Colonisation of Group B Streptococcus and its effects on pregnancy outcomes in pregnant women in Guangzhou, China: a retrospective study.

OBJECTIVES: This study was to investigate the colonisation rate of Group B Streptococcus (GBS) during pregnancy, and to evaluate the influence of GBS colonisation on pregnancy outcomes. DESIGN: A retrospective cohort study. SETTING: Data of 47 380 pregnant women from 2016 to 2022 were collected from the Maternal and Child Health Hospital of Huadu District, Guangzhou City, China. PARTICIPANTS: A total of 15 040 pregnant women were eligible for this study, of which 32 340 were excluded due to non-native pregnant women, in vitro fertilization infants, malformed fetuses, habitual abortion, abortions due to poor reproductive or obstetrical history, artificial insemination, umbilical cord torsion, and other diseases during pregnancy. PRIMARY OUTCOME MEASURES: The incidence rates of GBS colonisation and premature delivery, fetal distress, premature rupture of membranes (PROM), low birth weight (LBW), abortion and stillbirth. RESULTS: Of the 15 040 pregnant women included in this study, 1445 developed GBS colonisation, with a prevalence of 9.61% (95% CI, 9.15 to 10.09). Advanced maternal age (≥35 years) predisposed women to GBS colonisation, and the occurrence of GBS colonisation varied among different ethnic groups. Our data revealed that fetal distress, PROM and LBW were more common in pregnant women colonised with GBS than in pregnant women not colonised with GBS. The incidence for premature delivery, fetal distress, PROM and LBW in infants of pregnant women colonised with GBS was 41.0% (OR=1.410, 95% CI, 1.134 to 1.753), 282.5% (OR=3.825, 95% CI, 3.185 to 4.593), 14.9% (OR=1.149, 95% CI, 1.005 to 1.313), and 29.7% (OR=1.297, 95% CI, 1.010 to 1.664), respectively. CONCLUSIONS: GBS colonisation was relatively low in pregnant women in Guangzhou. Women of advanced maternal age were more prone to GBS colonisation, and pregnant women colonised with GBS were more predisposed to fetal distress, PROM and LBW.

Glycated Casein by TGase-Type Exerts Protection Potential against DSS-Induced Colitis via Inhibiting TLR4/NF-κB Signaling Pathways in C57BL/6J Mice.

Glycation by transglutaminase (TGase)-type could effectively improve the structure and functional properties of proteins. However, the influence on intestinal inflammation or the underlying mechanisms has not been investigated. The goal of this research was to compare the bioactivities between glycated casein generated from the TGase-catalyzed reaction and oligochitosan as well as casein using a mouse model of dextran sulfate sodium (DSS)-induced intestinal inflammation to examine the protective effects and the underlying mechanism of glycated casein on intestinal inflammation. Eight groups of C57BL/6 mice were randomly assigned in this study: Control group: standard diet for 35 days; Model group: standard diet for 28 days and then colitis induction; Pretreated groups: different levels (200, 400, 800 mg/kg BW) of casein or glycated casein for 28 days before colitis induction. The mice were drinking water containing a 3% DSS solution for seven days of mice to cause colitis. The results indicated that glycated casein and casein at 200-800 mg/kg BW all relieved DSS-induced weight loss, reduced disease activity index (DAI) score, alleviated colon length shortening, weakened the destruction of colonic mucosal structure, decreased serum LPS, and MPO, IL-1ß, IL-6 and TNF-α levels in serum and colon, as well as regulated the expression of proteins involved in the TLR4/NF-κB signaling pathway in a concentration-dependent manner. Glycated caseinate showed a better protective effect against DSS-induced colitis than casein, highlighting that the TGase-type glycation of proteins as a potential functional food ingredient might be a helpful method for gut health.

Role of body mass index in pregnancy outcomes after emergency cerclage for cervical insufficiency in singleton pregnant patients.

BACKGROUND: The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs. METHODS: A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m2 and a non-obesity group of 39 patients with BMIs < 28 kg/m2. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses. RESULTS: Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031). CONCLUSIONS: Pregnant cervical insufficiency patients with BMIs > 28 kg/m2 may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.

Mixed-Valence CuI /CuIII Metal-Organic Frameworks with Non-innocent Ligand for Multielectron Transfer.

