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Abstract Magnetic fields from the linear motor, suspended electromagnet, and collector shoe arcing are the three main electromagnetic interference (EMI) sources for the medium–low-speed maglev train interior. Under their collective influence, the field intensity may exceed the standard threshold, consequently affecting the operational reliability of the train system. However, in previous studies, the EMI sources were analyzed separately, and studies regarding the influence of factors such as the motor states and the train body (TB) shielding against arcing EMI were lacking. Therefore, in this paper, all three EMI source are considered, and an EM disturbance source modeling scheme is proposed using the COMSOL software platform. Its effectiveness is demonstrated and the train interior magnetic field is analyzed, primarily with respect to prior simulations and tests. Subsequent analyses enable a comparative assessment of the individual contributions of each EMI source to the overall interference, considering the EMI control standards. The influence of other EMI source parameters, such as different motor states, is analyzed, and the potential for modifying the material composition and structural thickness of the TB is explored to determine the appropriate EMI inhibition strategy.

To study the support design of deep thick coal seam roadway, we propose three support design schemes from the perspective of safety and support cost based on the 432 belt transportation roadway in Tangyang Coal Mine. Theoretical analysis, numerical simulation and engineering practice were used to study the values of the support parameters, displacement and deformation, plastic zone and the actual support effect of each scheme. The theoretical analysis results show that the anchor parameters and row spacing of the three support schemes are in line with the theoretical calculation values. Numerical simulation results show that: the relative displacement and deformation of the top and bottom plates and the two sides of support scheme I are 77.6 mm and 103.4 mm, respectively; the relative displacement and deformation of support scheme II are 79.7 mm and 105.5 mm, which are similar to those of support scheme I and have the least plastic failure elements; the maximum displacement and deformation of support scheme III are 83.8 mm and 111.1 mm, respectively. The support cost of support scheme II is only 64.7% of that of scheme I when the support effect is similar. The engineering practice results show that the actual support effect of support scheme II can realize the safety support of roadway.

Abstract Background Gender is a significant risk factor for late-onset Alzheimer’s disease (AD), often attributed to the decline of estrogen. The plant estrogen secoisolariciresinol diglucoside (SDG) has demonstrated anti-inflammatory and neuroprotective effects. However, the protective effects and mechanisms of SDG in female AD remain unclear. Methods Ten-month-old female APPswe/PSEN1dE9 (APP/PS1) transgenic mice were treated with SDG to assess its potential ameliorative effects on cognitive impairments in a female AD model through a series of behavioral and biochemical experiments. Serum levels of gut microbial metabolites enterodiol (END) and enterolactone (ENL) were quantified using HPLC-MS. Correlation analysis and broad-spectrum antibiotic cocktail (ABx) treatment were employed to demonstrate the involvement of END and ENL in SDG’s cognitive improvement effects in female APP/PS1 mice. Additionally, an acute neuroinflammation model was constructed in three-month-old C57BL/6J mice treated with lipopolysaccharide (LPS) and subjected to i.c.v. injection of G15, an inhibitor of G protein-coupled estrogen receptor (GPER), to investigate the mediating role of the estrogen receptor GPER in the cognitive benefits conferred by SDG. Results SDG administration resulted in significant improvements in spatial, recognition, and working memory in female APP/PS1 mice. Neuroprotective effects were observed, including enhanced expression of CREB/BDNF and PSD-95, reduced β-amyloid (Aβ) deposition, and decreased levels of TNF-α, IL-6, and IL-10. SDG also altered gut microbiota composition, increasing serum levels of END and ENL. Correlation analysis indicated significant associations between END, ENL, cognitive performance, hippocampal Aβ-related protein mRNA expression, and cortical neuroinflammatory cytokine levels. The removal of gut microbiota inhibited END and ENL production and eliminated the neuroprotective effects of SDG. Furthermore, GPER was found to mediate the inhibitory effects of SDG on neuroinflammatory responses. Conclusion These findings suggest that SDG promotes the production of gut microbial metabolites END and ENL, which inhibit cerebral β-amyloid deposition, activate GPER to enhance CREB/BDNF signaling pathways, and suppress neuroinflammatory responses. Consequently, SDG exerts neuroprotective effects and ameliorates cognitive impairments associated with AD in female mice.

Abstract Identification of tumor neoantigens is indispensable for the development of cancer immunotherapies. However, we are still lacking knowledge about the potential neoantigens derived from sequences outside protein-coding regions. Here, we comprehensively characterized the immunopeptidome landscape by integrating multi-omics data in acute myeloid leukemia (AML). Both canonical and non-canonical MHC-associated peptides (MAPs) in AML were identified. We found that the quality and characteristics of ncMAPs are comparable or superior to cMAPs, suggesting ncMAPs are indispensable sources for tumor neoantigens. We further proposed a computational framework to prioritize the neoantigens by integrating additional transcriptome and immunopeptidome in normal tissues. Notably, 6 of prioritized 13 neoantigens were derived from ncMAPs. The expressions of corresponding source genes are highly related to infiltrations of immune cells. Finally, a risk model was developed, which exhibited good performance for clinical prognosis in AML. Our findings expand potential cancer immunotherapy targets and provide in-depth insights into AML treatment, laying a new foundation for precision therapies in AML.

Abstract Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation.

Research investigating the effects of milk fat globule membranes (MFGM) on Salmonella typhimurium-induced colitis, intestinal barrier integrity, and gut-associated immune responses remains scarce. This study aimed to investigate the potential of dietary MFGM to alleviate S. typhimurium-induced colitis in mice. Male C57BL/6J mice were administered S. typhimurium to induce colitis and were then subjected to dietary interventions with either bovine MFGM (BMFGM) or goat MFGM (GMFGM). Both BMFGM and GMFGM mitigated S. typhimurium-induced colitis, as evidenced by increased body weight, decreased mRNA levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the colon, reduced intestinal permeability, and increased mRNA expression of tight junction-associated genes (Claudin-1 and ZO-1). Additionally, there was a reduction in the number of S. typhimurium in the mesenteric lymph nodes and an improvement in CD4 T cell activation status. Furthermore, liver and spleen injury was reduced, and serum levels of pro-inflammatory cytokines (IFN-γ, IL-1β, IL-4, IL-2, IL-6, and TNF-α) were decreased by both type of MFGM. Overall, BMFGM and GMFGM effectively alleviated S. typhimurium-induced colitis and associated hepatic and splenic injuries.

Glucose metabolism disturbances may result in diabetes-associated cognitive decline (DACI). Methionine restriction (MR) diet has emerged as a potential dietary strategy for managing glucose homeostasis. However, the effects and underlying mechanisms of MR on DACI have not been fully elucidated. Here, we found that a 13-week MR (0.17 % methionine, w/w) intervention starting at 8 weeks of age improved peripheral insulin sensitivity in male db/db mice, a model for type 2 diabetes. Notably, MR significantly improved working as well as long-term memory in db/db mice, accompanied by increased PSD-95 level and reduced neuroinflammatory factors, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). We speculate that this effect may be mediated by MR activating hepatic fibroblast growth factor 21 (FGF21) and the brain FGFR1/AMPK/GLUT4 signaling pathway to enhance brain glucose metabolism. To further delineate the mechanism, we used intracerebroventricular injection of adeno-associated virus to specifically knock down FGFR1 in the brain to verify the role of FGFR1 in MR-mediated DACI. It was found that the positive effects of MR on DACI were offset, reflected in decreased cognitive function, impaired synaptic plasticity, upregulated neuroinflammation, and balanced enzymes regulating reactive oxygen species (Sod1, Sod2, Nox4). Of note, the FGFR1/AMPK/GLUT4 signaling pathway and brain glucose metabolism were inhibited. In summary, our study demonstrated that MR increased peripheral insulin sensitivity, activated brain FGFR1/AMPK/GLUT4 signaling through FGF21, maintained normal glucose metabolism and redox balance in the brain, and thereby alleviated DACI. These results provide new insights into the effects of MR diet on cognitive dysfunction caused by impaired brain energy metabolism.

ObjectiveTo understand the medication preference of type 2 diabetes mellitus (T2DM) patients with different insurance coverages, and to provide reference for improving the patient-centered clinical treatment decision.MethodsThis study used Discrete Choice Experiment (DCE) to elicit preferences of T2DM patients with different insurance coverages in China. A multistage stratified cluster-sampling procedure for data collection and a total of 1,409 valid respondent were conducted.ResultsSeven attributes have significant influence on the preference of T2DM patients with Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI) (p

Abstract Background The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. Methods We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. Results The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. Conclusions Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. Methods: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150–200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1–14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9–18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5–21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3–23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2–57.2; P = 0.004) were associated with a significantly shorter PFS. Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Abstract Duchenne muscular dystrophy (DMD) is a rare X‐linked recessive disorder characterized by loss‐of‐function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformities. Three‐dimensional gait analysis (3DGA) has been used as a tool to analyze gait pathology through the quantification of altered joint kinematics, kinetics, and muscle activity patterns. Among 3DGA indices, the Gait Profile Score (GPS), has been used as a sensitive overall measure to detect clinically relevant changes in gait patterns in children with DMD. To enhance our understanding of the clinical translation of 3DGA, we report here the development of a population nonlinear mixed‐effect model that jointly describes the disease progression of the 3DGA index, GPS, and the functional endpoint, North Star Ambulatory Assessment (NSAA). The final model consists of a quadratic structure for GPS progression and a linear structure for GPS‐NSAA correlation. Our model was able to capture the improvement in function in GPS and NSAA in younger subjects, as well as the decline of function in older subjects. Furthermore, the model predicted NSAA (CFB) at 1 year reasonably well for DMD subjects ≤7 years old at baseline. The model tended to slightly underpredict the decline in NSAA after 1 year for those >7 years old at baseline, but the prediction summary statistics were well maintained within the standard deviation of observed data. Quantitative models such as this may help answer clinically relevant questions to facilitate the development of novel therapies in DMD.

Abstract Delayed diagnosis in patients with pulmonary tuberculosis (PTB) often leads to serious public health problems. High throughput sequencing was used to determine the expression levels of lncRNAs, mRNAs, and miRNAs in the lesions and adjacent health lung tissues of patients with PTB. Their differential expression profiles between the two groups were compared, and 146 DElncRs, 447 DEmRs, and 29 DEmiRs were obtained between lesions and adjacent health tissues in patients with PTB. Enrichment analysis for mRNAs showed that they were mainly involved in Th1, Th2, and Th17 cell differentiation. The lncRNAs, mRNAs with target relationship with miRNAs were predicted respectively, and correlation analysis was performed. The ceRNA regulatory network was obtained by comparing with the differentially expressed transcripts (DElncRs, DEmRs, DEmiRs), then 2 lncRNAs mediated ceRNA networks were established. The expression of genes within the network was verified by quantitative real-time PCR (qRT-PCR). Flow cytometric analysis revealed that the proportion of Th1 cells and Th17 cells was lower in PTB than in controls, while the proportion of Th2 cells increased. Our results provide rich transcriptome data for a deeper investigation of PTB. The ceRNA regulatory network we obtained may be instructive for the diagnosis and treatment of PTB.

Abstract This study assesses the effect of stone content on the stability of soil–rock mixture slopes and the dynamics of ensuing large displacement landslides using a material point strength reduction method. This method evaluates structural stability by incrementally decreasing material strength parameters. The author created four distinct soil–rock mixture slope models with varying stone contents yet consistent stone size distributions through digital image processing. The initial conditions were established by linearly ramping up the gravity in fixed proportionate steps until the full value was attained. Stability was monitored until a sudden shift in displacement marked the onset of instability. Upon destabilization, the author employed the material point method to reconstruct the landslide dynamics. Due to the substantial computational requirements, the author developed a high-performance GPU-based framework for the material point method, prioritizing the parallelization of the MPM algorithm and the optimization of data structures and memory allocation to exploit GPU parallel processing capabilities. Our results demonstrate a clear positive correlation between stone content and slope stability; increasing stone content from 10 to 20% improved the safety factor from 1.9 to 2.4, and further increments to 30% and 40% ensured comprehensive stability. This study not only sheds light on slope stability and the mechanics of landslides but also underscores the effectiveness of GPU-accelerated methods in handling complex geotechnical simulations.

Abstract Background Surgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment. Methods A dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic_Sig), Radiomics Signature (Rad_Sig) and the Deep Transformer Learning Signature (DTL_Sig). Additionally, we fused the Rad_Sig with the DTL_Sig to create the Deep Learning Radiomic Signature (DLR_Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA). Results The DLR_Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97–0.99) for the training cohort and 0.79(95% CI: 0.67–0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR_Sig was significantly better than that of the Clinic_Sig(P

[Objective] In view of the functional orientation of city railway and the inconsistency in passengers demand for travel convenience, ride comfort, and economy under the current economic and social development, it is necessary to study the train operation scheme for city railway which takes the passenger travel time value into account. [Method] A train operation scheme model considering passenger travel time value is built. In the model, passenger travel cost and train operation cost are taken as the objective function, and train capacity, inter-station passenger flow and the operating train quantity are the main constraint conditions. Meanwhile, Pareto model is used to standardize the time value of various passengers and the operating cost of trains with different marshalling. Targeting the Shanghai urban rail transit airport link as the research background, two types of train marshalling for 4-car and 8-car trains are considered to calculate, analyze and evaluate the train operation scheme for the single trip during peak hours from Hongqiao Railway Station to Shanghai East Station. [Result & Conclusion] The train operation scheme which takes the passenger travel time value into account can minimize the passenger travel cost and better meet the time demands of various passengers. Extending the travel time for passengers with lower time value and shortening the travel time for passengers with higher time value can effectively achieve the economic efficiency of the train operation scheme.

[Objective] To scientifically set up the ticket gate, improve its actual passing capacity, and reduce the congestion risk caused by abnormal stagnation of the passengers, it is necessary to study the characteristics of passenger stagnation behavior spectrum at the ticket gate in urban rail transit stations. [Method] The video trajectory tracking technology is used to collect the passengers′ moving data from the monitor video at the ticket gate of the urban rail transit station. The passenger stagnation behaviors are determined as the characterization indicators. The passenger stagnation behavior spectrum at the ticket gate in urban rail transit station is established from the three elements i.e. types of the ticket gate, passenger flow and individual stagnation behaviors, and the quartile difference method is used to determine the upper and lower threshold values of the above indicators. The differences of the four characterization indicators of passenger stagnation behaviors are analyzed, including longitudinal and lateral distances from the starting point of passenger stagnation behavior to the center of the gate wing/gate rod, stagnation range, and stagnation time. The characteristics of the stagnation behavior spectrum under different gate types and different passenger flow rate are fully explained and analyzed. [Result & Conclusion] Passengers tend to strand in front of the ticket gate, and the longitudinal distance from the stagnation starting point to the center of the gate wing/ gate rod is much longer than its lateral distance. When the passenger flow rate is larger than 5~10 person times/min, the passenger stagnation range fluctuates the greatest. As the passenger flow increases, the available space for passengers, the stagnation range and the stagnation time decrease.

To ensure the safety of urban rail transit operations and uncover the transmission dynamics of risk sources, a key risk chain mining method for urban rail transit operation is proposed. Firstly, the H-Apriori association rule algorithm is proposed for the characteristics of low frequency but high riskiness of high hazard degree risk sources in urban rail transit operation, which adds a new hazard degree evaluation index to the traditional Apriori algorithm and couples with support degree two-dimensionally to mine the strong association rules among risk sources. Secondly, we construct a weighted risk network with risk sources as network nodes and strong association rules as network edges, and propose a key risk chain mining method for urban rail transit operation based on path search theory to mine key risk chains from the weighted risk network. Finally, using the actual urban rail transit operation data of a city in China as an example, a total of 17 key risk chains are mined, and then 5 key risk sources and 8 key chain break locations are obtained by riskiness and frequency analysis of key risk chains, and control plans are proposed. The research outcomes introduce a novel approach to mining risk chains in urban rail transit operations, shedding light on the propagation mechanisms, triggering probabilities, and degrees of unsafety associated with risk sources. The results not only provide theoretical support but also offer methodological guidance for pinpointing locations of risk chain breaks and refining the control of risk sources.

Long noncoding RNAs (lncRNAs) are crucial regulators of various biological processes. However, it remains unclear how lncRNAs can be involved in the immune response to Nocardia seriolae invasion in largemouth bass (Micropterus salmoides). Here we leveraged the whole transcriptome RNA-seq technique to screen lncRNAs associated with the head kidney infected with Nocardia seriolae. A total of 5,661 lncRNAs were identified, comprising 2,427 known lncRNAs and 3,234 novel lncRNAs. Among these, 531 lncRNAs were found to be differentially expressed, with 213 showing increased expression and 318 showing reduced expression. In these differentially expressed lncRNAs, 176 lncRNAs may have cis-regulatory relationships with 243 protein-coding genes. For example, MSTRG.17818.1, MSTRG.10160.1 target mapk1 and rela, respectively, thereby regulating gene expression. We then exploited Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the enrichment of target genes of lncRNAs. These target genes were found to be significantly enriched in immune signaling pathways, including RIG-I-like receptor signaling and Toll-like receptor signaling. Furthermore, we harnessed a total of 12 mRNAs, 33 miRNAs, and 167 lncRNAs to construct two lncRNA-miRNA-mRNA network maps. CeRNA maps revealed that some lncRNAs can competitively bind to the same miRNA and affect the expression of immune-related genes. For instance, MSTRG.13668.1 and MSTRG.5180.1 can simultaneously bind to mir-155–5p to increase irak4 expression. These findings suggest that lncRNAs may participate in the immune response process of infected largemouth bass with Nocardia seriolae. Overall, this work presents a thorough lncRNAs expression profile of Nocardia seriolae-infected largemouth bass and offers insights into the ceRNA regulatory processes that influence fish's immune response to bacterial infections.

Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of Bacteroides sartorii (B. sartorii), Parabacteroides distasonis (P. distasonis), and Akkermansia muciniphila (A. muciniphila), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched B. sartorii, P. distasonis, and A. muciniphila can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women’s sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women’s sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women’s sleep quality. The underlying mechanisms need to be explored in the future.

ObjectiveTo characterize the gas production phenomenon in the animal model of left ventricular assist device (LVAD), and study its mechanism.MethodsAn in vitro bubble precipitation experiment was conducted, and the blood samples of Parma spp. animals were divided into ordinary group and oxygen-enriched group according to whether they were oxygenated or not at the time of blood collection, and a static control group was set up respectively. Blood gases were drawn and analyzed before and after the experiment. Activate the pump, and the number of air bubbles in the loop was measured by ultrasound at different rotational speeds; CFD was applied to simulate the flow field in the blood pump, and pressure, fluid velocity vector and shear force diagrams were plotted, and a thrombus model was constructed and the flow field was simulated and plotted as a cloud diagram.ResultsThere was a statistical difference in the number of bubbles in the inflow and outflow tubes of the blood pump (P values of 0.04 and 0.023, respectively), and the number of bubbles in the outflow tubes of both groups was significantly higher than the number of bubbles in the inflow tubes. The number of bubbles in the tubes of both the oxygen-enriched and normal groups was significantly higher than that in the inflow group. In both the normal and oxygen-enriched groups, more gas was produced at higher speeds than at lower speeds. Blood gas analysis showed that the reduced gas composition in the blood was mainly oxygen. Flow field simulation results: the high rotation speed group had lower central pressure and greater scalar shear. The thrombus simulation group was more prone to turbulence, sudden pressure changes, and greater shear than the normal group.ConclusionBlood gas production is associated with higher partial pressures of blood oxygen, higher rotation speed, and intrapump thrombosis, and the mechanism of pump gas production is degassing of dissolved gases rather than cavitation of water, and the gas released is most likely to have oxygen. The degassing phenomenon is an warning factor for pump thrombosis.

Objectives: Co-agonists at the glucagon-like peptide-1 and glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Although most co-agonists to date have been heavily GLP1R-biased, glucagon directly acts on the liver to reduce fat content. The aims of this study were to investigate a GCGR-biased co-agonist as treatment for hepatic steatosis in mice. Methods: Mice with diet-induced obesity (DIO) were treated with Dicretin, a GLP1/GCGR co-agonist with high potency at the GCGR, Semaglutide (GLP1R monoagonist) or food restriction over 24 days, such that their weight loss was matched. Hepatic steatosis, glucose tolerance, hepatic transcriptomics, metabolomics and lipidomics at the end of the study were compared with Vehicle-treated mice. Results: Dicretin lead to superior reduction of hepatic lipid content when compared to Semaglutide or equivalent weight loss by calorie restriction. Markers of glucose tolerance and insulin resistance improved in all treatment groups. Hepatic transcriptomic and metabolomic profiling demonstrated many changes that were unique to Dicretin-treated mice. These include some known targets of glucagon signaling and others with as yet unclear physiological significance. Conclusions: Our study supports the development of GCGR-biased GLP1/GCGR co-agonists for treatment of MASLD and related conditions.

Abstract Accurate detection of circulating tumor cells (CTCs) in blood and non-blood body fluids enables generation of deterministic cancer diagnosis and represent a less invasive and safer liquid biopsy approach. Although genomic alternations have been widely used in circulating tumor DNA (ctDNA) analysis, studies on cell-based genomic alternations profiling for CTC detection are rare due to major technical limitations in single-cell whole genome sequencing (WGS) including low throughput, low accuracy and high cost. We report a single-cell low-pass WGS-based protocol (scMet-Seq) for sensitive and accurate CTC detection by combining a metabolic function-associated marker Hexokinase 2 (HK2) and a Tn5 transposome-based WGS method with improved cell fixation strategy. To explore the clinical use, scMet-Seq has been investigated with blood and non-blood body fluids in diagnosing metastatic diseases, including ascites-based diagnosis of malignant ascites (MA) and blood-based diagnosis of metastatic small-cell lung cancer (SCLC). ScMet-Seq shows high diagnostic sensitivity (MA: 79% in >10 cancer types; metastatic SCLC: 90%) and ~100% of diagnostic specificity and positive predictive value, superior to clinical cytology that exhibits diagnostic sensitivity of 52% in MA diagnosis and could not generate blood-based diagnosis. ScMet-Seq represents a liquid biopsy approach for deterministic cancer diagnosis in different types of cancers and body fluids.

Abstract Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure–activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1β, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.

Objective To explore the nuanced relationship between sleep patterns, chronotype, quality and the influence of health and lifestyle factors on cognitive performance.Design, setting, participants This cross-sectional analysis used ordinary least squares regression within the UK Biobank database, assessing 26 820 participants aged 53–86 years, categorised into two cohorts: Cohort 1 (10 067 participants, 56% female; completed all four cognitive tests of Fluid Intelligence/reasoning, Pairs Matching, Reaction Time and Prospective Memory) and Cohort 2 (16 753 participants, 56% female; completed only two cognitive assessments of Pairs Matching and Reaction Time).Exposures Participant’s self-reported sleep duration, chronotype and quality. Cognitive function was assessed through standardised computerised tests. The analysis was adjusted for demographic and comorbidity covariates.Main outcomes and measures Cognitive performance scores were evaluated against sleep parameters and health and lifestyle factors including sex, age, vascular and cardiac conditions, diabetes, alcohol intake, smoking habits and body mass index.Results The regression highlighted a positive association between normal sleep duration (7–9 hours) and cognitive scores in Cohort 1 (β=0.0567, 95% CI 0.0284 to 0.0851), while extended sleep duration negatively impacted scores across both cohorts (Cohort 1: β=−0.188, 95% CI −0.2938 to −0.0822; Cohort 2: β=−0.2619, 95% CI −0.3755 to −0.1482). Chronotype distinctions, particularly intermediate and evening types, were linked to superior cognitive function. Gender, age, angina, high blood pressure, diabetes, alcohol intake and smoking emerged as significant cognitive influencers.Conclusions and relevance The study delineates a multifaceted and nuanced relationship between sleep variables, health and lifestyle factors in determining cognitive outcomes. These findings highlight the vital role of sleep quality on cognitive health.

Brown planthopper Nilaparvata lugens, which can transmit rice ragged stunt virus, is a serious and damaging pest to rice plants. Rice plants can protect themselves from the associated diseases of N.lugens by either suppressing or replacing N.lugens by releasing N.lugens infected by a special strain of Wolbachia wStri. The long-distance migration habit of N.lugens is one of the important precursors leading up to the large-scale occurrence of N.lugens. To study the effect of migration on the transmission of Wolbachia in N.lugens, a Wolbachia spreading dynamics model with migration of N.lugens between two patches is put forward. The existence and local stability conditions of equilibrium points of the system and its subsystems are obtained. Moreover, the effects of migration on the dynamic properties and the control of N.lugens are analyzed; the results show that the system can exhibit a bistable phenomenon, and the migration can change the stability of equilibrium infected with wStri from stable to unstable. The quantitative control methods for the migration of the insect N.lugens are proposed, which provide a theoretical guidance for future field experiments. Lastly, we use the Markov chain Monte Carlo (MCMC) method to estimate the parameters of the wild N.lugens migration model based on limited observational data; the numerical simulation results show that migration can increase the quantity of N.lugens, which is consistent with the relevant experimental results.

Abstract When the voltage fluctuation of the traction network occurs in high‐speed railways, the interharmonics in the grid‐side voltage will propagate to the traction motor, which results in the motor torque ripple of running trains. The ripple can cause abnormal vibrations of key train components and even influence train operation safety. However, the traditional proportional‐integral controller used in the inverter‐motor system has a weak anti‐interference capability when facing nonlinear disturbances. This paper proposes an improved passivity‐based control (IPBC) to suppress the impact of interharmonics on trains. First, the Euler‐Lagrange mathematical model of the traction inverter‐motor system is established. Then, the PBC for this system is designed by damping injection, ensuring the asymptotic stability of the system. Furthermore, to purposely suppress the impact of the periodic disturbance on the system, a repetitive controller is designed in parallel with the PBC to control the inverter‐motor system. Finally, through the offline simulation and HIL simulation, it has been verified that the proposed IPBC can effectively suppress the motor torque ripple and the vibrations of key train components. The control strategy proposed in this paper has a reference significance for improving the operational stability of high‐speed trains.

Abstract To alleviate peak-hour congestion in urban rail transit, this study proposes a new off-peak fare discount strategy to incentivize passengers to shift their departure time from peak to off-peak hours. Firstly, a questionnaire survey of Shanghai metro passengers is conducted to analyze their willingness to change departure time under different fare strategies. Secondly, based on the survey results, a time-differentiated fare discount model is constructed, considering both the company’s revenue and passengers’ travel benefits, and with the optimization objective of achieving balanced peak-hour and off-peak-hour train loads throughout the day. Subsequently, a genetic algorithm with nested fmincon functions is designed and combined with the actual data of Shanghai rail transit line 9 for arithmetic analysis. Finally, the effectiveness of the model is validated using the survey data. The research results show that the off-peak fare discount strategy can incentivize 6.88% of passengers traveling in the morning peak and 6.66% of passengers traveling in the evening peak to shift to off-peak travel. This research provides theoretical support and decision-making guidance for implementing time-differentiated pricing in urban rail transit systems.

Abstract Immune checkpoint inhibitors (CPIs) are a relatively newly licenced cancer treatment, which make a once previously untreatable disease now amenable to a potential cure. Combination regimens of anti-CTLA4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. To probe the impact of immune checkpoints on intestinal homoeostasis, mice are challenged with anti-CTLA4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota. The immune profile of the colon of these mice with CPI-colitis is analysed using bulk RNA sequencing, single-cell RNA sequencing and flow cytometry. CPI-colitis in mice is dependent on the composition of the intestinal microbiota and by the induction of lymphocytes expressing interferon-γ (IFNγ), cytotoxicity molecules and other pro-inflammatory cytokines/chemokines. This pre-clinical model of CPI-colitis could be attenuated following blockade of the IL23/IFNγ axis. Therapeutic targeting of IFNγ-producing lymphocytes or regulatory networks, may hold the key to reversing CPI-colitis.

Aiming at the problem of long slopes and weak power grids along the railway in high altitude mountainous areas, an optimization method of power supply mode and access to external power grid of CZ railway traction station is proposed. First, combined with the terrain and altitude along the railway and the characteristics of the regional power grid, a sample library of the power supply mode and access to external power grid of CZ railway traction station is designed. Secondly, combined with the train operation diagram and line ramp parameters, the full-day periodic load of each power supply arm is simulated. Then, according to the sample library, a “source-net-load” integrated simulation model is constructed in Simulink. Then, the three-phase voltage unbalance evaluation model of the power system is constructed in combination with relevant standards. Finally, the optimal wiring scheme is selected by using the evaluation model and the simulated voltage unbalance index.

Premature ovarian insufficiency (POI) is a clinical syndrome that declines ovarian function in women. Berberine (BBR) is a compound with anti-inflammatory, antioxidant, and anti-apoptotic activities. However, the role of BBR on POI is still unknown. In this study, we investigated the role of BBR on ovarian function decline by establishing a POI mouse model using cyclophosphamide (CTX) and busulfan (BU). Our results showed that POI was attenuated by BBR, which was evidenced by enhanced body weight and ovarian weight, improved morphology of ovary, increased the number of healthy follicles, decreased the production of atretic follicles and restored serum hormone levels, including estradiol, anti-Müllerian hormone and follicle-stimulating hormone. In addition, we showed that germ cell function markers, mouse vasa homologue (MVH) and octamer-binding transcription factor 4 (OCT4) were enhanced by BBR, at both protein and mRNA levels. Furthermore, our results revealed that BBR inhibited inflammation and oxidative stress by reducing nuclear factor kappa B (NF-κB) and enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Taken together, we demonstrate that BBR can effectively improve ovarian function in POI mice, which is mainly mediated by reducing oxidative stress and inflammatory response. Our study also provides new strategy for POI treatment.

