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Abstract Consecutive photoinduced electron transfer (conPET) processes accumulate the energies of two photons to overcome the thermodynamic limit of traditional photoredox catalysis. However, the excitation wavelength of conPET systems mainly focused on short wavelength visible light, leading to photodamage and incompatibility with large-scale reactions. Herein, we report on conPET systems triggered by near-infrared (NIR) and red light. Specifically, a blue-absorbing conPET photocatalyst, perylene diimide (PDI) is sensitized by a palladium-based photosensitizer to triplet excited state (3PDI*), which generates PDI radical anion (PDI•– ) over 100-fold faster than that in the conventional conPET. Accordingly, photoreduction with superior reaction rate and penetration depth, as well as reduced photodamage is detected. More importantly, our work offers comprehensive design rules for the triplet-mediated conPET strategy, whose versatility is confirmed by metal-free dye pairs and NIR-active PtTNP/PDI. Notably, our work achieves NIR-driven atom transfer radical polymerization using an inert aromatic halide as the initiator.

Abstract Background The triglyceride-glucose (TyG) index is a new and good biomarker of insulin resistance (IR). The prognostic utility of the TyG index for patients with type 2 diabetes mellitus (T2DM) remains uncertain. Our study seeks to elucidate the connection between the TyG index and adverse renal outcomes within a T2DM population, while also examining if these relationships are influenced by subgroup variations. Methods We analyzed data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, involving 10,196 T2DM participants, to assess the link between triglyceride-glucose levels and adverse renal outcomes. This evaluation included Restricted Cubic Spline (RCS) analysis, Kaplan–Meier survival analysis, and Multivariate Cox proportional regression. Additionally, we examined the interaction between subgroups concerning adverse renal outcomes. Results During a 7-year follow-up, 5824 patients (57.1%) experienced worsening renal function, 2309 patients (23.2%) developed albuminuria, and 280 patients (2.7%) advanced to renal failure. After adjusting for a range of confounding variables, triglyceride-glucose levels were significantly linked to both worsening renal function (p

Abstract Influenza virus infection remains a major global health problem and requires a universal vaccine with broad protection against different subtypes as well as a rapid-response vaccine to provide immediate protection in the event of an epidemic outbreak. Here, we show that intranasal administration of probiotic Escherichia coli Nissle 1917 activates innate immunity in the respiratory tract and provides immediate protection against influenza virus infection within 1 day. Based on this vehicle, a recombinant strain is engineered to express and secret five tandem repeats of the extracellular domain of matrix protein 2 from different influenza virus subtypes. Intranasal vaccination with this strain induces durable humoral and mucosal responses in the respiratory tract, and provides broad protection against the lethal challenge of divergent influenza viruses in female BALB/c mice. Our findings highlight a promising delivery platform for developing mucosal vaccines that provide immediate and sustained protection against respiratory pathogens.

Abstract Background Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication. Methods To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients’ medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal. Results The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time. Conclusions Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.

Abstract Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.

Abstract Background Lung adenocarcinoma, a leading cause of cancer-related mortality, demands precise prognostic indicators for effective management. The presence of spread through air space (STAS) indicates adverse tumor behavior. However, comparative differences between 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)/computed tomography(CT) and CT in predicting STAS in lung adenocarcinoma remain inadequately explored. This retrospective study analyzes preoperative CT and 18F-FDG PET/CT features to predict STAS, aiming to identify key predictive factors and enhance clinical decision-making. Methods Between February 2022 and April 2023, 100 patients (108 lesions) who underwent surgery for clinical lung adenocarcinoma were enrolled. All these patients underwent 18F-FDG PET/CT, thin-section chest CT scan, and pathological biopsy. Univariate and multivariate logistic regression was used to analyze CT and 18F-FDG PET/CT image characteristics. Receiver operating characteristic curve analysis was performed to identify a cut-off value. Results Sixty lesions were positive for STAS, and 48 lesions were negative for STAS. The STAS-positive was frequently observed in acinar predominant. However, STAS-negative was frequently observed in minimally invasive adenocarcinoma. Univariable analysis results revealed that CT features (including nodule type, maximum tumor diameter, maximum solid component diameter, consolidation tumor ratio, pleural indentation, lobulation, spiculation) and all 18F-FDG PET/CT characteristics were statistically significant difference in STAS-positive and STAS-negative lesions. And multivariate logistic regression results showed that the maximum tumor diameter and SUVmax were the independent influencing factors of CT and 18F-FDG PET/CT in STAS, respectively. The area under the curve of maximum tumor diameter and SUVmax was 0.68 vs. 0.82. The cut-off value for maximum tumor diameter and SUVmax was 2.35 vs. 5.05 with a sensitivity of 50.0% vs. 68.3% and specificity of 81.2% vs. 87.5%, which showed that SUVmax was superior to the maximum tumor diameter. Conclusion The radiological features of SUVmax is the best model for predicting STAS in lung adenocarcinoma. These radiological features could predict STAS with excellent specificity but inferior sensitivity.

Abstract Background Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. Methods We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. Results Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1–0.7%) and 1.4% (1.0–1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5–0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5–1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8–30.3%) and 12.7% (10.8–14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. Conclusions Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Regional budget assessments of methane (CH4) are critical for future climate and environmental management. CH4 emissions from rice cultivation (CH4-rice) constitute one of the most significant sources. However, previous studies mainly focus on historical emission estimates and lack consideration of future changes in CH4-rice under climate change or anthropogenic policy intervention, which hampers our understanding of long-term trends and the implementation of targeted emission reduction efforts. This study investigates the spatiotemporal variations of CH4-rice over the past two decades, using an integrated method to identify the major drivers and predict future emissions under climate change scenarios and policy perspectives. Results indicate that the CH4-rice emissions in China ranged between 6.21 and 6.57 Tg yr−1 over the past two decades, with a spatial distribution characterized by decreases in the south and increases in the north, associated with economic development, dietary shifts, technological advancements, and climate change. Factors such as the rate of straw added (RSA), fertilization, soil texture, temperature, and precipitation significantly influence CH4 emissions per unit rice production (CH4-urp), with RSA identified as the most significant tillage management factor, explaining 32 % of the variance. Lowering RSA to 8 % is beneficial for reducing CH4-urp. Scenario analysis indicates that under policies focusing on production or demand, CH4-rice is expected to increase by 0.3 % to 5.6 %, while adjusting RSA can reduce CH4-rice by 9.4 % to 10.0 %. Structural adjustments and regional cooperation serve as beneficial starting points for controlling and reducing CH4-rice in China, while optimizing industrial layouts contributes to regional development and CH4-rice control. Implementing policies related to maintaining field and crop yields can achieve a balance between rice supply and demand ahead of schedule. Dynamic adjustment of rice cultivation based on supply–demand balance can effectively reduce CH4-rice from excess rice production. By 2060, the reduction effect could reach 8.95 %–12.01 %. Introducing policy-driven tillage management measures as reference indicators facilitates the reduction of CH4-rice.

