The currently identified S100 proteins include S100A2, S100A4, S100A7, S100A8, S100A9, S100A11, S100A12, S100A15, and S100B.2+ level elevations [Under normal physical conditions, keratinocytes produce dimeric S100A2 . S100A2 evations . Furtherevations  and tranevations . As a reevations . Moreoveevations . However2+ concentration, is constructed as an antiparallel homodimer [S100A4, a polypeptide that can oligomerize according to the Caomodimer . S100A4 omodimer . Followiomodimer . S100A4 omodimer . S100A4,omodimer . Macrophomodimer . Epidermomodimer .S100A4 plays functional roles in psoriasis . It is wN-terminal EF-hand motif, which has a twisted loop and lacks a critical calcium-binding residue [Although the general structure of S100A7 resembles that of other S100 proteins, there are several significant differences, particularly in the  residue .Psoriatic skin is prone to higher S100A7 levels in the epidermis ,44. The The binding of S100A7 to RAGE is necessary for inflammatory reactions. S100A7 enhances the chemotaxis of inflammatory cell infiltration into the skin . S100A7 As the regulatory mechanism of S100A7, IL-17 plays a role in its induction. As the signal pathway for the induction of S100A7 mediated by IL-17, IκBζ is an essential regulatory factor in the pathogenesis of psoriasis through IL-17A and IL-17F-mediated actions ,52. FurtAngiogenesis is an essential component of the pathophysiology of inflammatory skin diseases; vascular alterations occur early in the onset of psoriasis . PsoriasStaphylococcus aureus colonization [S100A7 plays an important role in the pathogenesis of AD. S100A7 is upregulated in AD skin and skin barrier dysfunction upregulates S100A7 in AD skin . S100A7 nization . Therefo2+ is present [The S100A8 and S100A9 subunits, which contain 93 and 114 amino acid residues, respectively, are always bound to one another and modify their self-structures to create polymers in the human body, particularly when Ca present ,68. The  present . S100A8  present ,71.S100A8 and S100A9 are located in the epidermal suprabasal layers and their expression is negligible in non-lesional psoriatic and healthy skin . PsoriasNotably, the risk of atherosclerotic events and early cardiovascular disease is associated with skin-derived inflammatory reactions in psoriasis . A lipidAs a mechanism of S100A8 and S100A9 induction, IL-12/23p40 or anti-IL-23p19 inhibition reduced S100A8 and S100A9 expression in murine skin lesions . FurtherIn addition, S100A8 and S100A9 are induced by TLR4-mediated pathways. Specific peptide sequences within the second calcium-binding EF-hands trigger a TLR4-mediated inflammatory reaction . The S10The mechanisms of S100A8 and S100A9 in psoriasis were revealed to some degree in previous studies. Recombinant S100A8/A9 proteins induce the expression of several inflammatory cytokine genes and the growth of keratinocytes . S100A9-S100A8 and S100A9 expressions are increased in AD skin ,62. They2+ binding state to the C-terminal EF-hand leads to exposure of the hydrophobic cleft of the protein which becomes a protein–protein interaction site in S100A11 [S100A11 exists as a dimer and each monomer exhibits two EF-hands. The Ca S100A11 .The involvement of S100A11 in AD pathogenesis is as follows: IL-4 and IL-13 downregulate S100A11 expression in keratinocytes, which also influences the upregulation of filaggrin and human beta-defensin 3 expression, indicating the role of the skin barrier function of S100A11 . AlthougS100A12 is highly expressed in psoriatic skin lesions  and subsThe epigenetic regulation of DNA or DNA-binding proteins is essential for determining gene expression  and is iS100A12 is increased in AD skin and even in non-lesional skin compared to healthy subjects . HoweverS100A15 was reportedly overexpressed in psoriasis ,98. S100Atherosclerosis is an important issue in psoriasis and S100A15 is associated with atherosclerogenesis. The intima–media thickness of the carotid arteries is associated with S100A15 and PASI scores . FurtherS100A15 is differentially regulated by IL-17A, TNF-α, and IL-22 [Patients with psoriasis show higher S100B levels; however, the S100B level is not associated with psoriasis severity . NotablyHere, we summarized the distribution of S100 proteins in psoriasis and AD. S100 proteins are widely distributed in the skin. The basal and spinous layers of the healthy epidermis contain S100A7 and S100A11. The basal layer of keratinocytes contains these proteins in the nucleus and cytoplasm. In addition, these proteins are located in the cytoplasm alone in the spinous layer of keratinocytes . S100A10The regulatory actions of S100 proteins in psoriasis and AD are summarized in A comprehensive understanding of S100 proteins in psoriasis and AD is summarized in Although the primary source of inflammatory triggers in psoriasis remains unclear, substances released from keratinocytes are considered essential for the onset of psoriasis and AD. Among multiple causal factors, S100 proteins, particularly those in keratinocytes, are considered the main positive drivers of the pathogenesis of psoriasis and AD. This review also demonstrated the complex relationship between S100 proteins and psoriasis-mediated inflammation in other organs and conditions such as PsA and cardiovascular disease. Therefore, larger cohort studies should ascertain whether S100 protein production is associated with psoriasis and AD.One of the major challenges for physicians is determining the best options for treating psoriasis and AD skin inflammation. The existing information derived from previous studies found that cytokine-targeted therapy displayed excellent therapeutic effects; however, the entire influence of these options for treatment may not be seen in all of these situations. Therefore, an unknown etiology of the development of psoriasis is necessary to unravel the unidentified influences of psoriatic skin inflammation and S100 proteins might be a clue to answer the unknown etiology of the pathogenesis of these inflammatory diseases.


Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions.3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines.We found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines.Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis.The online version contains supplementary material available at 10.1186/s13046-023-02641-0. Metastasis is a multi-step process that includes the degradation and the detachment from the extracellular matrix (ECM) of the primary site, the invasion of vascular and lymphatic vessels, and the formation of secondary tumors in remote sites –3. AmongκB, and Rho-GTPase signaling pathways .Overall, the present work shows that the integration of transcriptomic, proteomic, and metabolomic analyses is a powerful approach to unveiling in-depth global adaptive cellular responses and the interconnection of regulatory circuits involved in the ability of cancer cells to survive in non-adherent conditions. Indeed, our findings reveal that an extensive metabolic rewiring towards an increased glycolytic “metabotype” and an enhanced lactate production is mandatory to achieve a new homeostasis state that favors cancer cell survival in 3D culture conditions. This phenomenon is accompanied by multiple adaptive events of both transcriptional and translational machineries that merge to a hypoxic-mediated upregulation of anaerobic glycolytic cascade, maintenance of intracellular redox homeostasis, activation of autophagic and antiapoptotic pathways. Noteworthy, in all the transitions from 2 to 3D cultures, ALDOC and ENO2 glycolytic enzymes are upregulated both at transcriptional and translational levels and interfering with their activity is sufficient to repress lactate production and to reduce sphere-forming ability of both LUAD and breast cancer cell lines. This result suggests that ALDOC and ENO2 may represent new powerful targets to restrain 3D tumor spheroids generation of both lung and breast cancer cell lines cultured in different environmental nutrient availability.Additional file 1: Table S1. RNAseq data.Additional file 2: Table S2. GO_Biological_Process.Additional file 3: Table S3. GO_Molecular Function.Additional file 4: Table S4. GO_Cellular_Component.Additional file 5: Table S5. Proteomic data.Additional file 6: Figure S1. Correlations between mRNA expression and protein abundance. Sample-wise mRNA-protein correlation computed as Spearman’s Rho (y-axis). Samples are ordered along the x-axis based on increasing correlation. Additional file 7.Additional file 8: Figure S2. ALDOC and ENO2 levels increase in all H460 and MCF7 3D conditions compared to their 2D relative counterparts. A-B qRT-PCR and Western Blot analyses of ALDOC and ENO2 in H460 2D, H460 3D_SM, H460 3D_FBSlow, MCF7 2D, MCF7 3D_SM, and MCF7 3D_FBSlow. All the experiments were carried out in triplicate and results are presented as mean ± SD. p-value: *<0.05.Additional file 9: Figure S3. Schematic illustration of upstream and downstream events of ALDOC and/or ENO2 perturbation.Additional file 10: Fig. S4. ALDOC and ENO2 knock down with additional siRNAs confirms the reduction of sphere-forming ability of H460 and MCF7 cells. A qRT-PCR analyses of ALDOC and ENO2 in H460 3D_SM, H460 3D_FBSlow, MCF7 3D_SM, and MCF7 3D_FBSlow upon ALDOC and ENO2 silencing with additional siRNAs. B Cell viability of H460 3D_SM, H460 3D_FBSlow, T47D 3D_SM, and T47D 3D_FBSlow upon ALDOC and ENO2 silencing with additional siRNAs assessed by Cell titer-Glo 3D assay and expressed as relative light unit (R.L.U.). D Representative images and relative histograms of tumor spheroids morphology and diameter of H460 3D_SM, H460 3D_FBSlow, MCF7 3D_SM, and MCF7 3D_FBSlow upon ALDOC and ENO2 silencing with additional siRNAs. All the experiments were carried out in triplicate and results are presented as mean ± SD. p-value: *<0.05, **<0.01, ***<0.001. ns: not significant.Additional file 11: Fig. S5. ALDOC and ENO2 knock down with additional siRNAs also impairs glucose and L-lactic acid amounts in H460 and MCF7 3D tumor spheroids. A-B Intracellular glucose and L-lactic acid amounts measured by luminometric assays and reported as relative light units (R.L.U.) in H460 3D_ SM, H460 3D_FBSlow, MCF7 3D_SM and MCF7 3D_FBSlow upon ALDOC and ENO2 silencing with additional siRNAs. C Quantification of L-lactic acid within the culture media (extracellular) performed by emogas analysis and expressed as mmol/1 in H460 3D_SM, H460 3D_ FBSlow, MCF7 3D_SM and MCF7 3D_ FBSlow upon ALDOC and ENO2 silencing with additional siRNAs. All the experiments were carried out in triplicate and results are presented as mean = SD. ns: not significant.