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An axion insulator is a correlated topological phase, which is predicted to arise from the formation of a charge-density wave in a Weyl semimetal.sup.1,2--that is, a material in which electrons behave as massless chiral fermions. The accompanying sliding mode in the charge-density-wave phase--the phason--is an axion.sup.3,4 and is expected to cause anomalous magnetoelectric transport effects. However, this axionic charge-density wave has not yet been experimentally detected. Here we report the observation of a large positive contribution to the magnetoconductance in the sliding mode of the charge-density-wave Weyl semimetal (TaSe.sub.4).sub.2I for collinear electric and magnetic fields. The positive contribution to the magnetoconductance originates from the anomalous axionic contribution of the chiral anomaly to the phason current, and is locked to the parallel alignment of the electric and magnetic fields. By rotating the magnetic field, we show that the angular dependence of the magnetoconductance is consistent with the anomalous transport of an axionic charge-density wave. Our results show that it is possible to find experimental evidence for axions in strongly correlated topological condensed matter systems, which have so far been elusive in any other context. In the charge-density-wave Weyl semimetal (TaSe.sub.4).sub.2I, an axion is observed and identified as a sliding mode in the charge-density-wave phase characterized by anomalous magnetoelectric transport effects., Author(s): J. Gooth [sup.1] , B. Bradlyn [sup.2] , S. Honnali [sup.1] , C. Schindler [sup.1] , N. Kumar [sup.1] , J. Noky [sup.1] , Y. Qi [sup.1] , C. [...]

BACKGROUND/OBJECTIVES: Few studies have examined consumer acceptability or comprehension of cholesterol-lowering claims on food labels. Our objective was to assess consumer attitudes and understanding of cholesterol-lowering claims regarding plant sterols (PS) and oat fibre (OF). SUBJECTS/METHODS: We conducted two studies on: (1) PS claims and (2) OF claims. Both studies involved a randomized mock-packaged experiment within an online survey administered to Canadian consumers. In the PS study (n = 721), we tested three PS-related claims (disease risk reduction claim, function claim and nutrient content claim) and a 'tastes great' claim (control) on identical margarine containers. Similarly, in the OF study (n = 710), we tested three claims related to OF and a 'taste great' claim on identical cereal boxes. In both studies, participants answered the same set of questions on attitudes and understanding of claims after seeing each mock package. RESULTS: All claims that mentioned either PS or OF resulted in more positive attitudes than the taste control claim (P < 0.0001), despite all products within each study having the same nutrition profile. How consumers responded to the nutrition claims between the two studies was influenced by contextual factors such as familiarity with the functional food/component and the food product that carried the claim. CONCLUSIONS: Permitted nutrition claims are approved based on physiological evidence and are allowed on any food product as long as it meets the associated nutrient criteria. However, it is difficult to generalize attitudes and understanding of claims when they are so highly dependent on contextual factors. European Journal of Clinical Nutrition (2014) 68, 946-952; doi: 10.1038/ejcn.2014.107; published online 11 June 2014, INTRODUCTION Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in Canada. (1) Dietary and medical interventions to lower low-density lipoprotein cholesterol are the key strategies [...]

An amendment to this paper has been published and can be accessed via a link at the top of the paper., Author(s): J. Gooth [sup.1], B. Bradlyn [sup.2], S. Honnali [sup.1], C. Schindler [sup.1], N. Kumar [sup.1], J. Noky [sup.1], Y. Qi [sup.1], C. Shekhar [sup.1], Y. Sun [sup.1], Z. Wang [...]

Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03-1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20-65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders., (© 2024. The Author(s).)

Interleukin-33 (IL-33) is a pleiotropic molecule that plays various roles in the body. However, how exogenous IL-33 changes the tumor immune microenvironment remains unclear. Our study revealed that exogenous IL-33 exerts anti-tumor effects and effectively suppresses the progression of subcutaneous melanoma. scRNA-seq analysis revealed that exogenous IL-33 reduced neutrophils accumulation, thereby improving the inhibitory immune environment. Flow cytometry analysis revealed that exogenous IL-33 significantly increased the proportion of eosinophils and group 2 innate lymphoid cells (ILC2s). In addition, we identified genes encoding major histocompatibility complex (MHC) class II molecules in this group of ILC2s, suggesting that ILC2s may play a role in antigen presentation. In Il7r Cre Arg1 flox/flox mice, the decrease of ILC2s led to a reduction in the proportion of eosinophils. Furthermore, we found that exogenous IL-33 effectively promoted the differentiation of ILC2s and their accumulation in tumors, thereby enhancing the anti-tumor immune response. These findings may pave the way for developing new cancer immunotherapies that use IL-33 as an activator to enhance anti-tumor immune responses., (© 2024. The Author(s).)

Chronic Obstructive Pulmonary Disease (COPD) significantly impacts patients' quality of life and burdens healthcare systems. Magnesium is crucial for lung function and reducing respiratory disease risk. This study investigates the association between Magnesium Depletion Score (MDS) and COPD and explores whether inflammatory markers mediate this relationship. A cross-sectional analysis was conducted using data from 30,490 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. MDS was calculated based on diuretic use, proton pump inhibitors, renal function, and alcohol consumption. Univariable and multivariable logistic regression analyses were performed to assess the association between MDS and COPD, adjusting for potential confounders. Mediation analysis was used to examine the roles of neutrophils, serum albumin, and the Systemic Immune-Inflammation Index (SII). In the univariable logistic model, higher MDS was significantly associated with increased COPD risk. Specifically, compared to MDS = 0, the odds ratios (OR) for COPD were 2.50, 4.12, 6.13, 8.53, and 7.81 for MDS = 1, 2, 3, 4, and 5, respectively (all P < 0.001). In the multivariable model, the ORs were 1.79, 2.25, 2.71, and 3.44 for MDS = 1, 2, 3, and 4, respectively (all P < 0.001). Higher neutrophil levels and SII were positively associated with increased COPD risk, while higher serum albumin levels were inversely associated. Mediation analysis indicated that neutrophils, serum albumin, and SII significantly mediated the MDS-COPD relationship. Higher MDS is significantly associated with increased COPD risk, mediated by systemic inflammation markers. Improving magnesium levels could potentially reduce COPD risk, warranting further research on magnesium supplementation in COPD prevention and management., (© 2024. The Author(s).)

As the third most important temperate fruit, Pear (Pyrus spp.) exhibits a remarkable genetic diversity and is classified into two mainly categories known as Asian pear and European pear. Although several pear genomes are available, most of the released versions are fragmented and not chromosome-level high-quality. In this study, we report two high-quality genomes for Pyrus bretschneideri Rhed. cv. 'Danshansuli' (DS) and Pyrus communis L. cv. 'Conference' (KFL), which represent the predominant Asian and European cultivars, respectively, with nearly telomere-to-telomere (T2T) gap-free level. The finally assembled genome sizes for DS and KFL were 510.98 Mb and 510.71 Mb, respectively, with Contig N50 of 29.47 Mb and 30.47 Mb, where each chromosome was represented by a single contig. The DS and KFL genomes yielded a total of 46,394 and 44,702 protein-coding genes, respectively. Among these genes, the functional annotation accounted for 96.47% and 96.46% in the DS and KFL genomes. The two novels nearly T2T genomic information offers an invaluable resource for comparative genomics, genetic diversity analysis, molecular breeding strategies, and functional exploration., (© 2024. The Author(s).)

The judiciary protects the value of innovation through remedies such as injunctions and damages when patent rights are infringed, adjusting the expected returns on future innovation activities for firms. Based on data from 1,062 Chinese firms involved in Patent Infringement Litigations (PILs), this study uses three-way fixed-effects Poisson panel regression models to examine the dynamic impacts of a PIL win-or-lose decision on breakthrough and incremental innovation performance for plaintiff and defendant firms. The study finds that plaintiff micro and small-sized enterprises (MSEs) can only engage in short-term breakthrough innovation after winning a PIL. Plaintiff medium and large-sized enterprises (MLEs) tend to adopt the patent defence strategy after winning, while losing a case positively impacts their breakthrough and incremental innovation. Defendant firms adopt the strategy from incremental innovation to breakthrough innovation after winning, while losing inhibits their innovation. The current Chinese patent system has an imbalance in incentivizing innovation for MSEs. Whether winning or losing, defendant MSEs participating in litigation significantly inhibit their innovation performance at different levels. This paper provides a multidimensional angle for studying the relationship between patent protection and corporate innovation., (© 2024. The Author(s).)

Recent studies indicate that CISD3 is crucial in mitochondrial function and tumorigenesis. Using various databases, we systematically analyzed its expression, prognostic value, and immune activity. Our findings show CISD3 is mainly expressed in tumor cells across cancers, with higher mRNA but lower protein levels, degraded post-translationally via the lysosomal pathway. In certain cancers, CISD3 expression is positively correlated with tumor-infiltrating immune cells. Prognostic analysis suggests dual roles as both protective and risk factors, notably an independent prognostic predictor in renal cell carcinoma (RCC). CISD3 copy number variations are linked to homologous recombination defects and tumor-specific neoantigens, negatively correlated with methylation levels. Pathway analysis reveals CISD3 involvement in oncogenic processes, such as proliferation inhibition and epithelial-mesenchymal transition. Protein interactions underline its role in mitochondrial metabolism and redox balance. Experiments confirm low CISD3 expression in cancers, with overexpression reducing proliferation, migration, invasion, and tumor growth in mice. Mechanistic studies indicate CISD3 overexpression disrupts mitochondrial function, increases ROS levels, decreases GSH/GSSG ratios and mitochondrial membrane potential, inhibiting antioxidant activity and promoting cell damage and ferroptosis, thus impeding cancer progression. This study highlights CISD3's potential as a prognostic biomarker and therapeutic target., (© 2024. The Author(s).)

This study aims to investigate the responses of shield tunnel structures subjected to disturbances caused by bilateral pit excavation, and it systematically reveals for the first time the impact mechanism of bilateral pit excavation on the distribution of perimeter pressure and deformation patterns of shield tunnels. Using a bilateral pit excavation project in Nanjing as a case study, this research establishes methods for calculating longitudinal displacement and circumferential pressure of tunnels under bilateral pit excavation conditions, employing the image source method for analysis. A refined three-ring segment model is developed, and the load structure method is used to analyze the impact of deep foundation excavation on the tunnel located between the two excavation sites. The results indicate that, compared to unilateral excavation, bilateral excavation significantly increases the perimeter pressure at the top and bottom of the tunnel, with a smaller increase in pressure at the arch waist. The deformation pattern is characterized by contraction at the top and bottom and expansion at the waist, forming a transverse elliptical deformation. The maximum vertical convergence values of the middle segment ring are 25.00 mm at the top and 25.88 mm at the bottom, with a vertical absolute convergence value of 44.5 mm and a convergence ratio (ΔD t /D t ) of 0.72%. As the foundation coefficient increases, the perimeter pressure at the top and bottom of the tunnel also increases. When the tunnel is closer to the foundation pits (S p decreases), the perimeter pressure at the bottom of the tunnel increases. Conversely, as the distance between the two foundation pits (S) increases, the impact of excavation on the tunnel shifts from the upper part to the lower part, resulting in decreased upper perimeter pressure and increased lower perimeter pressure. The research findings provide important references for similar engineering projects., (© 2024. The Author(s).)

Telocytes (TCs) are a type of stromal cell discovered in the various organs of different animals and have many potential functions, including angiogenesis, signalling, and substance transport. However, the TCs have not been detected in the testis or epididymis of Tibetan sheep. This study investigated the position, characteristics, and distribution of TCs in the testis and epididymis of Tibetan sheep using transmission electron microscopy (TEM), toluidine blue staining, immunohistochemistry, and double immunofluorescence to elucidate their possible functions. TEM revealed that TCs were often found near basement membranes and capillaries and were characterised by large nuclei, elongated cytoplasmic protrusions, and many secretory vesicles. We also observed via toluidine staining that TCs were present near basement membrane and interstitial capillaries. Immunohistochemistry and double immunofluorescence revealed the positive expression of CD117, vimentin, platelet derived growth factor receptor α(PDGFRα), PDGFRα + CD117, and PDGFRα + vimentin in TCs. Additionally, we inferred that TCs participates in the formation of the blood-testis and blood-epididymis barriers, as well as in material transport and a stable microenvironment. This study presents the first evidence of the presence of TCs near the basement membrane and blood vessels in the testis and epididymis of Tibetan sheep. These findings provide new insights into the function of TCs in the reproductive systems of plateau animals., (© 2024. The Author(s).)

