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For decades micoorganisms have been engineered for the utilization of lignocellulose-based second-generation (2G) feedstocks, but with the concerns of increased levels of atmospheric CO2 causing global warming there is an emergent need to transition from the utilization of 2G feedstocks to third-generation (3G) feedstocks such as CO2 and its derivatives. Here, we established a yeast platform that is capable of simultaneously converting 2G and 3G feedstocks into bulk and value-added chemicals. We demonstrated that by adopting 3G substrates such as CO2 and formate, the conversion of 2G feedstocks could be substantially improved. Specifically, formate could provide reducing power and energy for xylose conversion into valuable chemicals. Simultaneously, it can form a concentrated CO2 pool inside the cell, providing thermodynamically and kinetically favoured amounts of precursors for CO2 fixation pathways, e.g., the Calvin–Benson–Bassham (CBB) cycle. Furthermore, we demonstrated that formate could directly be utilized as a carbon source by yeast to synthesize endogenous amino acids. The engineered strain achieved a one-carbon (C1) assimilation efficiency of 9.2%, which was the highest efficiency observed in the co-utilization of 2G and 3G feedstocks. We applied this strategy for productions of both bulk and value-added chemicals, including ethanol, free fatty acids (FFAs), and longifolene, resulting in yield enhancements of 18.4%, 49.0%, and ∼100%, respectively. The strategy demonstrated here for co-utilization of 2G and 3G feedstocks sheds lights on both basic and applied research for the up-coming establishment of 3G biorefineries.

Abstract Background Previous studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD. Purpose The aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients. Methods A total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time. Results COVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P

Abstract Background Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p

Abstract The objective of this study was to investigate the correlation between Rab10 (GTP binding protein RAB10), TLR4 (Toll-like receptor 4), and NF-κB (nuclear factor kappa-B) levels and therapeutic effects in peripheral blood of patients with breast cancer after surgery. The study included 160 patients with stage I-III breast cancer who underwent surgical treatment at our hospital’s Department of Breast Surgery and Oncology between January 2021 and June 2021. ELISA was used to assess Rab10, TLR4, and NF-κB levels in peripheral blood. Based on their levels of Rab10, TLR4, and NF-κB in peripheral blood, participants were categorized into two groups: the low marker expression group (72 participants with relatively low expression of Rab10, TLR4, and NF-κB: Rab10

Abstract Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21.

Fault-slip rockbursts are a major type of rockbursts in coal mine roadways, posing great hazards. Currently, there is a lack of systematic research on the entire process of fault-slip rockbursts, and prediction and prevention remain fundamental challenges. To achieve experimental simulation of fault-slip rockbursts, a testing system was developed, along with the development of low-strength high-brittleness similar simulation materials. A large-scale similar model containing faults and roadways was prepared, and a series of verification experiments were conducted, realizing the simulation of roadway shock failure and fault shear slip. The testing system is equipped with a triaxial six-face loading function, with a vertical loading capacity of 20 MPa and a model size of 1.50 m×0.75 m×0.75 m. The main frame innovatively adopts a key plate connection, ensuring high rigidity of the main frame. A honeycomb loading shell structure was invented, achieving oil cylinder group loading, which can meet the requirements of fault-slip rockburst simulation. A similar material suitable for fault-slip rockburst simulation was developed, which uses water glass as the binder, sodium fluosilicate as the curing agent, and talcum powder as the aggregate. The similar material has characteristics of both low strength and high brittleness, with a uniaxial compressive strength ranging from 3.44 to 7.81 MPa, an impact energy index of 9.2, and an elastic energy index of 8.83. Based on the test system and low-strength and high-brittleness materials, the bursting failure simulation of roadway under static load was realized, and the feasibility of simulating bursting failure of roadway using low-strength and high-brittleness materials was verified. The loading conditions of the critical equilibrium state of the roadway were obtained, with the continuous shedding of the roadway's side as a significant precursor characteristic of roadway damage. The shear slip of rough serrated faults was realized, confirming that the shear slip of rough faults would cause significant dynamic load disturbances to the roadway, obtaining a reasonable loading method for fault slip. The method of loading the top of the dynamic zone first and unloading the bottom later can achieve instantaneous slip of the fault and eliminate the influence on the static zone stress state.