IL-17 A is a promoter of colorectal cancer initiation and progression. Narciclasine is a polyhydroxy alkaloid compound isolated from Narcissus plants, which has potent anti-inflammatory and antitumor actions. The effects of narciclasine on colorectal tumors were evaluated, with a focus on IL-17 A. Narciclasine reduced the growth of HCT-116 and SW-480 colon cancer cells in vitro and in vivo in murine xenografts. The results of flow cytometry on JC-1 and Annexin V/PI revealed that narciclasine significantly reduced the mitochondrial membrane potential and induced apoptosis, findings confirmed by western blotting results of reduced Bcl-2 and enhanced Bax expression, as well as accumulation of cleaved Caspase-3, Caspase-8, Caspase-9, and cytoplasmic Cytochrome-c. After narciclasine incubation, IL-17 A, Act1, and TRAF6 were down-regulated, while p-P65 (Ser536) accumulated in the cytoplasm, a finding confirmed by laser scanning confocal microscopy. IL17A substitution could partly reverse these narciclasine effects while they were elevated by IL17A silencing. Moreover, IL-17 A, Act1, and TRAF6 were significantly expressed to greater extents in human colorectal cancer compared to normal adjacent tissue specimens and were closely linked with a poor prognosis. This study provided evidence that narciclasine may be a useful therapeutic drug for colorectal cancer treatment through its actions in down-regulating the L-17A/Act1/TRAF6/NF-κB anti-apoptotic signaling pathway.

Abstract The sensitivity of tree growth to precipitation regulates their responses to drought, and is a crucial metric for predicting ecosystem dynamics and vulnerability. Sensitivity may be changing with continuing climate change, yet a comprehensive assessment of its change is still lacking. We utilized tree ring measurements from 3,044 sites, climate data and CO2 concentrations obtained from monitoring stations, combined with dynamic global vegetation models to investigate spatiotemporal changes in the sensitivity over the past century. We observed an increasing sensitivity since around 1950. This increased sensitivity was particularly pronounced in arid biomes due to the combined effect of increased precipitation and elevated CO2. While elevated CO2 reduced the sensitivity of the humid regions, the intensified water pressure caused by decreased precipitation still increased the sensitivity. Our findings suggest an escalating vulnerability of tree growth to precipitation change, which may increase the risk of tree mortality under future intensified drought.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor β (GRβ) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRβ ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRβ signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRβ signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Introduction: Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina.Methods: Intravitreal or subcutaneous injection of STZ was performed on newborn rats. Electroretinogram (ERG) and H&E staining investigated retinal function and morphological changes. Retinal cell types, cell death, proliferation, inflammation, and angiogenesis were studied by immunostaining. RNA sequencing was performed to examine the transcriptome changes of retinal cells after intravitreal injection of STZ.Results: Intravitreal (5 μg or 10 μg) or subcutaneous (30 mg/kg) injection of STZ at the early stage of newborn rats couldn’t induce hyperglycemia but caused NSIR (Neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn’t induce SINR when all retinal progenitors exit the cell cycle.Conclusion: NSIR in rats is independent of hyperglycemia but due to STZ’s direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.

AimsThis study is designed to generalize and depict the research hotspots of endophthalmitis through bibliometric methods and software and analyze the evolutive tendency of the work on this severe disease over the past 30 years.MethodsThis study employed a rigorous bibliometric approach. We identified all endophthalmitis-related literature by conducting a comprehensive search of the Science Citation Index Expanded database under the Web of Science Core Collection. The data was then analyzed and visualized using CiteSpace and VOSviewer, two widely recognized software tools in the field of bibliometrics. CiteSpace was used to analyze the country distributions, dual map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to describe the authors and co-cited authors, the journals, the co-cited journals, and the keywords co-occurrence network. This robust methodology ensures the reliability and validity of the study’s findings.ResultsA total of 2960 publications, including 2695 articles and 265 reviews, were included in this bibliometric study. There has been no shortage of endophthalmitis-related publications since 1993, with an apparent upward trend during recent years. Possible correlations with the COVID-19 pandemic are also analyzed. These studies were finished by 11,048 authors from 75 countries worldwide, with the United States in the lead. In the keyword co-occurrence network, except for the endophthalmitis term, cataract surgery becomes the keyword with the highest frequency. Different categories of endophthalmitis, including postoperative, post-injection, post-traumatic, and endogenous endophthalmitis, and antibacterial and anti-inflammatory therapies of infectious endophthalmitis, are discussed by categories. From the perspective of the timeline, postoperative and post-injection endophthalmitis were the dominant forms before and after the year 2000, respectively. Co-citation analyses reveal that the Endophthalmitis Vitrectomy Study (EVS) conducted in 1995 provides pivotal guidance for later research. Diverse pathogenic bacteria (e.g., Coagulase-negative Staphylococci, Propionibacterium acnes, Viridians Streptococci, and Bacillus cereus) or fungi (e.g., Candida, Aspergillus, and Fusarium) contribute to varying treatment principles and clinical prognosis, which should be taken seriously. In addition, intravitreal and intracameral antibiotics are the mainstay for treating and preventing infectious endophthalmitis, respectively.ConclusionOur bibliometric analysis provides an overview of dynamic evolution and structural relationships in the research field of endophthalmitis. The displayed hotspots and developmental directions have reference values for future investigation.

