Strong Oxidizing Molten Salts for Strengthening Structural Restoration Enabling Direct Regeneration of Spent Layered Cathode.

As a mainstream technology for recycling spent lithium-ion batteries, direct regeneration is rapidly developed due to its high efficiency and green characteristics. However, efficient reuse of spent LiNixCoyMn1- x - yO2 cathode is still a significant challenge, as the rock salt/spinel phase on the surface hinders the Li replenishment and phase transformation to the layered structure. In this work, the fundamental understanding of the repair mechanism is confirmed that the oxidizing atmosphere is the crucial factor that can greatly improve the rate and degree of phase restoration. Particularly, a ternary-component molten salt system (LiOH-Li2CO3-LiNO3) is proposed for direct regeneration of LiNi0.5Co0.2Mn0.3O2 (NCM523), which can in situ generate the strong oxidizing intermediate of superoxide radicals. Additionally, it shows a liquid-like reaction environment at a lower temperature to acceclerate the transport rate of superoxide-ions. Therefore, the synergistic effect of LiOH-Li2CO3-LiNO3 system can strengthen the full restoration of rock salt/spinel phases and achieve the complete Li-supplement. As anticipated, the regenerated NCM523 delivers a high cycling stability with a retention of 91.7% after 100 cycles, which is even competitive with the commercial NCM523. This strategy provides a facile approach for the complete recovery of layer structure cathode, demonstrating a unique perspective for the direct regeneration of spent lithium-ion batteries.

Analysis of the occurrence and liver function characteristics of arsenic-associated liver injury during the treatment of pediatric patients with acute promyelocytic leukemia.

Liver injury during arsenic treatment for acute promyelocytic leukemia was previously reported in adults, but not comprehensively in children until now. This study aims to investigate liver injury in pediatric patients with APL, changes in liver function during treatment, and compare the effects of Arsenic trioxide (ATO) and Realgar-Indigo naturalis formula (RIF) on liver function. One hundred and eighty-six patients with 3076 patient tests were analyzed, who were enrolled in the Chinese Children's Leukemia Group (CCLG)-APL2016 Protocol database between November 2016 and November 2018 in 38 hospitals across China(ChiCTR-OIN-17011227). Twenty of 164 patients (12.2%) suffered from liver injury after treatment with arsenic. In addition, sixteen (80%) cases of liver injury occurred during the induction period of treatment. What's not disheartening was that 18 (90%) cases of liver injury were transient, occurring at a median time of 17 days after exposure to arsenic. More importantly, the risk of liver injury associated with RIF was not higher than that associated with ATO (RR = 0.854, 95% CI: 0.292-2.495). Otherwise, the ALP of 18 cases of liver injury was not higher than the ULN of ALP. Thus, the incidence of liver injury associated with arsenic in pediatric patients with APL was similar to that in adult patients and the risk of liver injury associated with RIF was not higher than that associated with ATO. Since ALP was not higher in pediatric APL patients with liver injury, further research is needed to explore whether ALP is an index of liver injury in children.

A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology. At present, emerging evidences suggest that metabolism alteration is closely associated with α-synuclein aggregation and PD progression, and improvement of key molecules in metabolism might be potentially beneficial in PD treatment. In this review, we highlight the tripartite relationship among metabolic changes, α-synuclein aggregation, and oxidative stress in PD, and offer updated insights into the treatments of PD, aiming to deepen our understanding of PD pathogenesis and explore new therapeutic strategies for the disease.

An interfacial host-guest inclusion complex regulated supramolecular nanocomposite hydrogel showing tunable mechanical strength, self-healing, strain sensitivity and NIR responsiveness.

The development of supramolecular nanocomposite hydrogels with good mechanical properties and multifunctional characteristics remains challenging. The reinforced role of interfacial weak interactions is important for the mechanical properties of nanocomposite hydrogels. Here, a dynamic host-guest inclusion complex from the host molecule CB[7] and guest units was employed to prepare Fe3O4 hybrid supramolecular nanocomposite hydrogels. The results show that the as-obtained hydrogel with a porous structure was prepared. The CB[7]-modified Fe3O4 (Fe3O4@CB[7]) nanoparticles severed as a cross-linker for fabricating the hydrogel's network. By changing the Fe3O4@CB[7] content, their tensile stress ranged from 0.102 to 0.403 MPa and their compression stress ranged (70% compression strain) from 0.059 to 0.775 MPa. By changing the guest units, their tensile stress ranged from 0.3 MPa to 0.403 MPa. The self-healing efficiency of the hydrogels was 99% after 48 h at room temperature. The as-obtained hydrogels with strain sensitivity can be applied for detecting the movement of an elbow and finger. The supramolecular hydrogel exhibits NIR responsiveness, self-healing, injectability, tunable mechanical strength and conductive ability, and can be used in flexible electronics.