We report two novel three-dimensional copper-benzoquinoid metal-organic frameworks (MOFs), [Cu4 L3 ]n and [Cu4 L3 ⋅ Cu(iq)3 ]n (LH4 =1,4-dicyano-2,3,5,6-tetrahydroxybenzene, iq=isoquinoline). Spectroscopic techniques and computational studies reveal the unprecedented mixed valency in MOFs, formal Cu(I)/Cu(III). This is the first time that formally Cu(III) species are witnessed in metal-organic extended solids. The coordination between the mixed-valence metal and redox-non-innocent ligand L, which promotes through-bond charge transfer between Cu metal sites, allows better metal-ligand orbital overlap of the d-π conjugation, leading to strong long-range delocalization and semiconducting behavior. Our findings highlight the significance of the unique mixed valency between formal Cu(I) and highly-covalent Cu(III), non-innocent ligand, and pore environments of these bench stable Cu(III)-containing frameworks on multielectron transfer and electrochemical properties.

Inhibition of TMEM16A improves cisplatin-induced acute kidney injury via preventing DRP1-mediated mitochondrial fission.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca2+-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown. In this study, we established cisplatin AKI mice model and found that TMEM16A expression was upregulated in the injured kidney. In vivo knockdown of TMEM16A effectively prevented cisplatin-induced tubular cell apoptosis, inflammation and kidney function loss. Western blot and transmission electron microscopy (TEM) revealed that TMEM16A knockdown inhibited Drp1 translocation from the cytoplasm to mitochondria and prevented mitochondrial fission in tubular cells. Consistently, in cultured HK2 cells, knockdown or inhibition of TMEM16A by shRNA or its specific inhibitor suppressed cisplatin-induced mitochondrial fission and its associated energy dysfunction, ROS accumulation, and cell apoptosis via inhibiting Drp1 activation. Further investigation showed that genetic knockdown or pharmacological inhibition of TMEM16A inhibited cisplatin-induced Drp1 Ser-616 site phosphorylation through ERK1/2 signaling pathway, whereas overexpression of TMEM16A promoted this effect. Treatment with Drp1 or ERK1/2 inhibitor could efficiently prevent cisplatin-induced mitochondrial fission. Collectively, our data suggest that TMEM16A inhibition alleviated cisplatin-induced AKI by preventing tubular cell mitochondrial fission through the ERK1/2 / Drp1 pathway. Inhibition of TMEM16A may be a novel therapeutic strategy for AKI.

The change in the relationship between temperature and respiratory diseases among children in Guangzhou, China.

Temperature is closely associated with respiratory disease (RD) in children, but few studies have examined whether the relationship between ambient temperature and RD in children changed after the COVID-19 epidemic. The aim of this study was to assess the relationship between temperature and RD in children after the COVID-19 epidemic in Guangzhou, China. We used a distributed lag nonlinear model to compare the relationship between temperature and RD among children in Guangzhou from 2018 to 2022. The results showed an S-shaped relationship between temperature and RD in the post-COVID-19 period with a reference minimum risk at a temperature of 21 °C and an increasing relative risk (RR) at extremely low temperature (ELT) and extremely high temperature (EHT). The highest RR associated with EHT was 1.935 (95% confidence interval [CI]: 1.314-2.850) at a lag of 0-14 days. The on-the-day lag effects were found to be strongest at the lag 0 day of EHT with a RR of 1.167 (95% CI: 1.021-1.334). Furthermore, each 1 °C increase in post-COVID-19 temperature increased the risk of RD by 8.2% (95% CI: 1.044-1.121). Our study provides evidence that the relationship between temperature and RD in children in Guangzhou changed after the COVID-19 epidemic, and high temperature is more likely to cause RD in children. Relevant government departments and parents should understand the relationship between temperature and RD in children and develop new preventive measures.

PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.

