A new artificial intelligence system for both stomach and small bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence (AI) in small bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning (DL)-based SmartScan (SS), which has been described previously. A total of 1,069 magnetically controlled gastrointestinal (GI) CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new AI algorithm named SS Plus. 342 fully automated, magnetically controlled CE (FAMCE) examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-Assisted Reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (1000) (median, IQR 814.50-1,000) versus 44,322.73 (42,393) (median, IQR 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 min (8.51) (median, IQR 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded DL-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn's disease.

The pathogenesis of Crohn's disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti-tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Fabrication and Characterization of Silicon-Based Antimonene Thin Film via Electron Beam Evaporation.

Antimonene has attracted much attention due to its excellent characteristics of high carrier mobility, thermoelectric properties and high stability. It has great application prospects in Q-switched lasers, laser protection and spintronics. At present, the epitaxy growth of antimonene mainly depends on molecular beam epitaxy. We have successfully prepared antimonene films on silicon, germanium/silicon substrates for the first time using electron beam evaporation coating and studied the effects of the deposition rate and substrate on the preparation of antimonene; film characterization was performed via confocal microprobe Raman spectroscopy, via X-ray diffraction and using a scanning electron microscope. Raman spectroscopy showed that different deposition rates can lead to the formation of different structures of antimonene, such as α phase and ß phase. At the same time, it was found that the growth of antimonene is also affected by different substrates and ion beams.

Intrinsic edge states and strain-tunable spin textures in the Janus 1T-VTeCl monolayer.

Using first-principles calculations and micro-magnetic simulations, we investigate the electronic structures, the effect of biaxial strain on the topological characteristics, magnetic anisotropy energy (MAE), Dzyaloshinskii-Moriya interaction (DMI) and spin textures in the Janus 1T phase VTeCl (1T-VTeCl) monolayer. Our results show that 1T-VTeCl has an intrinsic edge state, and a topological phase transition with a sizeable band gap is achieved by applying biaxial strain. Interestingly, the MAE can be switched from the in-plane to the off-plane with a compressive strain of -5%. Microscopically, the origin of MAE is mainly associated with the large spin-orbit coupling (SOC) from the heavy nonmagnetic Te atoms rather than that from the V atoms. Furthermore, the induced DMI (0.09 meV) can occur stabilizing magnetic merons without applying temperatures and magnetic fields. Then, the skyrmions, frustrated antiferromagnetism and vortex are induced after applying a suitable compressive strain. Our study provides compelling evidence that the 1T-VTeCl monolayer with topological properties holds great potential for application in spintronic devices, as well as information storage devices based on different magnetic phases achievable through strain engineering.

LncRNA HCG18 affects diabetic cardiomyopathy and its association with miR-9-5p/IGF2R axis.

This paper aimed to investigate the role of lncRNA HCG18 (HCG18) in the progression of diabetic cardiomyopathy (DCM) and potential mechanisms. Streptozocin (STZ) was used to induce DCM model in rats, which was confirmed by blood glucose concentration, body weight, and HE staining. Myocardial apoptosis was detected by TUNEL. H9c2 cardiomyocytes were used to construct cell models of DCM through treatment of high glucose. The results showed that HCG18 was overexpressed in STZ induced DCM rat model and high glucose induced H9c2 cardiomyocytes. Si-HCG18 significantly increased cell viability, reduced cell apoptosis, attenuated activities of myocardial enzymes and enhanced activities of antioxidant enzymes in STZ induced DM model and high glucose induced H9c2 cardiomyocytes, while the results of upregulation of HCG18, in high glucose induced H9c2 cardiomyocytes, were opposite with that of si-HCG18. MiR-9-5p was a target of HCG18, and which was down-regulated in cardiomyocytes of DCM. The overexpression of miR-9-5p could neutralize the high glucose induced cardiomyocyte injury, and the silence of miR-9-5p could reverse the effect of si-HCG18 on high glucose induced cardiomyocytes. MiR-9-5p could directly target to IGF2R, and IGF2R was overexpressed in cardiomyocytes of DCM. Up-regulation of IGF2R can reverse the protective effect of si-HCG18 on cardiomyocytes. Taken together, HCG18 is significantly increased in cardiomyocytes of DCM. Down-regulation of HCG18 can improve cardiomyocyte injury through miR-9-5p/IGF2R axis in DCM.

Clinical value of multi-gene testing in distinguishing benign and malignant thyroid nodules.