Novel cow dung-doped sludge biochar as an efficient ozone catalyst: Synergy between graphitic structure and defects induces free radical pathways.

A composite material, cow dung-doped sludge biochar (Zn@SBC-CD), was synthesized by one-step pyrolysis using ZnCl2 as an activating agent and applied to a catalytic ozonation process (COP) for methylene blue (MB) removal. SEM, XRD, FTIR, XPS and BET analyses were performed to characterize the biochar (BC) catalysts. Zn@SBC-CD had high graphitization degree, abundant active sites and uniform distribution of Zn on its surface. Complete removal of MB was achieved within 10 min, with a removal rate much higher than that of ozone alone (32.4%), implying the excellent ozone activation performance of Zn@SBC-CD. The influence of experimental parameters on MB removal efficiency was examined. Under the optimum conditions in terms of ozone dose 0.04 mg/mL, catalyst dose 400 mg/L and pH 6.0, COD was completely removed after 20 min. Electron paramagnetic resonance (EPR) analysis revealed radical and non-radical pathways were involved in MB degradation. The Zn@SBC-CD/O3 system generated superoxide anion radicals (•O2-), which were the main active species for MB removal, through adsorption, transformation, and transfer, Furthermore, Zn@SBC-CD exhibited good reusability and stability in cycling experiments. This study provides a novel approach for the utilization of cow dung and sludge in synthesis of functional biocatalysts and application in organic wastewater treatment.

Eutrophication driven macrophyte-derived organic matter decomposition to methane emission relates to co-metabolism effect in freshwater sediments.

Lakes and wetlands play pivotal roles in global organic matter storage, receiving significant inputs of organic material. However, the co-metabolic processes governing the decomposition of these organic materials and their impact on greenhouse gas emissions remain inadequately understood. This study aims to assess the effects of mixed decomposition involving macrophytes and cyanobacteria on carbon emissions. A series of microcosms was established to investigate the decomposition of macrophyte residues and algae over a period of 216 days. A two-component kinetic model was utilized to estimate methane (CH4) production rates. Gas isotope technology was employed to discern the contributions of CH4 produced by macrophyte residues or algae. Quantitative PCR and analysis of 16S rRNA gene amplicons were employed to assess changes in functional genes and microbial communities. There were significant differences in the cumulative carbon release from the decomposition of different plant types due to the addition of carbon sources. After adding algae, the cumulative emission of CH4 increased significantly. The δ13C-CH4 partitioning indicated that CH4 originated exclusively from the fresh organic carbon of macrophyte residues, while it shifted to algae source after adding algae. The synergistic effect of the mixed decomposition on the CH4 emissions was greater than the sum of the individual decompositions. The microbial community richness was higher in the single plant residue treatment compared to the mixed treatment with algae addition, while microbial evenness in the sediment increased steadily in each treatment. Our findings emphasize the pronounced co-metabolic effect observed during the mixed decomposition of macrophytes and cyanobacteria.

Circulating miR-423-5p levels are associated with carotid atherosclerosis in patients with chronic kidney disease.

BACKGROUND AND AIMS: Carotid atherosclerosis is associated with an elevated risk of stroke in patients with chronic kidney disease. However, the molecular basis for the incidence of carotid atherosclerosis in patients with CKD is poorly understood. Here, we investigated whether circulating miR-423-5p is a crucial link between CKD and carotid atherosclerosis. METHODS AND RESULTS: We recruited 375 participants for a cross-sectional study to examine the occurrence of carotid plaque and plaque thicknesses. Levels of miR-423-5p were determined by qPCR analysis. We found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels, and dialysis-dependent patients had lower miR-423-5p levels than non-dialysis CKD patients. After excluding for the influence of dialysis patients, linear regression analysis indicated that levels of circulating miR-423-5p are negatively correlated with eGFR (P < 0.001). Higher plasma miR-423-5p levels were associated with the incidence and severity of carotid plaques. In parallel, we constructed a murine model of CKD with a 5/6 nephrectomy protocol and performed RNA sequencing studies of aortic tissues. Consistent with these findings in CKD patients, circulating exosomal miR-423-5p levels in CKD mice were elevated. Furthermore, our RNA-seq studies indicated that the putative target genes of miR-423-5p were related to oxidative stress functions for aorta of CKD mice. CONCLUSION: Levels of miR-423-5p are associated with the presence and severity of carotid plaque in CKD. Data from our mouse model suggests that miR-423-5p likely influences gene expression programs related to oxidative stress in aorta of CKD mice.