In the current study, an improved method of adding Zn ion doping to the 0.5BZT–0.5BCT–based films with high pyroelectric properties was designed. Under different Zn ion doping ratios, the structure, dielectric constant, phase transition relationship and other characteristics of the test product were analyzed experimentally to obtain the optimal ratio parameters. The experimental results demonstrate that the dielectric properties of the 0.5BZT–0.5BCT–xZn–based films proposed in this study can be far superior to those of other films under the optimal preparation process. The optimal dielectric properties and ferroelectric properties are obtained when the doped data are 0.008. Considering the comprehensive dielectric and energy storage capacity, the optimal doping ratio is 0.01, which can take into account dielectric data and energy storage performance. The energy storage density is 1.842 J/cm3, and the energy storage efficiency exceeds 30%. From 0 to 0.02, the properties of the material, such as the hysteresis loop and phase transition relationship are excellent. The properties of the materials studied in this study are excellent, and they are excellent candidate materials for the future application of ferroelectric materials, and provide ideas for related work.

Abstract The influence of environmental factors like smoking and alcohol on myopia and astigmatism is controversial. However, due to ethical concerns, alternative study designs are urgently needed to assess causal inference, as mandatory exposure to cigarettes and alcohol is unethical. Following comprehensive screenings, 326 single nucleotide polymorphisms (SNPs) related to myopia and astigmatism were included in the dataset. To validate the causal association between exposures such as cigarette smoking, alcohol consumption, and coffee intake, and outcomes namely astigmatism and myopia, five regression models were employed. These models encompassed MR-Egger regression, random-effects inverse-variance weighted (IVW), weighted median estimator (WME), weighted model, and simple model. The instrumental variables utilized in these analyses were the aforementioned SNPs. Apply Cochran’s Q test to determine heterogeneity of SNPs; if heterogeneity exists, focus on IVW model results. The IVW model showed a 1.379-fold increase in the risk of astigmatism (OR = 1.379, 95%CI 0.822~2.313, P = 0.224) and a 0.963-fold increase in the risk of myopia (OR = 0.963, 95%CI 0.666~1.393, P = 0.841) for each unit increase in smoking. For each unit increase in coffee intake, the risk of astigmatism increased 1.610-fold (OR = 1.610, 95%CI 0.444~5.835, P = 0.469) and the risk of myopia increased 0.788-fold (OR = 0.788, 95%CI 0.340~1.824, P = 0.578). For each additional unit of alcohol consumption, the risk of astigmatism increased by 0.763-fold (OR = 0.763, 95%CI 0.380~1.530, P = 0.446), and none of the differences were statistically significant. However, for each unit of alcohol consumption, the risk of myopia increased by 1.597 times, and the difference was statistically significant (OR = 1.597, 95%CI 1.023~2.493, P = 0.039). The findings indicate that alcohol consumption is a risk factor for myopia but smoking and coffee intake do not affect its development. Additionally, there is no association between smoking, alcohol consumption, coffee intake, and the risk of astigmatism.

Abstract Multiferroic materials offer a promising avenue for manipulating digital information by leveraging the cross-coupling between ferroelectric and ferromagnetic orders. Despite the ferroelectricity has been uncovered by ion displacement or interlayer-sliding, one-unit-cell of multiferroic materials design and wafer-scale synthesis have yet to be realized. Here we develope an interface modulated strategy to grow 1-inch one-unit-cell of non-layered chromium sulfide with unidirectional orientation on industry-compatible c-plane sapphire. The interfacial interaction between chromium sulfide and substrate induces the intralayer-sliding of self-intercalated chromium atoms and breaks the space reversal symmetry. As a result, robust room-temperature ferroelectricity (retaining more than one month) emerges in one-unit-cell of chromium sulfide with ultrahigh remanent polarization. Besides, long-range ferromagnetic order is discovered with the Curie temperature approaching 200 K, almost two times higher than that of bulk counterpart. In parallel, the magnetoelectric coupling is certified and which makes 1-inch one-unit-cell of chromium sulfide the largest and thinnest multiferroics.

Abstract Now, no recommendations of gestational weight gain (GWG) after gestational diabetes mellitus (GDM) diagnosis for Chinese women was made. This study aimed to explore the optimal GWG after oral glucose tolerance test (OGTT) for Chinese women with GDM. The GWG status of 11,570 women was retrospectively analyzed. Binary regression model and restricted cubic spline were used to estimate the association between GWG after OGTT and the predicted probability of adverse outcomes. Based on above, the optimal GWG was defined as the range that not exceed 1% increase in the predicted probability from the lowest point. Results shown that every increased one unit GWG after OGTT was associated with higher risks of macrosomia, cesarean section and LGA, and lower risk of preterm birth. According to the WHO and Working Group on Obesity in China (WGOC) recommended pre-pregnancy BMI category, the optimal GWG were proposed: 3.66 to 6.66 kg/3.66 to 6.66 kg in underweight group, 3.07 to 6.50 kg/3.02 to 6.40 kg in normal weight group, 1.06 to 2.73 kg/0 to 1.99 kg in overweight group, and not applicable/− 0.22 to 2.53 kg in obese group, respectively. Therefore, it is necessary to classified Chinese population based on the WGOC recommended pre-pregnancy BMI category, that influenced the contribution of pre-pregnancy BMI groups and the optimal GWG recommendation for GDM women with overweight or obesity.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Abstract COVID‐19 can lead to adverse outcomes in patients with pre‐existing diseases. Azvudine has been approved for treating COVID‐19 in China, but the real‐world data is limited. It is aimed to investigate the efficacy of Azvudine in patients with COVID‐19 and pre‐existing cardiovascular diseases. Patients with confirmed COVID‐19 and pre‐existing cardiovascular diseases are retrospectively enrolled. The primary outcome is all‐cause death during hospitalization. Overall, 351 patients are included, with a median age of 74 years, and 44% are female. 212 (60.6%) patients are severe cases. Azvudine is used in 106 (30.2%) patients and not in 245 (69.8%). 72 patients died during hospitalization. After multivariate adjustment, patients who received Azvudine a lower risk of all‐cause death (hazard ratio: 0.431; 95% confidence interval: 0.252–0.738; p = 0.002) than controls. Azvudine therapy is also associated with lower risks of shock and acute kidney injury. For sensitivity analysis in the propensity score‐matched cohort (n = 90 for each group), there is also a significant difference in all‐cause death between the two groups (hazard ratio: 0.189; 95% confidence interval: 0.071–0.498; p

Alzheimer’s disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin–hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aβ1–42 aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability. 6b and 6c have a good ability to alleviate oxidative stress induced by hydrogen peroxide. 6b and 6c possess metal-chelating properties with the chelation ratio being 2:1. Furthermore, 6b can significantly mitigate metal-induced Aβ aggregation. This work may provide a new multi-target treatment strategy for Alzheimer’s disease.

BackgroundShift work can disrupt sleep quality and gut health. Nurses and midwives constitute approximately half of the global healthcare shift-working workforce. Our previous study revealed that most midwives were experiencing suboptimal health conditions, characterized by poor sleep quality and a high prevalence of gastrointestinal diseases. The gut–brain axis theory highlights the potential interplay between sleep quality and gut health. However, limited research focuses on this relationship among midwives.MethodsA cross-sectional survey included 2041 midwives from 87 Chinese hospitals between March and October 2023. Participants completed standardized questionnaires assessing sleep quality, gut health, depression, anxiety, and work stress. Binary logistic regression analyzed factors associated with poor sleep, and multiple linear regression examined the influence of sleep quality on gut health.ResultsOver 60% of midwives reported poor sleep, with many experiencing gastrointestinal disorders. We observed a bidirectional relationship between sleep quality and gut health among midwives. After multivariable adjustments, midwives with higher gut health scores were more likely to experience poor sleep quality (odds ratio = 1.042, 95% confidence interval = 1.03–1.054). Conversely, midwives with higher sleep quality scores were also more likely to have poor gut health (β = 0.222, 95% confidence interval = 0.529–0.797). These associations remained robust across sensitivity analyses. Furthermore, depression, anxiety, and work stress significantly affected both sleep quality and gut health among midwives.ConclusionThis study enhances our understanding of the intricate relationship between sleep quality and gut health among midwives. Poor gut health was associated with a higher risk of poor sleep, and vice versa. To improve the overall wellbeing of midwives, the findings emphasize the importance of addressing poor sleep quality and promoting gut health through maintaining a healthy diet, lifestyle, and good mental health. Further studies are needed to confirm our findings and clarify the underlying mechanisms.

Background: This study aims to evaluate the efficacy and safety associated with ibrexafungerp in the treatment of vulvovaginal candidiasis infection patients. Methods: We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, and Clinical Trials databases up to December 25, 2022. The primary outcomes were clinical cure rate and mycological eradication rate, whereas the secondary outcomes were the risk of an adverse events. Results: In total of four studies encompassing 880 patients diagnosed with vulvovaginal candidiasis (VVC) were included in the analysis. The findings demonstrated that ibrexafungerp exhibited superior clinical cure ratio (RR = 1.33 [1.07, 1.66]), mycological eradication rate (RR = 1.72 [1.00, 2.95]), and overall success ratio (RR = 1.64 [0.92, 2.92]) when compared to the fluconazole/placebo in the treatment of VVC. Furthermore, patients treated with ibrexafungerp demonstrated significantly higher clinical cure rates, mycological eradication, and overall success ratio compared to those receiving other treatments for vulvovaginal candidiasis caused by C. albicans. When ibrexafungerp was compared to fluconazole/placebo, the duration of any treatment-related treatment-emergent adverse events (TEAE), nausea, and diarrhea during therapy was significantly longer. Conclusion: In summary, the use of ibrexafungerp was linked to superior clinical cure ratio, and mycological eradication when compared to fluconazole/placebo.

INF2 mutations cause Charcot-Marie-Tooth disease (CMT), and /or focal segmental glomerulosclerosis (FSGS) in an autosomal dominant inheritance mode, whose underlying mechanism remains unclear. Here, we report the generation of an iPSC line from a female patient with CMT and FSGS. The iPSC line from the patient's PBMCs carried a heterozygous INF2 deletion mutation (c.315_323delGCGCGCCGT) within the conserved E2. This line exhibited a normal karyotype, high expression of pluripotency markers, and trilineage differentiation potential. This line can be used to dissect the complex pathomechanism through further induction of differentiation into related cells and as a drug screening tool for INF2-associated diseases.

Abstract In the latter half of the twentieth century, a significant climate phenomenon “diurnal asymmetric warming” emerged, wherein global land surface temperatures increased more rapidly during the night than during the day. However, recent episodes of global brightening and regional droughts and heatwaves have brought notable alterations to this asymmetric warming trend. Here, we re-evaluate sub-diurnal temperature patterns, revealing a substantial increase in the warming rates of daily maximum temperatures (Tmax), while daily minimum temperatures have remained relatively stable. This shift has resulted in a reversal of the diurnal warming trend, expanding the diurnal temperature range over recent decades. The intensified Tmax warming is attributed to a widespread reduction in cloud cover, which has led to increased solar irradiance at the surface. Our findings underscore the urgent need for enhanced scrutiny of recent temperature trends and their implications for the wider earth system.

BackgroundPublic places are frequently polluted by cigarette smoking, and there is a lack of accurate, real-time, and intelligent monitoring technology to identify smoking behavior. It is necessary to develop a tool to identify cigarette smoking behavior in public places for more efficient control of cigarette smoking and better indoor air quality. ObjectiveTo construct a model for recognizing cigarette smoking behavior based on real-time indoor concentrations of PM2.5 in public places. MethodsReal-time indoor PM2.5 concentrations were measured for at least 7 continuous days in 10 arbitrarily selected places (6 public service providers and and 4 office or other places) from Oct. to Nov. 2022 in Pudong New Area, Shanghai. Indoor nicotine concentrations were monitored with passive samplers simultaneously. Outdoor PM2.5 concentration data were obtained from three municipal environmental monitoring stations which were nearest to each monitoring point during the same period. Mann-Whitney U test was used to compare indoor and outdoor means of PM2.5 concentrations, and Spearman rank correlation was used to analyze indoor PM2.5 and nicotine concentrations. An interactive plot and a random forest model was applied to examine the association between video observation validated indoor smoking behavior and real-time indoor PM2.5 concentrations in an Internet cafe. ResultsThe average indoor PM2.5 concentration in the places providing public services [(97.5±149.3) µg·m−3] was significantly higher than that in office and other places [(19.8±12.2) µg·m−3] (P=0.011). The indoor/outdoor ratio (I/O ratio) of PM2.5 concentration in the public service providers ranged from 1.1 to 19.0. Furthermore, the indoor PM2.5 concentrations in the 10 public places were significantly correlated with the nicotine concentrations (rs=0.969, P

Abstract Backgrounds Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent. Objective The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls. Methods PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model. Results A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH. Conclusion Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.

Abstract Objective Many studies have investigated the impact of precocious puberty on cardiovascular disease (CVD) outcomes and the association between lipid profile levels and precocious puberty. However, the results have been inconsistent. The aim of this meta-analysis was to evaluate whether triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL)and low density lipoprotein (LDL) levels were altered in girls with precocious puberty compared with healthy controls. Methods References published before June 2022 in the EMBASE, Cochrane Library, PubMed and Web of Science databases were searched to identify eligible studies. A DerSimonian-Laird random-effects model was used to evaluate the overall standard mean difference (SMD) between precocious puberty and healthy controls. Subgroup analyses and sensitivity analyses were preformed, and publication bias was assessed. Results A total of 14 studies featuring 1023 girls with precocious puberty and 806 healthy girls were selected for analysis. The meta-analysis showed that TG (SMD: 0.28; 95% CI: 0.01 to 0.55; P = 0.04), TC (SMD: 0.30; 95% CI: 0.01 to 0.59; P = 0.04), LDL (SMD: 0.45; 95% CI: 0.07 to 0.84; P = 0.02)levels were significantly elevated in girls with precocious puberty. HDL levels did not change significantly (SMD: -0.06; 95% CI: -0.12 to 0.61; P = 0.62). Subgroup analyses revealed that the heterogeneity in the association between lipid profile and precocious puberty in this meta-analysis may arise from disease type, region, sample size, chronological age, body mass index difference and drug usage. Conclusion Lipid profile levels altered in girls with precocious puberty compared with healthy controls. In order to minimize the risk of CVD morbidity and mortality, early interventions were needed to prevent obesity in children and adolescents, especially those with precocious puberty.

To address the challenges in recognizing various types of falls, which often exhibit high similarity and are difficult to distinguish, this paper proposes a human fall classification system based on the SE-Residual Concatenate Network (SE-RCNet) with adaptive weighted fusion. First, we designed the innovative SE-RCNet network, incorporating SE modules after dense and residual connections to automatically recalibrate feature channel weights and suppress irrelevant features. Subsequently, this network was used to train and classify three types of radar images: time–distance images, time–distance images, and distance–distance images. By adaptively fusing the classification results of these three types of radar images, we achieved higher action recognition accuracy. Experimental results indicate that SE-RCNet achieved F1-scores of 94.0%, 94.3%, and 95.4% for the three radar image types on our self-built dataset. After applying the adaptive weighted fusion method, the F1-score further improved to 98.1%.

Clubroot is a major disease and severe threat to Chinese cabbage, and it is caused by the pathogen Plasmodiophora brassicae Woron. This pathogen is an obligate biotrophic protist and can persist in soil in the form of resting spores for more than 18 years, which can easily be transmitted through a number of agents, resulting in significant economic losses to global Chinese cabbage production. Rhizosphere microbiomes play fundamental roles in the occurrence and development of plant diseases. The changes in the rhizosphere microorganisms could reveal the severity of plant diseases and provide the basis for their control. Here, we studied the rhizosphere microbiota after clubroot disease infections with different severities by employing metagenomic sequencing, with the aim of exploring the relationships between plant health, rhizosphere microbial communities, and soil environments; then, we identified potential biomarker microbes of clubroot disease. The results showed that clubroot disease severity significantly affected the microbial community composition and structure of the rhizosphere soil, and microbial functions were also dramatically influenced by it. Four different microbes that had great potential in the biocontrol of clubroot disease were identified from the obtained results; they were the genera Pseudomonas, Gemmatimonas, Sphingomonas, and Nocardioides. Soil pH, organic matter contents, total nitrogen, and cation exchange capacity were the major environmental factors modulating plant microbiome assembly. In addition, microbial environmental information processing was extremely strengthened when the plant was subjected to pathogen invasion, but weakened when the disease became serious. In particular, oxidative phosphorylation and glycerol-1-phosphatase might have critical functions in enhancing Chinese cabbage’s resistance to clubroot disease. This work revealed the interactions and potential mechanisms among Chinese cabbage, soil environmental factors, clubroot disease, and microbial community structure and functions, which may provide a novel foundation for further studies using microbiological or metabolic methods to develop disease-resistant cultivation technologies.

Abstract Increasing atmospheric CO2 causes substantial spatial and seasonal changes in air temperature and precipitation through its radiative (RAD) and vegetation physiological (PHY) effects. However, it remains poorly understood on how these two effects impact the integrated climate zone shifts over China. Here, we disentangle the RAD and PHY effects on the shifts of Köppen‐Geiger climate zones from pre‐industrial to 4 × CO2 in China using nine Earth system models. We find that climate zone changes over approximately 56.1% of China, and PHY contributes 15.2% of such changes at 4 × CO2. PHY shifts regional climate to warmer and wetter classifications, shrinking (−42.8%) the arid zone distributions and promoting (26.8%) the tropical zone northward extensions. Our findings highlight the critical role of vegetation in reshaping the overall climate zone distributions, yet introduce potential risk to climate mitigation and adaptation.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1β. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

The Multi-access Edge Computing (MEC) network enhances the processing capability of Internet of Things (IoT) terminals by deploying 3C resources (computing resources, cache resources, and communication resources) at the IoT edge side, effectively improving the quality of service (QoS) of IoT applications. The majority of current MEC network research focuses on task offloading and energy management, with few studies looking at resource allocation from a service provisioning perspective. In this paper, we focus on the resource allocation problem when processing multiple tasks requested by IoT terminal devices in the MEC network. Firstly, we transform various tasks requested by IoT end devices into an SFC-based resource allocation problem. Then, we model the problem as a graph theory-based virtualized network function (VNF) node deployment cost optimization problem. Furthermore, we propose two resource allocation and deployment strategies by jointly considering the computing cost and security cost in VNF node deployment. Finally, extensive simulation experiments show that the proposed method can significantly improve the success rate of SFC task processing by more than 30% and network resource utilization by more than 20% when compared to other deployment methods for processing multiple SFC tasks with dynamic requests.

Objective The association between prepregnancy body mass index (BMI) or gestational weight gain (GWG) and adverse pregnancy outcomes among Chinese women with gestational diabetes mellitus (GDM) is unknown. This study aims to evaluate such association by synthesising the evidence.Design Systematic review and meta-analysis.Data sources PubMed, Web of Science, Scopus, EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wangfang, and China Science and Technology Journal Database searched from inception to 11 August 2023.Eligibility criteria Prospective cohort studies, retrospective cohort studies and case–control studies estimating the relationship of abnormal prepregnancy BMI (including underweight, overweight or obesity) or inappropriate GWG (including excess GWG or insufficient GWG) with adverse pregnancy outcomes of interest were included. Outcomes included macrosomia, caesarean section, preterm birth, gestational hypertension, large for gestational age (LGA) and small for gestational age (SGA).Data extraction and synthesis Two reviewers independently selected studies, extracted the data and assessed the risk of bias. OR estimate and its 95% CI were pooled using Stata software fixed-effect model. Subgroup analysis, meta-regression and sensitivity analysis were performed to ensure credibility of the results.Results Twenty-three studies (eighteen retrospective cohort studies, three prospective cohort studies and two case control studies) involving 57 013 Chinese women with GDM were identified. Meta-analysis results showed that compared with GDM women with normal weight, GDM women with underweight were at a higher risk of SGA (OR=1.79 (1.54 to 2.07), five studies involving 31 967 women); women with overweight had higher risks of macrosomia (OR=1.65 (1.49 to 1.82), eleven studies involving 41 683 women), caesarean section (OR=1.48 (1.38 to 1.59), ten studies involving 34 935 women), preterm birth (OR=1.27 (1.13 to 1.43), eight studies involving 38 295 women) and LGA (OR=1.73 (1.54 to 1.95), seven studies involving 31 342 women) and women with obesity had higher risks of macrosomia (OR=2.37 (2.04 to 2.76), eleven studies involving 41 683 women), caesarean section (OR=2.07 (1.84 to 2.32), nine studies involving 34 829 women), preterm birth (OR=1.31 (1.09 to 1.57), eight studies involving 38 295 women) and LGA (OR=2.63 (2.15 to 3.21), six studies involving 31 236 women). Regard to GWG, compared with Chinese GDM women with sufficient GWG, GDM women with excessive GWG had higher risks of macrosomia (OR=1.74 (1.58 to 1.92), twelve studies involving 40 966 women), caesarean section (OR=1.44 (1.36 to 1.53), nine studies involving 36 205 women) and LGA (OR=2.12 (1.96 to 2.29), twelve studies involving 42 342 women); women with insufficient GWG conversely had higher risks of preterm birth (OR=1.59 (1.45 to 1.74), nine studies involving 37 461 women) and SGA (OR=1.38 (1.27 to 1.51), ten studies involving 41 080 women).Conclusions For Chinese women with GDM, abnormal prepregnancy BMI or inappropriate GWG were related to higher risks of many adverse pregnancy outcomes. Therefore, medical staff should pay more attention to the weight management of GDM women during pregnancy.

Background Small for gestational age (SGA) poses a significant concern for newborns, being linked to neonatal complications and potential metabolic disorders in adulthood, especially when born to mothers with gestational diabetes mellitus (GDM), elevating their risk of complications and mortality. However, the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM remain unclear.Aim To identify the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM.Method This case–control study was conducted among 1910 women with GDM in China. Data were collected by the integrated electronic medical record system. Using 1:4 propensity score matching analysis, we adjusted for gestational age as confounder. Univariate and multivariate analyses were performed to identify risk factors.Results Risk factors for SGA born to mothers with GDM included a history of low birth weight, gestational hypertension, oligohydramnios, short maternal height, underweight pre-pregnancy body mass index and inadequate weight growth. While SGA was protected by weakly positive ketonuria levels in the first trimester, multiparous, anaemia and previous uterine scar were protective factors for SGA. Moreover, 2-hour postprandial glucose and haemoglobin A1c in the second trimester, as well as the 0-hour and 2-hour 75 g oral glucose tolerance test (OGTT) were linked to risk of SGA.Conclusions SGA infants are the result of multifactorial interactions among GDM pregnant women. Notably, glycaemic control levels were associated with SGA. There is a need for enhanced perinatal monitoring and antenatal care to reduce SGA.

Amid the ever-expanding landscape of financial data, the importance of predicting potential risks through artificial intelligence methodologies has steadily risen. To achieve prudent financial data management, this manuscript delves into the domain of intelligent financial risk forecasting within the scope of system design. It presents a data model based on the variational encoder (VAE) enhanced with an attention mechanism meticulously tailored for forecasting a company’s financial peril. The framework called the ATT-VAE embarks on its journey by encoding and enhancing multidimensional data through VAE. It then employs the attention mechanism to enrich the outputs of the VAE network, thereby demonstrating the apex of the model’s clustering capabilities. In the experimentation, we implemented the model to a battery of training tests using diverse public datasets with multimodal features like AWA and CUB and verified with the local finance dataset. The results conspicuously highlight the model’s commendable performance in comparison to publicly available datasets, surpassing numerous deep clustering networks at this juncture. In the realm of financial data, the ATT-VAE model, as presented within this treatise, achieves a clustering accuracy index exceeding 0.7, a feat demonstrably superior to its counterparts in the realm of deep clustering networks. The method outlined herein provides algorithmic foundations and serves as a pivotal reference for the prospective domain of intelligent financial data governance and scrutiny.