BACKGROUND: The ubiquitin-proteasome and autophagy-lysosomal systems collaborate in regulating the levels of intracellular proteins. Dysregulation of protein homeostasis is a central feature of malignancy. The gene encoding 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) of the ubiquitin-proteasome system is an oncogene in various types of cancer. However, the detailed role of PSMD2 in autophagy and its relationship to tumorigenesis in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we have investigated the tumor-promoting roles of PSMD2 in the context of autophagy in ESCC. METHODS: Molecular approaches including DAPgreen staining, 5-Ethynyl-2'-deoxyuridine (EdU), cell counting kit 8 (CCK8), colony formation, transwell assays, and cell transfection, xenograft model, immunoblotting and Immunohistochemical analysis were used to investigate the roles of PSMD2 in ESCC cells. Data-independent acquisition (DIA) quantification proteomics analysis and rescue experiments were used to study the roles of PSMD2 in ESCC cells. RESULTS: We demonstrate that the overexpression of PSMD2 promotes ESCC cell growth by inhibiting autophagy and is correlated with tumor progression and poor prognosis of ESCC patients. DIA quantification proteomics analysis shows a significant positive correlation between argininosuccinate synthase 1 (ASS1) and PSMD2 levels in ESCC tumors. Further studies indicate that PSMD2 activates the mTOR pathway by upregulating ASS1 to inhibit autophagy. CONCLUSIONS: PSMD2 plays an important role in repressing autophagy in ESCC, and represents a promising biomarker to predict prognosis and a therapeutic target of ESCC patients.

Association between air pollution exposure and gestational diabetes mellitus in pregnant women: a retrospective cohort study.

The global prevalence of gestational diabetes mellitus (GDM) is increasing annually, and previous research reports on the relationship between exposure to air pollutants and GDM are not completely consistent. We investigated the association between air pollutant exposure and GDM in pregnant women in a retrospective cohort study in Guangzhou. We found that in the first trimester, exposure to PM2.5 and CO showed a significant association with GDM. In the second trimester, exposure to PM10 was significantly associated with GDM. In the third trimester, exposure to PM2.5, PM10, NO2, SO2, and CO at IQR4 (odds ratio [OR] = 1.271, 95% confidence interval [CI]: 1.179-1.370; OR = 1.283, 95% CI: 1.191-1.383; OR = 1.230, 95% CI: 1.145-1.322; OR = 1.408, 95% CI: 1.303-1.522; OR = 1.150, 95% CI: 1.067-1.240, respectively) compared with IQR1 was positively associated with GDM. However, exposure to NO2 was negatively associated with GDM in the first and second trimesters, and O3 was negatively associated with GDM in the second and third trimesters. We found that the correlation between air pollutants and GDM in different trimesters of pregnancy was not completely consistent in this retrospective cohort study. During pregnancy, there may be an interaction between air pollutant exposure and other factors, such as pregnant women's age, occupation, anemia status, pregnancy-induced hypertension status, and pregnancy season.

Real-world effectiveness of regorafenib in the treatment of patients with metastatic colorectal cancer: A retrospective, observational study.

AIM: To evaluate the real-world usage pattern and factors associated with the effectiveness of regorafenib in patients with metastatic colorectal cancer (mCRC). METHODS: This retrospective study analyzed data for 209 patients with mCRC treated with regorafenib as third or later line of therapy. TheKaplan-Meier method was used to draw the survival curves. Cox proportional hazard regression models were used to analyze the prognostic value for overall survival (OS). RESULTS: Of 209 patients, 156 (75%) were treated with regorafenib, and 53 (25%) were given regorafenib combined with programmed cell death-1 (PD-1) inhibitors. About 182 (87%) patients had a dose record of regorafenib. The initial daily doses of regorafenib were 160, 120, 80, and 40 mg, accounting for 29%, 17%, 48%, and 6% of patients, respectively. The median follow-up time was 11.3 months, and the median OS was 12.0 months (95% CI: 9.7-14.3). Patients treated with PD-1 inhibitors plus regorafenib had a longer OS than the non-PD-1 group (13.5 vs. 10.1 months, hazard ratio [HR] = .534, 95% CI: .325-.879; p = .014). A total of 49 patients with microsatellite stable or mismatch repair-proficient genotype treated with PD-1 inhibitors plus regorafenib had a longer OS than the non-PD-1 group (13.5 vs. 9.7 months; HR = .563, p = .027). The median OS of patients continuing treatment with regorafenib after progression (n = 19, with five patients receiving additional immunotherapy) was marginally longer than patients discontinuing regorafenib after progression (12.7 vs. 11.9 months, p = .425) observed in a smaller cohort. CONCLUSION: In real-world practice, patients with mCRC in whom standard regimens had failed have a good survival benefit with regorafenib. Combination with PD-1 inhibitor may further prolong survival of the patients.