Synthesis and biological evaluation of sulfonamide derivatives containing imidazole moiety as ALK5 inhibitors.

Four series of sulfonamide derivatives (13a-b, 14a-d, 15a-b, and 16a-d) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibitory activities. Of these, compounds 13b (IC50 = 0.130 µM) and 15a (IC50 = 0.130 µM) showed the highest inhibitory activities against ALK5 kinase, with activities similar to the positive control LY-2157299. Notably, we discovered that introduction of sulfonamide group at the 2-position of the central imidazole ring significantly increased ALK5 inhibitory activity. Compounds 13b and 15a did not show toxicity in A549 cells up to the maximum concentration of 50 µM, and effectively inhibited TGF-ß1-induced Smad-signaling and cell motility in A549 cells. The results indicate that compounds 13b and 15a are worth of further development as anticancer agents.

Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti-cardiac fibrosis activity.

Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW-7197 (vactosertib) and 14 times that of the clinical candidate LY-2157299. The selectivity index of 16f against p38α mitogen-activated protein kinase was >109, which was much higher than that of positive controls (EW-7197: >41, and LY-2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α-smooth muscle actin (α-SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP-1)/matrix metalloproteinase 13 (MMP-13) in transforming growth factor-ß-induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.

No-Reference Image Quality Assessment Combining Swin-Transformer and Natural Scene Statistics.

No-reference image quality assessment aims to evaluate image quality based on human subjective perceptions. Current methods face challenges with insufficient ability to focus on global and local information simultaneously and information loss due to image resizing. To address these issues, we propose a model that combines Swin-Transformer and natural scene statistics. The model utilizes Swin-Transformer to extract multi-scale features and incorporates a feature enhancement module and deformable convolution to improve feature representation, adapting better to structural variations in images, apply dual-branch attention to focus on key areas, and align the assessment more closely with human visual perception. The Natural Scene Statistics compensates information loss caused by image resizing. Additionally, we use a normalized loss function to accelerate model convergence and enhance stability. We evaluate our model on six standard image quality assessment datasets (both synthetic and authentic), and show that our model achieves advanced results across multiple datasets. Compared to the advanced DACNN method, our model achieved Spearman rank correlation coefficients of 0.922 and 0.923 on the KADID and KonIQ datasets, respectively, representing improvements of 1.9% and 2.4% over this method. It demonstrated outstanding performance in handling both synthetic and authentic scenes.

Stabilization of heavy metals in solid waste and sludge pyrolysis by intercalation-exfoliation modified vermiculite.

Increasing amounts of solid waste and sludge have created many environmental management problems. Pyrolysis can effectively reduce the volume of solid waste and sludge, but there is still the problem of heavy metal contamination, which limits the application of pyrolysis in environmental management. The intercalated-exfoliated modified vermiculite (IEMV) by intercalators of sodium dodecylbenzene sulfonate, hexadecyltrimethylammonium bromide and octadecyltrimethylammonium bromide were used to control the release of Cd, Cr, Cu, Zn and Pb during pyrolysis process of sludge or solid waste. The retention of heavy metals in sludge was generally better than that in solid waste. The IEMV by octadecyltrimethylammonium bromide as the intercalator calcined 800 °C (STAB-800) was the best additive for heavy metal retention, and the retention of Cr, Cu and Zn was significantly better than that of Pb and Cd. Cr, Cu, Zn and Pb were at low risk, while Cd had considerable risk under certain circumstances. New models were proposed to comprehensively evaluate the results of the risk and forms of heavy metals, and the increasing temperature was beneficial in reducing the hazards of heavy metals by the addition of STAB-800. The reaction mechanism of heavy metals with vermiculite was revealed by simulation of reaction sites, Fukui Function and Frontier Molecular Orbital. Thermal activation-intercalated-exfoliated modified vermiculite (T-IEMV) is more reactive and had more active sites for heavy metals. Mg atoms and outermost O atoms are the main atoms for T-IEMV to react with heavy metals. The Cr, Cu and Zn have better adsorption capacity by T-IEMV than Pb and Cd. This study provides a new insight into managing solid waste and sludge and controlling heavy metal environmental pollution.

Intensity coupling characteristics of dual-longitudinal mode ring lasers with Ne dual-isotope.