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level 1 . Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target 1 . However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states-the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Rapidly progressive necrotizing enterocolitis (RP-NEC) is a particular subtype of NEC known for its rapid progression and high mortality rate. The objective of this study was to establish a predictive model for RP-NEC., Methods: This was a retrospective single-center cohort study. Patients were newborn infants with NEC (Bell's stage ≥ IIB) admitted from January 1, 2016 to December 31, 2023. The primary outcome was RP-NEC defined as the need for surgical intervention and/or death within 48 hours of the onset of NEC., Results: Totally 334 newborn infants were included, among which 82 (24.6%) were RP-NEC cases with a gestation age 34.1 (31.0, 37.0) weeks and birth weight 2100 (1413, 2800) g. Plasma sodium <135 mmol/L, C-reactive protein ≥10 mg/L, platelet count <100 × 10 9 /L, lymphocyte count <1.5 × 10 9 /L, pH <7.2 in blood gas, and ascites at NEC onset were identified as independent risk factors for RP-NEC. The model established presented an AUC value of 0.983 (95% CI 0.97-0.99). The calibration curve for validation was applied revealing a slope close to unity while the Hosmer-Lemeshow test yielded χ 2  = 2.550 (p = 0.636)., Conclusion: The predictive model established on the above 6 items of RP-NEC is highly promising., Impact: Currently, there is a paucity of research on this specific type of severe necrotizing enterocolitis (NEC) characterized by rapid progression. Our study was to investigate the risk factors associated with surgical intervention and/or death within 48 hours following onset in infants with NEC, establish a predictive model for infants with rapidly progressive NEC. The new data presented in this study was the ROC curve combining the above factors as well as hyponatremia., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neoadjuvant therapy (NAT) is an important treatment for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC), but neoadjuvant resistance affects the overall treatment outcome. Therefore, it is particularly important to accurately screen the population for NAT and explore the mechanism of resistance. Usually, different chemotherapy regimens cause different drug resistance mechanisms. Prior to combining immunotherapy with chemotherapy, extensive research has been conducted on previous drug resistance mechanisms. Currently, the mainstream NAT for ESCC involves chemotherapy combined with immunotherapy. We have witnessed the remarkable effect of this combination therapy; however, there are still a considerable number of patients whose tumor tissues show no change or even progress after NAT, and their drug resistance mechanisms remain unclear. Hence, we aim to identify relevant evidence that can distinguish and predict the effectiveness of NAT from a clinical perspective in order to provide a clinical basis for future screening of suitable populations for NAT and discovery of drug resistance mechanisms. This study is based in China's high incidence area of esophageal cancer, where enrolled patients all receive the current mainstream NAT regimen resulting in more reliable outcomes., (© 2024. The Author(s).)

Carbon fiber reinforced polyamide-6 (CF/PA-6) composites have been widely applied in automobile, aerospace, and biomedical industries for their high mechanical properties, high thermal resistance and recyclability. On the purpose of finding ways to improve the interfacial properties, the investigation of the nanostructure and nanomechanical properties of the interphase in CF/PA-6 composites were essential. In this study, MD simulation was carried out to show the interfacial formation and nanostructure of the CF/PA-6 composite model directly at the atomic level and compute the radial distribution function, interfacial energy, total energy. Then the nanomechanical properties of the CF/PA-6 composite, such as interfacial thickness, interfacial modules, interfacial adhesion, were investigated by AFM PF-QNM model. The changes of the radical distribution function and energies over the MD simulation time indicated that the PA-6 chains adsorbed and then regularly folded on the CF surface, displaying the interfacial crystallization of the CF/PA-6 composite model. What stood out in the AFM PF-QNM tests were the abrupt decreasing of the interfacial modulus and the sharp increasing of the interfacial adhesion from those of the carbon fiber to those of the PA-6. The average interfacial thickness of the CF/PA-6 composite was 72 nm. Consistent with the simulation results, the interfacial properties were distinct from the properties of the carbon fiber and PA-6, owning to the adsorption and orderly folding of the PA-6 chains on the CF surface and the changes of the RDF and energies., (© 2024. The Author(s).)

To investigate the effect of low-doses esketamine on spinal anesthesia-induced hypotension in women with preoperative anxiety undergoing elective cesarean section, the randomized controlled trial enrolled 120 women aged 18-35 years who preoperative State-Trait Anxiety Inventory State scores > 40, conducted from September 2022 to August 2023 in Xuzhou Central Hospital, China. Women in the esketamine group received a single intravenous injection of 0.2 mg/kg esketamine after sensory block level achieved. The incidence of hypotension in the esketamine group was significantly lower than the control group at T2 (10% [6 of 60]; P < 0.001), T3 (5.0% [3 of 60]; P = 0.007) and T4(5.0% [3 of 60]; P = 0.004). Despite being higher in the esketamine group, the overall rates of hypertension (11.7% [7 of 60]; P = 0.186), tachycardia (23.3% [14 of 60]; P = 0.246), and bradycardia (0.0% [0 of 60]; P = 0.079) were no significantly difference between the two groups. STAI-S scores was significantly lower in the esketamine group (mean [SD] 37.52[7.14]) than in the control group (mean [SD] 41.03[9.66], P = 0.39) in postoperative day 1. Spinal anesthesia combined with intravenous low-doses esketamine infusion can significantly reduce the incidence of hypotension in women with preoperative anxiety undergoing elective cesarean section., (© 2024. The Author(s).)

With the advancement of science and technology, coal-washing plants are transitioning to intelligent, information-based, and professional sorting systems. This shift accelerates the construction a modern economic system characterized by green and low-carbon development, thereby promoting the high-quality advancement of the coal industry. Traditional manual gangue picking and multi-axis robotic arm gangue selection currently suffer from low recognition accuracy, slow sorting efficiency, and high worker labor intensity. This paper proposes a deep learning-based, non-contact gangue recognition and pneumatic intelligent sorting system. The system constructs a dynamic database containing key feature information such as the target gangue's contour, quality, and center of mass. The system elucidates the relationships between ejection speed, mass, volume, angle of incidence, and the impact energy matching mechanism. Demonstration experiments using the system prototype for coal gangue sorting reveal that, compared to existing robotic arm sorting methods in coal washing plants, this system achieves a gangue identification accuracy exceeding 97%, a sorting rate above 91%, and a separation time of less than 3 s from identification to separation, thereby effectively enhancing raw coal purity., (© 2024. The Author(s).)

