TRF1 uses a noncanonical function of TFIIH to promote telomere replication.

Telomeric DNA challenges the replisome and requires TRF1 for efficient duplication. TRF1 recruits the BLM helicase, but BLM loss does not explain the extensive telomere fragility, ATR signaling, and sister telomere associations (STAs) induced by TRF1 deletion. Here, we document that Helix2 of the TRFH domain and Helix1 of the Myb domain of TRF1 are required for efficient telomere replication. Mutation of both helices generated a TRF1 separation-of-function mutant (TRF1-E83K/LW-TI) that induced severe telomere replication defects but no ATR signaling or STAs. We identified the transcription and nucleotide excision repair (NER) factor TFIIH as a critical effector of TRF1. Loss of TFIIH subunits, but no other NER factors, caused the same telomere replication phenotypes as the TRF1-E83K/LW-TI mutant independent of the effects on TRF1 expression. TFIIH subunits coimmunoprecipitated with wild-type TRF1 but not with TRF1-E83K/LW-TI. These results establish that the major mechanism by which TRF1 ensures telomere replication involves a noncanonical function of TFIIH.

Break-induced replication promotes fragile telomere formation.

TRF1 facilitates the replication of telomeric DNA in part by recruiting the BLM helicase, which can resolve G-quadruplexes on the lagging-strand template. Lagging-strand telomeres lacking TRF1 or BLM form fragile telomeres-structures that resemble common fragile sites (CFSs)-but how they are formed is not known. We report that analogous to CFSs, fragile telomeres in BLM-deficient cells involved double-strand break (DSB) formation, in this case by the SLX4/SLX1 nuclease. The DSBs were repaired by POLD3/POLD4-dependent break-induced replication (BIR), resulting in fragile telomeres containing conservatively replicated DNA. BIR also promoted fragile telomere formation in cells with FokI-induced telomeric DSBs and in alternative lengthening of telomeres (ALT) cells, which have spontaneous telomeric damage. BIR of telomeric DSBs competed with PARP1-, LIG3-, and XPF-dependent alternative nonhomologous end joining (alt-NHEJ), which did not generate fragile telomeres. Collectively, these findings indicate that fragile telomeres can arise from BIR-mediated repair of telomeric DSBs.

The transcription factor HBP1 promotes ferroptosis in tumor cells by regulating the UHRF1-CDO1 axis.

The induction of ferroptosis in tumor cells is one of the most important mechanisms by which tumor progression can be inhibited; however, the specific regulatory mechanism underlying ferroptosis remains unclear. In this study, we found that transcription factor HBP1 has a novel function of reducing the antioxidant capacity of tumor cells. We investigated the important role of HBP1 in ferroptosis. HBP1 down-regulates the protein levels of UHRF1 by inhibiting the expression of the UHRF1 gene at the transcriptional level. Reduced levels of UHRF1 have been shown to regulate the ferroptosis-related gene CDO1 by epigenetic mechanisms, thus up-regulating the level of CDO1 and increasing the sensitivity of hepatocellular carcinoma and cervical cancer cells to ferroptosis. On this basis, we constructed metal-polyphenol-network coated HBP1 nanoparticles by combining biological and nanotechnological. MPN-HBP1 nanoparticles entered tumor cells efficiently and innocuously, induced ferroptosis, and inhibited the malignant proliferation of tumors by regulating the HBP1-UHRF1-CDO1 axis. This study provides a new perspective for further research on the regulatory mechanism underlying ferroptosis and its potential role in tumor therapy.

MiR-92a-2-5p suppresses esophageal squamous cell carcinoma cell proliferation and invasion by targeting PRDX2.

