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Limited knowledge currently exists regarding the shared genetic architecture influencing human cognitive ability-related traits. We utilized Genomic Structural Equation Modeling (Genomic-SEM) along with multiple post-GWAS methods to estimate potentially causal single nucleotide polymorphisms (SNPs) associated with cognitive ability phenotypic variation. Our study identified 3,842 genome-wide significant loci, including 275 novel loci. Applying multiple transcriptome-wide association methods, we analyzed susceptibility gene signal loci highly correlated with cognitive ability GWAS from tissue, cellular, and genomic element perspectives, identifying 13 high-confidence candidate causal genes and related functional element information. Subsequently, we systematically evaluated 80–90% of currently known human common disease data in the IEU database, along with 3,935 brain imaging-derived phenotypes from UK Biobank and cortical morphological features from 51,665 individuals in the ENIGMA database to determine cognitive ability-related susceptibility factors. We applied the BrainXcan pipeline for brain imaging genetic analysis of cognitive abilities. Additionally, we used summary data-based polygenic scoring methods to systematically analyze the genetic contribution of different chromosomes to cognitive abilities and their risk prediction value. Our study, through multivariate GWAS analysis of cognitive ability common genetic factors, contributes to mapping the shared genetic architecture of human cognitive abilities.

3D cell culture models replicating the complexity of cell–cell interactions and biomimetic extracellular matrix (ECM) are novel approaches for studying liver cancer, including in vitro drug screening or disease mechanism investigation. Although there have been advancements in the production of 3D liver cancer models to serve as drug screening platforms, recreating the structural architecture and tumor-scale microenvironment of native liver tumors remains a challenge. Here, using the dot extrusion printing (DEP) technology reported in our previous work, we fabricated an endothelialized liver lobule-like construct by printing hepatocyte-laden methacryloyl gelatin (GelMA) hydrogel microbeads and HUVEC-laden gelatin microbeads. DEP technology enables hydrogel microbeads to be produced with precise positioning and adjustable scale, facilitating the construction of liver lobule-like structures. The vascular network was achieved by sacrificing the gelatin microbeads at 37 °C to allow HUVEC proliferation on the surface of the hepatocyte layer. Finally, we used the endothelialized liver lobule-like constructs for anti-cancer drug (Sorafenib) screening, and stronger drug resistance results were obtained when compared to either mono-cultured constructs or hepatocyte spheroids alone. The 3D liver cancer models presented here successfully recreate liver lobule-like morphology, and may have the potential to serve as a liver tumor-scale drug screening platform.

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to late diagnosis, high malignancy, and profound resistance to therapy. Traditional two-dimensional (2D) cell cultures fail to recapitulate the complex tumor microenvironment (TME), especially the fibrotic stroma, which is crucial for the progression of PDAC and drug response. In vitro three-dimensional (3D) models, which provide more physiologically relevant features such as tight cell–cell and cell-extracellular matrix (ECM) interactions, as well as 3D architecture, have been regarded as highly promising models in PDAC research. This review summarizes some representative in vitro PDAC models, including 3D spheroids, tumor-on-a-chip, bioprinted constructs, and patient-derived organoids (PDOs), particularly focused on the advances in bioengineering strategies for the integration of the key stomal components for microenvironment recapitulation and their applications. Additionally, we discuss the current challenges facing 3D models and propose potential strategies for constructing in vitro models that more accurately simulate the pathophysiology of the fibrotic stroma, aiming for their application in clinical settings.

Aim. To assess the efficacy of berberine in the treatment of nonalcoholic fatty liver disease through meta-analysis. Method. We searched Embase, Pubmed, Cochrane Library, and so forth, until March 2016 for randomized controlled trials using berberine to treat NAFLD. Result. Six randomized controlled trials involving 501 patients were included in this study. The results showed that the efficacy of reducing TC, LDL, ALT, 2hPG, and HbA1c in NAFLD patients of the berberine group were significantly higher than that of control group. The subgroup analyses on TG, AST, and FBG indicated that treatment combined with berberine decreased TG level in NAFLD patients significantly. Compared with other drugs, berberine alone decreased TG level in NAFLD patients significantly. We also conducted a descriptive analysis on insulin resistance and radiography results that berberine can improve NAFLD patients’ insulin resistance and fatty liver. Conclusion. According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, liver function, insulin resistance, and fatty liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.

