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Abstract Background Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that is partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk of malaria infection, and copper accumulation-induced cuproptosis triggers M1 macrophage polarization. It is thus hypothesized that cuproptosis could act as a critical mediator in the pathogenesis of MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore the role of cuproptosis in the severity of murine MA-ALI/ARDS. Methods We utilized an experimental model of MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA infection, and treated these animals with the potent copper ion carrier disulfiram (DSF) or copper ion chelator tetrathiomolybdate (TTM). The RAW 264.7 macrophages, which were stimulated with infected red blood cells (iRBCs) in vitro, were also targeted with DSF-CuCl2 or TTM-CuCl2 to further investigate the underlying mechanism. Results Our findings showed a dramatic elevation in the amount of copper and the expression of SLC31A1 (a copper influx transporter) and FDX1 (a key positive regulator of cuproptosis) but displayed a notable reduction in the expression of ATP7A (a copper efflux transporter) in the lung tissue of experimental MA-ALI/ARDS mice. Compared to the P. berghei ANKA-infected control group, mice that were administered DSF exhibited a remarkable increase in parasitemia/lung parasite burden, total protein concentrations in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, vascular leakage, and pathological changes in lung tissue. Strikingly, the experimental MA-ALI/ARDS mice with DSF treatment also demonstrated dramatically elevated copper levels, expression of SLC31A1 and FDX1, numbers of CD86+, CD68+, SLC31A1+-CD68+, and FDX1+-CD68+ macrophages, and messenger RNA (mRNA) levels of pro-inflammatory cytokines (tumor necrosis factor [TNF-α] and inducible nitric oxide synthase [iNOS]) in lung tissue, but showed a remarkable decrease in body weight, survival time, expression of ATP7A, number of CD206+ macrophages, and mRNA levels of anti-inflammatory cytokines (transforming growth factor beta [TGF-β] and interleukin 10 [IL-10]). In contrast, TTM treatment reversed these changes in the infected mice. Similarly, the in vitro experiment showed a notable elevation in the mRNA levels of SLC31A1, FDX1, CD86, TNF-α, and iNOS in iRBC-stimulated RAW 264.7 cells targeted with DSF-CuCl2, but triggered a remarkable decline in the mRNA levels of ATP7A, CD206, TGF-β, and IL-10. In contrast, TTM-CuCl2 treatment also reversed these trends in the iRBC-stimulated RAW 264.7 cells. Conclusions Our data demonstrate that the activation of cuproptosis with DSF aggravated the severity of MA-ALI/ARDS by partially inducing M1 polarization of pulmonary macrophages, while inhibition of cuproptosis with TTM contrarily ameliorated the severity of MA-ALI/ARDS by promoting macrophage M2 polarization. Our findings suggest that blockage of cuproptosis could be a potential therapeutic strategy for treatment of MA-ALI/ARDS. Graphical Abstract

Abstract Background An increasing number of orphan medicinal products (OMPs) are being included in social health insurance schemes, significantly improving access to medicines for patients with rare diseases. However, high-priced OMPs are still not covered, primarily due to health equity controversies and inadequate data systems required for economic evaluation. The aim of this study was to estimate the burden of drug expenditures and the size of the reimbursement budget required for high-priced OMPs from the perspectives of society and healthcare payers. Methods The study performed a budget impact analysis using data from multiple sources to estimate the reimbursement budget for high-priced OMPs in Chengdu, a densely populated metropolis in China. The budget analysis consisted of three main elements: the number of patients, the price of drugs, and the simulated policy scenario. By adjusting the combinations of these elements, the budget fluctuations for payers were estimated. Furthermore, the study predicted the budget trend for the next three years to validate its sustainability. Results The analysis indicated that 98 rare disease patients in Chengdu required high-priced OMPs in 2019. This suggested a projected budget of CNY 179 million for these patients without reimbursement policies, from a societal perspective. Under six assumed policy scenarios, this budget ranged from CNY 32 million to CNY 156 million. Over the next three years, the annual budget was estimated to range from CNY 200 million to CNY 1.303 billion. Conclusion Integration of multi-source data helps to obtain more scientifically reliable results on budget impacts. The study found that the budgetary impacts of high-priced OMPs on society and payers are relatively limited. Health policymakers can choose appropriate reimbursement strategies based on financial affordability among a diverse mix of elements. The results of related studies provided insights for optimizing the allocation of health resources and improving patient access to medications.

The catalyst layers (CLs) electrode is the key component of the membrane electrode assembly (MEA) in proton exchange membrane fuel cells (PEMFCs). Conventional electrodes for PEMFCs are composed of carbon-supported, ionomer, and Pt nanoparticles, all immersed together and sprayed with a micron-level thickness of CLs. They have a performance trade-off where increasing the Pt loading leads to higher performance of abundant triple-phase boundary areas but increases the electrode cost. Major challenges must be overcome before realizing its wide commercialization. Literature research revealed that it is impossible to achieve performance and durability targets with only high-performance catalysts, so the controllable design of CLs architecture in MEAs for PEMFCs must now be the top priority to meet industry goals. From this perspective, a 3D ordered electrode circumvents this issue with a support-free architecture and ultrathin thickness while reducing noble metal Pt loadings. Herein, we discuss the motivation in-depth and summarize the necessary CLs structural features for designing ultralow Pt loading electrodes. Critical issues that remain in progress for 3D ordered CLs must be studied and characterized. Furthermore, approaches for 3D ordered CLs architecture electrode development, involving material design, structure optimization, preparation technology, and characterization techniques, are summarized and are expected to be next-generation CLs for PEMFCs. Finally, the review concludes with perspectives on possible research directions of CL architecture to address the significant challenges in the future.

Highlights The types, working principles, advantages and limitations of pattern recognition methods based on chemiresistive gas sensor array are reviewed and discussed comprehensively. Outstanding and novel advancements in the application of machine learning methods for gas recognition in different important areas are compared, summarized and evaluated. The current challenges and future prospects of machine learning methods in artificial olfactory systems are discussed and justified.

Air traffic scenario evaluation can support the optimisation of traffic flow and airspace configuration to improve the safety of air traffic control. Since the air traffic scenario is influenced by the interaction of multiple factors, and real labelled data are lacking, the feature index selection and scenario evaluation are challenging endeavours. In this study, indicators were selected from three dimensions: airspace structure, traffic characteristics and meteorological conditions. The evaluation indicators were quantitatively screened according to information importance and overlap. Utilising the flow control and traffic flow information, the authors defined the free and saturated states of the state interval and developed a metric-based learning method to calibrate the state samples. A multilayer perceptron regression model was employed to establish the mapping relationship between the feature indicators and air traffic scenario. The evaluation accuracy of the sample set from three sectors in Shanghai exceeded 80%, which verified the effectiveness of the scenario evaluation model. This contribution holds practical significance in enhancing the safety of airspace operations.