MicroRNAs (miRNAs) can function as negative regulators of gene expression by binding to the 3'-untranslated region (3'-UTR) of target genes. The aberrant expression of miRNAs in neoplasm is extensively associated with tumorigenesis and cancer progression, including esophageal squamous cell carcinoma (ESCC). Our previous investigation has identified the oncogenic roles of Peroxiredoxin2 (PRDX2) in ESCC progression; however, its upstream regulatory mechanism remains to be elucidated. By merging the prediction results from miRWalk2.0 and miRNA differential expression analysis results based on The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) database, eight miRNA candidates were predicted to be the potential regulatory miRNAs of PRDX2, followed by further identification of miR-92a-2-5p as the putative miRNA of PRDX2. Subsequent functional studies demonstrated that miR-92a-2-5p can suppress ESCC cell proliferation and migration, as well as tumor growth in subcutaneous tumor xenograft models, which might be mediated by the suppression of AKT/mTOR and Wnt3a/ß-catenin signaling pathways upon miR-92a-2-5p mimic transfection condition. These data revealed the tumor suppressive functions of miR-92a-2-5p in ESCC by targeting PRDX2.

BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response.

Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body-mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS.

Empowering ultrathin polyamide membranes at the water-energy nexus: strategies, limitations, and future perspectives.

Membrane-based separation is one of the most energy-efficient methods to meet the growing need for a significant amount of fresh water. It is also well-known for its applications in water treatment, desalination, solvent recycling, and environmental remediation. Most typical membranes used for separation-based applications are thin-film composite membranes created using polymers, featuring a top selective layer generated by employing the interfacial polymerization technique at an aqueous-organic interface. In the last decade, various manufacturing techniques have been developed in order to create high-specification membranes. Among them, the creation of ultrathin polyamide membranes has shown enormous potential for achieving a significant increase in the water permeation rate, translating into major energy savings in various applications. However, this great potential of ultrathin membranes is greatly hindered by undesired transport phenomena such as the geometry-induced "funnel effect" arising from the substrate membrane, severely limiting the actual permeation rate. As a result, the separation capability of ultrathin membranes is still not fully unleashed or understood, and a critical assessment of their limitations and potential solutions for future studies is still lacking. Here, we provide a summary of the latest developments in the design of ultrathin polyamide membranes, which have been achieved by controlling the interfacial polymerization process and utilizing a number of novel manufacturing processes for ionic and molecular separations. Next, an overview of the in-depth assessment of their limitations resulting from the substrate membrane, along with potential solutions and future perspectives will be covered in this review.

Polar Solvent-Induced Spontaneous Nanofoaming for Synthesizing Ultra-High-Performance Polyamide Nanofiltration Membranes.

Nanofiltration membranes with both high water permeance and selectivity are perpetually studied because of their applications in water purification. However, these two critical attributes are considered to be mutually exclusive. Here, we introduce a polar solvent, dichloromethane, in place of the apolar hexane used for decades as the organic phase for membrane interfacial polymerization synthesis to solve this dilemma. When a polar solvent as the organic phase is combined with a solvent-resistant aramid nanofibrous hydrogel film as the water phase, monomer enrichment in the reaction zone leads to a polyamide nanofiltration membrane with densely distributed nanobubble features, enhanced nanoporosity, and a loosened backbone. Benefiting from these structural features, the resulting membrane exhibits superior properties with a combination of high water permeance (52.7 L m-2 h-1 bar-1) and selectivity (water/Na2SO4, 36 bar-1; NaCl/Na2SO4, 357 bar-1), outperforming traditional nanofiltration membranes. We envision that this novel technology involving polar solvent systems and the water phase of nanofibrous hydrogel would provide new opportunities for membrane development for environmental engineering.

Highlights of how single-cell analyses are illuminating differentiation and disease in the gastric corpus.

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique to identify novel cell markers, developmental trajectories, and transcriptional changes during cell differentiation and disease onset and progression. In this review, we highlight recent scRNA-seq studies of the gastric corpus in both human and murine systems that have provided insight into gastric organogenesis, identified novel markers for the various gastric lineages during development and in adults, and revealed transcriptional changes during regeneration and tumorigenesis. Overall, by elucidating transcriptional states and fluctuations at the cellular level in healthy and disease contexts, scRNA-seq may lead to better, more personalized clinical treatments for disease progression.

Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.

Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.