With growing concerns about global warming, it is crucial to adopt agronomic practices that enhance rice yields from paddy fields while reducing greenhouse gas (GHG) emissions for sustainable agriculture. An optimal nitrogen (N) fertilization rate and planting density are vital to ensure high rice yields, minimize GHG emissions, and understand emission behavior for better field management. We hypothesized that optimizing N application rates and planting density to improve nitrogen use efficiency (NUE) in rice cultivation would reduce resource losses and GHG emissions. To test this hypothesis, we implemented five treatments with a rice straw return cultural system: two planting densities (16 hills m−2 (traditional density, D1) and 20 hills m−2 (25% higher density, D2)) and three N application rates (no N fertilizer (N0), 180 kg N ha−1 (N1), and 144 kg N ha−1 (N2)). The control treatment (CK) was traditional planting density with no N fertilizer. The four new cropping modes were N1D1, N1D2, N2D1, and N2D2. We investigated the effects of N application rates and planting density on rice grain yield, NUE, and GHG emissions in multiple rice-growing seasons. The N1D2 treatment exhibited the highest grain yield over the three years, with a value of 10,452 kg ha−1, representing an increase of 12.2% compared to CK. Moreover, N uptake in N1D2 was the highest, averaging 39.2% (p < 0.05) higher than CK, and 8.5%, 3.5%, and 2.8% (p < 0.05) higher than N1D1, N2D1 and N2D2, respectively. N2D2 exhibited the highest NUE, with a value of 58.99 kg kg−1, surpassing all other treatments over the three years. GHG emissions, global warming potential (GWP), and greenhouse gas intensity (GHGI) in N2D2 were lower than in N1D1, N1D2, and N2D1. Additionally, reducing N application (comparing N1D1 to N2D1) and increasing plant density (comparing N1D1 to N1D2) improved N agronomic efficiency (NAE) and N partial productivity (PFPN). The negative correlation between the NAE and PFPN with GWP and GHG emissions further supports the potential for optimized N management and denser planting density to reduce environmental impact. These findings have important implications for sustainable rice cultivation practices in Southwest China and similar agroecosystems, emphasizing the need for integrated nutrient management strategies to achieve food security and climate change mitigation goals.

The culture of mandarin fish using artificial feed has been gaining increasing attention in China. Ensuring good water quality in the ponds is crucial for successful aquaculture. Recently, the trial of pond-based rice floating beds (PRFBs) in aquaculture ponds has shown promising results. This research assessed the impact of PRFBs on the microbial community structure and overall quality of the aquaculture pond, thereby enhancing our understanding of its functions. The results revealed that the PRFB group exhibited lower levels of NH4+-N, NO2−-N, NO3−-N, TN, TP, and Alk in pond water compared to the control group. The microbial diversity indices in the PRFB group showed a declining trend, while these indices were increasing in the control group. At the phylum level, there was a considerable increase in Proteobacteria abundance in the PRFB group throughout the culture period, suggesting that PRFBs may promote the proliferation of Proteobacteria. In the PRFB group, there was a remarkable decrease in bacterial populations related to carbon, nitrogen, and phosphorus metabolism, including genera Rhodobacter, Rhizorhapis, Dinghuibacter, Candidatus Aquiluna, and Chryseomicrobium as well as the CL500_29_marine_group. Overall, the research findings will provide a basis for the application of aquaculture of mandarin fish fed an artificial diet and rice floating beds.

Sun-induced chlorophyll fluorescence (SIF) holds enormous potential for accurately estimating terrestrial gross primary productivity (GPP). However, current studies often overlook the spatial representativeness of satellite SIF and GPP observations. This research downscaled TROPOMI SIF (TROPOSIF) and its enhanced product (eSIF) in China’s Saihanba Forest Region to obtain high-resolution SIF data. SIF was simulated using the SCOPE model, and the downscaled SIF’s reliability was validated at two forest eddy covariance (EC) sites (SHB1 and SHB2) in the study area. Subsequently, the downscaled SIF data were matched to the EC footprint of the two forest sites, and the relationship between SIF and GPP was compared at various observational scales. Additionally, the ability of downscaled TROPOSIF and eSIF to track GPP was compared, along with the correlations among several vegetation indices (VIs) and GPP. The findings reveal the following: (1) Downscaled TROPOSIF and eSIF showed a strong linear relationship with SCOPE-modeled SIF (R2 ≥ 0.86). The eSIF closely matched the SCOPE simulation (RMSE: 0.06 mw m−2 nm−1 sr−1) and displayed a more consistent seasonal variation pattern with GPP. (2) Comparisons among coarse-resolution SIF, EC footprint-averaged SIF (SIFECA), and EC footprint-weighted SIF (SIFECW) demonstrated significant improvements in the linear relationship between downscaled SIF and GPP (the R2 increased from the range of 0.47–0.65 to 0.78–0.85). SIFECW exhibited the strongest relationship with GPP, indicating that matching SIF to flux footprints improves their relationship. (3) As the distance from the flux tower increased, the relationship between SIF and GPP weakened, reaching its lowest point beyond 1 km from the tower. Moreover, in the highly heterogeneous landscape of the SHB2 site, the relationship between VIs and GPP was poor, with no clear pattern as distance from the flux tower increased. In conclusion, the strong spatial dependency of SIF and tower-based GPP emphasizes the importance of using high-resolution SIF to accurately quantify their relationship.

Healthy, nutritious, and delicious mulberry wine is loved by everyone, but there is no specific yeast for mulberry wine. To screen for yeasts with low-yield higher alcohols for the fermentation of mulberry wine, we tested five commonly used commercial yeasts available on the market to ferment mulberry wine. All five yeasts were able to meet the requirements in terms of yeast fermentation capacity, speed, and physical and chemical markers of mulberry wine. The national standards were met by the fermentation requirements and the fermented mulberry wine. We identified yeast DV10 as a yeast with low-yield higher alcohols suitable for mulberry wine fermentation. The total higher alcohol content in fermented mulberry wine was 298 mg/L, which was 41.9% lower than that of fermented mulberry wine with yeast EC118. The contents of 17 free amino acids and five sugars in mulberry juice and five yeast-fermented mulberry wines were tested. The results showed that the higher the amino acid and sugar content in yeast-fermented mulberry wine, the higher the content of higher alcohols produced by fermentation. A correlation analysis performed on each higher alcohol produced when yeast DV10 fermented the mulberry wine indicated decreased sugar and related amino acids. The findings demonstrated a substantial negative correlation among the levels of increased alcohol, decreased sugar, and matching amino acid content. Considering the correlation values among increased alcohol, decreased sugar, and related amino acids, the very slight difference suggests that both sugar anabolism and amino acid catabolism pathways have an equivalent impact on the synthesis of higher alcohols during the fermentation of mulberry wine. These results provide a theoretical basis for reducing the content of higher alcohols in mulberry wines, given the history and foundation for producing mulberry wine.

Aiming to solve the problem of thermal decay of resin-based friction materials at high temperatures, rare-earth-lanthanum-oxide-/cerium-oxide-reinforced resin-based friction plates were prepared using a hot-pressing molding process. The effect of lanthanum/cerium oxide with different contents on the mechanical and tribological properties of the resin-based friction of materials was studied, and its mechanism was explored. The result shows that lanthanum/cerium oxide improves the mechanical and tribological properties of materials so that the coefficient of friction of the specimen is more stable on adding lanthanum/cerium oxide at 5% and 1%. Lanthanum/cerium oxide improves antidegradation properties of resin-based material and reduces the high-temperature wear rate by enhancing the interfacial effect so that the wear form of the specimen changes from predominantly adhesive wear to predominantly abrasive wear.

Supercritical water gasification (SCWG) technology is highly promising for its ability to cleanly and efficiently convert biomass to hydrogen. This paper developed a model for the gasification of rice straw in supercritical water (SCW) to predict the direction and limit of the reaction based on the Gibbs free energy minimization principle. The equilibrium distribution of rice straw gasification products was analyzed under a wide range of parameters including temperatures of 400–1200 °C, pressures of 20–50 MPa, and rice straw concentrations of 5–40 wt%. Coke may not be produced due to the excellent properties of supercritical water under thermodynamic constraints. Higher temperatures, lower pressures, and biomass concentrations facilitated the movement of the chemical equilibrium towards hydrogen production. The hydrogen yield was 47.17 mol/kg at a temperature of 650 °C, a pressure of 25 MPa, and a rice straw concentration of 5 wt%. Meanwhile, there is an absorptive process in the rice straw SCWG process for high-calorific value hydrogen production. Energy self-sufficiency of the SCWG process can be maintained by adding small amounts of oxygen (ER < 0.2). This work would be of great value in guiding rice straw SCWG experiments.

Abstract Background Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential that may be a treatment for aplastic anemia (AA). Method Umbilical cord-derived MSCs were cultured in three media (Mesencult-XF, MCL, and StemPro MSC SFM CTS). HGF, PGE2, ANG-1, TGF-β1, IFN-γ, and TNF-α were detected using ELISA. The AA mouse model was built via post-irradiation lymphocyte infusion. After different treatments, routine blood, VEGF, and Tregs were detected every week. On day 28, all mice were killed, and their femurs were stained with HE. Results Umbilical cord-derived MSCs cultured in the three media all conformed to the general characteristics of MSCs. HGF secreted by MSCs in the Mesencult-XF, and MCL was greater than that in the StemPro MSC SFM CTS; ANG-1 and TGF-β1 in the MCL were more than that in Mesencult-XF and StemPro MSC SFM CTS; PGE2 in the MCL and StemPro MSC SFM CTS was more than that in the Mesencult-XF. MSCs in the MCL and StemPro MSC SFM CTS inhibited IFN-γ and TNF-α more than those in the Mesencult-XF. The peripheral blood cell in the AA groups was at a low level while that in the MSC group recovered rapidly. The Treg ratio and VEGF level in the MSC group were higher than those in the AA group. The bone marrow (BM) recovered significantly after MSC infusion. Conclusion MSCs in the MCL were advantageous in supporting hematopoiesis and modulating immunity and had the potential for effective treatment of AA.

Abstract A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-l-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-l-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.

Agricultural chemicals with multifunctional applications in crop protection have attracted increasing attention. Herein, two new series of thiazole and imidazo[1,2-a]pyridine derivatives containing a hydrazone substructure were designed and synthesized via a concise synthesis route. Bioassay results showed that most of the thiazole derivatives exhibited broad-spectrum fungistatic activities, which were exemplified by compounds 1c, 1e, 1g, 1h and 1j. In particular, compound 1e displayed excellent in vitro inhibitory effects with the EC50 values of 5.00, 18.24, 6.94, and 3.03 μg/mL against the fungi Botrytis cinerea, Cytospora sp, Fusarium graminearum, and Fusarium solani, respectively. Detached fruit experiments against tomato gray mold (caused by B. cinerea) in vivo revealed that the control efficiency of compound 1e at 10, 20 and 40 μg/mL for 5 days was 35.05%, 54.14% and 81.83%, respectively, which was comparable and even superior to that of the fungicide carbendazim. Additionally, the title compounds also showed remarkable larvicidal activity against M. separata and some compounds exhibited good aphicidal activity. In a word, the bioassay indicated that a certain number of title compounds had multiple biological activities. Given their excellent antifungal and larvicidal characteristics, these interesting derivatives based on the title compounds could be served as new scaffolds for the development of pesticide with multifunctional applications.