BACKGROUND: The newly released 2022 WHO Classification of Neuroendocrine Neoplasms (version 5) and a recent update on thyroid tumor classifications have emphasized genetic testing to an unprecedented level. Fine needle aspiration (FNA) has been widely applied for the preoperative diagnosis of thyroid nodules. However, it is limited mainly to testing for a single gene-BRAFV600E, whereas multi-gene testing data are scarce, especially in the Asian population. This study aimed to explore the clinical value of multi-gene testing in the differential diagnosis of benign and malignant thyroid nodules based on the 2023 Bethesda System for Reporting Thyroid Cytopathology (BSRTC). METHODS: A total of 615 thyroid nodules underwent ultrasound-guided fine-needle aspiration cytology (FNAC) were collected from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. The next-generation sequencing platform was applied for multi-gene testing. A panel of well-recognized commonly mutated genes in thyroid cancer were analyzed, including BRAFV600E, KRAS, NRAS, HRAS, TERT, TP53, PAX8/PPARG, CCDC6/ RET and NCOA4/ RET. RESULTS: Gene mutations were identified in 324 nodules (52.7%), with BRAFV600E being the most prevalent driver gene alteration observed in this cohort (233/324; 79.1%), followed by RAS (77/324, 23.8%). The overall malignancy rate of gene mutations was 89.7% in our cohort, of which the lymph node metastasis rate was 45.3%. The combination of multi-gene testing and cytology resulted in 89.3% sensitivity, 95.2% specificity, 98.9% positive predictive value, 64.5% negative predictive value and 90.3% accuracy, which were significantly higher than those from mere cytology (sensitivity 68.6%, specificity 87.5%, positive predictive value 95.9%, negative predictive value 39.8%, accuracy 72.2%). CONCLUSIONS: Multi-gene testing could substantially enhance the detection rate of malignant thyroid nodules and protect patients with benign nodules from unnecessary surgeries. Multi-gene testing provides a valuable reference for individualized preoperative decision-making, which may serve as a crucial method for postoperative treatment and prognosis assessment.

The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

Mucosal Architectural Change is an Important Feature in Distinguishing Crohn's Disease From Others in Terminal Ileum Ulcer Biopsy.

BACKGROUND: Besides Crohn's disease (CD), there are a variety of other causes that can also lead to ulcerations in the terminal ileum. The purpose of this study was to identify useful diagnostic features for CD when evaluating terminal ileum biopsies in patients with endoscopic finding of ulcers. METHODS: Five hundred and seventy-one patients with endoscopic finding of ulcers were included in this retrospective study. Five main histological features were analysed, which were crypt irregularity, mucosal thickening, villous stromal widening (including villous atrophy), granulomas, and pseudopyloric gland metaplasia. Clinical and pathological features were determined by uni- and multivariable logistic regression. Then another independent cohort of 99 patients was established for verifying this nomogram. RESULTS: The crypt irregularity, mucosal thickening, and villous stromal widening were combined to be considered as one new variable named mucosal architectural change which was an independent variable in diagnosing CD. We found that mucosal architectural change, age <40 years, the presence of granulomas, and the presence of pseudopyloric gland metaplasia were independent factors for the pathological diagnosis of CD. Then nomogram was developed, with receiver operating characteristic (ROC) curve (area under the ROC curve [AUC] = 0.927) in training sets, and ROC curve (AUC = 0.913) in validation sets. CONCLUSIONS: We found mucosal architectural change is very helpful in distinguishing CD from non-CD patients. In the context of small biopsy which may lack full scope of changes, the model developed by combining these key features is valuable in predicting a diagnosis of CD, especially in younger patients (age <40 years).

Patterns of de novo metastasis and survival outcomes by age in breast cancer patients: a SEER population-based study.