We aimed to implement four data partitioning strategies evaluated with four federated learning (FL) algorithms and investigate the impact of data distribution on FL model performance in detecting steatosis using B-mode US images. A private dataset (153 patients; 1530 images) and a public dataset (55 patient; 550 images) were included in this retrospective study. The datasets contained patients with metabolic dysfunction-associated fatty liver disease (MAFLD) with biopsy-proven steatosis grades and control individuals without steatosis. We employed four data partitioning strategies to simulate FL scenarios and we assessed four FL algorithms. We investigated the impact of class imbalance and the mismatch between the global and local data distributions on the learning outcome. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. AUCs were 0.93 (95% CI 0.92, 0.94) for source-based partitioning scenario with FedAvg, 0.90 (95% CI 0.89, 0.91) for a centralized model, and 0.83 (95% CI 0.81, 0.85) for a model trained in a single-center scenario. When data was perfectly balanced on the global level and each site had an identical data distribution, the model yielded an AUC of 0.90 (95% CI 0.88, 0.92). When each site contained data exclusively from one single class, irrespective of the global data distribution, the AUC fell in the range of 0.34-0.70. FL applied to B-mode US images provide performance comparable to a centralized model and higher than single-center scenario. Global data imbalance and local data heterogeneity influenced the learning outcome., (© 2024. The Author(s).)

Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy., (© 2024. The Author(s).)

Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib., (© 2024. The Author(s).)

Blood-based gene expression signatures could potentially be used as biomarkers for PD. However, it is unclear whether genetically-regulated transcriptomic signatures can provide novel gene candidates for use as PD biomarkers. We leveraged on the Genotype-Tissue Expression (GTEx) database to impute whole-blood transcriptomic expression using summary statistics of three large-scale PD GWAS. A random forest classifier was used with the consensus whole-blood imputed gene signature (IGS) to discriminate between cases and controls. Outcome measures included Area under the Curve (AUC) of Receiver Operating Characteristic (ROC) Curve. We demonstrated that the IGS (n = 37 genes) is conserved across PD GWAS studies and brain tissues. IGS discriminated between cases and controls in an independent whole-blood RNA-sequencing study (1176 PD, 254 prodromal, and 860 healthy controls) with mean AUC and accuracy of 64.8% and 69.4% for PD cohort, and 78.8% and 74% for prodromal cohort. PATL2 was the top-performing imputed gene in both PD and prodromal PD cohorts, whose classifier performance varied with biological sex (higher performance for males and females in the PD and prodromal PD, respectively). Single-cell RNA-sequencing studies (scRNA-seq) of healthy humans and PD patients found PATL2 to be enriched in terminal effector CD8+ and cytotoxic CD4+ cells, whose proportions are both increased in PD patients. We demonstrated the utility of GWAS transcriptomic imputation in identifying novel whole-blood transcriptomic signatures which could be leveraged upon for PD biomarker derivation. We identified PATL2 as a potential biomarker in both clinical and prodromic PD., (© 2024. The Author(s).)

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways., (© 2024. The Author(s).)

Observational studies have found a potential bidirectional positive association between multiple sclerosis and psoriasis, but these studies are susceptible to confounding factors. We examined the directionality of causation using Mendelian randomization and estimated the genetic correlation using the linkage disequilibrium score. We performed Mendelian randomization analysis using large-scale genome-wide association studies datasets from the International Multiple Sclerosis Genetics Consortium (IMSGC, 115,803 individuals of European ancestry) and FinnGen (252,323 individuals of European ancestry). We selected several Mendelian randomization methods including causal analysis using summary effect (CAUSE), inverse variance-weighted (IVW), and pleiotropy-robust methods. According to CAUSE and IVW the genetic liability to MS reduces the risk of psoriasis (CAUSE odds ratio [OR] 0.93, p = 0.045; IVW OR 0.93, p = 2.51 × 10 -20 ), and vice versa (CAUSE OR 0.72, p = 0.001; IVW OR 0.71, p = 4.80 × 10 -26 ). Pleiotropy-robust methods show the same results, with all p-values < 0.05. The linkage disequilibrium score showed no genetic correlation between psoriasis and MS (rg =  - 0.071, p = 0.2852). In summary, there is genetic evidence that MS reduces the risk of psoriasis, and vice versa., (© 2024. The Author(s).)

Since the 1980s, low-permeability slurry trench cutoff walls have been widely constructed as barriers to retard the migration of contaminants. The thickness of the cutoff walls is a key determinant of the wall service life. Through a series of theoretical derivations, simplified methods for determining the flux limit and concentration limit were proposed to determine the thickness of cutoff walls for contaminated sites with constant pollutant flux. The relative errors of both the flux-based and concentration-based methods increase as the breakthrough criterion of the ratio between the specified limit concentration of the contaminant to the source concentration (C * ) and the ratio of the limited value of contaminant flux to the constant source flux (F * ) increases, with a given Peclet number P L . The maximum relative error reaches 4% and 6% when C * and F * are both 0.1, which covers most practical situations in cutoff wall design. Good agreements of wall thickness were obtained between the proposed simplified methods and analytical solutions via a clear example. The proposed method can efficiently simplify the design process of cutoff walls with high accuracy, providing a basis for containing contaminated sites., (© 2024. The Author(s).)

Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach., (© 2024. The Author(s).)

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI., (© 2024. The Author(s).)

Globe-LFMC 2.0, an updated version of Globe-LFMC, is a comprehensive dataset of over 280,000 Live Fuel Moisture Content (LFMC) measurements. These measurements were gathered through field campaigns conducted in 15 countries spanning 47 years. In contrast to its prior version, Globe-LFMC 2.0 incorporates over 120,000 additional data entries, introduces more than 800 new sampling sites, and comprises LFMC values obtained from samples collected until the calendar year 2023. Each entry within the dataset provides essential information, including date, geographical coordinates, plant species, functional type, and, where available, topographical details. Moreover, the dataset encompasses insights into the sampling and weighing procedures, as well as information about land cover type and meteorological conditions at the time and location of each sampling event. Globe-LFMC 2.0 can facilitate advanced LFMC research, supporting studies on wildfire behaviour, physiological traits, ecological dynamics, and land surface modelling, whether remote sensing-based or otherwise. This dataset represents a valuable resource for researchers exploring the diverse LFMC aspects, contributing to the broader field of environmental and ecological research., (© 2024. The Author(s).)

Purpose: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE)., Methods: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay., Results: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P 7th  < 0.001, P 30th  = 0.039, and P 60th  = 0.031) and TBUT (P 7th  = 0.009, P 30th  = 0.003, and P 60th  = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores., Conclusions: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

The integrated development of agricultural land and finance not only promotes rural financial innovation and breaks the bottleneck of agricultural financing but also facilitates agricultural land transfer and scaled operations. This leads to the advancement of the effective growth of contemporary agriculture. The reform of the 'separation of three rights' in agricultural land promotes land circulation, which, in turn, offers an institutional guarantee for the tandem development of rural finance and agricultural land management. This paper measures the comprehensive development index of agricultural land management and rural finance in 30 provinces of China from 2005 to 2020. In light of this, it calculates the degree of coupling and coordination between China's agricultural land management and rural financial development. The Dagum Gini coefficient, kernel density, and the Moran index were used to analyze regional differences and patterns of agglomeration. The study found that the degree of coupling coordination between China's agricultural land management and rural finance is increasing annually. However, there remains a significant gap in achieving high-quality coupling. Notably, the growth rate of rural financial development exceeds that of agricultural land management, and hypervariable density is a major source of regional variation. There is polarization in the coupled development of farmland management and rural finance. Provinces in the eastern and central regions tend to be located in the high-high agglomeration (H-H) in terms of the level of development of agricultural land and financial integration, while the western region tends to fall in low-low aggregation (L-L)., (© 2024. The Author(s).)

Danmakus are user-generated comments that overlay on videos, enabling real-time interactions between viewers and video content. The emotional orientation of danmakus can reflect the attitudes and opinions of viewers on video segments, which can help video platforms optimize video content recommendation and evaluate users' abnormal emotion levels. Aiming at the problems of low transferability of traditional sentiment analysis methods in the danmaku domain, low accuracy of danmaku text segmentation, poor consistency of sentiment annotation, and insufficient semantic feature extraction, this paper proposes a video danmaku sentiment analysis method based on MIBE-RoBERTa-FF-BiLSTM. This paper constructs a "Bilibili Must-Watch List and Top Video Danmaku Sentiment Dataset" by ourselves, covering 10,000 positive and negative sentiment danmaku texts of 18 themes. A new word recognition algorithm based on mutual information (MI) and branch entropy (BE) is used to discover 2610 irregular network popular new words from trigrams to heptagrams in the dataset, forming a domain lexicon. The Maslow's hierarchy of needs theory is applied to guide the consistent sentiment annotation. The domain lexicon is integrated into the feature fusion layer of the RoBERTa-FF-BiLSTM model to fully learn the semantic features of word information, character information, and context information of danmaku texts and perform sentiment classification. Comparative experiments on the dataset show that the model proposed in this paper has the best comprehensive performance among the mainstream models for video danmaku text sentiment classification, with an F1 value of 94.06%, and its accuracy and robustness are also better than other models. The limitations of this paper are that the construction of the domain lexicon still requires manual participation and review, the semantic information of danmaku video content and the positive case preference are ignored., (© 2024. The Author(s).)

The proposed study presents an enhanced combination weighting cloud model for accurate assessment of coal and gas outburst risks. Firstly, a comprehensive evaluation index system for coal and gas outburst risks is established, consisting of primary indicators such as coal rock properties and secondary indicators including 13 factors. Secondly, the improved Analytic Hierarchy Process (IAHP) based on the 3-scale method and the improved CRITIC based on indicator correlation weight determination method are employed to determine subjective and objective weights of evaluation indicators respectively. Additionally, the Lagrange multiplier method is introduced to fuse these weights in order to obtain optimal weights. Subsequently, a prominent danger assessment model is developed based on cloud theory. Finally, using a mine in Hebei Province as an example, the results obtained from IAHP combined with improved CRITIC weighting method are compared with those from traditional AHP method and AHP-CRITIC combination weighting method. The findings demonstrate that among all methods considered, IAHP combined with improved CRITIC exhibits superior performance in terms of distribution expectation Ex, entropy value En, and super entropy He within cloud digital features; thus indicating that the risk level of coal and gas outbursts in this particular mine can be classified as general risk. These evaluation results align well with actual observations thereby validating the effectiveness of this approach. Consequently, this constructed model enables rapid yet accurate determination of coal and gas outburst risks within mines., (© 2024. The Author(s).)

The analysis of ceramide (Cer) and sphingomyelin (SM) lipid species using liquid chromatography-tandem mass spectrometry (LC-MS/MS) continues to present challenges as their precursor mass and fragmentation can correspond to multiple molecular arrangements. To address this constraint, we developed ReTimeML, a freeware that automates the expected retention times (RTs) for Cer and SM lipid profiles from complex chromatograms. ReTimeML works on the principle that LC-MS/MS experiments have pre-determined RTs from internal standards, calibrators or quality controls used throughout the analysis. Employed as reference RTs, ReTimeML subsequently extrapolates the RTs of unknowns using its machine-learned regression library of mass-to-charge (m/z) versus RT profiles, which does not require model retraining for adaptability on different LC-MS/MS pipelines. We validated ReTimeML RT estimations for various Cer and SM structures across different biologicals, tissues and LC-MS/MS setups, exhibiting a mean variance between 0.23 and 2.43% compared to user annotations. ReTimeML also aided the disambiguation of SM identities from isobar distributions in paired serum-cerebrospinal fluid from healthy volunteers, allowing us to identify a series of non-canonical SMs associated between the two biofluids comprised of a polyunsaturated structure that confers increased stability against catabolic clearance., (© 2024. The Author(s).)

Excessive alternating current (AC) arcs generated in electric systems will accumulate heat and easily cause fire. This paper studies the thermal characteristics of different numbers of AC arc plasma generated in a short gap of copper-cored wires in the air. The number of AC arcs is controlled in the AC arc experiment and an infrared thermal imager measures the temperature change at the specified position. Based on magnetohydrodynamics (MHD), a two-dimensional axisymmetric AC arc discharge numerical simulation model is established. The volt-ampere characteristic of the AC arc is used to solve the MHD simulation model to obtain the same 'zero current' characteristics as the real AC arc in the experiment. A large amount of heat accumulates in the electrode gaps when the arc generation, and then the heat dissipates in the 'zero current' stage. The continuously generated arc makes the temperature higher. The volume of the space area with a temperature higher than 10,000 K increases with the arc current, but is unrelated to the number of arcs. The volume of the space area with a temperature higher than 524.15 K and the temperature on the electrode are both positively correlated with the number of AC arcs and arc current. The results of this study can provide a reference for the detection standard of AC arc faults and the prevention of electrical fire., (© 2024. The Author(s).)

Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers., (© 2024. The Author(s).)

The feasibility and accuracy of the risk prediction of gas extraction borehole spontaneous combustion is improved to avoid the occurrence of spontaneous combustion in the gas extraction borehole. A gas extraction borehole spontaneous combustion risk prediction model (PSO-BPNN model) coupling the PSO algorithm with BP neural network is established through improving the connection weight and threshold values of BP neural network by the particle swarm optimization (PSO) algorithm. The prediction results of the PSO-BPNN model are compared and analyzed with that of the BP neural network model (BPNN model), GA-BPNN model, SSA-BPNN model and MPA-BPNN model. The results showed as follows: the average relative error of the PSO-BPNN model was 4.38%; the average absolute error was 0.0678; the root mean square error was 0.0934; and the determination coefficient was 0.9874. Compared with the BPNN model, the average relative error, average absolute error and root mean square error decreased by 9.35%, 0.1707 and 0.2056 respectively; and the determination coefficient increased by 0.1169. Compared with the GA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 3.19%, 0.0602 and 0.0821 respectively; and the determination coefficient increased by 0.0320. Compared with the SSA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 5.70%, 0.0820 and 0.1100 respectively; and the determination coefficient increased by 0.0474. Compared with the MPA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 3.50%, 0.0861 and 0.1125 respectively; and the determination coefficient increased by 0.0488, proving that the PSO-BPNN model is more accurate than the BPNN model, GA-BPNN model, SSA-BPNN model and MPA-BPNN model as for prediction. When the PSO-BPNN model was applied to three extraction boreholes A, B, and C in a coal mine of Shanxi, the prediction results were better than the BPNN model, GA-BPNN model, SSA-BPNN model and MPA-BPNN model, proving the accuracy and stability of the PSO-BPNN model in predicting risk of borehole spontaneous combustion in other mine., (© 2024. The Author(s).)

Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity 1 , is one of the long-standing pursuits in fundamental research 2,3 . Although the initial report of 4 He supersolid turned out to be an artefact 4 , this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases 5-8 . Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na 2 BaCo(PO 4 ) 2 (ref. 9 ). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages 10,11 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Transcription factor EB (TFEB) mediates gene expression through binding to the coordinated lysosome expression and regulation (CLEAR) sequence. TFEB targets include subunits of the vacuolar ATPase (v-ATPase), which are essential for lysosome acidification. Single-nucleus RNA sequencing of wild-type and PS19 (Tau) transgenic mice expressing the P301S mutant tau identified three unique microglia subclusters in Tau mice that were associated with heightened lysosome and immune pathway genes. To explore the lysosome-immune relationship, we specifically disrupted the TFEB-v-ATPase signaling by creating a knock-in mouse line in which the CLEAR sequence of one of the v-ATPase subunits, Atp6v1h, was mutated. CLEAR mutant exhibited a muted response to TFEB, resulting in impaired lysosomal acidification and activity. Crossing the CLEAR mutant with Tau mice led to higher tau pathology but diminished microglia response. These microglia were enriched in a subcluster low in mTOR and HIF-1 pathways and were locked in a homeostatic state. Our studies demonstrate a physiological function of TFEB-v-ATPase signaling in maintaining lysosomal homeostasis and a critical role of the lysosome in mounting a microglia and immune response in tauopathy and Alzheimer's disease., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The mixed-ownership reform of job invention achievements (MOJIA) is an important exploration of China's sound long-term incentive mechanism for transforming job-related inventions. Based on the data of MOJIA pilot universities and regions from 2012 to 2022, this paper analyzes the relationship and mechanism between MOJIA and university innovation (UI) in China by combining resource dependence theory and institutional theory. The study found that MOJIA has a promotive effect on UI. The findings continue to hold after using parallel trend tests, lagged regressions, alternative UI measures, endogeneity control, and placebo tests. MOJIA can enhance the technology achievement marketability in the regions where universities are located. Moreover, MOJIA can facilitate the technological achievements marketability by improving UI. Heterogeneity analysis found that the lower the administrative level and the university's social reputation, the stronger the promotion effect of MOJIA on UI. The research in this paper provides implications for further improving MOJIA., (© 2024. The Author(s).)

Numerous coal pillars are left after the coal mining process. The composite structure comprising a roof and coal pillar has prominent creep characteristics, which threaten safe underground mining. Therefore, the creep characteristics of coal-rock combinations should be studied to ensure the safety of quarry and surface. Uniaxial creep tests under static load axial pressure and different height ratios were performed using a self-designed rock creep disturbance test device to determine the effect of height ratio and axial pressure on the creep characteristics of coal-rock combinations. From the test results, a creep damage model for coal-rock combinations was established by combining the elastomer, fractional Kelvin body, plastic body, Abel dashpot, and modified nonlinear viscoplastic body; introducing damage variables D related to stress, height ratio, and time; and deriving a one-dimensional creep equation. An improved nonlinear least squares method based on pattern search was utilized to invert the creep parameters. The results of the creep equation calculation were fitted with the experimental results with good results. The creep curve with a height ratio of 2:1 was predicted with good results. The research results provide theoretical references for long-term stability analysis of rock engineering., (© 2023. The Author(s).)

To investigate the value of metagenomic next-generation sequencing (mNGS) in acute leukemia (AL) patients with febrile neutropenia (FN). We retrospectively reviewed 37 AL patients with FN and compared the results of mNGS with blood culture (BC) and the clinical features of the mNGS-positive group and the mNGS-negative group. A total of 14 detected pathogens were the final clinical diagnosis, of which 9 strains were detected only by mNGS and 5 strains were detected by both mNGS and BC. The top pathogens were Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. A total of 67.57% (25/37) were bacterial infections, and 2.7% (1/37) were fungal or viral infections. The diagnostic positivity rate of mNGS (25/37, 67.6%) was significantly higher than that of BC (7/37, 18.9%), and the difference was statistically significant (p < 0.05). Then, we explored the clinical distinction between the mNGS-positive group and the mNGS-negative group, and 3 features were filtered, including lymphocyte count (LY), creatinine levels (Cr), and white blood cell count (WBC). Our study demonstrated that early implementation of mNGS can effectively improve the efficacy of pathogen detection in AL patients with FN. The higher diagnostic positivity rate and the ability to detect additional pathogens compared to BC made mNGS a valuable tool in the management of infectious complications in this patient population. Furthermore, the identified clinical features associated with mNGS results provided additional insights for the clinical indication of infection in AL patients with FN., (© 2023. The Author(s).)

Rainfall forecasting is an important means for macro-control of water resources and prevention of future disasters. In order to achieve a more accurate prediction effect, this paper analyzes the applicability of the "full decomposition" and "stepwise decomposition" of the VMD (Variational mode decomposition) algorithm to the actual prediction service; The MAVOA (Modified African Vultures Optimization Algorithm) improved by Tent chaotic mapping is selected; and the DNC (Differentiable Neural Computer), which combines the advantages of recurrent neural networks and computational processing, is applied to the forecasting. The different VMD decompositions of the MAVOA-DNC combination together with other comparative models are applied to example predictions at four sites in the Huaihe River Basin. The results show that SMFSD (Single-model Fully stepwise decomposition) is the most effective, and the average Root Mean Square Error (RMSE) of the forecasts for the four sites of SMFSD-MAVOA-DNC is 9.02, the average Mean Absolute Error (MAE) of 7.13, and the average Nash-Sutcliffe Efficiency (NSE) of 0.94. Compared with the traditional VMD full decomposition, the RMSE is reduced by 7.42, the MAE is reduced by 4.83, and the NSE is increased by 0.05; the best forecasting results are obtained compared with other coupled models., (© 2023. The Author(s).)

To improve the accuracy of runoff forecasting, a combined forecasting model is established by using the kernel extreme learning machine (KELM) algorithm optimised by the butterfly optimisation algorithm (BOA), combined with the variational modal decomposition method (VMD) and the complementary ensemble empirical modal decomposition method (CEEMD), for the measured daily runoff sequences at Jiehetan and Huayuankou stations and Gaochun and Lijin stations. The results show that the combined model VMD-CEEMD-BOA-KELM predicts the best. The average absolute errors are 30.02, 23.72, 25.75, 29.37, and the root mean square errors are 20.53 m 3 /s, 18.79 m 3 /s, 18.66 m 3 /s, and 21.87 m 3 /s, the decision coefficients are all above 90 percent, respectively, and the Nash efficiency coefficients are all more than 90%, from the above it can be seen that the method has better results in runoff time series prediction., (© 2023. The Author(s).)

Cuproptosis is a unique type of cell death that may influence tumour formation by targeting lipoylated tricarboxylic acid cycle proteins. Solute carrier family 31 member 1 (SLC31A1), an important copper transporter, influences dietary copper absorption in the cell membrane. However, various SLC31A1 properties in pan-cancer profiles remain unknown. This study investigated the role of SLC31A1 in human malignancies and analysed its prognostic value. Raw data were obtained from The Cancer Genome Atlas database and processed using numerous internet databases, including UALCAN, GEPIA, cBioPortal, TIMER2.0, and Human Protein Atlas. SLC31A1 expression was found to be elevated in cervical, endometrial, and breast cancers compared to that in normal tissues, but reduced in clear cell renal cell carcinoma, liver hepatocellular carcinoma, and lung adenocarcinoma. Furthermore, SLC31A1 expression was strongly associated with overall survival and disease-free survival in several cancers. SLC31A1 gene mutations and methylations were identified in 33 cancers. SLC31A1 expression was positively correlated with immune cells in immune infiltration data. Single-cell sequencing revealed that SLC31A1 may play key roles in DNA repair, DNA damage, and proliferation. These findings may lead to better understanding of SLC31A1 in pan-cancer profiles and suggest that SLC31A1 could be a viable predictive biomarker, particularly in gynaecological cancers., (© 2023. Springer Nature Limited.)

In order to enhance the simulation of BMPs (Best Management Practices) reduction effects in unmonitored watersheds, in this study, we combined the physically-based hydrological model Soil & Water Assessment Tool (SWAT) and the data-driven model Bi-directional Long Short-Term Memory (Bi-LSTM), using the very-high-resolution (VHR) Land Use and Land Cover (LULC) dataset SinoLC-1 as data input, to evaluate the feasibility of constructing a water environment model for the Ba-River Basin (BRB) in central China and improving streamflow prediction performance. In the SWAT-BiLSTM model, we calibrated the top five SWAT parameters sorted by P-Value, allowing SWAT to act as a transfer function to convert meteorological data into base flow and storm flow, serving as the data input for the Bi-LSTM model. This optimization improved the Bi-LSTM's learning process for the relationship between the target and explanatory variables. The daily streamflow prediction results showed that the hybrid model had 9 regions rated as "Very good," 2 as "Good," 2 as "Satisfactory," and 1 as "Unsatisfactory" among the 14 regions. The model achieved an NSE of 0.86, R 2 of 0.85, and PBIAS of -2.71% for the overall daily streamflow prediction performance during the verification period of the BRB. This indicates that the hybrid model has high predictive accuracy and no significant systematic bias, providing a sound hydrodynamic environment for water quality simulation. The simulation results of different BMPs scenarios showed that in the scenarios with only one BMP measure, stubble mulch had the best reduction effect, with average reductions of 17.83% for TN and 36.17% for TP. In the scenarios with a combination of multiple BMP measures, the combination of stubble mulch, soil testing and formula fertilization, and vegetative filter strip performed the best, achieving average reductions of 42.71% for TN and 50.40% for TP. The hybrid model provides a novel approach to simulate BMPs' reduction effects in regions without measured hydrological data and has the potential for wide application in BMP-related decision-making., (© 2023. Springer Nature Limited.)

Although sluggish cognitive tempo (SCT) symptoms are often observed in children with attention deficit hyperactivity disorder (ADHD), an increasing number of studies have highlighted its uniqueness. Nevertheless, no national survey on SCT among children and adolescents has been conducted in China. Hence, this research aims to study SCT in China and to evaluate the differences between SCT and ADHD symptoms by comparing their risk factors in terms of life events (LE) and parental rearing behaviors (PRB). This cross-sectional study used data from a survey on 71,929 children and adolescents in 5 province-level regions in China to study the incidence and demographic information of SCT in the Chinese population. Subsequently, the study investigated the comorbidity of ADHD and SCT, and conducted three logistic regressions on the LE and PRB scores to predict whether participants develop symptoms of ADHD or SCT, or neither symptom. 6658 participants were allocated into the SCT group, and the weighted point prevalence of SCT was 9.78%. 36.34% of participants with ADHD (n = 676) were found to demonstrate SCT symptoms, whereas no statistically significant difference was observed in its comorbidity to the three ADHD subtypes (χ 2  = 1.668, p > 0.05, Δ = 2). The regression results on the presence or absence of ADHD revealed paternal excessive-interference and rejection, and maternal favoring were associated with ADHD diagnosis, whereas paternal punishment and favoring and maternal emotional warmth was related to the absence of ADHD symptoms. Academic stress and maternal excessive-interference were associated with SCT symptoms, and maternal emotional warmth associated with SCT absence. Concerning the presence of ADHD-only or SCT-only symptoms, LE adaptation was found to relate to SCT-only symptoms, while PRB paternal rejection and maternal favoring were associated with ADHD-only symptoms. While evidencing the high prevalence of SCT in China, our findings supported that although ADHD and SCT were highly comorbid, they may be considered two independent disorders with different risk factors. Specifically, participants with SCT symptoms are more vulnerable to stress from LE and tend to face more maladjustment than ADHD and normally-developing participants, and maternal rearing behaviours are the key factors to SCT symptoms. SCT brings global challenges in its diagnosis and treatment, and the challenge is more severe in a mentally stressful environment. Therefore, stress management and SCT etiology studies are recommended., (© 2023. Springer Nature Limited.)

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population., (© 2023. The Author(s).)

A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart 1-3 , raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by Ca V 1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Against the backdrop of accelerated global climate change and urbanization, the frequency and severity of flood disasters have been increasing. In recent years, influenced by climate change, the Hai-River Basin (HRB) has experienced multiple large-scale flood disasters. During the widespread extraordinary flood event from July 28th to August 1st, 2023, eight rivers witnessed their largest floods on record. These events caused significant damage and impact on economic and social development. The development of hydrological models with better performance can help researchers understand the impacts of climate change, provide risk information on different disaster events within watersheds, support decision-makers in formulating adaptive measures, urban planning, and improve flood defense mechanisms to address the ever-changing climate environment. This study examines the potential for enhancing streamflow simulation accuracy in the HRB located in Northeast China by combining the physically-based hydrological model with the data-driven model. Three hybrid models, SWAT-D-BiLSTM, SWAT-C-BiLSTM and SWAT-C-BiLSTM with SinoLC-1, were constructed in this study, in which SWAT was used as a transfer function to simulate the base flow and quick flow generation process based on weather data and spatial features, and BiLSTM was used to directly predict the streamflow according to the base flow and quick flow. In the SWAT-C-BiLSTM model, SWAT parameters with P values less than 0.4 in each hydrological station-controlled watershed were calibrated, while the SWAT-D-BiLSTM model did not undergo calibration. Additionally, this study utilizes both 30 m resolution land use and land cover (LULC) map and the first 1 m resolution LULC map SinoLC-1 as input data for the models to explore the impact on streamflow simulation performance. Among five models, the NSE of SWAT-C-BiLSTM with SinoLC-1 reached 0.93 and the R 2 reached 0.95 during the calibration period, and both of them stayed at 0.92 even in the validation period, while the NSE and R 2 of the other four models were all below 0.90 in the validation period. The potential impact of climate change on streamflow in the HRB was evaluated by using predicted data from five global climate models from CMIP6 as input for the best-performing SWAT-C-BiLSTM with SinoLC-1. The results indicate that climate change exacerbates the uneven distribution of streamflow in the HRB, particularly during the concentrated heavy rainfall months of July and August. It is projected that the monthly streamflow in these two months will increase by 34% and 49% respectively in the middle of this century. Furthermore, it is expected that the annual streamflow will increase by 5.6% to 9.1% during the mid-century and by 6.7% to 9.3% by the end of the century. Both average streamflow and peak streamflow are likely to significantly increase, raising concerns about more frequent urban flooding in the capital economic region within the HRB., (© 2023. Springer Nature Limited.)

Autophagy plays an important role in the development of diabetic cardiomyopathy. Cellular repressor of E1A-stimulated genes 1 (CREG1) is an important myocardial protective factor. The aim of this study was to investigate the effects and mechanisms of CREG1 in diabetic cardiomyopathy. Male C57BL/6 J mice, Creg1 transgenic mice and cardiac-specific knockout mice were used to establish a type 2 diabetes model. Small animal ultrasound, Masson's staining and western blotting were used to evaluate cardiac function, myocardial fibrosis and autophagy. Neonatal mouse cardiomyocytes (NMCMs) were stimulated with palmitate, and the effects of CREG1 on NMCMs autophagy were examined. CREG1 deficiency exacerbated cardiac dysfunction, cardiac hypertrophy and fibrosis in mice with diabetic cardiomyopathy, which was accompanied by exacerbated autophagy dysfunction. CREG1 overexpression improved cardiac function and ameliorated cardiac hypertrophy and fibrosis in diabetic cardiomyopathy by improving autophagy. CREG1 protein expression was decreased in palmitate-induced NMCMs. CREG1 knockdown exacerbated cardiomyocyte hypertrophy and inhibited autophagy. CREG1 overexpression inhibited cardiomyocyte hypertrophy and improved autophagy. LAMP2 overexpression reversed the effect of CREG1 knockdown on palmitate-induced inhibition of cardiomyocyte autophagy. CREG1 inhibited LAMP2 protein degradation by inhibiting the protein expression of F-box protein 27 (FBXO27). Our findings indicate new roles of CREG1 in the development of diabetic cardiomyopathy., (© 2023. The Author(s).)