The erosion-corrosion mechanism in rotary flowing seawater is hugely complicated due to the multiscale coupling processes of particle-surface impact, ion mass transfer, and interface electrochemistry. Therefore, developing erosion-corrosion resistant material and exploring the synergistic mechanism between sand erosion and electrochemical corrosion is vital. This study conducted the erosion-corrosion test on Ni2FeCrMo0.2 high-entropy alloy under the particle-seawater flow. Based on a coupled analysis of multi-component weight loss, electrochemical behavior, and microscopic damage morphology, the multiscale coupling processes of sand transportation, particle-surface impact, ion mass transfer, and interface electrochemistry were revealed. The present study found that with the increase of sand size, the energy carried by the particles promoted impact erosion. Additionally, particle movement enhanced ion mass transfer through turbulent effects, and the impact behavior disrupted the passivation film to promote electrochemical processes by reducing the thickness of the passivation film, leading to an increase in the erosion-corrosion rate. However, when the particle size continued to increase to a certain extent, the impact frequency decreased, reducing the erosion-corrosion rate. As the sand size grew, the dominant damage mechanism transitioned from pure corrosion (100 μm) to synergistic effects (200 μm, 400 μm) and then to pure erosion (800 μm). This study provides an in-depth understanding of the erosion-corrosion mechanism in seawater from the perspective of particle-ion-fluid-surface interaction by multi-element characterization.

Abstract Background Triglyceride-glucose (TyG) index is linked to a poor prognosis for cardiovascular condition and is a valid indicator of insulin resistance. This study evaluated the potential predicting usefulness of the TyG index for all-cause mortality, both short- and long-term, for those concerning critical coronary artery disease (CAD). Methods In this study, information from 5452 critically-ill individuals with CAD in intensive care units were gathered from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database. Depending on the TyG index degree, the patients were categorized into three categories. Clinical outcomes included short-term (30-day) and long-term (365-day) all-cause mortality. The corresponding relationships involving the TyG index and clinical outcomes were examined by deploying restricted cubic spline (RCS) regression analysis and Cox proportional risk regression. Results An increased TyG index was associated with increased 30-day (Tertile 1: 6.1%, Tertile 2: 7.3%, Tertile 3: 9.2%, P = 0.001) and 365-day (Tertile 1: 15.2%, Tertile 2: 17.0%, Tertile 3: 19.6%, P = 0.002) death rates across all causes. Cox regression with multiple variables indicates that higher TyG indices were linked to higher all-caused mortality hazard ratios throughout the short and long terms, with a larger predictive value for the former. RCS regression analyses suggested that the risk of death was notably and linearly that is associated with TyG index. Conclusions The TyG index is a reliable predictor of all-cause mortality at different stages in critically ill CAD patients, with a higher predictive ability for short-term mortality. Early intervention in patients with elevated TyG index may improve their survival outcomes. Future research should delve into understanding its pathophysiological mechanisms and develop intervention strategies based on the TyG index, providing new insights and strategies to enhance the outlook for critically ill CAD patients.

Abstract Background The attrition rate of Chinese medical students is high. This study utilizes a nomogram technique to develop a predictive model for dropout intention among Chinese medical undergraduates based on 19 individual and work-related characteristics. Method A repeated cross-sectional study was conducted, enrolling 3536 medical undergraduates in T1 (August 2020-April 2021) and 969 participants in T2 (October 2022) through snowball sampling. Demographics (age, sex, study phase, income, relationship status, history of mental illness) and mental health factors (including depression, anxiety, stress, burnout, alcohol use disorder, sleepiness, quality of life, fatigue, history of suicidal attempts (SA), and somatic symptoms), as well as work-related variables (career choice regret and reasons, workplace violence experience, and overall satisfaction with the Chinese healthcare environment), were gathered via questionnaires. Data from T1 was split into a training cohort and an internal validation cohort, while T2 data served as an external validation cohort. The nomogram’s performance was evaluated for discrimination, calibration, clinical applicability, and generalization using receiver operating characteristic curves (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Result From 19 individual and work-related factors, five were identified as significant predictors for the construction of the nomogram: history of SA, career choice regret, experience of workplace violence, depressive symptoms, and burnout. The AUC values for the training, internal validation, and external validation cohorts were 0.762, 0.761, and 0.817, respectively. The nomogram demonstrated reliable prediction and discrimination, with adequate calibration and generalization across both the training and validation cohorts. Conclusion This nomogram exhibits reasonable accuracy in foreseeing dropout intentions among Chinese medical undergraduates. It could guide colleges, hospitals, and policymakers in pinpointing students at risk, thus informing targeted interventions. Addressing underlying factors such as depressive symptoms, burnout, career choice regret, and workplace violence may help reduce the attrition of medical undergraduates. Trial registration This is an observational study. There is no Clinical Trial Number associated with this manuscript.

Abstract Background While body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States. Methods The data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD. Results The cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07–3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77–2.29) in the T2 group, no statistically significant difference was observed. Conclusions The increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

Abstract Background Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. Results The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light–sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. Conclusions This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.