Abstract Background Systemic inflammation and frailty have been implicated in osteoporosis (OP) and fracture risks; however, existing evidence remains limited and inconclusive. This study aimed to assess the associations of systemic inflammation and frailty phenotype with incident OP and fracture and to evaluate the mediating role of frailty phenotype. Methods The present study analysed data from the UK Biobank, a comprehensive and representative dataset encompassing over 500 000 individuals from the general population. Baseline peripheral blood cell counts were employed to calculate the systemic inflammation markers, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and systemic immune‐inflammation index (SII). Frailty phenotype was assessed using five criteria, defined as frail (≥3 items met), pre‐frail (1–2 items met) and non‐frail (0 items met). OP and fracture events were confirmed through participants' health‐related records. Multivariable linear and Cox regression models were utilized, along with mediation analysis. Results Increased systemic inflammation was associated with increased risks of OP and fracture. The corresponding hazard ratios and 95% confidence intervals (CIs) for OP risk per standard deviation increase in the log‐transformed NLR, PLR and SII were 1.113 (1.093–1.132), 1.098 (1.079–1.118) and 1.092 (1.073–1.111), and for fracture risk, they were 1.066 (1.051–1.082), 1.059 (1.044–1.075) and 1.073 (1.058–1.089), respectively. Compared with the non‐frail individuals, the pre‐frail and frail ones showed an elevated OP risk by 21.2% (95% CI: 16.5–26.2%) and 111.0% (95% CI: 98.1–124.8%), respectively, and an elevated fracture risk by 6.1% (95% CI: 2.8–9.5%) and 38.2% (95% CI: 30.7–46.2%), respectively. The systemic inflammation level demonstrated a positive association with frailty, with β (95% CI) of 0.034 (0.031–0.037), 0.026 (0.023–0.029) and 0.008 (0.005–0.011) in response to per standard deviation increment in log‐transformed SII, NLR and PLR, respectively. The frailty phenotype mediated the association between systemic inflammation and OP/fracture risk. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusions Systemic inflammation and frailty phenotype are independently linked to increased risks of OP and fracture. The frailty phenotype partially mediates the association between systemic inflammation and osteoporotic traits. These results highlight the significance of interventions targeting systemic inflammation and frailty in OP and fracture prevention and management.

ABSTRACT Aim To develop and test different machine learning algorithms for predicting nocturnal hypoglycaemia in patients with type 2 diabetes mellitus. Design A retrospective study. Methods We collected data from dynamic blood glucose monitoring of patients with T2DM admitted to the Department of Endocrinology and Metabolism at a hospital in Shanghai, China, from November 2020 to January 2022. Patients undergone the continuous glucose monitoring (CGM) for ≥ 24 h were included in this study. Logistic regression, random forest and light gradient boosting machine algorithms were employed, and the models were validated and compared using AUC, accuracy, specificity, recall rate, precision, F1 score and the Kolmogorov–Smirnov test. Results A total of 4015 continuous glucose‐monitoring data points from 440 patients were included, and 28 variables were selected to build the risk prediction model. The 440 patients had an average age of 62.7 years. Approximately 48.2% of the patients were female and 51.8% were male. Nocturnal hypoglycaemia appeared in 573 (14.30%) of 4015 continuous glucose monitoring data. The light gradient boosting machine model demonstrated the highest predictive performances: AUC (0.869), specificity (0.802), accuracy (0.801), precision (0.409), recall rate (0.797), F1 score (0.255) and Kolmogorov (0.603). The selected predictive factors included time below the target glucose range, duration of diabetes, insulin use before bed and dynamic blood glucose monitoring parameters from the previous day. Patient or Public Contribution No Patient or Public Contribution.

Sweet potato pulp water (SPPW) is a kind of sweet potato starch processing by-product with rich nutrition but low utilization. The impacts of different proportions of Coriolus versicolor (C. versicolor, CV) fermented sweet potato pulp water (CV-SPPW) on the physicochemical, structural and metabolic properties of yogurt were investigated. Compared with 0% group, the hardness index, elasticity index and cohesion of the 10% sample group increased by 1.9-fold, 55.7% and 1.39-fold, respectively. When CV-SPPW was added at an amount of 10%, the microstructure and sensory scores of yogurts were considered as the optimal. Metabolic pathway analysis indicated that the changes of yogurts were mainly involved in sugar metabolism and amino acid metabolism, and that the carbohydrate metabolites produced mainly included cellobiose, maltitol, d-trehalose and d-maltose. The CV-SPPW improved the structural characteristics of yogurts to varying degrees and the fermented yogurts exhibited better viscosity properties.

Abstract The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Abstract Patients with decreased levels of CD18 (β2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMβ2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the β-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the “outside-in signaling” for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1β release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance.

Abstract Alzheimer’s disease (AD) has a complex pathogenesis, and multiple studies have indicated that histone post-translational modifications, especially acetylation, play a significant role in it. With the development of mass spectrometry and proteomics, an increasing number of novel HPTMs, including lactoylation, crotonylation, β-hydroxybutyrylation, 2-hydroxyisobutyrylation, succinylation, and malonylation, have been identified. These novel HPTMs closely link substance metabolism to gene regulation, and an increasing number of relevant studies on the relationship between novel HPTMs and AD have become available. This review summarizes the current advances and implications of novel HPTMs in AD, providing insight into the deeper pathogenesis of AD and the development of novel drugs.

Insecticides play a crucial role in safeguarding crops from pest. However, prior to their release, it is essential to assess the efficacy and potential effects of these protectants. Flupyradifurone (FBF) and sulfoxaflor (SFX), two insecticides commonly used to control aphids, have been found to exert negative effects on the growth and development of Binodoxys communis Gahan, a beneficial parasitic wasp that targets aphids. However, it remains unknown if FBF and SFX influence the symbiotic bacteria residing within B. communis. In this study, 16SrRNA sequencing was utilized to assess the populations of B. communis symbionts exposed to sublethal concentrations (LC10 and LC25) of FBF and SFX. The control and treatment groups exhibited similar bacterial community structures, with Bacteroidota identified as the dominant phylum in each. After exposure to FBF and SFX, the diversity and richness of symbionts (Firmicutes, Bacteroidota, and Actinobacteriota) in B. communis changed notably. The two different insecticides and exposure durations exerted distinct effects on the microbial community. For instance, SFX stress resulted in a decrease in Akkermansia and an increase in Escherichia Shigella 1h after exposure, with both returning to baseline levels after 3d. In contrast, FBF exposure caused a reduction in Akkermansia presence after 1h, which persisted even after 3d. This study represents the first assessment of the effects of FBF and SFX exposure on symbiotic bacteria in B. communis, expanding our understanding of how insecticides influence natural enemies and their symbiotic bacterial relationships. This study provides theoretical guidance for field applications of FBF and SFX, as well as a reasonable basis for exploring chemical resistance conferred by symbiotic bacteria.

Nocardiosis in fish, caused by Nocardia seriolae (a kind of filamentous bacterium), is a severe disease in aquaculture, affecting over 40 species of marine and freshwater fish and causing great losses. To investigate the relationship between fish nocardiosis and the gut microbiota, we first artificially infected hybrid snakehead (female Channa maculata × male Channa argus) with N. seriolae (1.0 × 107 CFU/mL), then utilized techniques such as high-throughput sequencing of 16 S rRNA, histopathology, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to analyze the changes in microbial community structure, intestinal histopathological characteristics, and related immune genes expression in hybrid snakehead. Changes in gut microbial community structure and diversity were observed starting from day 2, followed by fluctuations on day 4, and significant alterations on day 6. Four major phyla (Actinomycetes, Proteobacteria, Firmicutes, and Bacteroidetes), particularly Actinomycetes, reflected the temporal variations in the gut microbiota structure. The composition of the gut microbiota also underwent significant changes, with beneficial microorganisms such as Lactobacillus decreasing and harmful microorganisms such as Aeromonas and Nocardia increasing. The pathological sections showed that after N. seriolae injection, the fish intestinal villi became distorted and widely spaced, with increasing damage over time, leading to severe shrinkage and atrophy by the sixth day. Additionally, immune-related genes, such as TLR2 and IRF2, exhibited higher mRNA expression levels (P < 0.01) in the intestinal tissues of the infected fish. Overall, this study provides preliminary insights into the dynamic changes in gut microbial community, immune response, and intestinal pathogenic mechanisms during N. seriolae infection in hybrid snakehead, at both the levels of gut microbial composition and mRNA expression. These findings are important for better understanding and managing Nocardia infection in fish.