The aim of the current study was to explore the association between urinary glycosaminoglycans and the onset of acute respiratory distress syndrome (ARDS) in sepsis patients. We conducted a prospective cohort study of 49 sepsis patients and collected clinical characteristics, urine, and blood samples within 24 h of admission to the Surgical Intensive Care Unit (SICU) of Peking University Third Hospital. Samples from patients who did not develop ARDS were collected from day 1 to day 7 after SICU admission, while samples from patients who developed ARDS were collected from day 1 to the day of onset, forming time-series data. A liquid chromatography-mass spectrometry (LC-MS) system was used to determine urinary dermatan sulfate (DS), chondroitin sulfate (CS), and heparan sulfate (HS) concentrations; enzyme-linked immunosorbent assay (ELISA) and cytometric bead array (CBA) were used to measure plasma inflammatory factors. The endpoint was the onset of ARDS. We used generalized estimating equations to identify associations between urinary glycosaminoglycans and ARDS onset in sepsis patients. Twenty-two of the 49 sepsis patients developed ARDS, and 132 plasma samples and 132 urine samples were obtained. Between the ARDS and non-ARDS groups, sex, pneumonia, Acute Physiology and Chronic Health Evaluation II (APACHE II), Lung Injury Prediction Score (LIPS), and PaO 2 /FiO 2 showed statistically significant differences. Generalized estimating equations showed that DS and tumor necrosis factor-α (TNF-α) were independently associated with ARDS onset in sepsis patients, but their generalizability across ARDS subtypes warrants further validation.

Controversial results of the association between coffee consumption and bladder cancer (BC) risk were reported among epidemiological studies. Therefore, we conducted this meta-analysis to clarify the association. Relevant studies were identified according to the inclusion criteria. Totally, 34 case-control studies and 6 cohort studies were included in our meta-analysis. The overall odds ratio (OR) with 95% confidence interval (CI) between coffee consumption and BC risk was 1.33 (95% CI 1.19 to 1.48). The summary ORs of BC for an increase of 1 cup of coffee per day were 1.05 (95% CI 1.03 to 1.06) for case-control studies and 1.03 (95% CI 0.99 to 1.06) for cohort studies. The overall ORs for male coffee drinkers, female coffee drinkers and coffee drinkers of both gender were 1.31 (95% CI: 1.08 to 1.59), 1.30 (95% CI: 0.87 to 1.96) and 1.35 (95% CI: 1.20 to 1.51). Compared with smokers (OR = 1.24, 95% CI: 0.91 to 1.70), non-smokers had a higher risk (OR = 1.72, 95% CI: 1.25 to 2.35) for BC. Results of this meta-analysis suggested that there was an increased risk between coffee consumption and BC. Male coffee drinkers and non-smoking coffee drinkers were more likely to develop BC.

Mango fruit is prone to decay after harvest and premature senescence, which significantly lowers its quality and commercial value.BackgroundMango fruit is prone to decay after harvest and premature senescence, which significantly lowers its quality and commercial value.The mango fruit (Mangifera indica L.cv. Guixiang) was treated with 0 (control), 2, 5, and 8 mM of reduced glutathione (GSH) after harvest. The fruit was stored at 25 ± 1 °C for 12 days to observe the changes in the antioxidant capacity and postharvest quality.MethodsThe mango fruit (Mangifera indica L.cv. Guixiang) was treated with 0 (control), 2, 5, and 8 mM of reduced glutathione (GSH) after harvest. The fruit was stored at 25 ± 1 °C for 12 days to observe the changes in the antioxidant capacity and postharvest quality.Compared with the control, the 5 mM GSH treatment significantly decreased the weight loss by 44.0% and 24.4%, total soluble solids content by 25.1% and 4.5%, and soluble sugar content by 19.0% and 27.0%. Conversely, the 5 mM GSH treatment increased the firmness by 25.9% and 30.7% on days 4 and 8, respectively, and the titratable acidity content by 115.1% on day 8. Additionally, the 5 mM GSH treatment decreased the malondialdehyde and hydrogen peroxide contents and improved the antioxidant capacity of mango fruit by increasing the superoxide dismutase and peroxidase activities and upregulating the expression of the encoding genes. Meanwhile, the higher levels of monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase enzyme activities and gene expressions accelerated the AsA-GSH cycle, thereby increasing the accumulation of AsA and GSH and maintaining the redox balance.ResultsCompared with the control, the 5 mM GSH treatment significantly decreased the weight loss by 44.0% and 24.4%, total soluble solids content by 25.1% and 4.5%, and soluble sugar content by 19.0% and 27.0%. Conversely, the 5 mM GSH treatment increased the firmness by 25.9% and 30.7% on days 4 and 8, respectively, and the titratable acidity content by 115.1% on day 8. Additionally, the 5 mM GSH treatment decreased the malondialdehyde and hydrogen peroxide contents and improved the antioxidant capacity of mango fruit by increasing the superoxide dismutase and peroxidase activities and upregulating the expression of the encoding genes. Meanwhile, the higher levels of monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase enzyme activities and gene expressions accelerated the AsA-GSH cycle, thereby increasing the accumulation of AsA and GSH and maintaining the redox balance.Overall, the experimental results suggest that 5 mM GSH maintains high antioxidant capacity and postharvest quality of mangoes and can use as an effective preservation technique for postharvest mangoes.ConclusionsOverall, the experimental results suggest that 5 mM GSH maintains high antioxidant capacity and postharvest quality of mangoes and can use as an effective preservation technique for postharvest mangoes.