Abstract It is essential to find environment-friendly agrochemicals to cope with the problems of nutrient imbalance, fruit quality decline, and physiological disorders during apple fruit production, which is beneficial for improving the quality and yield of apple. A natural extract from Paecilomyces variotii (ZNC), an endophytic fungus, has been used widely to enhance crop performance. However, an understanding of the mechanism underlying ZNC-triggered growth and alleviation of nutrient deficiency-associated symptoms in apples remains elusive. Here, the photosynthesis, leaf growth, and fruit quality were enhanced by adding ZNC. In addition, ZNC relieved nutrient deficiency-related symptoms promoted the differentiation of root morphology and vitality, and reduced the accumulation of osmoprotectants and reactive oxygen species, thereby promoting growth under normal and nutrient-deficient conditions. Finally, genome-wide RNA sequencing reveals the ZNC-regulated mechanisms involved in hormone and metal ion pathways. Our study reveals the role of ZNC in promoting growth and improving the quality of apple, providing a new direction for reducing the use of chemical fertilizers and pesticides.

Abstract Bacterial diseases are one of the most common issues that result in crop loss worldwide, and the increasing usage of chemical pesticides has caused the occurrence of resistance in pathogenic bacteria and environmental pollution problems. Nanomaterial mediated gene silencing is starting to display powerful efficiency and environmental friendliness for improving plant disease resistance. However, the internalization of nanomaterials and the physiological mechanisms behind nano-improved plant disease resistance are still rarely understood. We engineered the polyethyleneimine (PEI) functionalized gold nanoparticles (PEI-AuNPs) with fluorescent properties and ROS scavenging activity to act as siRNA delivery platforms. Besides the loading, protection, and delivery of nucleic acid molecules in plant mature leaf cells by PEI-AuNPs, its fluorescent property further enables the traceability of the distribution of the loaded nucleic acid molecules in cells. Additionally, the PEI-AuNPs-based RNAi delivery system successfully mediated the silencing of defense-regulated gene AtWRKY1. Compared to control plants, the silenced plants performed better resistance to Pseudomonas syringae, showing a reduced bacterial number, decreased ROS content, increased antioxidant enzyme activities, and improved chlorophyll fluorescence performance. Our results showed the advantages of AuNP-based RNAi technology in improving plant disease resistance, as well as the potential of plant nanobiotechnology to protect agricultural production.

Abstract Nutrition is a limiting feature of species evolution. The differences in nutritional requirements are the evolutionary result of differential adaptations to environmental changes, explaining differences in their ecological traits. Cnaphalocrocis medinalis and Cnaphalocrocis exigua, two related species of rice leaffolders, have similar morphology and feeding properties but different migration and overwintering behaviors. However, it is unclear whether they have evolved adult nutritional differentiation traits to coexist. To explore this issue, this study examined the effects of carbohydrates and amino acids on their reproductive and demographic parameters. The findings indicate that carbohydrate intake prolonged the longevity and population growth of two rice leaffolders, but amino acid intake promoted egg hatching only. However, nutrient deficiency made it impossible for C. medinalis to reproduce successfully and survive, but it did not affect C. exigua. The population expansion and survival of migratory C. medinalis relied on adult nutritional intake. Conversely, the nutrients necessary for C. exigua overwintering activity mostly came from the storage of larvae. The difference in nutritional requirements for population growth and survival between the two rice leaffolders partially explained their differences in migration and overwintering.

Abstract Electronic cigarettes (e-cigs) use, especially among youngsters, has been on the rise in recent years. However, little is known about the long-term effects of the use of e-cigs on brain functional activity. We acquired the resting-state functional magnetic resonance imaging (rs-fMRI) data from 93 e-cigs users with nicotine dependence and 103 health controls (HC). The local synchronization was analyzed via the regional homogeneity (ReHo) method at voxel-wise level. The functional connectivity (FC) between the nucleus accumbens (NAcc), the ventral tegmental area (VTA), and the insula was calculated at ROI-wise level. The support vector machining classification model based on rs-fMRI measures was used to identify e-cigs users from HC. Compared with HC, nicotine-dependent e-cigs users showed increased ReHo in the right rolandic operculum and the right insula (p

Abstract The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice.