Cyclin-dependent kinase-like 3 (CDKL3) has been identified as an oncogene in certain types of tumors. Nonetheless, its function in hepatocellular carcinoma (HCC) is poorly understood. In this study, we conducted a comprehensive analysis of CDKL3 based on data from the HCC cohort of The Cancer Genome Atlas (TCGA). Our analysis included gene expression, diagnosis, prognosis, functional enrichment, tumor microenvironment and metabolic characteristics, tumor burden, mRNA expression-based stemness, alternative splicing, and prediction of therapy response. Additionally, we performed a cell counting kit-8 assay, TdT-mediated dUTP nick-end Labeling staining, migration assay, wound healing assay, colony formation assay, and nude mouse experiments to confirm the functional relevance of CDKL3 in HCC. Our findings showed that CDKL3 was significantly upregulated in HCC patients compared to controls. Various bioinformatic analyses suggested that CDKL3 could serve as a potential marker for HCC diagnosis and prognosis. Furthermore, CDKL3 was found to be involved in various mechanisms linked to the development of HCC, including copy number variation, tumor burden, genomic heterogeneity, cancer stemness, and alternative splicing of CDKL3. Notably, CDKL3 was also closely correlated with tumor immune cell infiltration and the expression of immune checkpoint markers. Additionally, CDKL3 was shown to independently function as a risk predictor for overall survival in HCC patients by multivariate Cox regression analysis. Furthermore, the knockdown of CDKL3 significantly inhibited cell proliferation in vitro and in vivo, indicating its role as an oncogene in HCC. Taken together, our findings suggest that CDKL3 shows promise as a biomarker for the detection and treatment outcome prediction of HCC patients.

Abstract Background Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI. Methods Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism. Results Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1β). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1β and 4-HNE in the iRBC-stimulated Raw264.7 cells. Conclusions Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI. Graphical Abstract

The rice planthopper, Sogatella furcifera, is a piercing-sucking insect pest of rice, Oryza sativa. It is responsible for significant crop yield losses, and has developed moderate to high resistance to several commonly used chemical insecticides. We investigated the effects of the insect fungal pathogen Isaria javanica, alone and in combination with the chemical insecticide dinotefuran, on S. furcifera under both laboratory and field conditions. Our results show that I. javanica displays high infection efficiency and mortality for different stages of S. furcifera, reducing adult survival, female oviposition and ovary development. Laboratory bioassays showed that the combined use of I. javanica with a low dose (4–16 mg L–1) of dinotefuran resulted in higher mortality in S. furcifera than the use of I. javanica or dinotefuran alone. The combined treatment also had more significant effects on several host enzymes, including superoxide dismutase, catalase, peroxidase, and prophenol oxidase activities. In field trials, I. javanica effectively suppressed populations of rice planthoppers to low levels (22–64% of the level in untreated plots). Additional field experiments showed synergistic effects, i.e., enhanced efficiency, for the control of S. furcifera populations using the combination of a low dose of I. javanica (1×104 conidia mL–1) and a low dose of dinotefuran (~4.8–19.2% of normal field use levels), with control effects of >90% and a population level under 50 insects per 100 hills at 3–14 days post-treatment. Our findings indicate that the entomogenous fungus I. javanica offers an attractive biological control addition as part of the integrated pest management (IPM) practices for the control of rice plant pests.

Abstract The coding privilege of end-spectral hues (red and blue) in the early visual cortex has been reported in primates. However, the origin of such bias remains unclear. Here, we provide a complete picture of the end-spectral bias in visual system by measuring fMRI signals and spiking activities in macaques. The correlated end-spectral biases between the LGN and V1 suggest a subcortical source for asymmetric coding. Along the ventral pathway from V1 to V4, red bias against green peaked in V1 and then declined, whereas blue bias against yellow showed an increasing trend. The feedforward and recurrent modifications of end-spectral bias were further revealed by dynamic causal modeling analysis. Moreover, we found that the strongest end-spectral bias in V1 was in layer 4C $$\beta$$ β . Our results suggest that end-spectral bias already exists in the LGN and is transmitted to V1 mainly through the parvocellular pathway, then embellished by cortical processing.

AbstractContext (-)-Epigallocatechin-3-gallate (EGCG) is involved in cell proliferation and ischemia/reperfusion (I/R) injury of several organs.Objective To identify the role of EGCG in intestinal epithelial proliferation and barrier exposed to I/R injury.Material and methods Fifty Sprague-Dawley rats were divided into sham, I/R, I/R + EGCG (12.5 mg/kg), I/R + EGCG (25 mg/kg) and I/R + EGCG (50 mg/kg). I/R group rats were subjected to intestinal ischemia for 1 h and 6 h reperfusion. The rats were supplemented with EGCG 12.5, 25 and 50 mg/kg daily for 3 days via intraperitoneal injection before surgery. We used IEC-6 to expose to hypoxia/reoxygenation (H/R) injury to mimic I/R in vivo. IEC-6 cells were divided into control, H/R and H/R + EGCG (40 μmol/L). The effects of EGCG and its mechanism was explored.Results Pharmacological treatment with EGCG notably improves intestinal epithelial proliferation (12.5 mg/kg, 1.74-fold; 25 mg/kg, 2.93-fold, and 50 mg/kg, 4.33-fold) and barrier function after I/R injury. EGCG promoted cell proliferation (2.99-fold) and increased the expression of occludin (2.36-fold) and ZO-1 (1.64-fold) in IEC-6 cells after H/R injury. EGCG promoted proliferation of IEC-6 cells with ED50 values of 18.16 μmol/L. Further investigations indicated that EGCG activated Nurr1 expression in intestine after I/R injury. EGCG promote cell proliferation and increased the expression of occludin and ZO-1 in IEC-6 cells after H/R injury were abrogated in the knockdown of Nurr1 by siRNA.Discussion and conclusion Our findings indicate that EGCG promotes intestinal epithelial cell proliferation and barrier function after I/R injury in vitro and in vivo via activation of Nurr1.

With the growing demand for new energy sources, electrochemical water splitting for hydrogen production is a technology that must be vigorously promoted. Therefore, to improve the efficiency of the oxygen evolution reaction (OER) at the anode, high-performance OER catalysts are essential. Given their advantages in electrocatalysis, nanoporous materials have garnered considerable attention in previous studies for OER applications. This review provides a comprehensive overview of various strategies to optimize active site utilization in nanoporous materials. These strategies include regulating pore size and porosity, constructing hierarchical nanoporous structures, and enhancing material conductivity. Additionally, it covers approaches to boost the intrinsic OER activity of nanoporous materials, such as tuning the composition of anions and cations, creating vacancies, constructing interfaces, and forming boundary active sites. While nanoporous materials offer significant potential for advancing OER, challenges remain, including difficulties in quantifying activity within nanopores, the unclear impact of nanoporous material morphology, challenges in accessing nanopore interiors with in situ techniques, and a lack of theoretical calculations on pore structure. However, these challenges also present opportunities, and we hope this review provides a fresh perspective to inspire future research.