In this study, a high sensitive and selective hydrogen peroxide (H2O2) sensor was successfully constructed with Pt-Au bimetallic nanoparticles (Pt-Au NPs)/reduced graphene sheets (rGSs) hybrid films. Various molar ratios of Au to Pt and different electrodeposition conditions were evaluated to control the morphology and electrocatalytic activity of the Pt-Au bimetallic nanoparticles. Upon optimal conditions, wide linear ranges from 1 µM to 1.78 mM and 1.78 mM to 16.8 mM were obtained, with a detection limit as low as 0.31 µM. Besides, due to the synergetic effects of the bimetallic NPs and rGSs, the amperometric H2O2 sensor could operate at a low potential of 0 V. Under this potential, not only common anodic interferences induced from ascorbic acid, uric acid and dopamine, but also the cathodic interference induced from endogenous O2 could be effectively avoided. Furthermore, with rat pheochromocytoma cells (PC 12) as model, the proposed sensor had been successfully used in the detection of H2O2 released from the cancer cells. This method with wide linear ranges and excellent selectivity can provide a promising alternative for H2O2 monitoring in vivo in the fields of physiology, pathology and diagnosis.

Improving production efficiency can help overcome the constraints of resource scarcity and fragile environments in oasis agriculture. However, there are few studies about the effect of farmers’ cognition of resources and the environment on their production efficiency. Taking farmers in the Ganzhou District of Zhangye—a typical representative of oasis agriculture in an inland river basin in Northwest China—this study empirically analyzed the effect of farmers’ cognition of resources and the environment on agricultural production efficiency. The average agricultural productivity of the surveyed farmers is 0.64, which is much lower than the average level in China. Farmers’ cognition of resources and the environment is related to green production willingness and behavior. Green production willingness, green production behavior between cognition of resources and the environment, and agricultural production efficiency play a chain mediating role, showing that farmers’ cognition of resources and the environment indirectly affects production efficiency. Green planting willingness is formed based on cognition of resources and the environment; when farmers translate willingness into behavior, it will further improve agricultural production efficiency. Recommendations are made based on the findings, such as strengthening the cognition of resources and the environment, mobilizing enthusiasm for green production, and promoting the practice of green planting.

Malic enzyme 2 (ME2), a pivotal enzyme related to the tricarboxylic acid (TCA) cycle, has been implicated in multiple cancers due to its overexpression and metabolic role in regulating the NADP + /NADPH balance. Malic enzyme 2 has been reported to regulate mitochondrial biogenesis and fusion; however, whether malic enzyme 2 participates in mitophagy regulation has remained unclear. Here, we reported that malic enzyme 2 depletion enhances PINK1-Parkin-mediated mitophagy. Mechanistically, ME2 competes with the E3 ubiquitin ligase TRIM25, disrupting its binding with ATPase family AAA domain-containing protein 3 A (ATAD3A), a mitochondrial protein crucial for the degradation of PINK1. Loss of malic enzyme 2 strengthens the TRIM25-ATAD3A interaction, resulting in ATAD3A ubiquitination and proteasomal degradation. The consequent PINK1 accumulation drives mitophagy activation. Hyperactivated mitophagy caused by malic enzyme 2 knockdown disrupts mitochondrial homeostasis, which suppresses the proliferative capacity of hepatoma cells. Moreover, pharmacological inhibition of mitophagy partially rescued the suppressed cell proliferation in the malic enzyme 2-knockdown cells. Our findings reveal a previously unrecognized role of malic enzyme 2 in mitochondrial quality control and highlight the ME2-ATAD3A-PINK1 axis as a potential regulatory node for mitophagy modulation.