Abstract Background The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. Methods Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. Results There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p

Abstract Background The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. Results In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. Conclusion A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

Abstract Background Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. Methods We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. Results Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. Conclusion The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Abstract Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447–0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327–0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996–1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Abstract The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option. Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

Background: This study investigates the association between dietary flavonoid intake and the incidence of mild cognitive impairment (MCI) through a matched case-control design. Methods: Dietary intake was assessed using a food frequency questionnaire, comparing the intake of flavonoids between individuals with MCI and those with normal cognitive function. Logistic regression analysis was employed to evaluate the correlation between dietary flavonoid intake and the risk of MCI. Additionally, blood concentrations of S100β, a marker of the blood-brain barrier (BBB) integrity, were measured using electrochemiluminescence immunoassay, and Pearson correlation analysis was conducted to explore the relationship between dietary flavonoid intake and blood S100β levels. Results: Compared to participants with normal cognition, those with MCI had significantly lower dietary intakes of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, flavonols, and anthocyanidins, while the intake of peonidin was significantly higher. Univariate logistic regression analysis indicated that high dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, and flavonols was negatively correlated with MCI, whereas peonidin intake was positively correlated with MCI. Multivariate logistic regression analysis confirmed these findings. Pearson correlation analysis revealed a significant negative correlation between dietary intake of kaempferol and myricetin and blood S100β levels. Conclusion: Increasing the dietary intake of total flavonoids, isoflavones, daidzein, glycitein, genistein, and flavonols appears to be a protective factor against MCI, while higher intake of peonidin is associated with an increased risk of MCI. The protective or adverse effects of these flavonoids may not be related to the permeability of the BBB. Myricetin and kaempferol intake may protect cognitive function by maintaining BBB integrity.

IntroductionEnvironmental stresses, such as soil salinity or alkalinity, usually affect crop growth and secondary plant metabolism, with follow on effects on foliar-feeding insects. Nevertheless, the underlying mechanism of how saline-alkali stress affects the key cotton pest Aphis gossypii Glover is poorly understood. MethodsIn this study, we first considered effects of three types of saline-alkali stress (i.e., salinity alone, alkalinity alone – both at different concentration – and their mixed effects) on cotton plants. We then measured impacts of stress on (1) above and below plant growth traits (e.g., plant height, leaf area, root volume), (2) levels of nutrients and secondary metabolites in cotton leaves, and (3) feeding behavior, life-table parameters, and population growth of A. gossypii. We then used a path analysis to evaluate cascading effects of changes in plant growth (due to stress) and changes in levels of nutrients or secondary metabolites on growth of individual cotton aphids and aphid populations.ResultsWe found either salinity or alkalinity stresses significantly reduced cotton growth, increased the content of tannin, soluble sugars, and proline in the leaves, and suppressed aphid growth and development, (including longevity, fecundity, and intrinsic rate of increase) and aphid population growth. Alkalinity had stronger effects on these traits than did salinity. DiscussionThis work provides insights into the bottom-up interaction mechanism by which these environmental stresses mediate aphid infestation levels in the cotton agricultural ecosystem.

Abstract (−)‐Ambrox, a highly prized and commercially significant component of ambergris, finds widespread application in perfumery, cigarettes, cosmetics, and the food industry. Despite considerable attention to this research area over the years, an environmentally friendly and practical method for synthesizing (−)‐ambrox has remained elusive. This study presents a succinct and efficient approach to (−)‐ambrox synthesis, involving two consecutive alkylations at C‐6, followed by an acid‐catalyzed cyclization to give bicyclic ketones starting from (R)‐carvone. Subsequent reduction, Barton Vinyl Iodide synthesis, alkylation, and an acid‐catalyzed cyclization collectively achieved the synthesis of (−)‐ambrox with a satisfactory yield of 26.2 %.

A 33-year-old young woman with a rare female appendage tumor of suspected Wolffian origin was initially diagnosed with a benign lesion after the resection of a tubal lesion due to the benign cytomorphology of the tumor tissue. However, 1 year after surgery, she was diagnosed with stage IV fallopian tube cancer due to a recurrence, which presented with substantial ascites and invasion of multiple organs, including the bilateral ovaries, intestines, pelvic peritoneum, greater omentum, and appendix. After tumor cytoreduction, the patient responded well to treatment, which included a regimen of platinum-based drugs combined with docetaxel, aromatase inhibitors such as letrozole, antihormonal therapy, and targeted therapy with bevacizumab.

BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies.MethodsCommonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments.ResultWe discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only ATRNL1 and WNT9A were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of ATRNL1 in the HCM model, and all three drugs suppressed WNT9A expression.ConclusionWe identified several novel genes in HCM development, among which ATRNL1 and WNT9A were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide.