Abstract Epidermal growth factor receptor‐targeted (EGFR‐targeted) therapies show promise for non‐small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild‐type NSCLC. A genome‐wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild‐type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild‐type NSCLC cells. Additionally, PAICS silencing led to cell‐cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild‐type NSCLC. PAICS silencing also caused DNA damage and cell‐cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K–AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild‐type NSCLC and represents a potential therapeutic target for this disease.

Continuous cropping obstacles seriously constrained the sustainable development of the ginseng industry. The allelopathic autotoxicity of ginsenosides is the key “trigger” of continuous cropping obstacles in ginseng. During harvest, the ginseng plants could be broken and remain in the soil. The decomposition of ginseng residue in soil is one of the important release ways of ginsenosides. Therefore, the allelopathic mechanism of ginsenosides through the decomposed release pathway needs an in-depth study. To investigate this allelopathic regulation mechanism, the integrated analysis of transcriptomics and metabolomics was applied. The prototype ginsenosides in ginseng were detected converse to rare ginsenosides during decomposition. The rare ginsenosides caused more serious damage to ginseng hairy root cells and inhibited the growth of ginseng hairy roots more significantly. By high-throughput RNA sequencing gene transcriptomics study, the significantly differential expressed genes (DEGs) were obtained under prototype and rare ginsenoside interventions. These DEGs were mainly enriched in the biosynthesis of secondary metabolites and metabolic pathways, phytohormone signal transduction, and protein processing in endoplasmic reticulum pathways. Based on the functional enrichment of DEGs, the targeted metabolomics analysis based on UPLC-MS/MS determination was applied to screen endogenous differential metabolized phytohormones (DMPs). The influence of prototype and rare ginsenosides on the accumulation of endogenous phytohormones was studied. These were mainly involved in the biosynthesis of diterpenoid, zeatin, and secondary metabolites, phytohormone signal transduction, and metabolic pathways. After integrating the transcriptomics and metabolomics analysis, ginsenosides could regulate the genes in phytohormone signaling pathways to influence the accumulation of JA, ABA, and SA. The conclusion was that the prototype ginsenosides were converted into rare ginsenosides by ginseng decomposition and released into the soil, which aggravated its allelopathic autotoxicity. The allelopathic mechanism was to intervene in the response regulation of genes related to the metabolic accumulation of endogenous phytohormones in ginseng. This result provides a reference for the in-depth study of continuous cropping obstacles of ginseng.

Abstract Background The association of dyslipidemia with embryo development and pregnancy outcomes is largely unknown, especially in unexplained recurrent implantation failure (uRIF) patients. Here, this study aimed to explore the impact of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) from a clinical perspective. Methods This study retrospectively analyzed 502 patients diagnosed as uRIF. They were divided into four groups according to the levels of cholesterol and triglyceride: nonhyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). At the same time, patients were divided into non-low HDL-C group and low HDL-C group according to their HDL-C level. The outcomes of embryos genetic testing and pregnancy outcomes after PGT-A was analyzed between groups. Binary logistic regression and/or generalized estimating equation (GEE) model were conducted to investigate the association of different types of dyslipidemia with embryonic aneuploidy rate and cumulative live-birth rate. Results 474 women who met the inclusion criteria were divided into four groups: NonH group (N = 349), SHC group (N = 55), SHT group (N = 52) and MixH group (N = 18). Compared with the NonH group, SHC group had a significantly increased rate of embryo aneuploidy [48.3% vs. 36.7%, P = 0.006; adjusted OR (95% confidence interval) = 1.52(1.04–2.22), P = 0.029], as well as a reduced number of good-quality embryos on day 5 or 6 [3.00 ± 2.29 vs. 3.74 ± 2.77, P = 0.033]. The SHC group showed a tendency of a lower cumulative live birth rate (47.0% vs. 40.0%), a lower incidence of good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%), but did not reach statistical significance (P > 0.05). The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Whether patients have low HDL-C did not differ in pregnancy outcomes. Conclusions We found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced proportion of high-quality embryos, while different types of hyperlipidemia had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.

Abstract Background Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully elucidated yet, and sepsis is an important cause of ALI. Among the organ injuries caused by sepsis, the lungs are the earliest damaged ones. Radix cyathulae is reported to have analgesic, anti-inflammatory, and anti-aging effects. Cyasterone is extracted from Radix cyathulae. However, it is not known whether cyasterone has protective effects for ALI. This study aims to investigate the effect of cyasterone on sepsis-related ALI and its mechanism. Methods We used the cecal ligation peferation (CLP) method to establish a mouse sepsis model, and cyasterone was given intraperitoneally on days 1–3 to observe its preventive effect on sepsis-related acute lung injury. Primary murine peritoneal macrophages were used to investigate the molecular mechanism of cyasterone in vitro. Results Cyasterone pretreatment inhibits pro-inflammatory cytokine production, NLRP3 inflammasome activation, and oxidative stress in vivo and in vitro. In addition, cyasterone attenuates sepsis-induced ALI by activating nuclear factor erythroid2-related factor (Nrf2), which may be associated with AKT(Ser473)/GSK3β(Ser9) pathway activation. Conclusions Cyasterone defends against sepsis-induced ALI by inhibiting inflammatory responses and oxidative stress, which depends heavily on the upregulation of the Nrf2 pathway through phosphorylation of AKT(Ser473)/GSK3β(Ser9). These results suggest cyasterone may be a valuable drug candidate for preventing sepsis-related ALI.

Abstract Bacillus coagulans have recently revealed its anticancer effects, but few investigations are available on their effects on liver cancer proliferation, and the precise mechanism to mark its impact on apoptosis-related signaling pathways has yet to be elucidated. The aim of this study was to evaluate the anti-proliferative effect of B. coagulans MZY531 and apoptosis induction in the mouse H22 hepatocellular carcinoma cell line. The anti-proliferative activity of B. coagulans MZY531 was evaluated by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis was revealed with Terminal Deoxynucleotidyl Transferase (TDT)-mediated dUTP Nick-End Labeling (TUNEL) staining and flow cytometric analysis. The expressions of apoptosis-related protein were determined by western blot analysis. The CCK-8 assay revealed that B. coagulans MZY531 inhibited the H22 cells proliferation in a concentration-dependent manner. TUNEL staining revealed an increased apoptosis rate in H22 cells following intervention with B. coagulans MZY531. Furthermore, flow cytometric analysis showed that B. coagulans MZY531 treatment (MOI = 50 and 100) significantly alleviated the H22 cells apoptosis compared with the control group. Western blot analysis found B. coagulans MZY531 significantly decreased level of phospho-PI3K (p-PI3K), phospho-AKT (p-AKT), and phospho-mTOR (p-mTOR) compared with the control group. Furthermore, H22 cells treatment with B. coagulans MZY531 enhanced the expression of caspase-3 and Bax and jeopardized the expression of Bcl-2. Taken together, apoptosis induction and cell proliferation inhibition via PI3K/AKT/mTOR and Bax/Bcl-2/Caspase-3 pathway are promising evidence to support B. coagulans MZY531 as a potential therapeutic agent for cancer.