Background: The role of age in metastatic disease, including breast cancer, remains obscure. This study was conducted to determine the role of age in patients with de novo metastatic breast cancer. Methods: Breast cancer patients diagnosed with distant metastases between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results database. Comparisons were performed between young (aged ≤ 40 years), middle-aged (41-60 years), older (61-80 years), and the oldest old (> 80 years) patients. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazard models. Survival analysis was performed by the Kaplan-Meier method. Results: This study included 24155 (4.4% of all patients) de novo metastatic breast cancer patients. The number of young, middle-aged, older, and the oldest old patients were 195 (8.3%), 9397 (38.9%), 10224 (42.3%), and 2539 (10.5%), respectively. The 5-year OS rate was highest in the young (42.1%), followed by middle-aged (34.8%), older (28.3%), and the oldest old patients (11.8%). Multivariable Cox regression analysis showed that middle-aged (aHR, 1.18; 95% CI, 1.10-1.27), older (aHR, 1.42; 95% CI, 1.32-1.52), and the oldest old patients (aHR, 2.15; 95% CI, 1.98-2.33) had worse OS than young patients. Consistently, middle-aged (aHR, 1.16; 95% CI, 1.08-1.25), older (aHR, 1.32; 95% CI, 1.23-1.43), and the oldest old patients (aHR, 1.86; 95% CI, 1.71-2.03) had worse BCSS than young patients. Conclusion: This study provided clear evidence that de novo metastatic breast cancer had an age-specific pattern. Age was an independent risk factor for mortality in patients with de novo metastatic breast cancer.

A Combination of Pathological Features Identifies Crohn's Disease in Surgical Bowel Resection Specimens.

BACKGROUND: Diagnosis of Crohn's disease is challenging. This study aims to compare the histological features of Crohn's disease and non-Crohn's disease (other intestinal inflammatory diseases) in surgical specimens to identify a set of histologic features distinguishing Crohn's disease from non-Crohn's disease. METHODS: Patients with Crohn's disease (N = 171) and patients with non-Crohn's disease (N = 215) diagnosed between 2010 and 2015 who had surgical bowel resection were identified. The frequency of histological features in surgical resection specimens was compared between these two groups. RESULTS: Univariate analysis revealed that transmural inflammation, subserosal lymphoid aggregates, fissures or sinus-like structures, granulomas or granuloma-like nodules, abnormalities of the enteric nervous system, and mucosa structure alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia) were more frequent in Crohn's disease than non-Crohn's disease cases (p < 0.001 for all). Some of the above histologic features were further grouped as chronic inflammatory change which includes granulomas or granuloma-like nodules, lymphoid aggregates in the muscularis propria or subserosa, fissures or sinus-like structures, and architectural abnormality which is defined as the presence of abnormal enteric nervous system and/or mucosa structural alterations (muscularis mucosa thickening or mucosal atrophy with pseudopyloric gland metaplasia). A combination of transmural inflammation, chronic inflammatory change, and architectural abnormality had a sensitivity of 92.4% and a specificity of 97.7% for Crohn's disease. CONCLUSIONS: In surgical bowel resection specimens, a combination of transmural inflammation, chronic inflammatory change, and architectural abnormality help diagnose Crohn's disease.

Electronic properties, skyrmions and bimerons in Janus CrXY (X, Y = S, Se, Te, Cl, Br, I, and X ≠ Y) monolayers.

Using first-principles calculations, we systematically investigate the electronic properties, chiral skyrmions and bimerons in two-dimensional (2D) Janus CrXY (X, Y = S, Se, Te, Cl, Br, I, and X ≠ Y) monolayers. We found that the categories of nonmagnetic atoms (X and Y in CrXY) determine whether CrXY is a ferromagnetic metal or a semiconductor. Unexpectedly, the CrBrS monolayer of these CrXY materials is a room temperature ferromagnetic semiconductor with a Curie temperature of 303 K, and it possesses an off-plane magnetic anisotropy energy of 0.06 meV. Besides, a strong Dzyaloshinskii-Moriya interaction (DMI) of 3.10 meV is found in CrTeI and is mainly induced by the strong spin-orbit coupling of the nonmagnetic atoms Te(I) rather than that of the magnetic Cr atoms. Furthermore, using micromagnetic simulations, skyrmions can be stabilized in CrSeBr without external magnetic fields. More importantly, the bimerons in CrSeCl with in-plane magnetic anisotropy can be transformed into skyrmions or a ferromagnetic state by controlling the direction of external magnetic fields. Our work investigates fourteen kinds of Janus monolayers, serving as guidelines for materials research on DMI, skyrmions and bimerons.

Multilevel resistive switching memory in lead-free double perovskite La[Formula: see text]NiFeO[Formula: see text] films.