BackgroundThis study aimed to identify prognostic factors for survival and develop a prognostic nomogram to predict the survival probability of elderly patients with lower-grade gliomas (LGGs).MethodsElderly patients with histologically confirmed LGG were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. These individuals were randomly allocated to the training and validation cohorts at a 2:1 ratio. First, Kaplan−Meier survival analysis and subgroup analysis were performed. Second, variable screening of all 13 variables and a comparison of predictive models based on full Cox regression and LASSO-Cox regression analyses were performed, and the key variables in the optimal model were selected to construct prognostic nomograms for OS and CSS. Finally, a risk stratification system and a web-based dynamic nomogram were constructed.ResultsA total of 2307 elderly patients included 1220 males and 1087 females, with a median age of 72 years and a mean age of 73.30 ± 6.22 years. Among them, 520 patients (22.5%) had Grade 2 gliomas, and 1787 (77.5%) had Grade 3 gliomas. Multivariate Cox regression analysis revealed four independent prognostic factors (age, WHO grade, surgery, and chemotherapy) that were used to construct the full Cox model. In addition, LASSO-Cox regression analysis revealed five prognostic factors (age, WHO grade, surgery, radiotherapy, and chemotherapy), and a LASSO model was constructed. A comparison of the two models revealed that the LASSO model with five variables had better predictive performance than the full Cox model with four variables. Ultimately, five key variables based on LASSO-Cox regression were utilized to develop prognostic nomograms for predicting the 1-, 2-, and 5-year OS and CSS rates. The nomograms exhibited relatively good predictive ability and clinical utility. Moreover, the risk stratification system based on the nomograms effectively divided patients into low-risk and high-risk subgroups.ConclusionVariable screening based on LASSO-Cox regression was used to determine the optimal prediction model in this study. Prognostic nomograms could serve as practical tools for predicting survival probabilities, categorizing these patients into different mortality risk subgroups, and developing personalized decision-making strategies for elderly patients with LGGs. Moreover, the web-based dynamic nomogram could facilitate its use in the clinic.

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017–2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P

Abstract Background Nowadays, moderate gaming behaviors can be a pleasant and relaxing experiences among adolescents. However, excessive gaming behavior may lead to gaming disorder (GD) that disruption of normal daily life. Understanding the possible risk factors of this emerging problem would help to suggest effective at preventing and intervening. This study aimed to investigate the prevalence of GD and analyze its possible risk factors that adolescents with GD. Methods Data were collected between October 2020 and January 2021. In total, a sample of 7901 students (4080 (52%) boys, 3742 (48%) girls; aged 12–18 years) completed questionnaires regarding the Gaming-Related Behaviors Survey, Gaming Disorder Symptom Questionnaire-21 (GDSQ-21); Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale); Emotion Regulation Questionnaire (ERQ); Short-form Egna Minnenav Barndoms Uppfostran for Chinese (s-EMBU-C); and Adolescent Self-Rating Life Events Checklist (ASLEC). Results The prevalence of GD was 2.27% in this adolescent sample. The GD gamers were a little bit older (i.e., a higher proportion of senior grades), more boys, with more gaming hours per week in the last 12 months, with more reward responsiveness, maternal rejecting and occurrence of negative life events (e.g., interpersonal relationships, being punished and bereavement factors). Conclusion These possible risk factors may influence the onset of GD. Future research in clinical, public health, education and other fields should focus on these aspects for provide target prevention and early intervention strategies.

Abstract Background Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer’s disease and related dementias (ADRD), Parkinson’s disease (PD), and neurodegenerative deaths. Methods This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. Results During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. Conclusion Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

Abstract Due to the BCS theory, hydrogen, the lightest element, would be the prospect of room-temperature superconductor after metallization, but because of the difficulty of the hydrogen metallization, the theory about hydrogen pre-compression was proposed that the hydrogen-rich compounds could be a great option for the high T c superconductors. The superior properties of TmH6, YbH6 and LuH6 indicated the magnificent potential of heavy rare earth elements for low-pressure stability. Here, we designed XTmH12 (X = Y, Yb, Lu, and La) to obtain higher T c while maintaining low pressure stability. Most prominently, YbTmH12 can stabilize at a pressure of 60 GPa. Compared with binary TmH6 hydride, its T c was increased to 48 K. The results provide an effective method for the rational design of moderate pressure stabilized hydride superconductors.

The melt-spun structure of a Fe85.5B13Cu1.5 alloy was regulated by the addition of corrosion-resistant Cr with a moderate enhancement in amorphous-forming ability, which further refines the nanostructure and improves the soft magnetic properties and corrosion resistance of corresponding nanocrystalline alloys. The results show that high-number-density α-Fe grains in size of below 10 nm are formed in the amorphous matrix of melt-spun Fe85.5-xB13Cu1.5Crx (x = 0–6) alloy ribbons, and the grain size and number density gradually decrease with the increase in Cr content. After annealing, the α-Fe average grain size (Dα-Fe) and coercivity (Hc) of corresponding nanocrystalline alloys reduce significantly with increasing x from 0 to 3, and the reduction becomes less pronounced within x = 3–6, while the saturation magnetic flux densities (Bs) steadily decreases as x increases from 0 to 6. A Fe82.5B13Cu1.5Cr3 nanocrystalline alloy with the Dα-Fe of 14.9 nm possesses excellent comprehensive soft magnetic properties with the Hc and Bs of 13.8 A/m and 1.74 T, respectively. The fine nanostructure and good magnetic softness results from the optimum combination of pre-existing α-Fe competitive growth and Cr-inhibited atom diffusion. The nanocrystalline alloys show improved corrosion resistance in NaCl solution compared to their respective melt-spun precursors, and the addition of Cr further enhances the corrosion resistance. The alloyed Cr also reduces the annealing embrittlement of the nanocrystalline alloys.

ObjectiveTo establish an indicator system for multi-point trigger surveillance and early warning of infectious diseases, providing valuable evidence to improve the overall prevention and control framework. MethodsThe pool of indicators was initially developed through a literature review and focus group discussions, followed by two rounds of Delphi expert consultations with 21 experts nationwide. Based on the experts' ratings of the importance, usability and familiarity of the indicators, the indicators were screened, statistically analyzed and their final weights determined. ResultsThe positive coefficients of experts in the two rounds of consultation were both 100%, the authority coefficients of experts were both ≥ 0.79, and the coordination coefficients of expert opinions were 0.34 – 0.46 (all P < 0.001). According to the occurrence and development process of infectious diseases and the requirements of related multi-source data fusion and collision, the indicator system was divided into three dimensions: single-source data, multi-source data fusion and risk factors. Finally, 82 indicators for multi-point trigger surveillance and early warning of infectious diseases were established. ConclusionThe index system developed in this study for multi-point trigger surveillance and early warning of infectious diseases is based on sound scientific principles and reasoning. It has the potential to expand the channels of infectious disease monitoring and achieve multi-point trigger surveillance and early warning.

Early warning of geo-hazards based on meteorological factors has played an important supportive role in disaster prevention and mitigation in China since its inception in 2003. This paper summarizes the the 20-year development process, technical methods, and disaster reduction effects of the early warning works. (1) The development process of early warning work process is divided into three stages: initiation and promotion (2003-2009), deepening cooperation (2010-2017), and reform and enhancement (2018-2022). (2) With 24-hour early warning work as the main content, a progressive warning model and a relatively complete warning service system have been gradually formed. (3) Three sets of early warning model technology and method systems have been gradually developed, including critical precipitation threshold model, the threshold model based on geo-hazards risk, and the dynamic early warning models, with the publication of industry standards for warning. (4) The spatial and temporal accuracy of warning products continues to improve, with the national and 26 provincial warning spatial accuracies exceeding 5 km × 5 km. The focus is on 24-hour warnings, with development towards 72-hour and medium- to long-term forecasts. Over 8 provincial-level and some municipal and county-level authorities have implemented 3-hour short-term warnings, gradually forming a work system to support service short impending warning response, medium-term prevention and long term deployment. (5) Where there is warning, there is response. The Ministry of Natural Resources has taken the national early warning as one of the bases for initiating defense responses, and 18 provinces have clarified the working mechanisms of the early warning response linkage. (6) The awareness of multi-party disaster prevention has been continuously enhanced. With strengthened inspections,evacuations, and successful risk aversion after receiving early warning information, the effectiveness of disaster prevention and mitigation is evident. The experience of early warning works in the past 20-year can provide reference for the next step in promoting the early warning of geo-hazards based on meteorological factors, supporting the enhancement of China’s capability and level of geo-hazards prevention and control work.

Early warning of geo-hazards based on meteorological factors in China began in 2003, and early warning informations are issued to the public every year during the flood season to alert the public to guard against geo-hazards such as landslides, debris flows, and mudslides caused by rainfall. To better understand the current situation and future trends of research for early warning of geo-hazards based on meteorological factors, the visualization tool CiteSpace was utilized to review the domestic and foreign literature on geo-hazards meteorological risk warning published from 2003 to 2023 and construct the scientific knowledge map. The CNKI database and SCI-Expanded databases were used as data sources. The result show that: (1) The study of critical rainfall thresholds based on the relationship between historical rainfall and disaster is in the leading position in research on early warning of geo-hazards based on meteorological factors, and the study of rainfall-related thresholds will continue to be a research hotspot in the future. (2) Keyword cluster analysis shows that a large number of studies have conducted research on early warning and prediction models and critical thresholds of geo-hazards under different formation conditions, meteorological conditions, different types, and genetic models, indicating that refinement is an important direction for the development of early warning of geo-hazards based on meteorological factors. (3) In the international research, Chinese scholars account for 39% of the total number of publications, showing an absolute advantage in research on geo-hazards meteorological risk early warning. The research results objectively demonstrate the development context, domestic and foreign research hotspots, and trends of research on geo-hazards meteorological risk warning in China, aiming to contribute to the progress of geo-hazards research and early warning forcast business in China.