This paper investigates a parameter-free H∞ differential game approach for nonlinear active vehicle suspensions. The study accounts for the geometric nonlinearity of the half-car active suspension and the cubic nonlinearity of the damping elements. The nonlinear H∞ control problem is reformulated as a zero-sum game between two players, leading to the establishment of the Hamilton–Jacobi–Isaacs (HJI) equation with a Nash equilibrium solution. To minimize reliance on model parameters during the solution process, an actor–critic framework employing neural networks is utilized to approximate the control policy and value function. An off-policy reinforcement learning method is implemented to iteratively solve the HJI equation. In this approach, the disturbance policy is derived directly from the value function, requiring only a limited amount of driving data to approximate the HJI equation’s solution. The primary innovation of this method lies in its capacity to effectively address system nonlinearities without the need for model parameters, making it particularly advantageous for practical engineering applications. Numerical simulations confirm the method’s effectiveness and applicable range. The off-policy reinforcement learning approach ensures the safety of the design process. For low-frequency road disturbances, the designed H∞ control policy enhances both ride comfort and stability.

To improve the forecast accuracy of heavy precipitation, re-forecasts are conducted for the Henan 21.7 rainstorm. The Intermediate Complexity Atmospheric Research Model (ICAR) and the Weather Research and Forecasting Model (WRF) with a 1 km horizontal grid spacing are used for the re-forecasts. The results indicate that heavy precipitation forecasted by ICAR primarily accumulates on the windward slopes of the mountains. In contrast, some severe precipitation forecasted by WRF is beyond the mountains. The main difference between ICAR and WRF is that ICAR excludes the “impacts of physical processes on winds and the nonlinear interactions between the small resolvable-scale disturbances” (briefed as the “physical–dynamical interactions”). Thus, heavy precipitation beyond the mountains is attributed to the “physical–dynamical interactions”. Furthermore, severe precipitation on the windward slopes of the mountains typically aligns with the observations, whereas heavy rainfall beyond the mountains seldom matches the observations. Therefore, severe precipitation on the windward slopes of (beyond) the mountains is more (less) predictable. Based on these findings and theoretical thinking about the predictability of severe precipitation, a scheme of using the ICAR’s prediction to adjust the WRF’s prediction is proposed, thereby improving the forecast accuracy of heavy rainfall.

Ecological sustainability quantifies the capacity of an ecological system to sustain its health while fulfilling human survival needs and supporting future development. An accurate projection of ecological dynamics for sustainability is crucial for decision-makers to comprehend potential risks. However, the intricate interplay between climate change and human activity has hindered comprehensive assessments of future ecological sustainability, leaving it inadequately investigated thus far. This study aimed to assess future ecological sustainability shaped by the Shared Socioeconomic Pathways (SSPs) using remote sensing data from a typical arid farming–pastoral zone located at the northern foot of Yinshan Mountain (NFYM), Inner Mongolia, China. Five machine learning models were employed to evaluate the relationship between ecological sustainability and its driving factors. The results indicate that (1) overall ecological sustainability initially decreased and then increased during 2003–2022; (2) the Geophysical Fluid Dynamics Laboratory Earth System Model version 4 (GFDL-ESM4) mode and random forest model demonstrated the best performance in climate and ecological sustainability simulations; and (3) the annual change rates of ecological sustainability from 2023 to 2099 are projected to be +0.45%, −0.05%, and −0.46% per year under the SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, respectively, suggesting that stringent environmental policies can effectively enhance ecological sustainability. The proposed framework can assist decision-makers in understanding ecological changes under different SSPs and calls for strategies to enhance ecosystem resilience in the NFYM and similar regions.

Abstract The purpose of this trial was to clinically assess the effect and safety of Adipose Tissue-derived Stem Cells (ADSCs) treatment on primary Sjogren’s Syndrome (pSS). In this 6-month randomized, triple-blind, placebo-controlled clinical trial, pSS patients were randomly assigned to two groups. After demographic characteristics and clinical examination were achieved, local injection of ADSCs into bilateral glands was performed with patients in ADSCs group (n = 35) and placebo solution was used for another group (n = 39) at three time points. Patients were followed up at 1-, 3- and 6-month. At each visit, studies of clinical and laboratory outcomes, as well as subjective symptoms, were conducted. A total of 74 subjects who met the including criteria were allocated in two groups and eventually 64 subjects (86.5%) completed the treatments and the follow-up assessments. Secretion of salivary and lachrymal glands were significantly improved in 3-month (P

Abstract Background Fatigue is the most frequent and distressing symptom affecting the physical, cognitive, and affective domains of breast cancer patients. The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–F) has been widely used in patients with chronic diseases and has shown satisfactory reliability and validity. This study aimed to examine the psychometric properties of the FACIT–F among Chinese patients with breast cancer. Methods Using a convenience sampling method, a cross–sectional survey (January 2020 and September 2022) was used with patients recruited from two tertiary hospitals in Shanghai, Mainland China, and a total of 597 patients completed a demographic information questionnaire, the FACIT–F and the Functional Assessment of Cancer Therapy for Breast Cancer (FACT–B). Convergent validity was estimated by calculating the Pearson correlation coefficient of the FACIT–F with the FACT–B. Measurement invariance across age was performed by examining differential item functioning (DIF) across age groups (≤ 60 and > 60 years). The internal consistency and split–half reliability were performed for reliability analysis. Unidimensionality of the scale was evaluated by the principal component analysis by Rasch analysis. Additionally, Rasch analysis was performed for item difficulty levels, and an item–person map was used. Results No floor/ceiling effects were observed for the FACIT–F. Moderate correlations were found between FACIT–F and FACT–B (r = − 0.342, p

In order to explore the antagonistic mechanism of Lysinibacillus sphaericus AEB18 against Nocardia seriolae, the whole genome of strain AEB18 was sequenced, and the effect of strain AEB18 in controlling nocardiosis of hybrid snakehead was verified in vitro and in vivo. Strain AEB18 genome was a circular DNA of 4,653,716 base pairs (bp) and GC content of 37.4%, predicting 4,529 coding genes, 108 tRNAs, 37 rRNAs, and 95 non-coding (nc)RNAs. The eggNOG (Non-supervised Orthologous Groups), GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and the CAZy (Carbohydrate-Associated Enzyme) database annotated the strain AEB18 genome to 3,965, 3,325, 2,061, and 112 genes, respectively. Furthermore, nine gene clusters, including polyketones, non-ribosomal synthetic peptides, β-lactones, terpenes, ribosomal synthetic peptides, and other secondary metabolites with bacteriostatic effect were obtained through the prediction of secondary metabolites of strain AEB18. After the addition of L. sphaericus AEB18 (1 × 109 CFU/g) with a mass fraction of 1% to the basal diet for 21 days, the weight gain rate and the activity of amylase in intestinal chyme of hybrid snakehead were significantly increased (P< 0.05). In addition, hybrid snakehead fed with L. sphaericus AEB18 supplemented diets showed significantly reduced mortality rate (P< 0.05) after N. seriolae infection, compared with the control group (mortality rate was 100%). Overall, L. sphaericus AEB18 positively affected hybrid snakeheads, promoted growth and reduced mortality rate of hybrid snakeheads with nocardiosis. Taken together, the L. sphaericus AEB18 possesses great potential as a biocontrol agent, which can be commercially developed to improve disease control in freshwater aquaculture.