A noisy environment can considerably impact drivers' attention and fatigue, endangering driving safety. Consequently, this study designed a simulated driving experimental scenario to analyse the effects of noise generated during urban rail transit train operation on drivers' functional brain networks. The experiment recruited 16 participants, and the simulated driving scenario was conducted at noise levels of 50, 60, 70, and 80 dB. Functional connectivity between all electrode pairs across various frequency bands was evaluated using the weighted phase lag index (WPLI), and a brain network based on this was constructed. Graph theoretic analysis employed network global efficiency, degree, and clustering coefficient as metrics. Significant increases in the WPLI values of theta and alpha frequency bands were observed in high noise environments (70 dB, 80 dB), as well as enhanced brain synchronisation. Furthermore, concerning the topological metrics of brain networks, it was observed that the global efficiency of brain networks in theta and alpha frequency ranges, as well as the node degree and clustering coefficients, experienced substantial growth in high noise environments (70 dB, 80 dB) as opposed to 50 dB and 60 dB. This finding indicates that high-noise environments impact the reorganisation of functional brain networks, leading to a preference for network structures with improved global efficiency. Such findings may improve our understanding of the neural mechanisms of driving under noise exposure, and thus potentially reduce road accidents to some extent.

Wave energy is one of the primary sources of marine energy, representing a readily available and inexhaustible form of renewable clean energy. In recent years, wave energy generation has garnered increasing attention from researchers. To study wave energy generation technology, we have constructed a real wave energy generation system and designed wave simulation and hydraulic energy storage systems. The wave simulation system is mainly composed of a frequency converter and an electric boost pump, while the hydraulic energy storage system consists of a hydraulic control unit and hydraulic motors. Corresponding mathematical models have been established to investigate the characteristics of wave energy generation. Specifically, a mathematical model for wave input using the double-parameter JONSWAP wave spectrum has been created for wave simulation in the wave simulation system. For the hydraulic energy storage system, known as the Power Take Off (PTO) system, mathematical models have been developed for double-acting hydraulic cylinders, energy storage devices, and precise displacement hydraulic motors, taking into consideration fluid Reynolds numbers and leakage. During the generation of wave energy, there is a problem of prolonged power interruption when wave conditions are unfavorable, which hinders continuous power generation. To address this issue, a system structure with an energy storage unit and two parallel generator sets, as well as a power operation optimization scheme, have been proposed. This system structure and optimization approach efficiently and reasonably utilize wave energy, achieving the goal of uninterrupted power supply in the hydraulic wave energy generation system.

Abstract Modulating the traction converters produces current harmonics at the switching frequencies and their multiples. These harmonics should be minimized to meet the network specifications. The LC‐trapped filters, tuned to these frequencies, can easily meet this requirement, but the existing applicable trap filters have not been studied with the traditional traction system topologies. Thus, this paper presents a trapped LCL filter with an LC resonator on the converter side, called a fully integrated T‐LCL filter, for the traction power supply system. The model and analysis reported in this research demonstrate that the presented filter has several advantages, which can be summarized by: reducing the size by winding many coils through magnetic integration, attenuating the switching frequency and its multiple harmonics that reduce the current total harmonic distortion, assuring durability against the filter parameters differences, and preserving system stability under transient conditions. The proposed filter can become a promising trap filter based on these advantages. Simulation models of an ac/dc single‐phase traction rectifier with the proposed filter were created and tested in MATLAB/Simulink, verifying its superiority. Finally, the filter is validated by performing hardware‐in‐the‐loop experiments.

Abstract The WD‐repeat (WDR) family affects carcinogenesis, but its role in the immune microenvironment is poorly characterized. Although functional loss or gain of WDR6 does not markedly change in vitro proliferative and invasive capacity of HCC cells, its deficiency in hepa1‐6 cells drastically inhibits the growth and lung metastasis of orthotopically implanted tumors in immune‐competent C57BL/6J mice. Mechanistically, WDR6 targets tumor suppressor UVRAG to the CUL4A‐DDB1‐ROC1 E3 ubiquitin ligase complex through a unique WDxR motif and promotes its degradation. This upregulates chromatin accessibility at the TNFα locus by blocking autophagic degradation of p65, elevates intratumoral myeloid‐derived suppressor cell (MDSC) number, and reduces CD8+ T cell infiltration, thereby promoting HCC progression. These immunosuppressive effects are reversed by TNFα blockade. TNFα recruits NF‐κB to activate the transcription of WDR6, establishing a WDR6‐TNFα loop. Clinically, the WDR6/UVRAG/NF‐κB pathway is hyperactivated in HCC, predicting a poor prognosis. Importantly, a WDxR‐like peptide disrupts the WDR6/UVRAG complex and enhances the efficiency of anti‐PD‐L1 against HCC with WDR6 dysregulation.

Abstract This paper proposes an improved adaptive lion swarm optimization (LSO) algorithm integrating the chaotic search strategy and information entropy to address the problem that the standard LSO algorithm has slow convergence and easily falls into the local optimum in later iterations. At first, an adaptive factor is introduced to improve tent chaotic mapping and used for population position initialization to enhance population diversity and realize uniform traversal while ensuring random distribution, ultimately improving the global search ability. Second, to address the problem that the cub selection strategy is blind, resulting in insufficient traversal in the early stage, a dynamic step-size perturbation factor is established using the second-order norm and information entropy. Adaptive parameters are used to dynamically adjust the selection probability of different cub behaviors based on the number of iterations to suppress the premature convergence of the algorithm. Finally, tent chaotic search is employed to adaptively adjust the search range and improve the individuals with poor fitness through multiple neighborhood points of the local optimal solution, further improving the algorithm’s search speed and accuracy. Experimental results on 18 benchmark functions revealed that the proposed algorithm yields superior performance in terms of convergence speed, optimization accuracy, and ability to jump out of the local optimal solution compared with the standard LSO, gray wolf optimizer, and particle swarm optimization algorithms. Furthermore, the improved LSO algorithm was used to optimize the initial weights and thresholds of the BP neural network, and the effectiveness of the proposed algorithm was further verified by studying the house price prediction problem using two real-world datasets.

Abstract Background Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5–33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. Methods This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18–90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. Discussion This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. Trial registration Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.

Highlights We performed single-cell transcriptome sequencing in one case carrying adenoma and carcinoma, and explored process of colon cancer progression. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in colon carcinoma We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified.