Mesenchymal stem cells therapy for acute kidney injury: A systematic review with meta-analysis based on rat model.

Objective: To systematically evaluate the efficacy of mesenchymal stem cells (MSCs) for acute kidney injury (AKI) in preclinical studies and to explore the optimal transplantation strategy of MSCs by network meta-analysis with the aim of improving the efficacy of stem cell therapy. Methods: Computer searches of PubMed, Web of Science, Cochrane, Embase, CNKI, Wanfang, VIP, and CBM databases were conducted until 17 August 2022. Literature screening, data extraction and quality evaluation were performed independently by two researchers. Results and Discussion: A total of 50 randomized controlled animal studies were included. The results of traditional meta-analysis showed that MSCs could significantly improve the renal function and injured renal tissue of AKI rats in different subgroups. The results of network meta-analysis showed that although there was no significant difference in the therapeutic effect between different transplant routes and doses of MSCs, the results of surface under the cumulative ranking probability curve (SUCRA) showed that the therapeutic effect of intravenous transplantation of MSCs was better than that of arterial and intrarenal transplantation, and the therapeutic effect of high dose (>1×106) was better than that of low dose (≤1×106). However, the current preclinical studies have limitations in experimental design, measurement and reporting of results, and more high-quality studies, especially direct comparative evidence, are needed in the future to further confirm the best transplantation strategy of MSCs in AKI. Systematic Review Registration: identifier https://CRD42022361199, https://www.crd.york.ac.uk/prospero.

Signal Amplification-Based Biosensors and Application in RNA Tumor Markers.

Tumor markers are important substances for assessing cancer development. In recent years, RNA tumor markers have attracted significant attention, and studies have shown that their abnormal expression of post-transcriptional regulatory genes is associated with tumor progression. Therefore, RNA tumor markers are considered as potential targets in clinical diagnosis and prognosis. Many studies show that biosensors have good application prospects in the field of medical diagnosis. The application of biosensors in RNA tumor markers is developing rapidly. These sensors have the advantages of high sensitivity, excellent selectivity, and convenience. However, the detection abundance of RNA tumor markers is low. In order to improve the detection sensitivity, researchers have developed a variety of signal amplification strategies to enhance the detection signal. In this review, after a brief introduction of the sensing principles and designs of different biosensing platforms, we will summarize the latest research progress of electrochemical, photoelectrochemical, and fluorescent biosensors based on signal amplification strategies for detecting RNA tumor markers. This review provides a high sensitivity and good selectivity sensing platform for early-stage cancer research. It provides a new idea for the development of accurate, sensitive, and convenient biological analysis in the future, which can be used for the early diagnosis and monitoring of cancer and contribute to the reduction in the mortality rate.

3-Hydroxy-pyridin-4(1H)-ones as siderophores mediated delivery of isobavachalcone enhances antibacterial activity against pathogenic Pseudomonas aeruginosa.

The natural prenylated chalcone isobavachalcone (IBC) shows good antibacterial activity against Gram-positive bacteria but is ineffective against Gram-negative bacteria, most likely due to the outer membrane barrier of Gram-negative bacteria. The Trojan horse strategy has been shown to be an effective strategy to overcome the reduction in the permeability of the outer membrane of Gram-negative bacteria. In this study, eight different 3-hydroxy-pyridin-4(1H)-one-isobavachalcone conjugates were designed and synthesized based on the siderophore Trojan horse strategy. The conjugates exhibited 8- to 32-fold lower minimum inhibitory concentrations (MICs) and 32- to 177-fold lower half-inhibitory concentrations (IC50s) against Pseudomonas aeruginosa PAO1 as well as clinical multidrug-resistant (MDR) strains compared to the parent IBC under iron limitation. Further studies showed that the antibacterial activity of the conjugates was regulated by the bacterial iron uptake pathway under different iron concentration conditions. Studies on the antibacterial mechanism of conjugate 1b showed that it exerts antibacterial activity by disrupting cytoplasmic membrane integrity and inhibiting cell metabolism. Finally, conjugate 1b showed a lower cytotoxic effects on Vero cells than IBC and a positive therapeutic effect in the treatment of bacterial infections caused by Gram-negative bacteria PAO1. Overall, this work demonstrates that IBC can be delivered to Gram-negative bacteria when combined with 3-hydroxy-pyridin-4(1H)-ones as siderophores and provides a scientific basis for the development of effective antibacterial agents against Gram-negative bacteria.

Psychometric evaluation of the traditional chinese version of PedsQL™ 3.0 cardiac module scale in adolescents with congenital heart disease: reliability, validity, measurement invariance, and adolescent-parent agreement.

BACKGROUND: In recent decades, 95% of children with congenital heart disease (CHD) can survive to adolescence and adulthood. However, adolescents with CHD are prone to poorer health-related quality of life (HRQoL). It is imperative to develop a reliable and valid instrument for health professionals to monitor the HRQoL. This study aims to: (1) evaluate the psychometric properties of the traditional Chinese version of Pediatric Quality of Life™ 3.0 Cardiac Module (PedsQL-CM) and measurement invariance across adolescents with CHD and their parents; and (2) investigate the adolescent-parent agreement in HRQoL. METHODS: A total of 162 adolescents and 162 parents were recruited. Internal consistency was examined using Cronbach's alpha and McDonald's Omega. The criterion-related validity was evaluated with intercorrelations between the PedsQL-CM and PedsQL™ 4.0 Generic Core (PedsQL-GC) Scale. The construct validity was examined by second-order confirmatory factor analysis (CFA). Measurement invariance was evaluated using the multi-group CFA. The adolescent-parent agreement was analyzed with the intraclass correlation (ICC), paired t-tests, and Bland-Altman plots. RESULTS: PedsQL-CM showed acceptable internal consistency (self-reports 0.88, proxy-reports 0.91). The intercorrelations were medium to large effect size (self-reports 0.34-0.77, proxy-reports 0.46-0.68). The CFA supported the construct validity (CFI = 0.967, TLI = 0.963, RMSEA = 0.036, 90% CI = 0.026-0.046, SRMR = 0.065). The multi-group CFA proved scalar invariance between self and parent proxy-reports. Parents significantly underestimated their adolescents' HRQoL in cognitive problems (Cohen's d = 0.21) and communication (Cohen's d = 0.23) subscales, while there was a negligible difference in total HRQoL (Cohen's d = 0.16). ICCs were poor to moderate effect size with the highest and lowest agreement in heart problems and treatment subscale (ICC = 0.70) and communication subscale (ICC = 0.27), respectively. The Bland-Altman plots showed lesser variability in the heart problem and treatment subscale and the total scale. CONCLUSION: The traditional Chinese version of PedsQL-CM has acceptable psychometric properties to measure disease-specific HRQoL in adolescents with CHD. Parents may be proxies for adolescents with CHD to rate total HRQoL. When the patient-reported score is the primary outcome, the proxy-reported score could serve as a secondary outcome for research and clinical evaluation.

Safety and efficacy of apatinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma after the failure of two or more lines of chemotherapy (AHEAD): a prospective, single-arm, multicenter, phase IV study.

BACKGROUND: Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. METHODS: Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan-Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. RESULTS: Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6-5.4%), and DCR was 35.8% (95% CI, 33.7-38.0%). The median PFS was 2.7 months (95% CI 2.2-2.8), and the median OS was 5.8 months (95% CI 5.4-6.1). CONCLUSIONS: The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Research advances in imaging markers for predicting hematoma expansion in intracerebral hemorrhage: a narrative review.

Introduction: Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies. Recent advances: Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients. Conclusion: The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions.

Association between NET-1 Level in Placenta from Preeclampsia Pregnancies and Trophoblast Proliferation and Apoptosis: A Correlation Analysis.

Objective: This study investigates the expression pattern of neuroepithelial cell transforming 1 (NET-1) in placental tissues from pregnancies with preeclampsia (PE) and explores its role in mediating proliferative and apoptotic capacities of trophoblasts. Methods: The relative mRNA levels of NET-1 in placental tissues obtained from preeclampsia (PE) pregnancies (n = 60) and healthy pregnancies (n = 60) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Pearson correlation test was conducted to assess the correlation between NET-1 level and systolic (Sp) and diastolic pressure (Dp) in PE pregnancies. After the knockdown of NET-1 in HTR-8/SVneo cells, changes in proliferation and apoptosis were examined using cell counting kit-8 (CCK-8) and flow cytometry, respectively. Results: NET-1 was highly expressed in placental tissues from PE pregnancies. PE patients with a high level of NET-1 had higher Sp and Dp, and NET-1 level was positively correlated with both Sp and Dp. Knockdown of NET-1 in HTR-8/SVneo cells decreased the proliferative rate but increased the apoptotic rate. Conclusions: NET-1 stimulates the development of PE by triggering trophoblast proliferation and inhibiting apoptosis. Therefore, NET-1 could be a potential therapeutic target for treating PE and other related hypertensive disorders during pregnancy.