ABSTRACTReductive soil disinfestation (RSD) is an effective method to inhibit soilborne pathogens. However, it remains unclear how RSD combined with different types of organic materials affects the soil ecosystems of perennial plants. Pot experiments were conducted to investigate the effects of RSD incorporated with perilla (PF), alfalfa (MS), ethanol, and acetic acid on soil properties, enzyme activities, microbial communities and functions, and seedling growth. Results showed that RSD-related treatments improved soil properties and enzyme activities, changed microbial community composition and structure, enhanced microbial interactions and functions, and facilitated seedling growth. Compared with CK, RSD-related treatments increased soil pH, available nitrogen, and available potassium contents, sucrase and catalase activities, and decreased soil electric conductivity values. Meanwhile, RSD-related treatment also significantly reduced the relative abundance of Fusarium while increasing the relative abundance of Arthrobacter, Terrabacter, and Gemmatimonas. The reduction was more evident in PF and MS treatment, suggesting the potential for RSD combined with solid agricultural wastes to suppress pathogens. Furthermore, the microbial network of RSD-related treatment was more complex and interconnected, and the functions related to carbon, nitrogen, sulfur, and hydrogen cycling were significantly increased, while the functions of bacterial and fungal plant pathogens were decreased. Importantly, RSD-related treatments also significantly promoted seed germination and seedling growth. In summary, RSD combined with solid agricultural wastes is better than liquid easily degradable compounds by regulating the composition and function of microbial communities to improve soil quality and promote plant growth.IMPORTANCEReductive soil disinfestation (RSD) is an effective agricultural practice. We found that RSD combined with solid agricultural wastes is better than that of liquid easily degradable compounds, may improve soil quality and microbial community structure, inhibit the proliferation of pathogenic bacteria, and contribute to the growth of replanted crops. Thus, RSD combined with solid agricultural wastes is more effective than liquid easily degradable compounds.

PurposeRapid eye movement sleep behavior disorder (RBD) affects 30%–40% of patients with Parkinson’s disease (PD) and has been linked to a higher risk of cognitive impairment, especially executive dysfunction. The aim of this study was to investigate the brain activation patterns in PD patients with RBD (PD-RBD+) compared to those without RBD (PD-RBD−) and healthy controls (HCs), and to analyze the correlation between changes in cerebral cortex activity and the severity of RBD.MethodsWe recruited 50 PD patients, including 30 PD-RBD+, 20 PD-RBD−, and 20 HCs. We used functional near infrared spectroscopy during a verbal fluency task (VFT-fNIRS) and clinical neuropsychological assessment to explore the correlation between PD-RBD+ and executive function and changes in neural activity.ResultsThe VFT-fNIRS analysis revealed a significant reduction in activation among PD-RBD+ patients across multiple channels when compared to both the PD-RBD− and HC groups. Specifically, PD-RBD+ patients exhibited diminished activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and the right ventrolateral prefrontal cortex (VLPFC) relative to their PD-RBD− counterparts. Furthermore, compared to the HC group, PD-RBD+ patients displayed reduced activation specifically in the right DLPFC. Significantly, a noteworthy negative correlation was identified between the average change in oxygenated hemoglobin concentration (ΔHbO2) in the right DLPFC of PD-RBD+ patients and the severity of their RBD.ConclusionOur study offers compelling evidence that RBD exacerbates cognitive impairment in PD, manifested as executive dysfunction, primarily attributed to reduced prefrontal activation. These aberrations in brain activation may potentially correlate with the severity of RBD.

Epigenetics, specifically histone post-translational modification (HPTM) induced by environmental factors, plays a crucial role in the development of diabetes. Sodium benzoate (NAB) is a widely used additive, however, its potential contribution to diabetes has been largely overlooked. In 2018, a novel HPTM called benzoylation (Kbz) induced by NAB was discovered. This modification can be catalyzed by ACSS2 (acyl-CoA synthetase short-chain member 2) and acyltransferase P300/CBP, and can be reversed by erase enzymes SIRT2. Studies have indicated that Kbz may regulate insulin secretion, although the exact molecular mechanism remains unclear. In our study, C57BL/6J mice were divided into two groups: the NC group and the 1g/kg NAB water feeding group. In vivo experiments were conducted using β-TC-6 cells, with 6 mM NAB or 100 μM benzoyl-CoA as stimuli, and 10 μM A485 (P300 inhibitor), 5 μM ACSS2 inhibitor (inhibiting benzoyl-CoA synthesis), or 5 μM AGK2 (SIRT2 inhibitor) as intervention factors. Our study found that, although the experimental concentration of NAB is below the maximum allowable concentration in food, it still damaged the insulin secretion function of C57BL/6J mice and induced inflammation and apoptosis of islet β cells. We observed significant differences in serum benzoyl-CoA levels between healthy individuals and patients with type 2 diabetes. Furthermore, NAB concentration-dependently increases benzoyl-CoA and Kbz levels. When Kbz is down-regulated using A485 and ACSS2 inhibitor, we observed a reduction in β cell inflammation, apoptosis, and insulin secretion damage. Conversely, up-regulating Kbz using AGK2 resulted in increased levels of β cell inflammation and apoptosis. In conclusion, our data suggest that NAB, despite being within the safe dose range, may be an overlooked environmental risk factor contributing to the pathogenesis of diabetes through its impact on Kbz.

Early lipid accumulation is thought to contribute to liver regeneration through unclear functional mechanisms. Here the authors identify an epigenetic regulator, MIER1, that bridges the acute lipid accumulation and cell cycle gene transcription during liver regeneration after surgical resection in male mice.

Abstract Background Both contextual and cancer-related factors could be identified as causes of the interindividual variability observed for symptoms experienced during breast cancer treatment with chemotherapy. Understanding age differences and the predictors of latent class memberships for symptom heterogeneity could contribute to personalized interventions. This study aimed to identify the role of age differences on cancer-related symptoms in women undergoing chemotherapy for breast cancer in China. Methods A cross‑sectional survey was conducted among patients with breast cancer in three tertiary hospitals in central China between August 2020 to December 2021. The outcomes of this study included sociodemographic and clinical characteristics, Patient-Reported Outcomes Measurement Information System (PROMIS)-57 and PROMIS-cognitive function short form scores. Results A total of 761 patients were included, with a mean age of 48.5 (SD = 11.8). Similar scores were observed across age groups for all symptoms except for fatigue and sleep disturbance domains. The most central symptoms varied among each group, and were fatigue, depression, and pain interference for the young-aged, middle-aged, and elderly-aged groups, respectively. In the young-aged group, patients without health insurance (OR = 0.30, P = 0.048) and in the fourth round of chemotherapy or above (OR = 0.33, P = 0.005) were more likely to belong to low symptom classes. In the middle-aged group, patients in menopause (OR = 3.58, P = 0.001) were more likely to belong to high symptom classes. In the elderly-aged group, patients with complications (OR = 7.40, P = 0.003) tended to belong to the high anxiety, depression, and pain interference classes. Conclusions Findings from this study indicated that there is age-specific heterogeneity of symptoms present for Chinese women being treated for breast cancer with chemotherapy. Tailored intervention should consider the impact of age to reduce patients’ symptom burdens.