The intensity coupling characteristics of Ne dual-isotope inflation and dual-longitudinal-mode operation ring lasers were investigated based on the Lamb theory. Considering the contribution of the Ne isotope system to the polarization of the gain medium and gain saturation effects, the frequency coupling effects were analyzed. Combined with the plasma dispersion function, the optical cavity length is 0.47 m, Ne20: Ne22= 0.53:0.47; the frequency spacing of the adjacent longitudinal mode is 640 MHz, and the intensity tuning curve of the ring laser is simulated. The alterations in the gain self-saturation and mutual saturation coefficients between the four frequencies generated via dual-longitudinal mode splitting are comprehensively discussed. Finally, a detection experiment for the intensity-tuning curve is designed to verify the theoretical analysis.

The m6A Reader YTHDF1 Improves Sevoflurane-Induced Neuronal Pyroptosis and Cognitive Dysfunction Through Augmenting CREB-BDNF Signaling.

Sevoflurane is one of the most widely used anesthetics in surgery which is the main cause of postoperative cognitive dysfunction (POCD). Previous reports confirmed that YTHDF1 is differently expressed in sevoflurane-induced POCD, while the roles and mechanistic details remain unclear. The molecular expressions were assessed using qRT-PCR, western blot, immunofluorescence and immunohistochemistry. Pathological change in the hippocampus tissues was analyzed using HE staining. Cognitive ability in rats was measured using MWM test. Hippocampal neuronal viability and apoptosis were measured by MTT assay and flow cytometry, respectively. The levels of pro-inflammatory cytokines were assessed using ELISA. The interaction between YTHDF1 and CREB was analyzed by RNA immunoprecipitation assay. YTHDF1 was significantly decreased in hippocampus tissues by sevoflurane exposure, and its overexpression could improve sevoflurane-induced neuron damage and cognitive dysfunction. Meanwhile, YTHDF1 upregulation repressed sevoflurane-induced activation of NLRP3 inflammation and pyroptosis in hippocampus tissues. Subsequently, YTHDF1 directly interacted to CREB mRNA to augment its stability and translation via a m6A-dependent manner, thus activating CREB/BDNF pathway. In addition, the inactivation of CREB/BDNF pathway could reverse the protective effects of YTHDF1 overexpression on sevoflurane-mediated neuronal damage and pyroptosis. These findings revealed that YTHDF1 improved sevoflurane-induced neuronal pyroptosis and cognitive dysfunction through activating CREB-BDNF signaling.

High Mechanical Strength and Multifunctional Microphase-Separated Supramolecular Hydrogels Fabricated by Liquid-Crystalline Block Copolymer.

The development of multifunctional supramolecular hydrogels with high mechanical strength and multifunction is in high demand. In this work, the diblock copolymer poly(acrylamide-co-1-benzyl-3-vinylimidazolium bromide)-block-polyAzobenzene is synthesized through reversible addition-fragmentation chain transfer polymerization. The dynamic host-guest interactions between the host molecule cucurbit[8] uril and guest units are used to fabricate a 3D network of supramolecular hydrogels. Investigations on the properties of the supramolecular hydrogels show that the tensile stress of the sample is 1.46 MPa, eight times higher than that of hydrogel without liquid-crystalline block copolymer, and the self-healing efficiency of the supramolecular hydrogels at room temperature is 88.3% (fracture stress) and 100% (fracture strain) after 24 h. Results show that microphase-separated structure plays a key role in the high-strength hydrogel, whereas the host-guest interaction endows the hydrogel with self-healing properties. The supramolecular hydrogels with high mechanical strength, photo-responsivity, injectability, and biocompatibility can be used in various potential applications.

Coffee consumption and abdominal aortic calcification among adults with and without hypertension, diabetes, and cardiovascular diseases.

BACKGROUND AND AIMS: This study was performed to investigate the effect of coffee consumption on abdominal aortic calcification (AAC) among adults with and without hypertension, diabetes, and cardiovascular diseases (CVD). METHODS AND RESULTS: A total of 2548 participants from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Coffee consumption was obtained from 24-h dietary recalls. Dual-energy X-ray absorptiometry (DXA) was used to measure the severity of AAC. In the fully adjusted model, compared with non-drinkers, high coffee consumption (≥390 g/d) was associated with higher AAC scores among participants with hypertension (ß = 0.72, 95% CI: 0.21-1.22), diabetes (ß = 1.20, 95% CI: 0.35-2.05), and CVD (ß = 2.03, 95% CI: 0.71-3.36). We did not observe such an association among participants without hypertension, diabetes, and CVD. Furthermore, decaffeinated coffee was not associated with AAC. CONCLUSION: In conclusion, patients with hypertension, diabetes, and CVD should focus on coffee consumption, especially caffeinated coffee, to reduce the burden of AAC.

Disparities and determinants of maternal health services utilization among women in poverty-stricken rural areas of China: a cross-sectional study.

BACKGROUND: Reducing maternal mortality ratio (MMR) has been a worldwide public health challenge for a long time. Utilization of maternal health services including antenatal care (ANC), institutional delivery (ID), and postnatal care (PNC) is vital to prevent maternal mortality. China has made significant improvements in maternal health during the past 30 years, however, disparities in maternal health service utilization still exist among regions and the western rural areas had the lowest utilization rate. This study aims to assess the inequality and determinants of maternal health service utilization in western poverty-stricken rural areas based on Anderson's Behavioral Model of Health Service Use and provide evidence-based suggestions to improve equity and coverage of maternal service utilization in China. METHODS: A cross-sectional study was conducted in Gansu and Yunnan Province, Western China using primary data (n = 996) collected by the research team. A multistage, judgment, quota sampling procedure was employed to select the participants of the survey. Trained local health staff formed an interview team to help respondents answer a structured, pre-tested questionnaire designed based on Anderson's model. Data collected through interviews were used for descriptive analysis, range analysis, and univariate and multivariate binary logistic analysis to identify influencing factors of 5 + ANC, 8 + ANC, ID, and 2 + PNC utilization. RESULTS: Place of residence, age, education level, annual income, and health education during ANC were influencing factors of 5 + ANC; place of residence, education level, per capita household income, conditional cash transfer (CCT) participation, and distance to health facilities were influencing factors of 8 + ANC; place of residence, education level, and availability of financial incentive programs were influencing factors of ID; number of children, health education during ANC, CCT projects participation, and self-rated health status were influencing factors of 2 + PNC. CONCLUSIONS: Inequalities in maternal service utilization exist between Yunnan and Gansu provinces. This study shows a strong association between both predisposing and enabling factors and maternal services utilization. Predisposing factors such as place of residence, education level, and number of children, enabling factors such as CCT participation, annual income, health education during ANC, and distance to health facilities along with need factor self-rated health status all contribute to maternal services utilization. We conclude that many factors influence maternal service utilization and interventions targeted at various levels should be considered. Therefore, we suggest more health resources should be invested in underutilized areas, financial incentive projects targeting pregnant women should be implemented, and health education should be provided to improve women's health literacy.

Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA-pyroptosis pathway in cancer.

In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive "cold" tumor types into immuno-responsive "hot" ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, followed by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of oxidized mitochondrial DNA (OX-mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with phospholipids in the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety.

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 µg/mL) and 16d (MIC=0.5 µg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.

Prognostic prediction of idiopathic membranous nephropathy using interpretable machine learning.

BACKGROUND: Established prognostic models of idiopathic membranous nephropathy (IMN) were limited to traditional modeling methods and did not comprehensively consider clinical and pathological patient data. Based on the electronic medical record (EMR) system, machine learning (ML) was used to construct a risk prediction model for the prognosis of IMN. METHODS: Data from 418 patients with IMN were diagnosed by renal biopsy at the Fifth Clinical Medical College of Shanxi Medical University. Fifty-nine medical features of the patients could be obtained from EMR, and prediction models were established based on five ML algorithms. The area under the curve, recall rate, accuracy, and F1 were used to evaluate and compare the performances of the models. Shapley additive explanation (SHAP) was used to explain the results of the best-performing model. RESULTS: One hundred and seventeen patients (28.0%) with IMN experienced adverse events, 28 of them had compound outcomes (ESRD or double serum creatinine (SCr)), and 89 had relapsed. The gradient boosting machine (LightGBM) model had the best performance, with the highest AUC (0.892 ± 0.052, 95% CI 0.840-0.945), accuracy (0.909 ± 0.016), recall (0.741 ± 0.092), precision (0.906 ± 0.027), and F1 (0.905 ± 0.020). Recursive feature elimination with random forest and SHAP plots based on LightGBM showed that anti-phospholipase A2 receptor (anti-PLA2R), immunohistochemical immunoglobulin G4 (IHC IgG4), D-dimer (D-DIMER), triglyceride (TG), serum albumin (ALB), aspartate transaminase (AST), ß2-microglobulin (BMG), SCr, and fasting plasma glucose (FPG) were important risk factors for the prognosis of IMN. Increased risk of adverse events in IMN patients was correlated with high anti-PLA2R and low IHC IgG4. CONCLUSIONS: This study established a risk prediction model for the prognosis of IMN using ML based on clinical and pathological patient data. The LightGBM model may become a tool for personalized management of IMN patients.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.