Improving the geo-hazard meteorological risk warning capabilities is an important component of the comprehensive prevention system for geological disasters. Since 2003, Sichuan Province has been carrying out geo-hazard meteorological risk warning work. Building on the previous foundation, research has been focused on the analysis and establishment of warning models, system design and implementation, and graded warning operation modes since 2019. A geo-hazard warning model library, an integrated geological disaster meteorological risk warning interconnection system at the provincial, municipal, and county levels, and a graded warning mechanism have been created. We have achieved closed-loop management of interconnection and graded early warning based on integrated platform such as rainfall data transmission, early warning model analysis and calculation, and early warning information release in province, cities, and counties. This has solved the three problems of lack of technology, capacity, and funding in cities and counties, as well as the interference caused by multiple early warning information releases on grassroots levels. In 2023, 86% of the successful risk avoidance cases in Sichuan Province were affected by meteorological risk warning, effectively reducing casualties and property losses caused by geo-hazard.

Abstract Background Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements (“double hit”) transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive “double hit” HGBL following the treatment of FL/DLBCL. Case presentation This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB. The patient presented with BCL2/IGH translocation without MYC rearrangement, as well as the expressions of CD20, CD19, CD10 and BCL2 at the initial diagnosis of FL/DLBCL. MYC rearrangement and TdT expression occurred after the treatment. The targeted sequencing revealed mutations in KMT2D, FOXO1, CREBBP, ATM, STAT6, BCL7A, DDX3X, MUC4, FGFR3, ARID5B, DDX11 and PRKCSH genes were the co-mutations shared by the FL/DLBCL and TdT positive “double hit” HGBL, while CCND3, BIRC6, ROBO1 and CHEK2 mutations specifically occurred after the treatment. The overall survival time was 37.8 and 17.8 months after the initial diagnosis of FL/DLBCL and TdT positive “double hit” HGBL, respectively. Conclusion This study reports a rare case of TdT positive “double hit” HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive “double hit” HGBL transformed from FL/DLBCL.

Abstract Objective Ferritin heavy chain 1 (FTH1) is an important subunit of ferro-storing proteins and is indispensable for iron metabolism. Though it has been extensively studied in numerous organs and diseases, the relationship between FTH1 and osteoarthritis (OA) is unclear. Design Primary murine chondrocytes and cartilage explants were treated with FTH1 siRNA for 72 h. Mice were injected with adenovirus expressing FTH1 after destabilized medial meniscus (DMM) surgery. These approaches were used to determine the effect of FTH1 expression on the pathophysiology of OA. Results FTH1 expression was down regulated in OA patients and mice after DMM surgery. Knock down of FTH1 induced articular cartilage damage and extracellular matrix degradation in cartilage explants. Further, over expression of FTH1 reduced the susceptibility of chondrocytes to ferroptosis and reversed decrements in SOX9 and aggrecan after DMM surgery. Moreover, FTH1 relieved OA by inhibition of the chondrocyte MAPK pathway. Conclusion This study found FTH1 to play an essential role in extracellular matrix degradation, ferroptosis, and chondrocytes senescence during OA progression. Further, injection of adenovirus expressing FTH1 may be a potential strategy for OA prevention and therapy.

Abstract Background Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. Methods Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Result The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p

River bottom tearing scour (RBTS) has a strong effect on the scouring and moulding of channel in the Yellow River. Due to the special forming conditions, complex influencing factors, and limited observed data, it is difficult to predict whether RBTS will occur accurately. By collecting and disposing of the hydrodynamic, sediment, and initial boundary data of 246 flood events related to RBTS in three typical reaches of the Yellow River basin, the correlation between different characteristic influencing factors and the occurrence and absence of RBTS were analysed, and prediction models based on machine learning algorithms were constructed. The results showed that under the existing data conditions, the maximum sediment concentration Sm, average sediment concentration Sp, flood growth rate ν, and shape coefficient δ were the four key indices to more easily distinguish whether RBTS will occur. The support vector machine algorithm model had the best performance results and exhibited higher accuracy and precision in predicting its occurrence compared with other models under given water and sediment conditions. The method proposed in this study provides a new method for accurately predicting RBTS in the Yellow River. HIGHLIGHTS The maximum sediment concentration, average sediment concentration, flood growth rate, and shape coefficient are the four key indices for distinguishing whether RBTS will occur.; Prediction models of RBTS based on machine learning algorithms were built.; The SVM model showed the best predictive performance in the case study of the middle reach of the Yellow River.;