Pile spacing is an important factor affecting the bearing capacity of concrete expansion pile (CEP) groups. In this study, a pile group was simulated and analyzed using ANSYS software R19.0. The influence of pile spacing on the bearing capacity of the pile group under a vertical load was determined using three sets of four-, six-, and nine-pile models with different pile spacings. The grid division of the pile soil model adopts a mapping method, using the contact types of rigid and flexible bodies and applying surface loads to the model piles step-by-step. After vertical pressure was applied to the model pile, in-depth analysis was conducted on the displacement cloud map, pile top displacement, and other data. The different stress conditions of corner, edge, and center piles in each model group were compared and analyzed, revealing the relationship between the stress mechanism and failure law of the soil around the pile and the pile spacing. It was found that the soil displacement range of edge piles is slightly larger than that of corner piles. This phenomenon gradually decreases with increasing pile spacing. When the pile spacing increases to four times the cantilever diameter, the difference in soil displacement at different pile positions is small, and the pile spacing has little effect on the compressive bearing capacity of the pile group. Thus, it is reasonable to control the pile spacing at three to four times the cantilever diameter. In the nine-pile model, when the load is loaded to the 20-step level, the displacement value of the central pile is −72.278 mm, while the displacement values of the edge pile and corner pile are −69.012 mm and −66.806 mm. It is shown that increasing the pile spacing can effectively reduce the pile group effect and improve the bearing capacity of the pile foundation. At present, CEP pile groups are gradually being applied in practical engineering, but research on the influence of pile spacing on the compressive bearing performance of CEP pile groups is still at a very early stage. This article reinforces the influence of pile spacing on the compressive bearing performance of CEP pile groups. It provides theoretical support for its application in practical engineering.

The allelopathic autotoxicity of ginsenosides is an important cause of continuous cropping obstacles in ginseng planting. There is no report on the potential molecular mechanism of the correlation between polarity of ginsenoside components and their allelopathic autotoxicity. This study applied a combination of metabolomics and transcriptomics analysis techniques, combined with apparent morphology, physiological indexes, and cell vitality detection of the ginseng hairy roots, through which the molecular mechanism of correlation between polarity and allelopathic autotoxicity of ginsenosides were comprehensively studied. The hairy roots of ginseng presented more severe cell apoptosis under the stress of low-polarity ginsenoside components (ZG70). ZG70 exerted allelopathic autotoxicity by regulating the key enzyme genes of cis-zeatin (cZ) synthesis pathway, indole-3-acetic acid (IAA) synthesis pathway, and jasmonates (JAs) signaling transduction pathway. The common pathway for high-polarity ginsenoside components (ZG50) and ZG70 to induce the development of allelopathic autotoxicity was through the expression of key enzymes in the gibberellin (GA) signal transduction pathway, thereby inhibiting the growth of ginseng hairy roots. cZ, indole-3-acetamid (IAM), gibberellin A1 (GA1), and jasmonoyl-L-isoleucine (JA-ILE) were the key response factors in this process. It could be concluded that the polarity of ginsenoside components were negatively correlated with their allelopathic autotoxicity.

CeO2 is an outstanding support commonly used for the CuO-based CO oxidation catalysts due to its excellent redox property and oxygen storage–release property. However, the inherently small specific surface area of CeO2 support restricts the further enhancement of its catalytic performance. In this work, the novel mesoporous CeO2 nanosphere with a large specific surface area (~190.4 m2/g) was facilely synthesized by the improved hydrothermal method. The large specific surface area of mesoporous CeO2 nanosphere could be successfully maintained even at high temperatures up to 500 °C, exhibiting excellent thermal stability. Then, a series of CuO-based CO oxidation catalysts were prepared with the mesoporous CeO2 nanosphere as the support. The large surface area of the mesoporous CeO2 nanosphere support could greatly promote the dispersion of CuO active sites. The effects of the CuO loading amount, the calcination temperature, mesostructure, and redox property on the performances of CO oxidation were systematically investigated. It was found that high Cu+ concentration and lattice oxygen content in mesoporous CuO/CeO2 nanosphere catalysts greatly contributed to enhancing the performances of CO oxidation. Therefore, the present mesoporous CeO2 nanosphere with its large specific surface area was considered a promising support for advanced CO oxidation and even other industrial catalysts.

Previous studies have found that β-Hydroxybutyrate (BHB), the main component of ketone bodies, is of physiological importance as a backup energy source during starvation or induces diabetic ketoacidosis when insulin deficiency occurs. Ketogenic diets (KD) have been used as metabolic therapy for over a hundred years, it is well known that ketone bodies and BHB not only serve as ancillary fuel substituting for glucose but also induce anti-oxidative, anti-inflammatory, and cardioprotective features via binding to several target proteins, including histone deacetylase (HDAC), or G protein-coupled receptors (GPCRs). Recent advances in epigenetics, especially novel histone post-translational modifications (HPTMs), have continuously updated our understanding of BHB, which also acts as a signal transduction molecule and modification substrate to regulate a series of epigenetic phenomena, such as histone acetylation, histone β-hydroxybutyrylation, histone methylation, DNA methylation, and microRNAs. These epigenetic events alter the activity of genes without changing the DNA structure and further participate in the pathogenesis of related diseases. This review focuses on the metabolic process of BHB and BHB-mediated epigenetics in cardiovascular diseases, diabetes and complications of diabetes, neuropsychiatric diseases, cancers, osteoporosis, liver and kidney injury, embryonic and fetal development, and intestinal homeostasis, and discusses potential molecular mechanisms, drug targets, and application prospects.

Two patients with refractory nephrotic syndrome were treated with peritoneal dialysis (PD) for diuretic resistance, anasarca and acute kidney injury. Following PD, their fluid overload was promptly alleviated, accompanied by an increase in urine volume and an improvement in renal function. PD as an adjuvant approach enabled them to resume corticosteroids and immunosuppressive agents. Eventually, both patients could be withdrawn from PD and achieved remission of proteinuria.

The pathophysiology of osteoporosis (OP) is influenced by exposure to nonessential harmful metals and insufficient or excessive intake of necessary metals. Investigating multiple plasma metals, metabolites, and OP risk among older adults may reveal novel clues of underlying mechanisms for metal toxicity on bone mass. A total of 294 adults ≥ 55 years from Wuhan communities were included. Plasma concentrations of 23 metals and metabolites were measured via inductively coupled plasma-mass spectrometry and global metabolite detection. To investigate the relationships between plasma metals, OP risk, and OP-related metabolites, three different statistical techniques were used: generalized linear regression model, two-way orthogonal partial least-squares analysis (O2PLS), and weighted quantile sum (WQS). The mean ages were 66.82 and 66.21 years in OP (n = 115) and non-OP (n = 179) groups, respectively. Of all 2999 metabolites detected, 111 differential between-group members were observed. The OP risk decreased by 58.5% (OR=0.415, 95% CI: 0.237, 0.727) per quartile increment in the WQS index indicative of metal mixture exposure. Consistency remained for bone mineral density (BMD) measurements. The O2PLS model identified the top five OP-related metabolites, namely, DG(18:2_22:6), 3-phenoxybenzoic acid, TG(16:1_16:1_22:6), TG(16:0_16:0_20:4), and TG(14:1_18:2_18:3), contributing most to the joint covariation between the metal mixture and metabolites. Significant correlations between each of them and the metal mixture were found using WQS regression. Furthermore, the five metabolites mediated the associations of the metal mixtures, BMD, and OP risk. Our findings shed additional light on the mediation functions of plasma metabolites in the connection between multiple metal co-exposure and OP pathogenesis and offer new insights into the probable mechanisms underpinning the bone effects of the metal mixture.

Abstract Objective To study the feasibility, safety, and efficacy of thoracoscopic surgery in the treatment of pediatric mediastinal neurogenic tumors, and summarize the treatment experiences and surgical skills. Methods A single‐center retrospective analysis of 37 patients with pediatric mediastinal neurogenic tumors was conducted. Clinical charactersistics and postoperative complications were all analyzed. Results All the operations were successfully completed. There was no statistically significant difference in tumor diameter between the two groups (p > 0.05). The open surgery group had an average operation time of 96.5 ± 32.38 min, while the thoracoscopic surgery group had an average operation time of 78.3 ± 24.51 min (p

Propensity score (PS) based methods, such as matching, stratification, regression adjustment, simple and augmented inverse probability weighting, are popular for controlling for observed confounders in observational studies of causal effects. More recently, we proposed penalized spline of propensity prediction (PENCOMP), which multiply-imputes outcomes for unassigned treatments using a regression model that includes a penalized spline of the estimated selection probability and other covariates. For PS methods to work reliably, there should be sufficient overlap in the propensity score distributions between treatment groups. Limited overlap can result in fewer subjects being matched or in extreme weights causing numerical instability and bias in causal estimation. The problem of limited overlap suggests (a) defining alternative estimands that restrict inferences to subpopulations where all treatments have the potential to be assigned, and (b) excluding or down-weighting sample cases where the propensity to receive one of the compared treatments is close to zero. We compared PENCOMP and other PS methods for estimation of alternative causal estimands when limited overlap occurs. Simulations suggest that, when there are extreme weights, PENCOMP tends to outperform the weighted estimators for ATE and performs similarly to the weighted estimators for alternative estimands. We illustrate PENCOMP in two applications: the effect of antiretroviral treatments on CD4 counts using the Multicenter AIDS cohort study (MACS) and whether right heart catheterization (RHC) is a beneficial treatment in treating critically ill patients.

AbstractThere are few studies on denitrification related to the nitrogen cycle in Ebinur Lake wetland. This study aimed to explore the response of the diversity and composition of denitrifying bacteria to the environmental factors in wetland, so as to obtain more information about the community structure of denitrifying bacteria driven by environmental factors. Using the genes encoding nitrite reductase (nirS and nirK) as molecular markers, we analysed the seasonal changes in the diversity of denitrifying bacteria in halophyte soils by high-throughput sequencing technology. The results showed that the diversity of denitrifying bacteria was higher in July and lower in April, showing seasonal changes. The diversity index of denitrifying bacteria in rhizosphere soil was higher than that in non-rhizosphere soil. The diversity of denitrifying bacteria in the Phragmites australis rhizosphere soil was the highest. The diversity of nirK denitrifying bacteria was higher than that of nirS denitrifying bacteria, but the relative abundance was lower than that of nirS denitrifying bacteria. Three-way ANOVA showed that soil types, vegetation types and season had significant effects on the diversity of denitrifying bacteria. Furthermore, redundancy analysis indicated that nitrate was the environmental factor that significantly affected the community structure of nirS denitrifying bacteria in wetland, and electric conductivity, total nitrogen, ammonium and nitrate were the environmental factors that significantly affected the community structure of nirK denitrifying bacteria. These results provide data basis and theoretical support for the dynamic change of diversity of denitrifying bacteria in wetland.

Abstract Background Due to its high expression capability, recombination of Escherichia coli and pET vector has become the bioengineering preferred expression system. Because β-lactamases mediate bacterial antimicrobial resistance, these enzymes have a substantial clinical impact. Using the E. coli expression system, several kinds of β-lactamases have been produced. However, previous studies have been focused on characterizing target β-lactamases, and the effects of cultivation and induction conditions on the expression efficiency of target enzymes were not addressed. Results Using pET-28a as the cloning vector and E. coli BL21(DE3) as the expression host, this study originally elucidated the effects of IPTG concentration, culture temperature, induction time, and restriction sites on recombinant β-lactamase expression. Moreover, the effects of the target protein length and the 6 × His-tag fusion position on enzyme purification were also explored, and consequently, this study yielded several important findings. (i) Only the signal peptide–detached recombinant β-lactamase could exist in a soluble form. (ii) Low-temperature induction was beneficial for soluble β-lactamase expression. (iii) The closer to the rbs the selected restriction site was, the more difficult it was to express soluble β-lactamase. (iv) The short-chain recombinant protein and the protein with His-tag fused at its C-terminus showed high affinity to the Ni2+ column. Conclusions Based on our findings, researchers can easily design an effective program for the high production of soluble recombinant β-lactamases to facilitate other related studies.

Abstract The association between the expression of Lysyl oxidase (LOX) and its clinicopathological parameters and prognosis in patients with gastric cancer (GC) is still disputed. We performed this meta-analysis and bioinformatics analysis to clarify the relationship between the expression and methylation level of LOX with its clinicopathological parameters and prognostic value. We applied odds ratios with a 95% confidence interval to study the associations between LOX expression and clinicopathological parameters and overall survival (OS) in GC patients. In addition, association analysis of promoter methylation levels and expression of LOX with its prognostic value was performed using the Cancer Genome Atlas (TCGA) and four Gene Expression Omnibus (GEO) datasets. The PRISMA 2020 checklist was used to guide the data extraction and analysis. This meta-analysis includes seven clinical studies with a total of 1435 GC patients. LOX expression was related to lymph node metastasis and tumor distant metastasis in GC patients, but not to gender, tumor differentiation, Lauren classification, or tumor depth of invasion. Patients with GC grouped in high-expression of LOX had a much worse OS than those in low-expression. In addition, TCGA and four GEO datasets with 1279 samples were included in the bioinformatics analysis. The bioinformatics analysis showed that patients with high LOX levels had poor OS; low levels of methylation at some cg sites in the LOX gene were strongly related to poor OS and PFS; and methylation levels of LOX are negatively correlated with advanced tumor stage. The conclusion from comprehensive DNA methylation and gene expression analysis supports LOX as a specific diagnostic and prognosis biomarker in GC. LOX expression was related to lymph node metastasis, tumor distant metastasis and poor prognosis in GC. Low methylation levels were related to advanced tumor stage and poor prognosis in GC. Integrative analysis supports LOX as a specific diagnostic and prognosis biomarker in GC.

Abstract The incidence of myocardial ischaemia‒reperfusion injury (MIRI) is increasing every year, and there is an urgent need to develop new therapeutic approaches. Nrf2 is thought to play a protective role during MIRI and it is regulated by microRNAs (miRNAs). This study focused on PLGA nanoparticles camouflaged by platelet membrane vesicles (PMVs) (i.e., PMVs@PLGA complexes) carrying microRNA inhibitors, which regulate Nrf2 and can play a therapeutic role in the MIRI process. In vitro and in vivo characterization showed that PMVs@PLGA has excellent transfection efficiency, low toxicity and good targeting. MicroRNAs that effectively regulate Nrf2 were identified, and then PMVs@PLGA-miRNA complexes were prepared and used for in vitro and in vivo treatment. PMVs@PLGA-miRNA complexes can effectively target the delivery of inhibitors to cardiomyocytes. Our results suggest that PMVs@PLGA complexes are a novel delivery system and a novel biological approach to the treatment of MIRI.