Efficacy and safety of regorafenib as second-line treatment for patients with hepatocellular carcinoma and macrovascular invasion and(or) extrahepatic metastasis.

Background: Macrovascular invasion and(or) extrahepatic metastasis are the main clinical characteristics of Chinese patients with hepatocellular carcinoma (HCC) after entering the second-line treatment. The aim of this study was to explore the efficacy and safety of regorafenib as a second-line treatment for these patients with HCC. Methods: We selected 253 patients with primary liver cancer who were treated in Henan Cancer Hospital from June 2017 to September 2020. According to the inclusion and exclusion criteria, 63 patients with HCC with macrovascular invasion and/or extrahepatic metastasis were finally included. The clinical data of patients were obtained by consulting the electronic medical record system and through telephone follow-up. The median overall survival (mOS), duration of drug use, and disease control rate (DCR) of patients were evaluated, and the Cox regression model was used to analyze the risk factors of prognosis. Results: The mOS of 63 patients with HCC administered regorafenib as second-line treatment was 9.6 months, the duration of drug use was 3.8 months, and the DCR was 59% (37/63). Cox multivariate analysis showed that overall survival (OS) was closely related to the level of alpha-fetoprotein (AFP) and treatment method but not to the type of first-line drug. The mOS of patients with AFP ≥400 ng/mL was 7.4 months, which was significantly lower than that of those with AFP <400 ng/mL (12.5 months) (P=0.0052). The mOS of patients treated with regorafenib alone was 6.8 months, which was significantly lower than that of those treated with regorafenib combined with immunotherapy (24.3 months) and intervention therapy (17.5 months) (P<0.0001). The mOS of patients using regorafenib as second-line treatment in the first-line sorafenib group and first-line nonsorafenib group were 9.5 and 9.6 months, respectively (P=0.9766). The grade ≥3 adverse events (AEs) with an incidence of more than 10% included hand-foot syndrome, increased bilirubin, decreased albumin, and elevated transaminase, with incidences of 22%, 14%, 11%, and 10%, respectively. Conclusions: As second-line treatment for patients with HCC with macrovascular invasion and(or) extrahepatic metastasis, regorafenib has definite efficacy and tolerable adverse reactions. It is the preferred drug for the second-line treatment of patients with advanced HCC.

Research on Control Method of Waste Heat Utilization System Based on Multi-parameter Coupling.

The recovery of low-quality waste heat is a major problem in energy utilization. In order to solve this problem and improve energy utilization, the research group designed a low-quality waste heat power generation device with Roots power machine as the core. However, the device has poor ability to adjust the rotation speed and it is difficult to generate electricity stably. The fundamental reason is that the system has many variables and strong coupling. According to the actual working conditions, the power of the device is 10 kW, and the fluctuation range should be within ± 7%. On the one hand, it can be improved by hardware, on the other hand, the design of software is also very critical. At present, through the investigation of domestic and foreign researches on the control system, it is found that the stability of the system is gradually improved, but the problem of strong coupling between variables has not been effectively solved. Therefore, the research group modeled the variables in the system and obtained a coupled model. Based on the couple model, the research group introduced nonlinear multi-model adaptive closed-loop decoupling control and designed a control system. The simulation results show that the maximum overshoot of the control system is 3.9%, the adjustment time is also reduced, and it is stable in low quality waste heat recovery device. Experimental results show that under the control of the system, the rotational speed of roots motor can keep stable, the maximum deviation is not more than 21.4 r/min, and the fluctuation range is within ± 7%, which meets the requirements of the index. This has laid the foundation for the follow-up research of grid-connected power generation.

Optimized design of battery pole control system based on dual-chip architecture.