Background and aims: Obesity is one of the most prevalent diseases worldwide with less ideal approved agents in clinic. Activating the HSF1/PGC-1α axis in adipose tissues has been reported to induce thermogenesis in mice, which presents a promising therapeutic avenue for obesity treatment. The present study aimed to identified novel natural HSF1 activator and evaluated the therapeutic effects of the newly discovered compound on obesity-associated metabolic disorders and the molecular mechanisms of these effects.Methods: Our previous reported HSF1/PGC-1α activator screening system was used to identify novel natural HSF1 activator. The PGC-1α luciferase activity, immunoblot, protein nuclear-translocation, immunofluorescence, chromatin immunoprecipitation assays were used to evaluate the activity of compound HN-001 in activating HSF1. The experiments of mitochondrial number measurement, TG assay and imaging, cellular metabolic assay, gene assays, and CRISPR/Cas 9 were applied for investigating the metabolic effect of HN-001 in C3H10-T1/2 adipocytes. The in vivo anti-obesity efficacies and beneficial metabolic effects of HN-001 were evaluated by performing body and fat mass quantification, plasma chemical analysis, GTT, ITT, cold tolerance test, thermogenesis analysis.Results: HN-001 dose- and time-dependently activated HSF1 and induced HSF1 nuclear translocation, resulting in an enhancement in binding with the gene Pgc-1α. This improvement induced activation of adipose thermogenesis and enhancement of mitochondrial oxidation capacity, thus inhibiting adipocyte maturation. Deletion of HSF1 in adipocytes impaired mitochondrial oxidation and abolished the above beneficial metabolic effects of HN-001, including adipocyte browning induction, improvements in mitogenesis and oxidation capacity, and lipid-lowering ability. In mice, HN-001 treatment efficiently alleviated diet-induced obesity and metabolic disorders. These changes were associated with increased body temperature in mice and activation of the HSF1/PGC-1α axis in adipose tissues. UCP1 expression and mitochondrial biogenesis were increased in both white and brown adipose tissues of HN-001-treated mice.Conclusion: These data indicate that HN-001 may have therapeutic potential for obesity-related metabolic diseases by increasing the capacity of energy expenditure in adipose tissues through a mechanism involving the HSF1/PGC-1α axis, which shed new light on the development of novel anti-obesity agents derived from marine sources.

Abstract Background Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. Methods About 219 GC patients with ovarian metastasis in 2011–2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non‐conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. Results Ninety‐two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p

Abstract Fire carbon emissions over Equatorial Asia (EQAS) play a critical role in the global carbon cycle. Most regional fire emissions (89.0%) occur in the dry season, but how changes in the dry-season length affect the fire emissions remains poorly understood. Here we show that, the length of the EQAS dry season has decreased significantly during 1979–2021, and the delayed dry season onset (5.4 ± 1.6 (± one standard error) days decade−1) due to increased precipitation (36.4 ± 9.1 mm decade−1) in the early dry season is the main reason. The dry season length is strongly correlated with the length of the fire season. Increased precipitation during the early dry season led to a significant reduction (May: −0.7 ± 0.4 Tg C decade−1; August: −12.9 ± 6.7 Tg C decade−1) in fire carbon emissions during the early and peak fire season. Climate models from the Coupled Model Intercomparison Project Phase 6 project a continued decline in future dry season length in EQAS under medium and high-emission scenarios, implying further reductions in fire carbon emissions.

Previous reports have mainly investigated the long-term effects (>30 d), such as gut microbiota dysbiosis and systemic low-grade inflammation, in mice fed fried oil. However, short-term intake of deep-fried oil is more likely to occur in daily life, and such studies are lacking. This study aimed to investigate the short-term effects of fried oil intake on systemic low-grade inflammation. Male Kunming mice were fed non-fried soybean oil or low (25%), medium (50%), or high (100%)—fried oil at 4.4 g/kg for 6 d. Serum and fecal samples were collected on day 7. In all groups fed fried oil, the serum levels of tumor necrosis factor (TNF-α) were significantly elevated 2-4-fold. Among the gut microbiota, the abundance of Alloprevotella significantly decreased by up to 76%, while Lactobacilli significantly increased by up to 385%. The fecal valeric acid content was significantly increased and positively correlated with TNF-α levels. Both valeric acid and TNF-α levels were positively correlated with the abundance of Lactobacilli and negatively correlated with that of Alloprevotella. In summary, a short-term ingestion of even low doses of fried oil alters the gut microbiota Alloprevotella and Lactobacilli and increases fecal valeric acid content, which correlates with increased serum TNF-α levels.

The direct 1,6-nucleophilic difluoromethylation, trifluoromethylation, and difluoroalkylation of para-quinone methides (p-QMs) with Me3SiRf (Rf = CF2H, CF3, CF2CF3, CF2COOEt, and CF2SPh) under mild conditions are described. Although Me3SiCF2H shows lower reactivity than Me3SiCF3, it can react with p-QMs promoted by CsF/18-Crown-6 to give structurally diverse difluoromethyl products in good yields. The products can then be further converted into fluoroalkylated para-quinone methides and α-fluoroalkylated diarylmethanes.

Chronic stress (CS) endangers the physical and mental health of adolescents. Therefore, alleviating and preventing such negative health impacts are a top priority. This study explores the effect of feeding shrimp head hydrolysate (SHH) on gut microbiota, short-chain fatty acids (SCFAs), and neurotransmitters in growing C57BL/6 mice subjected to chronic unpredictable mild stress. Mice in the model group and three SHH groups were exposed to CS for 44 days, distilled water and SHH doses of 0.18, 0.45, 0.90 g/kg·BW were given respectively by gavage daily for 30 days from the 15th day. The results showed that SHH can significantly reverse depression-like behaviour, amino acids degradation, α diversity and β diversity, proportion of Firmicutes and Bacteroidota, abundance of genera such as Muribaculaceae, Bacteroides, Prevotellaceae_UCG-001, Parabacteroides and Alistipes, concentration of five short-chain fatty acids (SCFAs), 5-HT and glutamate induced by CS. Muribaculaceae and butyric acid may be a controlled target. This study highlights the potential and broad application of SHH as an active ingredient in food to combat chronic stress damage.

Abstract Background Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging. Results Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment. Conclusion Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

Abstract Background Metabolic reprogramming is a critical event for cell fate and function, making it an attractive target for clinical therapy. The function of metabolic reprogramming in Helicobacter pylori (H. pylori)-infected gastric intestinal metaplasia remained to be identified. Methods Xanthurenic acid (XA) was measured in gastric cancer cells treated with H. pylori or H. pylori virulence factor, respectively, and qPCR and WB were performed to detect CDX2 and key metabolic enzymes expression. A subcellular fractionation approach, luciferase and ChIP combined with immunofluorescence were applied to reveal the mechanism underlying H. pylori mediated kynurenine pathway in intestinal metaplasia in vivo and in vitro. Results Herein, we, for the first time, demonstrated that H. pylori contributed to gastric intestinal metaplasia characterized by enhanced Caudal-related homeobox transcription factor-2 (CDX2) and mucin2 (MUC2) expression, which was attributed to activation of kynurenine pathway. H. pylori promoted kynurenine aminotransferase II (KAT2)-mediated kynurenine pathway of tryptophan metabolism, leading to XA production, which further induced CDX2 expression in gastric epithelial cells. Mechanically, H. pylori activated cyclic guanylate adenylate synthase (cGAS)-interferon regulatory factor 3 (IRF3) pathway in gastric epithelial cells, leading to enhance IRF3 nuclear translocation and the binding of IRF3 to KAT2 promoter. Inhibition of KAT2 could significantly reverse the effect of H. pylori on CDX2 expression. Also, the rescue phenomenon was observed in gastric epithelial cells treated with H. pylori after IRF3 inhibition in vitro and in vivo. Most importantly, phospho-IRF3 was confirmed to be a clinical positive relationship with CDX2. Conclusion These finding suggested H. pylori contributed to gastric intestinal metaplasia through KAT2-mediated kynurenine pathway of tryptophan metabolism via cGAS-IRF3 signaling, targeting the kynurenine pathway could be a promising strategy to prevent gastric intestinal metaplasia caused by H. pylori infection. Video Abstract

Abstract Background Mitochondrial metabolism has been proposed as an attractive target for breast cancer therapy. The discovery of new mechanisms underlying mitochondrial dysfunction will facilitate the development of new metabolic inhibitors to improve the clinical treatment of breast cancer patients. DYNLT1 (Dynein Light Chain Tctex-Type 1) is a key component of the motor complex that transports cellular cargo along microtubules in the cell, but whether and how DYNLT1 affects mitochondrial metabolism and breast cancer has not been reported. Methods The expression levels of DYNLT1 were analyzed in clinical samples and a panel of cell lines. The role of DYNLT1 in breast cancer development was investigated using in vivo mouse models and in vitro cell assays, including CCK-8, plate cloning and transwell assay. The role of DYNLT1 in regulating mitochondrial metabolism in breast cancer development is examined by measuring mitochondrial membrane potential and ATP levels. To investigate the underlying molecular mechanism, many methods, including but not limited to Co-IP and ubiquitination assay were used. Results First, we found that DYNLT1 was upregulated in breast tumors, especially in ER + and TNBC subtypes. DYNLT1 promotes the proliferation, migration, invasion and mitochondrial metabolism in breast cancer cells in vitro and breast tumor development in vivo. DYNLT1 colocalizes with voltage-dependent anion channel 1 (VDAC1) on mitochondria to regulate key metabolic and energy functions. Mechanistically, DYNLT1 stabilizes the voltage-dependent anion channel 1 (VDAC1) by hindering E3 ligase Parkin-mediated VDAC1 ubiquitination and degradation. Conclusion Our data demonstrate that DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting Parkin-mediated ubiquitination degradation of VDAC1. This study suggests that mitochondrial metabolism can be exploited by targeting the DYNLT1-Parkin-VDAC1 axis to improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC).

Abstract The Li metal is an ideal anode material owing to its high theoretical specific capacity and low electrode potential. However, its high reactivity and dendritic growth in carbonate-based electrolytes limit its application. To address these issues, we propose a novel surface modification technique using heptafluorobutyric acid. In-situ spontaneous reaction between Li and the organic acid generates a lithiophilic interface of lithium heptafluorobutyrate for dendrite-free uniform Li deposition, which significantly improves the cycle stability (Li/Li symmetric cells >1200 h at 1.0 mA cm−2) and Coulombic efficiency (>99.3%) in conventional carbonate-based electrolytes. This lithiophilic interface also enables full batteries to achieve 83.2% capacity retention over 300 cycles under realistic testing condition. Lithium heptafluorobutyrate interface acts as an electrical bridge for uniform lithium-ion flux between Li anode and plating Li, which minimizes the occurrence of tortuous lithium dendrites and lowers interface impedance.

Abstract Background Emerging studies have shown that pyroptosis plays a non-negligible role in the development and treatment of tumors. However, the mechanism of pyroptosis in colorectal cancer (CRC) remains still unclear. Therefore, this study investigated the role of pyroptosis in CRC. Methods A pyroptosis-related risk model was developed using univariate Cox regression and LASSO Cox regression analyses. Based on this model, pyroptosis-related risk scores (PRS) of CRC samples with OS time > 0 from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were calculated. The abundance of immune cells in CRC tumor microenvironment (TME) was predicted by single-sample gene-set enrichment analysis (ssGSEA). Then, the responses to chemotherapy and immunotherapy were predicted by pRRophetic algorithm, the tumor immune dysfunction and exclusion (TIDE) and SubMap algorithms, respectively. Moreover, the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset (PRISM) were used to explore novel drug treatment strategies of CRC. Finally, we investigated pyroptosis-related genes in the level of single-cell and validated the expression levels of these genes between normal and CRC cell lines by RT-qPCR. Results Survival analysis showed that CRC samples with low PRS had better overall survival (OS) and progression-free survival (PFS). CRC samples with low PRS had higher immune-related gene expression and immune cell infiltration than those with high PRS. Besides, CRC samples with low PRS were more likely to benefit from 5-fluorouracil based chemotherapy and anti-PD-1 immunotherapy. In novel drug prediction, some compounds such as C6-ceramide and noretynodrel, were inferred as potential drugs for CRC with different PRS. Single-cell analysis revealed pyroptosis-related genes were highly expressed in tumor cells. RT-qPCR also demonstrated different expression levels of these genes between normal and CRC cell lines. Conclusions Taken together, this study provides a comprehensive investigation of the role of pyroptosis in CRC at the bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) levels, advances our understanding of CRC characteristics, and guides more effective treatment regimens. Graphical Abstract

Abstract The relationship between serum creatinine and type 2 diabetes is limited. We aimed to investigate the association of baseline serum creatinine and new-onset type 2 diabetes in Chinese population. This retrospective cohort study was conducted using data from the health screening program in China. The population were divided into four groups based on serum creatinine levels, and the outcome of interest was the occurrence of a diabetic event. Cox proportional risk model was used to assess the independent effect of baseline serum creatinine level on future diabetes risk. Sensitivity and subgroup analysis were used to verify the reliability of the results. After an average follow-up of 3.12 years, among 201,298 individuals aged ≥ 20 years, 3389 patients developed diabetes. Compared with participants in quartile 2–4 (> 51.6umol/L for female, > 71.8umol/L for male,), a significantly higher risk of new-onset Type 2 Diabetes (OR, 1.15; 95%CI: 1.07–1.23) was found in those in quartile 1 (

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.