Characterization of the natural peptidome of four leeches by integrated proteogenomics and pseudotargeted peptidomics.

Animal-derived drugs are an indispensable part of folk medicine worldwide. However, their chemical constituents are poorly approached, which leads to the low level of the quality standard system of animal-derived drugs and further causes a chaotic market. Natural peptides are ubiquitous throughout the organism, especially in animal-derived drugs. Thus, in this study, we used multi-source leeches, including Hirudo nipponica (HN), Whitmania pigra (WP), Whitmania acranulata (WA), and Poecilobdella manillensis (PM), as a model. A strategy integrating proteogenomics and novel pseudotargeted peptidomics was developed to characterize the natural peptide phenotype and screen for signature peptides of four leech species. First, natural peptides were sequenced against an in-house annotated protein database of closely related species constructed from RNA-seq data from the Sequence Read Archive (SRA) website, which is an open-sourced public archive resource. Second, a novel pseudotargeted peptidomics integrating peptide ion pair extraction and retention time transfer was established to achieve high coverage and quantitative accuracy of the natural peptides and to screen for signature peptides for species authentication. In all, 2323 natural peptides were identified from four leech species whose databases were poorly annotated. The strategy was shown to significantly improve peptide identification. In addition, 36 of 167 differential peptides screened by pseudotargeted proteomics were identified, and about one-third of them came from the leucine-rich repeat domain (LRR) proteins, which are widely distributed in organisms. Furthermore, six signature peptides were screened with good specificity and stability, and four of them were validated by synthetic standards. Finally, a dynamic multiple reaction monitoring (dMRM) method based on these signature peptides was established and revealed that one-half of the commercial samples and all of the Tongxinluo capsules were derived from WP. All in all, the strategy developed in this study was effective for natural peptide characterization and signature peptide screening, which could also be applied to other animal-derived drugs, especially for modelless species that are less studied in protein database annotation.

Diaporpyrone E, an undescribed α-pyrone from the endophytic fungus Diaporthe sp. CB10100.

An undescribed α-pyrone diaporpyrone E (1), and three known nucleotides, 5'-O-acetyl uridine (2), 5'-O-acetyl thymidine (3), and adenine (4), were identified from Diaporthe sp. CB10100, an endophytic fungus isolated from the medicinal plant Sinomenium acutum. The structure of 1 was determined by extensive analysis of its HRMS, 1D and 2D NMR spectroscopic data, as well as electronic circular dichroism calculations and comparison. The in vitro cytotoxic and antibacterial assays of 1 revealed that it has a 30.2% inhibitory effect on HepG2 cells at 50 µM, while no antibacterial activities against Staphylococcus aureus and Klebsiella pneumoniae at 64 µg/mL.

Wideband multiwavelength Brillouin fiber laser with switchable channel spacing.

A multiwavelength Brillouin fiber laser (MBFL) with a switchable channel spacing is demonstrated using a 1.55-µm single-mode AlGaInAs/InP hybrid square-rectangular laser as a seeding source. The scheme employs a highly nonlinear fiber loop with a feedback path to generate a 10-GHz-spacing MBFL. Then, assisted by a tunable optical bandpass filter, MBFLs with spacing from 20 GHz to 100 GHz at a step of 10 GHz are generated in another highly nonlinear fiber loop based on the cavity-enhanced four-wave mixing. More than 60 lasing lines with an optical signal-to-noise ratio over 10 dB are obtained successfully in all the switchable spacings. The total output power and the channel spacing of the MBFLs are proved to be stable.

Photoredox Cleavage of a Csp3-Csp3 Bond in Aromatic Hydrocarbons.

Functionalizing molecules through the selective cleavage of carbon-carbon bonds is an attractive approach in synthetic chemistry. Despite recent advances in both transition-metal catalysis and radical chemistry, the selective cleavage of inert Csp3-Csp3 bonds in hydrocarbon feedstocks remains challenging. Examples reported in the literature typically involve substrates containing redox functional groups or highly strained molecules. In this article, we present a straightforward protocol for the cleavage and functionalization of Csp3-Csp3 bonds in alkylbenzenes using photoredox catalysis. Our method employs two distinct bond scission pathways. For substrates with tertiary benzylic substituents, a carbocation-coupled electron transfer mechanism is prevalent. For substrates with primary or secondary benzylic substituents, a triple single-electron oxidation cascade is applicable. Our strategy offers a practical means of cleaving inert Csp3-Csp3 bonds in molecules without any heteroatoms, resulting in primary, secondary, tertiary, and benzylic radical species.

Uterine arteries pulsatility index by Doppler ultrasound in the prediction of preeclampsia: an updated systematic review and meta-analysis.

BACKGROUND: Preeclampsia is a common pregnancy complication with serious potential risks for maternal and neonatal health. Early prediction of preeclampsia is crucial for timely prevention, surveillance, and treatment to improve maternal and neonatal outcomes. This systematic review aimed to summarize the available evidence on the prediction of preeclampsia based on Doppler ultrasound of uterine arteries at different gestational ages. METHODS: A systematic literature search and meta-analysis were conducted to evaluate the sensitivity and specificity of the pulsatility index of Doppler ultrasound of uterine arteries for predicting preeclampsia. The timing of ultrasound scans within and beyond 20 weeks of gestational age was compared to assess its effect on the sensitivity and specificity of the pulsatility index. RESULTS: This meta-analysis included 27 studies and 81,673 subjects (3309 preeclampsia patients and 78,364 controls). The pulsatility index had moderate sensitivity (0.586) and high specificity for predicting preeclampsia (0.879) (summary point: sensitivity 0.59; 1-specificity 0.12). Subgroup analysis revealed that ultrasound scans performed within 20 weeks of gestational age did not significantly affect the sensitivity and specificity for predicting preeclampsia. The summary receiver operator characteristic curve showed the pulsatility index's optimal range of sensitivity and specificity. CONCLUSIONS: The uterine arteries pulsatility index measured by Doppler ultrasound is useful and effective for predicting preeclampsia and should be implemented in the clinical practice. The timing of ultrasound scans at different gestational age ranges does not significantly affect the sensitivity and specificity.

Preparation of cationic aggregates derived from sewage sludge for efficient capture of organic matter.

Capturing the abundant organic matter residing in wastewater can not only reduce the emission of CO2 from the source, but the enriched organics can also be used for anaerobic fermentation to generate and offset energy consumption in wastewater treatment processes. The key is to find or develop low-cost materials that can capture organic matter. Herein, sewage sludge-derived cationic aggregates (SBC-g-DMC) were successfully prepared via a hydrothermal carbonization process coupled with a graft copolymerization reaction for recovering organic matter from wastewater. Based upon preliminary screening of synthesized SBC-g-DMC aggregates regarding grafting rate, cationic degree, and flocculation performance, SBC-g-DMC2.5 aggregate prepared with 60 mg of initiator, DMC-to-SBC mass ratio of 2.5:1, 70 °C, and 2 h of reaction time was selected for further characterization and evaluation. Results showed that SBC-g-DMC2.5 aggregate has a positively-charged surface over a wide pH range of 3-11 and a hierarchical micro-/nano-structure, endowing it with an excellent organic matter capture efficiency (97.2% of pCOD, 68.8% of cCOD, and 71.2% of tCOD). Meanwhile, SBC-g-DMC2.5 exhibits inappreciable trapping ability for the dissolved COD, NH3-N, and PO43-, guaranteeing the regular running of subsequent biological treatment units. Electronic neutralization, adsorption bridging, and sweep coagulation between cationic aggregates surface and organic matter were identified as the primary mechanisms for SBC-g-DMC2.5 to capture organics. This development is expected to provide a theoretical reference for sewage sludge disposal, carbon reduction, and energy recovery during municipal wastewater treatment.

Highly efficient waveguide-coupled output in asymmetrically deformed square cavity microlasers.

We propose and demonstrate deformed square cavity microlasers for realizing highly efficient output from a connected waveguide. The square cavities are deformed asymmetrically by replacing two adjacent flat sides with circular arcs to manipulate the ray dynamics and couple the light to the connected waveguide. The numerical simulations show that the resonant light can efficiently couple to the fundamental mode of the multi-mode waveguide by carefully designing the deformation parameter utilizing global chaos ray dynamics and internal mode coupling. An enhancement of approximately six times in the output power is realized in the experiment compared to the non-deformed square cavity microlasers, while the lasing thresholds are reduced by about 20%. The measured far-field pattern shows highly unidirectional emission agreeing well with the simulation, which confirms the feasibility of the deformed square cavity microlasers for practical applications.

Polygonum orientale L. Alleviates Myocardial Ischemia-Induced Injury via Activation of MAPK/ERK Signaling Pathway.

Although Polygonum orientale L. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.

A new insight in enhancing phosphate enrichment in biofilm process: Comparison of the key metabolic pathways in highly-efficient and dominant PAOs based on metagenomics.

The formation of dominant phosphate-accumulating organisms (PAOs) is essential for the high enrichment of phosphate in biofilm sequencing batch reactors (BSBR) for phosphorus recovery. The dominant PAOs in the biofilm process have not been isolated and purified, and the key metabolic pathways that promote the formation of dominant PAOs are still unclear. In this study, four strains of highly-efficient PAOs were obtained by an innovative isolation procedure. The relationship between the abundance of highly-efficient and dominant PAOs and the phosphate removal ability was compared. We found that the abundance of PAOs was positively correlated with the phosphate removal efficiency in vitro pure culture and complex biofilm process. Metagenomics analysis revealed that compared with highly-efficient PAOs cultured in vitro, dominant PAOs in biofilms had unique key metabolic pathways, F-ATPases and N-Acyl homoserine lactones (AHLs). F-ATPases are important for maintaining the proton motive force (PMF) required for the uptake of carbon sources by PAOs, and AHLs are participating in phosphate metabolism through quorum sensing (QS) mediated secretion of extracellular polymeric substance (EPS). The formation of dominant PAOs was promoted by optimizing carbon source uptake and phosphate metabolism. This study revealed that the difficult isolation of dominant PAOs was due to the AHLs-mediated QS, and we identified the key pathways regulating the formation of dominant PAOs in biofilms through genomics analysis. Our findings provide insights in enhancing phosphate enrichment in BSBR by modulating the components of microbial community under the low concentration of carbon source consumption.

Full-scale application and performance of a new multi-self-reflow decentralized Wastewater treatment device: Impact of hydraulic and pollutant loads.

Decentralized treatment of wastewater in rural areas usually has several challenges, which include large fluctuations in pollutant concentration and water quantity, complicated operation and maintenance of conventional biochemical treatment equipment, resulting in poor stability and a low compliance rate of the wastewater treatment process. In order to solve the above problems, a new integration reactor is designed, which uses gravity and aeration tail gas self-reflux technology to realize the reflux of sludge and the nitrification liquid, respectively. The feasibility and operation characteristics of its application for decentralized wastewater treatment in rural areas are explored. The results demonstrated that, under constant influent, the device showed strong tolerance to the shock of pollutant load. The chemical oxygen demand, NH4+-N, total nitrogen and total phosphorus fluctuated in the ranges of 95-715 mg/L, 7.6-38.5 mg/L, 9.32-40.3 mg/L and 0.84-4.9 mg/L, respectively. The corresponding effluent compliance rates were 82.1%, 92.8%, 96.4% and 96.3%, respectively. When the wastewater discharge was non-constant and the maximum single-day Qmax/Qmin reached 5, all indicators of the effluent met the relevant discharge standard. The integrated device also demonstrated high phosphorus enrichment levels in its anaerobic zone; the concentration of phosphorus reached a maximum of 26.9 mg/L, which created a good environment for phosphorus removal. The microbial community analysis showed that sludge digestion, denitrification, and phosphorus-accumulating bacteria all played an important role in pollutant treatment.

Metformin inhibits ovarian granular cell pyroptosis through the miR-670-3p/NOX2/ROS pathway.

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and that NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance in women, whereas its role in OGC pyroptosis is unknown. This study aimed to investigate the impact of metformin on OGC pyroptosis and the underlying mechanisms. The results showed that treating a human granulosa-like tumor cell line (KGN) with metformin significantly decreased LPS-induced expression of miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; and the secretion of IL-1ß, IL-6, IL-18, and TNF-α were also diminished. These effects were amplified by adding N-acetyl-L-cysteine (NAC), a pharmacological inhibitor of ROS. In contrast, metformin's anti-pyroptosis and anti-inflammatory effects were robustly ameliorated by NOX2 overexpression in KGN cells. Moreover, bioinformatic analyses, RT-PCR, and Western blotting showed that miR-670-3p could directly bind to the NOX2 (encoded by the CYBB gene in humans) 3'UTR and decrease NOX2 expression. Metformin-induced suppression of NOX2 expression, ROS production, oxidative stress, and pyroptosis was significantly alleviated by transfection with the miR-670-3p inhibitor. These findings suggest that metformin inhibits KGN cell pyroptosis via the miR-670-3p/NOX2/ROS pathway.