Dense and flat La[Formula: see text]NiFeO[Formula: see text] (LNFO) films were fabricated on the indium tin oxide-coated glass (ITO/glass) substrate by sol-gel method. The bipolar resistive switching behavior (BRS) could be maintained in 100 cycles and remained after 30 days, indicating that the LNFO-based RS device owned good memory stability. Surprisingly, the multilevel RS characteristics were firstly observed in the Au/LNFO/ITO/glass device. The high resistance states (HRSs) and low resistance state (LRS) with the maximum ratio of [Formula: see text] 500 could be remained stably in 900 s and 130 cycles, demonstrating the fine retention and endurance ability of this LNFO-based RS device. The BRS behavior of Au/LNFO/ITO/glass devices primarily obeyed the SCLC mechanism controlled by oxygen vacancies (OVs) dispersed in the LNFO layer. Under the external electric field, injected electrons were captured or discharged by OVs during trapping or detrapping process in the LNFO layer. Thus, the resistive state switched between HRS and LRS reversibly. Moreover, the modulation of Schottky-like barrier formed at the Au/LNFO interface was contributed to the resistive states switchover. It was related to the change in OVs located at the dissipative region near the Au/LNFO interface. The multilevel RS ability of LNFO-based devices in this work provides an opportunity for researching deeply on the high density RS memory in lead-free double perovskite oxides-based devices.

Association of serum YKL-40 change with prognosis in acute ischemic stroke patients complicated with diabetes mellitus.

Objective: This study intended to explore the serum YKL-40 change and its prognostic implication in acute ischemic stroke (AIS) patients with diabetes mellitus (DM). Methods: YKL-40 was detected from serum by ELISA in 121 AIS patients with DM at baseline, day (D)1, D3, D7 and D30 after disease onset. Results: YKL-40 increased from baseline to D3, then decreased until D30 (p < 0.001). Notably, 20.7% of patients had stroke recurrence, and 6.6% of patients died during follow-up. YKL-40 at D1 (p = 0.043), D7 (p = 0.007) and D30 (p = 0.001) predicted higher stroke recurrence risk; additionally, YKL-40 at D3 (p = 0.010), D7 (p = 0.007) and D30 (p = 0.002) estimated higher mortality risk. Conclusion: Serum YKL-40 has a prognostic effect on the management of AIS patients with DM.

[Distribution, Tansformation, and Fate of Per-and Polyfluoroalkyl Substances in Drinking Water Treatment].

Per-and polyfluoroalkyl substances (PFASs) are present in surface water, tap water, and even commercial drinking water and pose a threat to human health. In this study, the occurrence and transformation of 14 PFASs were studied in large drinking water treatment plants (DWTPs) with Taihu Lake as the source, and the results showed that a total of 10 PFASs were detected in the water samples, indicating that PFAS were widely distributed in drinking water. The total concentration of PFASs in raw water was 127.4 ng·L-1, with the highest concentration being that of pentadecafluorooctanoic acid (PFOA, 49.8 ng·L-1). Pre-ozone caused a reverse increase in the concentration of PFASs, which may have been due to the presence of precursors or conversion from short to long chains. PFASs were not effectively removed by conventional treatment processes, andozone-biological activated carbon (O3-BAC) had a dominant role in the removal of PFASs (20.74%) from DWTPs. O3-BAC, the main removal process for DWTPs, contained high concentrations of PFASs in the backwash water with similar distribution characteristics to the raw water. Using a pilot plant, five common filter backwash water treatment processes were compared, and the results showed that GAC-ultrafiltration could adsorb and retain a certain amount of PFASs while ensuring a high removal rate of turbidity (99.08%). The 3D-EEM analysis indicated that GAC-ultrafiltration could also remove most of the fluorescent micro-pollutants, and for raw water containing high concentrations of PFASs DWTPs, it is practical to use it as a filter backwash water reuse treatment process.

Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity.

Clinical studies have shown that combination therapy of antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) significantly improves clinical benefit over PD-1 antibody alone. However, broad application of this combination has been limited by toxicities. Cadonilimab (AK104) is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possess higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

New methods based on a genetic algorithm back propagation (GABP) neural network and general regression neural network (GRNN) for predicting the occurrence of trihalomethanes in tap water.

Monitoring trihalomethanes (THMs) levels in water supply systems is of great significance in ensuring drinking water safety. However, THMs detection is a time-consuming task. Developing predictive THMs models using parameters that are easier to obtain is an alternative. To date, there is still no application of optimization algorithms and general regression neural networks in predicting disinfection by-products levels. This study was to explore the feasibility of back propagation neural network (BPNN), genetic algorithm back propagation (GABP) neural network and general regression neural network (GRNN) for predicting THMs occurrence in real water supply systems. The results showed that the BPNN models' prediction ability was limited (test rp = 0.571-0.857, N25 = 61.5 %-91.5 %). Optimized by the genetic algorithm (GA), GABP models were generated and exhibited better prediction performance (test rp = 0.573 and 0.696-0.863, N25 = 68.2 %-93.6 %). However, GABP models took a lot of time and their prediction performance was unstable. A GRNN was then used to generate simpler neural network models, and the resulting prediction performance was excellent (total trihalomethanes and bromodichloromethane: test rp = 0.657-0.824, N25 = 81.8 %-100 %). In general, GRNN was the best at predicting THMs concentrations among the three models. However, it is worth noting that the prediction accuracy of bromodichloromethane (BDCM) was not high, which may be due to the absence of key parameters affecting BDCM formation. Accurate predictions of THMs by GRNN with these nine water parameters made THMs monitoring in real water supply systems possible and practical.

Epithelial Gab1 calibrates RIPK3-dependent necroptosis to prevent intestinal inflammation.

As a hallmark of inflammatory bowel disease (IBD), elevated intestinal epithelial cell (IEC) death compromises the gut barrier, activating the inflammatory response and triggering more IEC death. However, the precise intracellular machinery that prevents IEC death and breaks this vicious feedback cycle remains largely unknown. Here, we report that Grb2-associated binder 1 (Gab1) expression is decreased in patients with IBD and inversely correlated with IBD severity. Gab1 deficiency in IECs accounted for the exacerbated colitis induced by dextran sodium sulfate owing to sensitizing IECs to receptor-interaction protein kinase 3-mediated (RIPK3-mediated) necroptosis, which irreversibly disrupted the homeostasis of the epithelial barrier and promoted intestinal inflammation. Mechanistically, Gab1 negatively regulated necroptosis signaling through inhibiting the formation of RIPK1/RIPK3 complex in response to TNF-α. Importantly, administration of RIPK3 inhibitor revealed a curative effect in epithelial Gab1-deficient mice. Further analysis indicated mice with Gab1 deletion were prone to inflammation-associated colorectal tumorigenesis. Collectively, our study defines a protective role for Gab1 in colitis and colitis-driven colorectal cancer by negatively regulating RIPK3-dependent necroptosis, which may serve as an important target to address necroptosis and intestinal inflammation-related disease.

SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis.

SIPRα on macrophages binds with CD47 to resist proengulfment signals, but how the downstream signal of SIPRα controls tumor-infiltrating macrophages (TIMs) is still poorly clarified. Here, we report that the CD47/signal regulatory protein α (SIRPα) axis requires the deneddylation of tyrosine phosphatase SHP2. Mechanistically, Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) was constitutively neddylated on K358 and K364 sites; thus, its autoinhibited conformation was maintained. In response to CD47-liganded SIRPα, SHP2 was deneddylated by sentrin-specific protease 8 (SENP8), which led to the dephosphorylation of relevant substrates at the phagocytic cup and subsequent inhibition of macrophage phagocytosis. Furthermore, neddylation inactivated myeloid-SHP2 and greatly boosted the efficacy of colorectal cancer (CRC) immunotherapy. Importantly, we observed that supplementation with SHP2 allosteric inhibitors sensitized immune treatment-resistant CRC to immunotherapy. Our results emphasize that the CRC subtype that is unresponsive to immunotherapy relies on SIRPαhiSHP2hiNEDD8lo TIMs and highlight the need to further explore the strategy of SHP2 targeting in CRC therapy.

Impact of biological activated carbon filtration and backwashing on the behaviour of PFASs in drinking water treatment plants.

PFASs are present in surface water, tap water and even commercial drinking water and pose a risk to human health. In this study, the treatment efficiency of 14 PFASs was studied in a large drinking water treatment plant (DWTP) using Taihu Lake as the source, and it was found that the ozone/biological activated carbon (O3-BAC) process was the most effective process for the removal of PFASs in DWTPs. For the O3-BAC process, there were differences in the removal of PFASs by BACs (1,4,7,13 years) of different ages. The sterilization experiments revealed that for GAC, its physical adsorption capacity reached saturation after one year, while for BAC with mature biofilms, biosorption was the main mechanism for the removal of PFASs. The abundance of Alphaproteobacteria and Gammaproteobacteria in biofilms was positively correlated with the age of the BAC. The microbial community with higher abundance is beneficial to the biodegradation of organic matter and thus provides more active sites for the adsorption of PFASs. PFASs can leak in the early stage of filtration after backwashing, so it is necessary to pay close attention to the influent and effluent concentrations of PFASs during biofilm maturation after backwashing.