The rainfall-induced shallow landslides are primarily debris landslides, which features simultaneity with significant hazard, and the hydrological response mechanism of water table and soil moisture content to precipitation of this type of landslide is sophisticated, which makes it difficult to predict the slope stability accurately. To further study the influence of the rainfall-triggered internal hydrological responses on slope-stability, on-site precipitation infiltration monitoring, correlation analysis and mechanical analysis were carried out on the Houshanli landslide in Qingchuan County, Sichuan Province. The relationship between precipitation and water table was proposed based on climate and hydrological monitoring data obtained within three year interval. The response of rainfall infiltration, soil volumetric water content and water table were analyzed. The results indicate that: (1) groundwater exhibits periodic fluctuations throughout the year, characterized by three phases of slow decline, rapid decline, and rapid ascent; a linear negative correlation between precipitation and water table was found, and no significant correlation was observed with the water table increment; (2) through the infinite slope model and the relationship between precipitation and water table, a prediction model for shallow landslide stability was constructed. The precipitation threshold (81.8 mm/d) and water table threshold (0.73 m) were determined which has good agreement with the actual situations. This provides an early warning method for rainfall-induced shallow landslides by monitoring these two factors.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. Methods Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. Results A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2–31.6%) and 26.2% (23.9–28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. Conclusions The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9 calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.

In this study, the erosion characteristics of eutectic high entropy alloy under the liquid–solid two-phase flow is investigated by a coupled numerical-experimental method, in order to reveal the intrinsic relationship between microscopic erosion mechanism (experimental test) and the related particle-fluid-surface interaction (CFD modelling). Furthermore, instead of the common relation between average erosion rate and mainstream flow velocity, the relationship between local erosion distribution and local particulate flow characteristics is clarified. The erosion rate and erosion pattern match well between the experiment and simulation. The results demonstrate that NiCoCrFeNb0.45 exhibits superior anti-erosion performance when compared to other widely used equipment metals. The erosion profile agrees well with the shape of surface velocity distribution, indicating a close relationship between surface erosion behaviour and flow characteristics. In particular, the erosion pattern at a normal angle appears as a symmetric ring due to the flow stagnation phenomenon, with slight erosion damage in the centre area and severe erosion in the surrounding, whereas the erosion profile at an oblique angle displays an elliptic shape, with severe erosion damage in centre. Notably, the primary erosion mechanism varies dramatically in different surface regions, induced by the various impact velocities and angles associated with the corresponding changes in the flow field. This study provides a deeper understanding of erosion behaviour in terms of the interrelationship among the material mechanical properties, particulate flow field and particle-surface impingement behaviour.

Tobacco black shank (TBS), caused by Phytophthora nicotianae, is a severe disease. Plant root exudates play a crucial role in mediating plant-pathogen interactions in the rhizosphere. However, the specific interaction between key secondary metabolites present in root exudates and the mechanisms of disease resistance remains poorly understood. This study conducted a comprehensive comparison via quasi-targeted metabolomic analysis on the root exudate metabolites from the tobacco cultivar Yunyan87 and K326, both before and after inoculation with P. nicotianae. The results showed that the root exudate metabolites changed after P. nicotianae inoculation, and the root exudate metabolites of different tobacco cultivar was significantly different. Furthermore, homovanillic acid, lauric acid, and isoliquiritigenin were identified as potential key compounds for TBS resistance based on their impact on the mycelium growth of the pathogens. The pot experiment showed that isoliquiritigenin reduced the incidence by 55.2%, while lauric acid reduced it by 45.8%. This suggests that isoliquiritigenin and lauric acid have potential applications in the management of TBS. In summary, this study revealed the possible resistance mechanisms of differential metabolites in resistance of commercial tobacco cultivar, and for the first time discovered the inhibitory effects of isoliquiritigenin and homovanillic acid on P. nictianae, and attempt to use plants secondary metabolites of for plant protection.

This paper considers the problem of event-triggered [Formula: see text] output tracking control for uncertain networked switched systems with both communication constraints and asynchronous switching. A new sampled delay-dependent error tracking uncertain networked switched system is constructed on the basis of event-triggered communication mechanism (ETCM) and the given reference model. By introducing a parameter-dependent Lyapunov–Krasovskii functional and employing the mode-dependent average dwell time (MDADT) method, results on exponential stability and robust [Formula: see text] performance are proposed. Furthermore, the gains of the output tracking controller with matched system mode are obtained by solving a set of linear matrix inequalities (LIMs), at the same time, the parallel results with the mismatched case are also obtained. Simulation results show that the proposed design scheme not only guarantees tracking performance but also saves communication resources effectively.