At present, the global demand for lithium batteries is still in a high growth state, and the traditional lithium battery pole mill control system is still dominated by ARM (Artificial Intelligence Enhanced Computing), DSP (Digital Signal Processing), and other single-chip control methods. There are problems such as poor anti-interference ability and insufficient real-time online analysis of production data. This paper adopts the dual-chip control system architecture based on "ARM+DSP", starting from the mechanical characteristics and operating signal features of the pole mill. The hardware system adopts a three-unit joint control hardware structure, which separates the control unit from the data processing unit and improves the operation of the system. The software system adopts fuzzy PID algorithm to realize deflection control and tension control, and verifies that the Fuzzy PID (Proportion Integration Differentiation) control algorithm can effectively improve the anti-interference ability of the deflection system and tension system. The results show that the data loss rate is low with the SPI communication between DSP and ARM. The tension error of the "ARM+DSP" control system does not exceed 5%, and the deviation of the correction band is within ±4mm. The dedicated dual-chip hardware architecture effectively improves the robustness and operation efficiency of the pole mill, solves the problem of low tension control accuracy, and provides a theoretical basis for the application of the dual-roll mill.

Evaluation of the Negative Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab Screening in the Medical Intensive Care Units and Its Effect on Antibiotic Duration.

Background: In addition to active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) carrier, MRSA nasal screening can be valuable for antibiotic de-escalation. This study aimed to assess the correlations between the MRSA nasal swab and subsequent culture results in patients admitted to medical intensive care units (MICU). The impact of MRSA nasal swab on the antibiotic duration was also evaluated. Materials and Methods: This retrospective study enrolled patients who received glycopeptides in the MICU of a medical center in 2019. Patients treated with glycopeptides for over 2 days before MICU admission were excluded. The associated data were collected through the electronic medical record system. The negative predictive value (NPV) of MRSA nasal swabs for MRSA infection was calculated, and their influence on empirical glycopeptide treatment duration was analyzed. Results: Of the 338 patients who met the inclusion criteria, 277 underwent MRSA nasal screening. The NPV of MRSA-negative nasal swab for subsequent MRSA infection was 98.4%. The glycopeptide treatment duration of the patients with and without nasal screening was not significantly different (4.2 ± 2.8 vs 4.4 ± 3.0 days, p = 0.577). Of the 120 patients with MRSA-negative nasal swab and no subsequent MRSA infection, 75 continued empirical glycopeptides therapy. The additional treatment time was 3 days (interquartile range: 2-6 days). Conclusion: The MRSA nasal swabs have high NPV for MRSA infection in critically ill patients. However, it has no impact on the empirical glycopeptide treatment duration. The value of MRSA nasal swabs should be advocated to optimize antibiotic therapy.

Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma.

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated transcription factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive cancer detection methods.

Magnetic Responsive Release of Nitric Oxide from an MOF-Derived Fe3O4@PLGA Microsphere for the Treatment of Bacteria-Infected Cutaneous Wound.

Nitric oxide (NO) is an essential endogenous signaling molecule regulating multifaceted physiological functions in the (cardio)vascular, neuronal, and immune systems. Due to the short half-life and location-/concentration-dependent physiological function of NO, translational application of NO as a novel therapeutic approach, however, awaits a strategy for spatiotemporal control on the delivery of NO. Inspired by the magnetic hyperthermia and magneto-triggered drug release featured by Fe3O4 conjugates, in this study, we aim to develop a magnetic responsive NO-release material (MagNORM) featuring dual NO-release phases, namely, burst and steady release, for the selective activation of NO-related physiology and treatment of bacteria-infected cutaneous wound. After conjugation of NO-delivery [Fe(µ-S-thioglycerol)(NO)2]2 with a metal-organic framework (MOF)-derived porous Fe3O4@C, encapsulation of obtained conjugates within the thermo-responsive poly(lactic-co-glycolic acid) (PLGA) microsphere completes the assembly of MagNORM. Through continuous/pulsatile/no application of the alternating magnetic field (AMF) to MagNORM, moreover, burst/intermittent/slow release of NO from MagNORM demonstrates the AMF as an ON/OFF switch for temporal control on the delivery of NO. Under continuous application of the AMF, in particular, burst release of NO from MagNORM triggers an effective anti-bacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). In addition to the magneto-triggered bactericidal effect of MagNORM against E. coli-infected cutaneous wound in mice, of importance, steady release of NO from MagNORM without the AMF promotes the subsequent collagen formation and wound healing in mice.