BACKGROUND: AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/ß tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo. METHODS: Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1. RESULTS: We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway. CONCLUSION: Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.

CT-based delta-radiomics nomogram to predict pathological complete response after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma patients.

BACKGROUND: This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). METHODS: The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. RESULTS: No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. CONCLUSIONS: The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.

Optical scattering measurement of highly reflective coatings with the cavity ring-down technique.

Cavity ringdown (CRD) is employed for the first time, to the best of our knowledge, to precisely measure the optical scattering of highly reflective (HR) optics with measurement sensitivity greatly enhanced via power trapping inside the ringdown cavity. The scattering measurement accuracy is significantly improved by calibrating the photo-detector for the scattering measurement with the low transmittance of the cavity mirror or test HR mirror, which is also accurately measured by CRD. The influence of environmental stray light (such as the probe light scattered by optics and mechanical parts outside the ringdown cavity) and other background noises on the scattering measurement is greatly eliminated by the temporal behavior of the scattering CRD signal. A scattering measurement sensitivity of 4.0 × 10-13 is experimentally achieved with a laser with output power of 12 mW.

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

EGR1 mediates MDR1 transcriptional activity regulating gemcitabine resistance in pancreatic cancer.

BACKGROUND: Gemcitabine is a cornerstone drug for the treatment of all stages of pancreatic cancer and can prolong the survival of patients with pancreatic cancer, but resistance to gemcitabine in pancreatic cancer patients hinders its efficacy. The overexpression of Early growth response 1(EGR1) in pancreatic ductal adenocarcinoma as a mechanism of gemcitabine chemoresistance in pancreatic cancer has not been explored. The major mechanisms of gemcitabine chemoresistance are related to drug uptake, metabolism, and action. One of the common causes of tumor multidrug resistance (MDR) to chemotherapy in cancer cells is that transporter proteins increase intracellular drug efflux and decrease drug concentrations by inducing anti-apoptotic mechanisms. It has been reported that gemcitabine binds to MDR1 with high affinity. The purpose of this research was to investigate the potential mechanisms by which EGR1 associates with MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. METHODS: The following in vitro and in vivo techniques were used in this research to explore the potential mechanisms by which EGR1 binds to MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. Cell culture; in vitro and in vivo study of EGR1 function by loss of function analysis. Binding of EGR1 to the MDR1 promoter was detected using the ChIP assay. qRT-PCR, Western blot assays to detect protein and mRNA expression; use of Annexin V apoptosis detection assay to test apoptosis; CCK8, Edu assay to test cell proliferation viability. The animal model of pancreatic cancer subcutaneous allograft was constructed and the tumours were stained with hematoxylin eosin and Ki-67 expression was detected using immunohistochemistry. FINDINGS: We revealed that EGR1 expression was increased in different pancreatic cancer cell lines compared to normal pancreatic ductal epithelial cells. Moreover, gemcitabine treatment induced upregulation of EGR1 expression in a dose- and time-dependent manner. EGR1 is significantly enriched in the MDR1 promoter sequence.Upon knockdown of EGR1, cell proliferation was impaired in CFPAC-1 and PANC-1 cell lines, apoptosis was enhanced and MDR1 expression was decreased, thereby partially reversing gemcitabine chemoresistance. In animal experiments, knockdown of EGR1 enhanced the inhibitory effect of gemcitabine on tumor growth compared with the sh-NC group. CONCLUSIONS: Our study suggests that EGR1 may be involved in the regulation of MDR1 to enhance gemcitabine resistance in pancreatic cancer cells. EGR1 could be a novel therapeutic target to overcome gemcitabine resistance in pancreatic cancer.

Overexpression of dehydroascorbate reductase gene IbDHAR1 improves the tolerance to abiotic stress in sweet potato.

