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Abstract Purpose Glycolysis and immune metabolism play important roles in acute myocardial infarction (AMI). Therefore, this study aimed to identify and experimentally validate the glycolysis-related hub genes in AMI as diagnostic biomarkers, and further explore the association between hub genes and immune infiltration. Methods Differentially expressed genes (DEGs) from AMI peripheral blood mononuclear cells (PBMCs) were analyzed using R software. Glycolysis-related DEGs (GRDEGs) were identified and analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for functional enrichment. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape software. Immune infiltration analysis between patients with AMI and stable coronary artery disease (SCAD) controls was performed using CIBERSORT, and correlation analysis between GRDEGs and immune cell infiltration was performed. We also plotted nomograms and receiver operating characteristic (ROC) curves to assess the predictive accuracy of GRDEGs for AMI occurrence. Finally, key genes were experimentally validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting using PBMCs. Results A total of 132 GRDEGs and 56 GRDEGs were identified on the first day and 4–6 days after AMI, respectively. Enrichment analysis indicated that these GRDEGs were mainly clustered in the glycolysis/gluconeogenesis and metabolic pathways. Five hub genes (HK2, PFKL, PKM, G6PD, and ALDOA) were selected using the cytoHubba plugin. The link between immune cells and hub genes indicated that HK2, PFKL, PKM, and ALDOA were significantly positively correlated with monocytes and neutrophils, whereas G6PD was significantly positively correlated with neutrophils. The calibration curve, decision curve analysis, and ROC curves indicated that the five hub GRDEGs exhibited high predictive value for AMI. Furthermore, the five hub GRDEGs were validated by RT-qPCR and western blotting. Conclusion We concluded that HK2, PFKL, PKM, G6PD, and ALDOA are hub GRDEGs in AMI and play important roles in AMI progression. This study provides a novel potential immunotherapeutic method for the treatment of AMI.

BackgroundAt present, occupational poisoning has become one of the most serious occupational diseases that jeopardize the health of workers in China, in addition to pneumoconiosis, with a wide range of impacts and heavy social and economic losses.ObjectiveTo analyze the characteristics and patterns of the incidence of occupational poisoning in Tianjin from 2006 to 2020, and to provide a scientific basis for the development of effective intervention measures and prevention strategies.MethodsThe Occupational Diseases and Health Hazards Monitoring Information System, a module of the China Disease Prevention and Control Information System, was the primary data source of the study. The case files of acute and chronic occupational poisoning diagnosed by occupational disease diagnostic institutions in Tianjin from January 1, 2006 to December 31, 2020 were retrieved from the system. The data included basic information, occupational history, disease characteristics, and employer information. Excel 2016 was used to establish database, and frequencies and composition ratios were reported.ResultsFrom 2006 to 2020, a total of 234 cases of occupational chemical poisoning were reported in Tianjin, including 49 cases of acute occupational poisoning (20.94%) and 185 cases of chronic occupational poisoning (79.06%). The number of acute occupational poisoning cases showed a rising and then falling trend, and the number of chronic occupational poisoning cases showed an overall decreasing trend. Acute occupational poisoning mainly occurred in the four districts around the city (22 cases, 44.90%), and chronic occupational poisoning mainly occurred in Binhai New Area (90 cases, 48.65%). More male cases were reported than female cases. The age of onset was concentrated at 45-55 years old. The acute occupational poisoning cases were concentrated in the group with less than 5 years of service (22 cases, 44.90%), mainly asphyxiating gas poisoning, and the highest incidence was reported in chemical raw materials and chemical products manufacturing industry. The chronic occupational poisoning cases were concentrated in the groups with a working age of 5-14 years (70 cases, 37.84%), mainly organic solvent poisoning, and the highest incidence was also reported in chemical raw materials and chemical products manufacturing industry.ConclusionThe prevention and control of occupational poisoning as well as health surveillance and management in Tianjin shall be carried out in a hierarchical and focused manner in accordance with types of acute and chronic occupational poisoning chemicals in the city, regional economic differences, types of industries, and distribution of workers.

Abstract Aims Few studies have investigated differences in sequential transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and simultaneous RFA‐TACE for the treatment of hepatocellular carcinoma (HCC) using the Milan criteria. This study explored the differences in safety and prognosis between sequential TACE‐RFA and simultaneous RFA‐TACE. Methods This retrospective real‐world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE‐RFA (n = 75) or simultaneous RFA‐TACE (n = 34) at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021. Postoperative complications, length of hospital stay, and long‐term prognosis were compared. The median follow‐up duration of these patients was 39.1 months. Overall survival (OS) and time to tumor recurrence (TTR) curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test. Independent risk factors for OS and tumor recurrence (TR) were analyzed using the Cox risk regression model. Results Multivariate analysis showed that tumor diameter >3 cm (hazard ratio [HR]: 2.201, 95% confidence interval [CI]: 1.106–4.378, p = 0.025; HR: 2.236, 95% CI: 1.271–3.934, p = 0.005, respectively) and alpha‐fetoprotein (AFP) > 400 μg/L (HR: 2.362, 95% CI: 1.195–4.668, p = 0.013; HR: 1.798, 95% CI: 1.048–3.086, p = 0.033, respectively) were independent risk factors for OS and TTR, whereas the presence of multiple tumors (HR: 2.352, 95% CI: 1.127–4.907, p = 0.023) was an independent risk factor for TTR. Simultaneous RFA‐TACE did not have an effect on OS or TTR. After propensity score‐matched, comparable results were obtained and RFA‐TACE still had no effect on OS or TTR. No significant differences were observed in grade III/IV complications (2/75 [2.7%] vs. 1/34 [2.9%], p = 1.000) between the two groups. However, the RFA‐TACE group had fewer complications than the TACE‐RFA group (24/34 [70.6%] vs. 66/75 [88.0%], p = 0.026). The RFA‐TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE‐RFA group (6.0 vs. 10.0 days, p

Abstract Anthropogenic climate warming is predicted to increase the intensity of global tropical cyclones (TCs) on decadal timescales, known as the ‘temperature-TC intensity’ paradigm. However, no proxy is currently available to directly quantify TC intensity in the northwestern Pacific region over centennial to millennial timescales. Here, we reconstruct the intensity of past TCs inferred from event-beds detected in two sedimentary systems in eastern China spanning approximately 1910 to 645 yr BP using an instrumental-calibrated technique, thereby encompassing a sufficiently wide range of temperatures to test the paradigm in the time domain. Intriguingly, our two intensity indices, based on flooding depth and wind speed, provide the initial quantitative evidence that TC intensity in eastern China has been anomalously weak since around 1485 ± 45 yr BP, with a reduction of approximately 30 ± 8% in intensity, despite no concurrent temperature shift. This reduction appears to have been pre-conditioned by a combined influence of a weaker El Niño-Southern Oscillation, a stronger Atlantic Meridional Overturning Circulation, and an increased level of Saharan dust. We suggest that the magnitudes of these factors may have crossed a tipping point and have not reverted to their pre-shift levels since that time, resulting in their impact on TC intensity exceeding that of temperature by triggering changes in the oceanic and atmospheric state within the tropical Pacific region where TCs originate.

Abstract Objectives This randomized controlled trial compared the efficacy and tolerability of danzhixiaoyao pills in the accurate treatment of patients with burning mouth syndrome (BMS). Method Collect a total of 78 patients (75 female patients and 3 male patients) from the oral mucosa department who were considered eligible fromOctober 2020 to October 2022.The patients were randomized and divided into trial group and control group.The trail group received danzhixiaoyao pills and mecobalamine tablets while the control group was given mecobalamine tablets.The Visual Analogue Scale (VAS), Beck Anxiety Inventory(BAI), Beck Depression Inventory (BDI), Oral Health Impact Profile (OHIP-14), Traditional Chinese medicine(TCM) syndrome integral and adverse reactions were performed at baseline and after 2, 4, and 6 weeks of treatment. Descriptive statistics, including the Wilcoxon rank-sum test and the Chi-square test for median comparisons between different times, were used. Result 1.After treatment, the VAS, BDI,OHIP-14, and TCM syndrome integral in the trial group had a significant decrease than the control group(P< 0.05).However, there was no statistical difference in the BAI scores between the two groups (P> 0.05). 2.According to the efficacy determination criteria , the total effective rate of the test group was 73.68% , the control group was 52.94% and the recurrence rate was 0. There was a significant difference between the two groups (Z=-2.688, P < 0.05). The results showed that the curative effect of test group was better than that of control group.3. No adverse effects occurred in patients in either group. Conclusion Danzhixiaoyao pills has demonstrated to have a positive effect in relieving BMS symptoms and in improving a patient's overall quality of life with no AEs compared with the control group. The efficacy evaluation systems that can be verified and complementary in this study provide a perfect, effective and referential evaluation system for the use of Chinese patent medicine in the treatment of oral mucosal diseases. Trial Registration Registry name: Chinese Clinical trail Registry Registration number: ChiCTR2000038189 Date of Registration: 2020-09-13 Please visit ( https://www.chictr.org.cn/showproj.html?proj=61462 ) to the protocol.

An in vitro simulation of digestion and fermentation model with feces bacteria was used to explore the probiotic capacity of Polyonatum cyrtonema Hua. polysaccharide (PCP) by 16S rDNA gene sequencing and determining changes in short-chain fatty acids via GC-MS. The results showed that the digestibility of PCP was not obviously found by in vitro simulating saliva-gastrointestinal digestion model. The addition of PCP could rapidly reduce the pH of fermentation broth. PCoA analysis showed that PCP had the effect of altering gut microbiota, which was similar with inulin. At the phylum level, compared to the blank control group, the relative abundance of Firmicutes and Actinomycetes was significantly increased (P

Collaborative programming is being increasingly used to overcome the difficulties of the individual programming process. In this study, we investigated the effect of collaborative perception on cognitive engagement and learning outcomes in collaborative programming. We used a quasi-experimental research to determine the differences in cognitive engagement and learning outcomes of three groups with different levels of collaborative perception. The findings highlight several important conclusions. First, there were significant differences in cognitive engagement and learning outcomes across collaborative perception groups. Students with high levels of collaborative perception demonstrate more comprehensive and diverse cognitive engagement, resulting in higher learning outcomes compared to those with lower perception. Second, students in the low collaborative perception group had more Clarification-Elaboration cognitive connections, and students in the high collaborative perception group had stronger Clarification-Positioning and Clarification-Verification cognitive connections. Third, collaborative perception positively moderated the relationship between cognitive engagement and learning outcomes. In particular, three cognitive engagement, Clarification, Elaboration, and Positioning, had a greater impact on performance when moderated by collaborative perceptions. These findings have practical implications for educators and course designers, emphasizing the importance of considering students' collaborative perception when forming groups and promoting effective collaborative programming.

BackgroundThe association between dietary zinc intake and epilepsy remains unclear. This study aimed to investigate the relationship between zinc intake from the diet and epilepsy, employing Mendelian randomization (MR) to explore potential causal links between zinc and epilepsy.MethodsThe cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. Among the 4,434 participants included, 1.5% (67/4,434) reported having epilepsy. Restricted cubic spline models and logistic regression models were employed to examine the relationships between dietary zinc intakes and epilepsy. Subsequently, a 2-sample Mendelian randomization (MR) analysis was conducted using the inverse variance weighted (IVW) approach as the primary analysis.ResultsIn the restricted cubic spline (RCS) analysis, the relationship between dietary zinc consumption and epilepsy displayed an L-shaped curve (nonlinear, p = 0.049). After multivariate adjustments, the adjusted odds ratios for epilepsy in T2 (5.0–11.0 mg/day) and T3 (≥11.0 mg/day) were 0.49 (95% confidence interval [CI]: 0.26–0.92, p = 0.026) and 0.60 (95% CI: 0.31–1.17, p = 0.132), respectively, compared to the lowest dietary zinc consumption tertile (T1, ≤5.0 mg/day). The IVW method indicated that genetically predicted zinc intake per standard-deviation increase was inversely associated with three types of epilepsy, including all types of epilepsy (OR = 1.06, 95% CI: 1.02–1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01–1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00–1.02, p = 0.025).ConclusionOur findings suggest that a daily zinc intake ranging from 5.0 to 11.0 mg is associated with the lowest risk of epilepsy. Furthermore, Mendelian randomization (MR) studies provide additional support for the existence of a causal relationship between zinc and epilepsy.

BackgroundPrevious observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM.MethodsTo investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO.ResultsThe results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41–0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings.ConclusionThis study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Zn2P2O7, a representative material in the A2P2O7 family, exhibits negative thermal expansion (NTE) and possesses a remarkable negative linear expansion coefficient. Here we employ variable temperature and high-pressure Raman spectroscopy to investigate the phonon anomalies arising from the α- to β-phase transition in Zn2P2O7. Combing with the refinement results of our X-ray diffraction (XRD) experiment, we have identified the specific variations of the bond lengths, bond angles and the polyhedral distortion indexes that result in the phonon anomalies. Some certain phonons, whose energy decreases with increasing pressure, have been demonstrated to give rise to negative Grüneisen parameters that can characterize phonon anharmonicity and lead to lower thermal expansion in the α-phase of Zn2P2O7 compared to the β-phase. These results provide new insight into the relationship between lattice deformation and phonon anomalies during the structural phase transition in the NTE material Zn2P2O7.

Abstract Background Early and exclusive breastfeeding may reduce neonatal and post-neonatal mortality in low-resource settings. However, prelacteal feeding (PLF), the practice of giving food or liquid before breastfeeding is established, is still a barrier to optimal breastfeeding practices in many South Asian countries. We used a prospective cohort study to assess the association between feeding non-breastmilk food or liquid in the first three days of life and infant size at 3–5 months of age. Methods The analysis used data from 3,332 mother-infant pairs enrolled in a randomized controlled trial in northwestern rural Bangladesh conducted from 2018 to 2019. Trained interviewers visited women in their households during pregnancy to collect sociodemographic data. Project staff were notified of a birth by telephone and interviewers visited the home within approximately three days and three months post-partum. At each visit, interviewers collected data on breastfeeding practices and anthropometric measures. Infant length and weight measurements were used to produce length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores. We used multiple linear regression to assess the association between anthropometric indices and PLF practices, controlling for household wealth, maternal age, weight, education, occupation, and infant age, sex, and neonatal sizes. Results The prevalence of PLF was 23%. Compared to infants who did not receive PLF, infants who received PLF may have a higher LAZ (Mean difference (MD) = 0.02 [95% CI: -0.04, 0.08]) score, a lower WLZ (MD=-0.06 [95% CI: -0.15, 0.03]) score, and a lower WAZ (MD=-0.02 [95% CI: -0.08, 0.05]) score at 3–5 months of age, but none of the differences were statistically significant. In the adjusted model, female sex, larger size during the neonatal period, higher maternal education, and wealthier households were associated with larger infant size. Conclusion PLF was a common practice in this setting. Although no association between PLF and infant growth was identified, we cannot ignore the potential harm posed by PLF. Future studies could assess infant size at an earlier time point, such as 1-month postpartum, or use longitudinal data to assess more subtle differences in growth trajectories with PLF. Trial registration ClinicalTrials.gov: NCT03683667 and NCT02909179.

Abstract Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Abstract Limited knowledge exists regarding the ramifications of climate warming on death burden from neurodegenerative diseases. Here, we conducted a nationwide, individual-level, case-crossover study between 2013 and 2019 to investigate the effects of non-optimal temperatures on various neurodegenerative diseases and to predict the potential death burden under different climate change scenarios. Our findings reveal that both low and high temperatures are linked to increased risks of neurodegenerative diseases death. We project that heat-related neurodegenerative disease deaths would increase, while cold-related deaths would decrease. This is characterized by a steeper slope in the high-emission scenario, but a less pronounced trend in the scenarios involving mitigation strategies. Furthermore, we predict that the net changes in attributable death would increase after the mid-21st century, especially under the unrestricted-emission scenario. These results highlight the urgent need for effective climate and public health policies to address the growing challenges of neurodegenerative diseases associated with global warming.

Abstract Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long‐term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro‐basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743–0.857, p

Purpose The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process.Participants The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively.Findings to date The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly Bacteroides dorei, Bacteroides vulgatus and Escherichia coli, which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study.Future plans Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0–3 years and investigate the contribution of dietary factors in the process.Trial registration number ChiCTR2100049972

AbstractDual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.

BackgroundThe preoperative inflammatory condition significantly influences the prognosis of malignancies. We aimed to investigate the potential significance of preoperative inflammatory biomarkers in forecasting the long-term results of lung carcinoma after microwave ablation (MWA).MethodThis study included patients who received MWA treatment for lung carcinoma from Jan. 2012 to Dec. 2020. We collected demographic, clinical, laboratory, and outcome information. To assess the predictive capacity of inflammatory biomarkers, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of inflammatory biomarkers in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses.ResultsA total of 354 individuals underwent MWA treatment, of which 265 cases were included in this study, whose average age was 69.1 ± 9.7 years. The AUC values for the Systemic Inflammatory Response Index (SIRI) to overall survival (OS) and disease-free survival (DFS) were 0.796 and 0.716, respectively. The Cox proportional hazards model demonstrated a significant independent association between a high SIRI and a decreased overall survival (hazard ratio [HR]=2.583, P

BackgroundSeveral studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.MethodsIn this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium’s genome-wide association study (GWAS) and the GWAS Catalog’s HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran’s Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.ResultsIn the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23–5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18–0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11–0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06–0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09–0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04–0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21–0.98, p = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1–1.03, p = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.ConclusionOur analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.

BackgroundPrevious research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.MethodsWe used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy.ResultsThe analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available.ConclusionThe drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.

Designing the appearance of clothing can effectively enhance its attractiveness and expand its marketability. This paper briefly introduces the Convolutional Neural Network (CNN) and applies it to the recognition and evaluation of clothing pattern styles to assist in evaluating clothing appearance design. A case analysis was then conducted. Firstly, the CNN algorithm was compared with the traditional Back-Propagation Neural Network (BPNN) algorithm, and then the design scheme proposed in this paper, called "Sanduo and Jiuru", was evaluated. The results showed that, compared to the BPNN algorithm, the CNN algorithm not only converged faster during training but also demonstrated superiority after the convergence became stable. In addition, the test set also verified the accuracy of the CNN algorithm in recognizing and evaluating clothing pattern styles. The evaluation of the "Sanduo and Jiuru" design was also very similar to human evaluation, and its excellence was analyzed accordingly.

The article compares two works — «Manchurian Princess» by Russian emigrant writer A. Heidok and «Spring in a Small Town» by Chinese writer Xiao Hong, which were created in approximately the same epoch and reproduce the same place of action — the north-east of China. Heidok’s work appealed to the mystical ideas of Chinese culture (the idea of reincarnation); Xiao Hong’s work was deeply influenced by Russian classical literature. Both stories present a story of tragic love, which breaks the traditions of a conservative society and radically changes the lives of the characters. The meaning of the characters’ lives lies in returning to the true nature of man — love, because only in it does existence find meaning; at the same time, the theme of love is closely intertwined with the theme of death. In both works there is an intersection of different epochs — the past and the present; at the same time, it is the past that determines the course of events of the present. Specific situations of the characters’ lives are revealed in a broad historical and cultural space, which allows the author to put before the readers the most important ethical and philosophical problems. A. Heidok’s story shows how life in the previous birth influences the actions of a person in subsequent births; in Xiao Hong’s story «the past» is the power of tradition, which does not allow a girl to get an education and determine her own destiny.

Abstract Neddylation is the writing of monomers or polymers of neural precursor cells expressed developmentally down-regulated 8 (NEDD8) to substrate. For neddylation to occur, three enzymes are required: activators (E1), conjugators (E2), and ligators (E3). However, the central role is played by the ubiquitin-conjugating enzymes E2M (UBE2M) and E2F (UBE2F), which are part of the E2 enzyme family. Recent understanding of the structure and mechanism of these two proteins provides insight into their physiological effects on apoptosis, cell cycle arrest and genome stability. To treat cancer, it is therefore appealing to develop novel inhibitors against UBE2M or UBE2F interactions with either E1 or E3. In this evaluation, we summarized the existing understanding of E2 interaction with E1 and E3 and reviewed the prospective of using neddylation E2 as a pharmacological target for evolving new anti-cancer remedies.

Corn straw is one kind of agricultural by-product containing 70–80% insoluble dietary fiber (IDF). In order to develop corn straw dietary fiber, this study was conducted to increase soluble dietary fiber (SDF) yield and improve the structure, functional and prebiotic properties of IDF and SDF from corn straw treated by alkali oxidation treatment, enzymatic hydrolysis, microbial fermentation and the combination of these methods. The results demonstrated that the yield of SDF was significantly increased from 2.64% to 17.15% after corn straw was treated by alkali oxidation treatment + Aspergillus niger fermentation + cellulase hydrolysis, compared with untreated corn straw. The SDF extracted from corn straw treated by alkali oxidation treatment + Aspergillus niger fermentation + cellulase hydrolysis (F-SDF) exhibited a honeycomb structure, low crystallinity (11.97%), good antioxidant capacity and high capacities of water holding, water solubility and cholesterol absorption and promoted short-chain fatty acids production by chicken cecal microbial fermentation in vitro. F-SDF enhanced the antibacterial activity against Escherichia coli and Staphylococcus aureus proliferations of Lactobacillus plantarum when it was used as a substrate for Lactobacillus plantarum fermentation. It could be concluded that the combined treatments could increase SDF yield from corn straw and improve its functional and prebiotic properties.

The economic and health significance of quinoa is steadily growing on a global scale. Nevertheless, the primary obstacle to achieving high yields in quinoa cultivation is pre-harvest sprouting (PHS), which is intricately linked to seed dormancy. However, there exists a dearth of research concerning the regulatory mechanisms governing PHS. The regulation of seed germination by various plant hormones has been extensively studied. Consequently, understanding the mechanisms underlying the role of endogenous hormones in the germination process of quinoa seeds and developing strategies to mitigate PHS in quinoa cultivation are of significant research importance. This study employed the HPLC-ESI-MS/MS internal standard and ELISA method to quantify 8 endogenous hormones. The investigation of gene expression changes before and after germination was conducted using RNA-seq analysis, leading to the discovery of 280 differentially expressed genes associated with the regulatory pathway of endogenous hormones. Additionally, a correlation analysis of 99 genes with significant differences identified 14 potential genes that may act as crucial “transportation hubs” in hormonal interactions. Through the performance of an analysis on the modifications in hormone composition and the expression of associated regulatory genes, we posit a prediction that implies the presence of a negative feedback regulatory mechanism of endogenous hormones during the germination of quinoa seeds. This mechanism is potentially influenced by the unique structure of quinoa seeds. To shed light on the involvement of endogenous hormones in the process of quinoa seed germination, we have established a regulatory network. This study aims to offer innovative perspectives on the breeding of quinoa varieties that exhibit resistance to PHS, as well as strategies for preventing PHS.

Abstract Background With the advancement of whole‐genome sequencing (WGS) technology, massively parallel sequencing (MPS) remains the mainstream due to its accuracy, low cost, and high throughput. The development of the analytical pipeline corresponding to MPS has always been of great importance. Increasingly large population genomics studies, as a specific type of big data research, pose new challenges for analysis solutions. Results Here, we introduce ZBOLT, a comprehensive analysis system that incorporates both software and hardware advancements, making it an appropriate choice for large‐scale population genomic studies that require extensive data processing. In this study, we first evaluate ZBOLT's calling accuracy using the Genome in a Bottle (GIAB) benchmark dataset. Then we apply ZBOLT to a large‐scale population genomics study with 5,616 high sequencing depth samples totaling 1.16Pbp (base pair). As the results show, ZBOLT demonstrates exceptional efficiency and low energy consumption, processing 100Tbp per day and using 1kWh per 100Gbp sequenced sample. Conclusion This research serves as a valuable reference for analyzing sequencing data from large population cohorts and underscores the significant potential of ZBOLT in large‐scale population genomics studies.

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease.

Summary: Background: It remains unknown how ambient temperature impact pneumonia of various infectious causes. Methods: Based on the national death registry covering all counties in Chinese mainland, we conducted an individual-level case-crossover study in China from 2013 to 2019. Exposures were assigned at residential addresses for each decedent. Conditional logistic regression model combined with distributed lag non-linear models were used to estimate the exposure-response associations. The attributable fractions due to non-optimum temperature were calculated after accounting for spatial and temporal patterns for the excess risks. Findings: The exposure-response curves were inversely J-shaped with both low and high temperature increasing the risks, and the effect of low temperature was stronger. Extremely low temperature was associated with higher magnitude of influenza-related pneumonia [relative risk (RR): 2.46, 95% confidence interval (CI): 1.62–3.74], than viral pneumonia (RR: 1.89, 95% CI: 1.55–2.30) and bacterial pneumonia (RR: 1.81, 95% CI: 1.56–2.09). The magnitudes of RRs associated with extremely high temperature were similar among the three categories of pneumonia. The mortality attributable fraction for influenza-related pneumonia (29.78%) was the highest. The effects were stronger in people of low education level or residence in the north. Interpretation: This nationwide study presents findings on the varied risk and burden of pneumonia mortality of various infectious causes, and highlights the susceptibility of influenza-related pneumonia to ambient low temperature. Funding: This study is supported by the National Key Research and Development Program (2022YFC3702701), the Shanghai Municipal Science and Technology Commission (21TQ015) and Shanghai International Science and Technology Partnership Project (21230780200).

This study delves into the exploration of genetic diversity and phylogenetic relationships within Camellia reticulata cultivars, providing a vital reference for horticultural research on this hetero-hexaploid species. Utilizing available transcriptome data from C. reticulata, novel low-copy nuclear gene sequences were successfully identified. With tailored primer design, these genes were amplified and sequenced from 100 C. reticulata cultivars originating from Kunming, Chuxiong, Dali, and Tengchong in China. Five distinct low-copy nuclear gene sequences were found to collectively span 3481 bp, showcasing 71 polymorphic mutation sites (Pi = 0.0077) and 91 haplotypes (Hd = 0.9974). The genetic diversity among cultivars from the four provenances ranked Tengchong > Dali > Kunming > Chuxiong. AMOVA analysis revealed that 96.50% of the genetic variation exists within the provenances. Low genetic distance and differentiation (Fst= 0.0199) were observed among cultivars from the four provenances. Ninety-nine cultivars were clustered into four clades, corresponding to the three ancestors of C. reticulata (diploid C. reticulata, C. pitardii, and C. saluenensis). The novel low-copy nuclear gene sequence markers developed in this study provide an effective tool for analyzing genetic diversity, phylogenetic relationships, and origination of C. reticulata cultivars.

Abstract Colonization and development of the gut microbiome are crucial for the growth and health of calves. In this review, we summarized the colonization, beneficial nutrition, immune function of gut microbiota, function of the gut barrier, and the evolution of core microbiota in the gut of calves of different ages. Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves. Disruption of the gut microbiome leads to digestive diseases in calves, such as diarrhea and intestinal inflammation. Microbiota already exists in the gut of calf fetuses, and the colonization of microbiota continues to change dynamically under the influence of various factors, which include probiotics, diet, age, and genotype. Colonization depends on the interaction between the gut microbiota and the immune system of calves. The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.

Abstract Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications. Graphical Abstract

Objectives To describe how systematic reviews with network meta-analyses (NMAs) that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) NMA approach addressed intransitivity when assessing certainty of evidence.Design Systematic survey.Data sources Medline, Embase and Cochrane Database of Systematic Reviews from September 2014 to October 2022.Eligibility criteria Systematic reviews of randomised controlled trials with aggregate data NMAs that used the GRADE NMA approach for assessing certainty of evidence.Data extraction and synthesis We documented how reviewers described methods for addressing intransitivity when assessing certainty of evidence, how often they rated down for intransitivity and their explanations for rating down.Results Of the 268 eligible systematic reviews, 44.8% (120/268) mentioned intransitivity when describing methods for assessing the certainty of evidence. Of these, 28.3% (34/120) considered effect modifiers and from this subset, 67.6% (23/34) specified the effect modifiers; however, no systematic review noted how they chose the effect modifiers. 15.0% (18/120) mentioned looking for differences between the direct comparisons that inform the indirect estimate. No review specified a threshold for difference in effect modifiers between the direct comparisons that would lead to rating down for intransitivity. Reviewers noted rating down indirect evidence for intransitivity in 33.1% of systematic reviews, and noted intransitivity for network estimates in 23.0% of reviews. Authors provided an explanation for rating down for intransitivity in 59.6% (31/52) of the cases in which they rated down. Of the 31 in which they provided an explanation, 74.2% (23/31) noted they detected differences in effect modifiers and 67.7% (21/31) specified in what effect modifiers they detected differences.Conclusions A third of systematic reviews with NMAs using the GRADE approach rated down for intransitivity. Limitations in reporting of methods to address intransitivity proved considerable. Whether the problem is that reviewers neglected to address rating down for transitivity at all, or whether they did consider but not report, is not clear. At minimum systematic reviews with NMAs need to improve their reporting practices regarding intransitivity; it may well be that they need to improve their practice in transitivity assessment. How to best address intransitivity may remain unclear for many reviewers thus additional GRADE guidance providing practical instructions for addressing intransitivity may be desirable.

ObjectTo investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC).Materials and methodsData of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE+TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses.ResultsCompared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference.ConclusionThe treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC.

Abstract: Quinoa has been recognized as the sole “comprehensive nutritional crop”; however, it is susceptible to pre-harvest sprouting (PHS). While quantitative reverse transcription polymerase chain reaction (RT-qPCR) has been extensively employed for gene expression level detection, the selection of suitable reference genes is imperative to ensure precise gene expression quantification across diverse conditions. This study aims to identify stable reference genes in quinoa seeds under ABA and GA, in order to provide a basis for subsequent research on PHS. Seeds were subjected to different concentrations of ABA and GA (10 μM, 50 μM, 100 μM, and 200 μM). The most suitable treatment concentration was determined based on seed viability. Here, MON1, GAPDH, EIF3, EF1α, ACT, TUB1, and TUB6 were selected as candidate genes. The suitability of these reference genes under different conditions was assessed using various methods including Ct values, geNorm, NormFinder, BestKeeper, Delta Ct, and RefFinder. Based on the results obtained from the hormone experiments, it was observed that the application of 100 μM ABA and 200 μM GA yielded the most advantageous outcomes. Additionally, the most appropriate reference genes for different treatments are ACT and TUB1 (H2O treatment), EIF3 and MON1 (ABA, GA treatment and also for the combined data set of the three groups). However, GAPDH exhibited the least stability across all treatments. In summary, ACT is recommended as the reference gene for natural quinoa germination, while EIF3 and MON1 should be used for ABA and GA treatments.

Background: Future warming is projected to increase the heat-related mortality burden, especially for vulnerable populations. However, most previous studies focused on non-accidental morbidity or mortality, with far less research on heat-related accidental events. Methods: We collected individual accidental death records among all residents in Chinese mainland from June to August during 2013–2019. Accidental deaths were further divided into several subtypes by different causes. We used an individual-level, time-stratified, case-crossover study design to estimate the association between daily mean temperature and accidental deaths, and estimate its variation in seven geo-climatic zones, age (5–64, 65–74, ≥75), and sex (male, female). We then estimated the temperature-related excess accidental deaths under global warming scenarios of 1.5, 2, and 3℃. Findings: A total of 711,929 accidental death records were included in our study. We found that higher temperatures were associated with increased risks of deaths from the total accidental events and four main subtypes, including traffic, falls, drowning, and unintentional injuries. We also found that younger individuals (ages 5–64) and males faced a higher risk of heat-related mortality due to total accidents, traffic incidents, and drowning. For future climate scenarios, even under the 1.5℃ climate change scenario, 6,939 (95% eCI (empirical Confidence Interval): 6,818–7,067) excess accidental deaths per year are attributed to higher summertime daily temperature over mainland China, and the number of accidental deaths would increase by 16.71% and 33.59% under the 2℃ and 3℃ climate change scenarios, respectively. For residents living in southern coastal and northwest inland regions, the projected increase in accidental death is higher. Conclusions: This nationwide study confirms that higher summer temperatures are linked to an increased risk of accidental deaths. Younger age groups and males face a higher risk. This indicates that current estimates of the health effects of climate change might be underestimated, particularly for younger populations.

BackgroundHepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusiveMethodsThe GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the ‘Limma’ R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases.ResultsNQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5’-TTCTGACTCTTTT-3’).ConclusionNOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.

Soil moisture (SM) plays a critical role in various fields such as agriculture, hydrology, and land-atmosphere interactions. This study aims to evaluate the performance of the categorical boosting algorithm (CatBoost) in comparison to other multiple-boosting algorithms for SM prediction. Appropriate feature selection is vital for achieving accurate predictions, and this study focuses on identifying relevant features and assessing CatBoost's suitability for the task. The study incorporates several boosting algorithms including Gradient Boosting Decision Tree (GBDT), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and CatBoost to estimate SM. Results indicate that radar backscatter coefficient, soil roughness, and digital elevation model (DEM) are crucial features for SM retrieval. Comparatively, CatBoost outperforms GBDT, XGBoost, and LightGBM in various feature combinations. The most favorable results are obtained when utilizing all features as inputs for the algorithm. These optimal results yield a mean absolute error (MAE) of 2.40 vol.%, mean relative error (MRE) of 0.16 vol.%, root mean square error (RMSE) of 3.26 vol.%, and Pearson correlation coefficient of 0.73. Additionally, the study analyzes the inversion results for different ranges of SM and Normalized Difference Vegetation Index (NDVI). Within the range of SM from 0 to 25 vol.% and NDVI from 0 to 0.7, utilizing all features yields the most accurate results. Using CatBoost, this approach achieves an MAE of 1.52 vol.%, MRE of 0.12 vol.%, RMSE of 2.11 vol.%, and R of 0.81. The study suggests that applying boosting algorithms, especially CatBoost, holds promise in accurately estimating surface SM.

Soil moisture (SM) is valuable basic data in climate, hydrological models, and agricultural applications. The rapid development of remote sensing technology can be used to monitor changes in SM at multiple spatial and temporal scales. In this article, we unfolded an SM retrieval method using ensemble learning combined with the Water Cloud Model (WCM) by Sentinel-1 and Sentinel-2 with multisource datasets. First, using the WCM, the influence of vegetation cover on the backscattering coefficient was removed, where we use three vegetation index (enhanced vegetation index (EVI), normalized difference vegetation index, and normalized difference water index) for analysis and comparison. Then, combined with other multisource datasets, an SM retrieval model was established based on the ensemble learning algorithm. Here, we choose two familiar ensemble learning algorithms for analysis and comparison, using Pearson correlation significance analysis, which are the random forest (RF) and the adaptive boosting (AdaBoost). The results revealed that the RF model performed is slightly superior to the AdaBoost model. The optimal performance mean absolute error, root-mean-square error (RMSE), and the unbiased RMSE of RF model are 2.289 vol%, 2.934 vol%, 2.934 vol%, respectively, which are slightly better than the AdaBoost model. EVI is suitable for WCM model to remove vegetation scattering effect. It shows that it is attainable to utilize the ensemble learning method to inversion of SM using radar data. The proposed framework maximizes the potential of WCM, RF model, and multisource datasets in deriving spatiotemporally continuous SM estimates, which should be valuable for SM inversion development.

Abstract Background Dl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD. Method In our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC–MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein–protein interactions (PPI) by Cytoscape, DEPs were verified by western blot. Result A total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p

Identifying important parameters in crop models is critical for model application. This study conducted a sensitivity analysis of 23 selected parameters of the advanced rice model ORYZA-N using the Extended FAST method. The sensitivity analysis was applied for three rice types (single-season rice in cold regions and double-season rice (early rice and late rice) in subtropical regions) and two irrigation regimes (traditional flood irrigation (TFI) and shallow–wet irrigation (SWI)). This study analyzed the parameter sensitivity of six crop growth outputs at four developmental stages and yields. Furthermore, we compared the variation in parameter sensitivity on model outputs between TFI and SWI scenarios for single-season rice, early rice, and late rice. Results indicated that parameters RGRLMX, FRPAR, and FLV0.5 significantly affected all model outputs and varied over developmental stages. Water stress in paddy fields caused by water-saving irrigation had more pronounced effects on single-season rice than on double-season rice.

Abstract Skin fibrosis, a pathological process featured by fibroblast activation and extracellular matrix (ECM) deposition, makes a significant contribution to morbidity. Studies have identified biomechanics as the central element in the complex network of fibrogenesis that drives the profibrotic feedback loop. In this study, we found that the acetylation of α‐tubulin at lysine 40 (K40) was augmented in fibrotic skin tissues. Further analysis showed that α‐tubulin acetylation is required for fibroblast activation, including contraction, migration, and ECM deposition. More importantly, we revealed that biomechanics‐induced upregulation of K40 acetylation promotes fibrosis by mediating mechanosensitive Yes‐associated protein S127 dephosphorylation and its cytoplasm nucleus shuttle. Furthermore, we demonstrated that the knockdown of α‐tubulin acetyltransferase 1 could rescue the K40 acetylation upregulation caused by increased matrix rigidity and ameliorate skin fibrosis both in vivo and in vitro. Herein, we highlight the critical role of α‐tubulin acetylation in matrix stiffness‐induced skin fibrosis and clarify a possible molecular mechanism. Our research suggests α‐tubulin acetylation as a potential target for drug design and therapeutic intervention.

Abstract It is important for territorial spatial planning to master meteorological disaster risk under the conditions of climate change and then carry out risk adaptation planning according to local conditions. Taking Beijing, a large city in China, as an example, a meteorological disaster risk assessment model was established based on the framework of hazard factors, disaster‐bearing body exposure, and vulnerability of underlying surface. Combined with 11 years of observation data from 293 high‐density weather stations, the rainstorm and high‐temperature risks of urban, agriculture, and ecological spaces were studied. The results show that (1) rainstorms and high‐temperature are mainly distributed in the built‐up areas of plain towns, which are the climate risk factors that need to be considered. (2) The central city of Beijing is at a high risk of rainstorms and high temperature, indicating that the underlying surface and disaster‐bearing body are highly vulnerable to meteorological disasters. (3) In suburbs with agricultural land, there is a certain rainstorm risk in Fangshan and Daxing districts, and a risk of high temperatures in the southern part of Tongzhou and Daxing. (4) The risk of high temperatures in the ecological space (eco‐zone) is relatively low, but the rainstorm risk is relatively high in Pinggu and Miyun. (5) The strategies of coping with rainstorm and high‐temperature disaster risk in Beijing's territorial space planning were discussed.

In this work, a metasurface consisting of disk-ring Si nanostructures on a SiO2 substrate is proposed and numerically simulated. The Si disk-ring structure can excite and manipulate anapole state, and periodic array supports lattice resonance simultaneously, which can improve the near-field enhancement in the gap region. The maximum E-field enhancement can be up to 346 times, and a transmission dip with an ultra-narrow bandwidth of 0.34 nm and a Q-factor of 4460 is shown. When the central disk has an offset, the near-field enhancement can be affected. In the case of y-direction offset, the maximum E-field enhancement can be up to 468 times. The near field energy is concentrated in the gap region, easy to interact with probing molecule in surrounding environment. Meanwhile, the designed metasurface shows a sensing performance of 387 nm/RIU. The strong energy confinement and high Q-factor of the proposed structure give an opportunity to enhance the interaction between light and matter, which may have potential applications in nonlinear optics, optical sensors and surface enhanced Raman scattering.

Platelets play important roles in thrombosis, hemostasis, inflammation, and infection. We aimed to evaluate the association between platelet count and its variation trend and prognosis of patient with infectious diseases in intensive care units (ICUs). This retrospective cohort study extracted 4,251 critically ill adult patients with infectious diseases from the eICU Collaborative Research Database, whose platelet counts were measured daily during the first 7 days after admission. In the survivors, platelet counts decreased in the first days after admission, reached a nadir on day 3, and then returned and continued to rise above the admission value. In non-survivors, the platelet counts decreased after admission, without a subsequent upturn. We defined three subgroups according to the nadir platelet counts within 7 days: ≤50, 50–130, and ≥130 × 109/L, corresponding to high, intermediate, and low ICU mortality. A decreased platelet count was associated with increased ICU mortality (intermediate vs. low: 1.676 [1.285–2.187]; high vs. low: 3.632 [2.611–5.052]). In conclusion, during the first 7 days, platelet counts decreased after ICU admission, while increased subsequently in the survivors but not in the non-survivors. ICU mortality risk increased as nadir platelet count decreased below 130 × 109/L, and further boosted when it reached below 50 × 109/L.

Abstract Background This study aims to explore appropriate model for predicting the disease burden of pneumoconiosis in Tianjin by comparing the prediction effects of Autoregressive Integrated Moving Average (ARIMA) model, Deep Neural Networks (DNN) model and multivariate Long Short-Term Memory Neural Network (LSTM) models. Methods Disability adjusted life year (DALY) was used to evaluate the disease burden of occupational pneumoconiosis. ARIMA model, DNN model and multivariate LSTM model were used to establish prediction model. Three performance evaluation metrics including Root Mean Squared Error (RMSE), Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE) were used to compare the prediction effects of the three models. Results From 1990 to 2021, there were 10,694 cases of pneumoconiosis patients in Tianjin, resulting in a total of 112,725.52 person-years of DALY. During this period, the annual DALY showed a fluctuating trend, but it had a strong correlation with the number of pneumoconiosis patients, the average age of onset, the average age of receiving dust and the gross industrial product, and had a significant nonlinear relationship with them. The comparison of prediction results showed that the performance of multivariate LSTM model and DNN model is much better than that of traditional ARIMA model. Compared with the DNN model, the multivariate LSTM model performed better in the training set, showing lower RMES (42.30 vs. 380.96), MAE (29.53 vs. 231.20) and MAPE (1.63% vs. 2.93%), but performed less stable than the DNN on the test set, showing slightly higher RMSE (1309.14 vs. 656.44), MAE (886.98 vs. 594.47) and MAPE (36.86% vs. 22.43%). Conclusion The machine learning techniques of DNN and LSTM are an innovative method to accurately and efficiently predict the burden of pneumoconiosis with the simplest data. It has great application prospects in the monitoring and early warning system of occupational disease burden.

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) 30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus. The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect. However, little is known about the kinetics and degradation products of PEP06 in vitro or in vivo. In this study, we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species; we further identified the degradation characteristics of its cleavage products. PEP06 underwent rapid enzymatic degradation in multiple types of living cells, and the liver, kidney, and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06. We identified metabolites of PEP06 using full-scan mass spectrometry (MS) and tandem MS (MS2), wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide, formed by successive losses of amino acids. The metabolites were C and N terminal truncated products of PEP06. The structures of 11 metabolites (M6, M7, M16, M17, M21, M25, M33, M34, M39, M40, and M42) were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites. We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06, which can support further drug research.

Abstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate of irradiated glioblastoma cells remains to be elucidated. Methods We erected the co-culture system of glioblastoma cells and microglia. After radiation, we analyzing the immunophenotype of microglia and the proliferation of radiated glioblastoma cells. By whole transcriptome sequencing, we analyzed of circRNAs in exosomes from glioblastoma cells and microglia. We used some methods, which included RT-PCR, dual-luciferase reporter, et al., to identify how circ_0012381 from radiated glioblastoma cell-derived exosomes regulated the immunophenotype of microglia to further affect the proliferation of radiated glioblastoma cells. Results Radiated glioblastoma cell-derived exosomes markedly induced M2 microglia polarization. These M2-polarized microglia promoted the proliferation of irradiated glioblastoma cells. Circ_0012381 expression was increased in the irradiated glioblastoma cells, and circ_0012381 entered the microglia via exosomes. Circ_0012381 induced M2 microglia polarization by sponging with miR-340-5p to increase ARG1 expression. M2-polarized microglia suppressed phagocytosis and promoted the growth of the irradiated glioblastoma cells by CCL2/CCR2 axis. Compared with the effects of radiotherapy alone, the inhibition of exosomes significantly inhibited the growth of irradiated glioblastoma cells in a zebrafish model. Conclusions Our data suggested that the inhibition of exosome secretion might represent a potential therapeutic strategy to increase the efficacy of radiotherapy in patients with glioblastoma.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.

Objective Hirschsprung disease (HSCR) is one of the common neurocristopathies in children, which is associated with at least 20 genes and involves a complex regulatory mechanism. Transcriptional regulatory network (TRN) has been commonly reported in regulating gene expression and enteric nervous system development but remains to be investigated in HSCR. This study aimed to identify the potential TRN implicated in the pathogenesis and diagnosis of HSCR.Methods Based on three microarray datasets from the Gene Expression Omnibus database, the multiMiR package was used to investigate the microRNA (miRNA)–target interactions, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF–miRNA–mRNA regulatory network and used cytoHubba to identify the key modules. Finally, the receiver operating characteristic (ROC) curve was determined and the integrated diagnostic models were established based on machine learning by the support vector machine method.Results We identified 58 hub differentially expressed microRNAs (DEMis) and 16 differentially expressed mRNAs (DEMs). The robust target genes of DEMis and DEMs mainly enriched in several GO/KEGG terms, including neurogenesis, cell–substrate adhesion, PI3K–Akt, Ras/mitogen-activated protein kinase and Rho/ROCK signaling. Moreover, 2 TFs (TP53 and TWIST1), 4 miRNAs (has-miR-107, has-miR-10b-5p, has-miR-659-3p, and has-miR-371a-5p), and 4 mRNAs (PIM3, CHUK, F2RL1, and CA1) were identified to construct the TF–miRNA–mRNA regulatory network. ROC analysis revealed a strong diagnostic value of the key TRN regulons (all area under the curve values were more than 0.8).Conclusion This study suggests a potential role of the TF–miRNA–mRNA network that can help enrich the connotation of HSCR pathogenesis and diagnosis and provide new horizons for treatment.

This study mapped the dynamic interaction of narratives regarding Nigeria's pursuit of rice self-sufficiency and related trade policies since the 1970s to explore whether agricultural protectionist policies can help achieve food security in Nigeria. Developing agricultural trade policies that simultaneously secure imported food supplies and protect domestic agricultural development is a challenging task. Nigeria's protectionist policies have a controversial agenda. Few studies have investigated the dynamic process of rice production and trade policy from a historical viewpoint; our study fills this gap. Through mapping Nigeria's pursuit of rice self-sufficiency over the past 50 years, we found that seesawed trade policy parallels complex rice development, leaving imported rice dependence unchanged. Regardless of when policies switch to trade protection or liberalization, the procedure does not directly lead to increased rice production. Since much exploration is needed regarding how to achieve food security in Nigeria, we also identify three new dimensions for future food security research based on our findings' optimal recommendations.