A clinical study of serum human epididymis protein 4 (HE4) in the diagnosis of pancreatic cancer.

Background: Pancreatic cancer (PC) has poor early diagnosis rates due to its insidious onset. Since human epididymis protein 4 (HE4) is highly expressed in patients with PC, we assessed whether serum HE4 could be a marker for the detection 3 of PC. Method: : Between May 2017 and October 2018, 127 patients with PC were recruited for the study along with 108 healthy controls who underwent health examinations. Serum HE4 concentrations were determined together with levels of carcinoembryonic antigen (CEA) and carbohydrate antigens (CA) 242 (CA242), CA19-9, CA15-3, and CA72-4 by electrochemiluminescence immunoassay (ECLIA) or chemiluminescence immunoassay (CLIA). Correlations between these biomarkers were assessed. Results: : Serum levels of all six biomarkers were higher in patients with PC than in controls (P < 0.05). No correlation was observed between the serum levels of HE4 and the five other tumor markers, although there were strongly significant positive correlations between CA19-9 and CA15-3, and between CA242 and CA72-4. The lack of correlation indicates that HE4 has independent value in the diagnosis of PC. The combined assessment of serum HE4 levels and the other tumor markers improved the sensitivity of diagnosis. In particular, HE4 combined with CA19-9 performed significantly better than HE4 alone, or CA19-9 combined with the other markers. The HE4/CA19-9 combination resulted in 94.49% sensitivity and 99.07% specificity (95% confidence interval: 96.9-100). Conclusion: : HE4 is a biomarker associated with PC with a high specificity , either used alone, or evaluated with other biomarkers together improving the detection of PC. This study may provide a new clinical diagnostic approach for PC detection.

Blockade of TMEM16A protects against renal fibrosis by reducing intracellular Cl- concentration.

BACKGROUND AND PURPOSE: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca2+ -activated chloride channel, contributes to the progression of renal fibrosis. EXPERIMENTAL APPROACH: Masson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular Cl- concentration. KEY RESULTS: TMEM16A expression was significantly up-regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high-fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A-shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh-A01 or T16Ainh-A01 effectively prevented UUO-induced renal fibrosis and decreased protein expression of fibronectin, α-SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF-ß1-induced epithelial-mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF-ß1 increased [Cl- ]i in HK2 cells, which was inhibited by knockdown or inhibition of TMEM16A. Reducing [Cl- ]i significantly blunted TGF-ß1-induced Smad2/3 phosphorylation and profibrotic factors expression. The profibrotic effects of TGF-ß1 were also reduced by inhibition of serum- and glucocorticoid-inducible protein kinase 1 (SGK1). SGK1 was also suppressed by reducing [Cl- ]i. CONCLUSION AND IMPLICATIONS: Blockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing [Cl- ]i/SGK1/TGF-ß1 signalling pathway. TMEM16A may be a potential new therapeutic target against renal fibrosis.

Research on rapier loom fault system based on cloud-side collaboration.

The electrical control system of rapier weaving machines is susceptible to various disturbances during operation and is prone to failures. This will seriously affect the production and a fault diagnosis system is needed to reduce this effect. However, the existing popular fault diagnosis systems and methods need to be improved due to the limitations of rapier weaving machine process and electrical characteristics. Based on this, this paper presents an in-depth study of rapier loom fault diagnosis system and proposes a rapier loom fault diagnosis method combining edge expert system and cloud-based rough set and Bayesian network. By analyzing the process and fault characteristics of rapier loom, the electrical faults of rapier loom are classified into common faults and other faults according to the frequency of occurrence. An expert system is built in the field for edge computing based on knowledge fault diagnosis experience to diagnose common loom faults and reduce the computing pressure in the cloud. Collect loom fault data in the cloud, train loom fault diagnosis algorithms to diagnose other faults, and handle other faults diagnosed by the expert system. The effectiveness of loom fault diagnosis is verified by on-site operation and remote monitoring of the loom human-machine interaction system. Technical examples are provided for the research of loom fault diagnosis system.

CstF64-Induced Shortening of the BID 3'UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2.

The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3'UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3'UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3'UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3'UTR length. Mechanistically, a shortened BID 3'UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3'UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3'UTR as a driver of disease progression.