Dehydroascorbate reductase (DHAR), an indispensable enzyme in the production of ascorbic acid (AsA) in plants, is vital for plant tolerance to various stresses. However, there is limited research on the stress tolerance functions of DHAR genes in sweet potato (Ipomoea batatas [L.] Lam). In this study, the full-length IbDHAR1 gene was cloned from the leaves of sweet potato cultivar Xu 18. The IbDHAR1 protein is speculated to be located in both the cytoplasm and the nucleus. As revealed by qRT-PCR, the relative expression level of IbDHAR1 in the proximal storage roots was much greater than in the other tissues, and could be upregulated by high-temperature, salinity, drought, and abscisic acid (ABA) stress. The results of pot experiments indicated that under high salinity and drought stress conditions, transgenic Arabidopsis and sweet potato plants exhibited decreases in H2O2 and MDA levels. Conversely, the levels of antioxidant enzymes APX, SOD, POD, and ACT, and the content of DHAR increased. Additionally, the ratio of AsA/DHA was greater in transgenic lines than in the wild type. The results showed that overexpression of IbDHAR1 intensified the ascorbic acid-glutathione cycle (AsA-GSH) and promoted the activity of the related antioxidant enzyme systems to improve plant stress tolerance and productivity.

ZMAT2 condensates regulate the alternative splicing of TRIM28 to reduce cellular ROS accumulation, thereby promoting the proliferation of HCC cells.

Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Prediction of the activity of early ankylosing spondylitis using radiomics texture analysis on short tau inversion recovery (STIR).

OBJECTIVES: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS. METHODS: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators. RESULTS: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05). CONCLUSIONS: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.

Iron Nanoparticles-Confined Graphene Oxide Membranes Coupled with Sulfite-Based Advanced Reduction Processes for Highly Efficient and Stable Removal of Bromate.

Advanced reduction processes (ARPs) are promising for pollutant removal in drinking water treatment. In this study, we demonstrated highly efficient reduction of bromate, a harmful disinfection byproduct, by coupling ARPs with an iron nanoparticles-intercalated graphene oxide (GO@FeNPs) catalytic membrane. In the presence of 1.0 mM sulfite (S(IV)), the GO@FeNPs membrane/S(IV) system achieved nearly complete removal of 80 µg/L bromate in 3 min. The first-order reaction rate constant for bromate removal in this system was 420 ± 42 min-1, up to 5 orders of magnitude faster than previously reported ARPs. The GO@FeNPs catalytic membrane may offer potential advantages of nanoconfinement and facilitated electron shuttling in addition to the high surface area of the fine FeNPs, leading to the remarkable ARP performance. The GO@FeNPs membrane showed excellent stability, maintaining >97.0% bromate removal over 20 cycles of repeated runs. The membrane can also be applied for fast catalytic reduction of other oxyanions, showing >98.0% removal of nitrate and chlorate. This work may present a viable option for utilizing high-performance reductive catalytic membranes for water decontamination.

A Single Amino Acid Residue Defines the Difference in NLRP3 Inflammasome Activation between NEK7 and NEK6.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that is activated by microbial infections and cellular stress signals. The molecular mechanism of NLRP3 inflammasome activation remains not fully understood. As an NLRP3-interacting partner, NEK7 has emerged as a critical mediator for NLRP3 inflammasome activation. In contrast to NEK7, NEK6, the closely related member of the NEK family, does not support NLRP3 inflammasome activation. In this study, we show that the mouse NEK7 catalytic domain, which shares high sequence identity with the counterpart of NEK6, mediates its interaction with NLRP3 and inflammasome activation in mouse macrophages. Within their catalytic domains, a single amino acid residue at a corresponding position (R121NEK7, Q132NEK6) differentiates their function in NLRP3 inflammasome activation. Surprisingly, substitution of the glutamine residue to an arginine residue at position 132 confers NEK6 the ability of NLRP3 binding and inflammasome activation in mouse macrophages. Furthermore, our results suggest a structural pocket surrounding the residue R121 of NEK7 that is essential for NLRP3 binding and inflammasome activation.

Assessing the suitability of video-assisted anal fistula treatment for obese patients compared to conventional surgery: a question worth investigating.

BACKGROUND AND AIMS: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection. MATERIALS AND METHODS: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index. RESULTS: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036). CONCLUSION: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries.