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Shaojie Bi,1 Juan Zhang,1 Ning Wei,2 Qingbo Zhou,3,4 Chunyan Wang3 1Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Information Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Chunyan Wang, Email 201062013735@email.sdu.edu.cnIntroduction: Anemia, characterized by low hemoglobin or erythrocyte levels, is a significant global health issue with severe implications for public health. Recent studies have explored the potential link between anemia and 25-hydroxyvitamin D [25(OH)D], yet the precise mechanisms remain unclear. This study aims to clarify the possible causal relationship between 25(OH)D levels and anemia risk.Methods: We conducted a comprehensive investigation combining observational and Mendelian randomization (MR) analyses. The observational study included detailed demographic, comorbidities, and laboratory data collected from 7160 hospitalized patients in China. For the MR analysis, genetic polymorphisms were utilized to assess causal effects.Results: Observational analysis revealed an inverse relationship between 25(OH)D levels and the risk of anemia, with stratified analysis indicating a nonlinear association and a threshold of 48.716 nmol/L. The MR analysis confirmed a protective causal relationship between higher 25(OH)D levels and a reduced risk of anemia. Bidirectional MR analysis found no evidence that anemia influences 25(OH)D levels.Discussion: This study provides strong evidence of a causal link between increased 25(OH)D levels and a lower incidence of anemia. The findings highlight the potential role of vitamin D in anemia prevention, supporting the need for further research into vitamin D supplementation as a strategy to reduce anemia risk.Conclusion: Our findings support the hypothesis that higher 25(OH)D levels are causally associated with a reduced risk of anemia, suggesting vitamin D’s potential role in anemia prevention and public health strategies.Keywords: anemia, 25-hydroxyvitamin D, Mendelian randomization

Jing Yang, Chengsen Shu, Xianfu Shang, Hao Xu, Ning Wei Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, People’s Republic of ChinaCorrespondence: Ning Wei, Email weiningjieru2006@163.comPurpose: This study aimed to investigate the prognostic value of systemic immune-inflammation index (SII) in patients with extrahepatic cholangiocarcinoma (EHCC) treated by percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation and further develop a predictive model related to SII.Methods: A total of 145 patients with EHCC who received PTBS combined with 125I seed implantation were retrospectively analyzed. The optimal cut-off value of SII was identified by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier curves and Cox regression were applied to estimate the prognostic value of SII and identify other significant factors of overall survival (OS). Additionally, a novel nomogram was constructed. The concordance index (C-index), calibration plots and decision curve analysis were used to evaluate the performance of the nomogram model.Results: The optimal cut-off value for preoperative SII of 890.2 stratified the patients into High-SII (H-SII) and Low-SII (L-SII) groups. Univariate and multivariate analyses demonstrated that SII was an independent factor for OS. We also found that better therapeutic effect could be obtained with combined postoperative chemotherapy (P < 0.001). Moreover, we revealed that elevated preoperative CA19-9 (P = 0.038) and TBIL level (P = 0.024) were reason for poor prognosis of EHCC. A well-discriminated and calibrated nomogram was developed to predict the 1-year and 2-year OS of EHCC (C-index: 0.709).Conclusion: The SII may be a feasible and convenient prognosis predictor for EHCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting OS in EHCC patients after PTBS combined with 125I seed intracavitary irradiation.Keywords: extrahepatic cholangiocarcinoma, biliary stenting, 125I seed, systemic immune-inflammation index, nomogram

Dadi Xie,1,&ast; Fengfeng Li,1,&ast; Deshui Pang,1 Shiyuan Zhao,2 Meihua Zhang,1 Zhongfa Ren,1 Chunmei Geng,2 Changshui Wang,3 Ning Wei,4 Pei Jiang2 1Tengzhou Central People’s Hospital, Tengzhou, 277500, People’s Republic of China; 2Jining First People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 3Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 4Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meihua ZhangTengzhou Central People’s Hospital, Xingtan Road, Tenzhou, 277500, People’s Republic of ChinaTel/Fax +86 0632-5512227Email meihua_zhang@126.comPei JiangJining First People’s Hospital, Jning Medical University, Jiankang Road, Jining, 272000, People’s Republic of ChinaTel/Fax + 86 0537-2106208Email jiangpeicsu@sina.comPurpose: Inflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment.Methods: Male Sprague–Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups.Results: Our results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis).Conclusion: Using GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.Keywords: inflammatory bowel disease, metabolite, GC-MS, dextran sodium sulfate, biomarker

Theresa Gillis, Megan Crane, Carly Hinkle, Nathan Wei Arthritis Treatment Center, Frederick, MD, USA Objective: Many types of treatment are available for patients with rheumatoid arthritis (RA), however, some patients fail to achieve remission. This report aims to determine the safety and efficacy of using repository corticotropin injection (RCI) as an adjunctive therapy in patients with RA refractory to at least three therapeutics with different mechanisms of action. Method: In this open-label, interventional, single-group study, patients received 80 U RCI twice weekly via subcutaneous injection over 12 weeks. Changes in the Ritchie–Camp Articular Index and health assessment questionnaire scores were monitored for changes from baseline measures. Results: Eight patients were enrolled and consisted of seven females and one male with an average age of 64.6 years and disease duration of 20.9 years. Use of RCI resulted in significant improvement in swollen and tender joint counts. The disease activity score 28 and the physician and patient visual analog scale scores were significantly reduced at treatment week 12. The reduction in health assessment questionnaire scores did not reach statistical significance after RCI treatment. Once RCI therapy was discontinued, all improvements in disease activity score 28, physician and patient visual analog scale, and tender and swollen joint counts achieved during treatment were lost by the week 16 follow-up visit. Conclusion: While larger clinical trials are necessary to further confirm the efficacy of RCI in patients with refractory RA, the response of patients with refractory RA in this study suggests that RCI can be an effective add-on therapy for patients who have exhausted several classes of treatments. Furthermore, this study suggests that RCI has an alternative mode of action, compared to other available antirheumatic drugs. Keywords: refractory rheumatoid arthritis, rheumatoid arthritis, adrenocorticotropic hormone, repository corticotropin injection

Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (TBP). The disease has a varied age at onset and clinical presentation. It is distinct from other SCAs for its association with dementia, psychiatric symptoms, and some patients presenting with chorea. For this reason, it is also called Huntington’s disease-like 4 (HDL-4). Here we examine the distribution of SCA17 allele repeat sizes in a United Kingdom-based cohort with ataxia and find that fully penetrant pathogenic alleles are very rare (5 in 1,316 chromosomes; 0.38%). Phenotype-genotype correlation was performed on 30 individuals and the repeat structure of their TBP genes was examined. We found a negative linear correlation between total CAG repeat length and age at disease onset and, unlike SCA1, there was no correlation between the longest contiguous CAG tract and age at disease onset. We were unable to identify any particular phenotypic trait that segregated with particular CAG/CAA repeat tract structures or repeat lengths. One individual within the cohort was homozygous for variable penetrance range SCA17 alleles. This patient had a similar age at onset to heterozygotes with the same repeat sizes, but also presented with a rapidly progressive dementia. A pair of monozygotic twins within the cohort presented 3 years apart with the sibling with the earlier onset having a more severe phenotype with dementia and chorea in addition to the ataxia observed in their twin. This appears to be a case of variable expressivity, possibly influenced by other environmental or epigenetic factors. Finally, there was an asymptomatic father with a severely affected child with an age at onset in their twenties. Despite this, they share the same expanded allele repeat sizes and sequences, which would suggest that there is marked difference in the penetrance of this 51-repeat allele. We therefore propose that the variable penetrance range extend from 48 repeats to incorporate this allele. This study shows that there is variability in the presentation and penetrance of the SCA17 phenotype and highlights the complexity of this disorder.

A great deal of progress has been made over the last three decades in research on pheromone-mediated mating disruption technology for the oriental fruit moth, Grapholita molesta (Busck). Pheromones can interrupt normal orientation, and the most likely mechanism of pheromone disruption, competitive-attraction (false-plume following), invokes competition between point sources of pheromone formulation and females for males. This technology, performed by broadcasting pheromones into orchards to disrupt mate finding, has been successfully implemented in oriental fruit moth control. Reservoir-style dispensers made of polyethylene tubes, which release pheromone throughout the full growing season, are the current industry standard. Although reasonably effective, they require labor-intensive hand application. Recently, a new formulation, paraffin wax, which maximizes competition between point sources of synthetic pheromone and feral females for males, was shown to have high disruption performance. As this formulation is highly effective, inexpensive, and easy to produce, further study and development are advisable. Increased understanding of the principles of mating disruption will aid in the design of more effective dispensers. Continued research is needed to meet grower concerns with regard to risk, efficacy, and cost and to identify other semiochemicals that can be applied to this delivery system. Greater knowledge of the integration of different biological control methods is therefore essential.

The future Sixth-Generation (6G) wireless systems are expected to encounter emerging services with diverse requirements. In this paper, 6G network resource orchestration is optimized to support customized network slicing of services, and place network functions generated by heterogeneous devices into available resources. This is a combinatorial optimization problem that is solved by developing a Particle Swarm Optimization (PSO) based scheduling strategy with enhanced inertia weight, particle variation, and nonlinear learning factor, thereby balancing the local and global solutions and improving the convergence speed to globally near-optimal solutions. Simulations show that the method improves the convergence speed and the utilization of network resources compared with other variants of PSO.

Abstract In recent years, under the background of exam-oriented physical education reform, the government has issued a lot of physical education documents and policies. As a result, many schools have made fundamental changes in physical education activities. These policies are mainly aimed at getting young people to be more active and autonomous in school sports. This requires physical education training teachers must adhere to the people-oriented, student-oriented, so as to highlight the subject status of students. Based on this, students should establish a good sports values and ethics and form a good habit of lifelong sports, so as to further promote the sustainable development of youth sports activities. Based on the ecological theory of sustainable development as the background, this study constructs a unified theory of Unified Theory of Acceptance and Use of Technology (UTAUT) model for the sustainable training and development of youth skating sports training institutions. This study selects the youth skating sports training institutions in Beijing, China as the investigation object, covering small, medium and large institutions of different sizes, and analyzes based on the statistical data in 2023 and the results of field research. The results show that the application of this model not only increases the willingness of youth skating training institutions to continue to participate by 3.66%, but also promotes the diversified development of youth skating training. In addition, this study also discusses the environmental protection measures implemented in the process of skating training to ensure that the training activities are sustainable while reducing the impact on the environment, so as to build a sustainable development of the new ecology of skating sports training.

BackgroundCurrently， there has been a gradual increase in the incidence of mental diseases， becoming a problem that has attracted great concern of the general public. Zhuhai is a core city of the Guangdong-Hong Kong-Macao Greater Bay Area， and the local government have attached great importance to the mental health of residents. The systematic study on the mental health has focused largely on pregnant women and medical workers， yet few are on the adult residents.ObjectiveTo investigate the prevalence and its influencing factors of anxiety and depression among adult residents in Zhuhai， so as to provide references for formulating targeted psychological intervention strategies.MethodsFrom September 1 to December 1， 2021， a cohort of 5 600 permanent residents aged 18 years and above in Zhuhai were selected through multistage sampling. All participants were subjected to complete Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7） and National Mental Health Literacy Questionnaire based on Wenjuanxing software. Then Logistic regression was employed to identify the factors associated with anxiety and depression among the residents.ResultsAmong the 5 600 residents， depressive symptoms were detected in 842 （15.04%） residents and anxiety symptoms in 579 （10.34%） residents. Logistic regression analysis yielded that female gender （OR=1.488）， living in Doumen district （OR=1.942）， junior college/undergraduate level （OR=3.602）， postgraduate and above （OR=5.904）， irregular meal pattern （OR=3.320）， comorbid chronic diseases （OR=3.244）， disqualification of self-assessment （OR=3.414） and disqualification of mental health skill （OR=2.131） were risk factors for depression symptoms， whereas age ≥25 years old （of all age groups OR20 000 yuan （OR=0.438） and exercising ≥3 times a week （OR=0.431） were protective factors for depression symptoms. Age of 25~34 years old （OR=2.051）， living in Jinwan district （OR=1.729） or Doumen district （OR=1.901）， junior college/undergraduate level （OR=2.955）， postgraduate and above （OR=6.662）， irregular meal pattern （OR=2.741）， comorbid chronic diseases （OR=3.535）， disqualification of self-assessment （OR=3.325） and disqualification of mental health skill （OR=1.838） were risk factors for anxiety symptoms， while monthly per capita income of 6 001~9 000 yuan （OR=0.665） and exercising ≥3 times a week （OR=0.572） were protective factors for anxiety symptoms.ConclusionThe mental health status of adult residents in Zhuhai is affected by various factors， including gender， age， region of residence， education level， meal pattern， exercise frequency and chronic diseases. ［Funded by 2023 Zhuhai Medical Research Project （number， 2220009000227）］

Abstract Background The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study. Methods We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios. Results In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores. Conclusions Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Abstract The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.

Objective The objective of this experiment was to determine the standard ileal digestibility (SID) of amino acid (AA) in 10 different sources of wheat bran fed to broilers and establish the SID AA prediction based on the chemical composition. Methods A total of 660 1-day-old broilers were randomly divided into 11 treatments with 6 replicates of 10 chickens each. Diets included 10 semi-purified mash diets and 1 nitrogen-free diet. Titanium dioxide (TiO2) 0.50% was used as an indigestible index. On day 13, 6 chickens from each replicate were selected for slaughter to collect ileal contents. On day 28, 4 chickens from each replicate were selected for slaughter to collect ileal contents. Results Results showed that the coefficient of variation of the conventional nutrients (except for gross energy, and dry matter) and all AAs was greater than 8.00%. The average SID of essential AA in wheat bran for 13-day-old broilers was 37.24% and the average SID of nonessential AA was 42.02%; the average SID of essential AA for 28-day-old broilers was 67.13% and the average SID of nonessential AA was 69.51%. A correlation was observed (p

Abstract In food circular economy, the utilization of food manufacturing side streams (FMSS) offers significant potential instead of being discarded. However, reincorporating FMSS into the food value chain raises food safety concerns due to potential food hazards. This perspective explores food safety risks associated with circular management of FMSS by using a ‘Quad-Modal hazard dynamic’ approach with case studies. Future research and advancements in food safety control strategies are also discussed.

Objective: To investigate whether angiotensin II type 1 receptor (AGTR1 A1166C) gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension. Methods: This retrospective analysis included 198 patients (⩾18 years of age) who received valsartan monotherapy (80 mg/day) for newly developed essential hypertension at the authors’ center between January 1, 2020 and December 31, 2023. Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction (PCR)-melting curve analysis of genomic DNA from peripheral blood samples. A dominant genetic model for AGTR1 A1166C (AA genotype versus AC + CC genotype) was used. Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment (

This study aimed to compare the effects of dietary methionine (Met) and 2-hydroxy-4-(methylthio)-butanoate (HMTBA) on the eggshell quality of broiler breeder hens and elucidate the mechanism of Met in improving eggshell quality from the perspectives of eggshell microstructure and shell gland physiological function. A total of 720 WOD188 broiler breeder hens at 40 weeks old were assigned to 3 groups, with 8 replicates per group and 30 birds per replicate. Over 7 weeks, birds were fed a basal diet or the same diet supplemented with 0.15% Met or 0.17% HMTBA. Our findings revealed significant improvements in the Met group for egg shape index, shell thickness, breaking strength, and fracture toughness (P 0.05). Met supplementation increased calcium and phosphorus levels in both serum and shell gland tissue (P

The network autoregressive model is a super high-dimensional time series model that can fully explain social relationships. This model can fully reflect the complex relationships in reality. Therefore, it plays a vital role in detecting the inflection point problem of this network autoregressive model for economics and finance. In this paper, we proposed the change-point problem of detecting network autoregressive models using empirical likelihood statistics based on the expected error term of the switching rule being 0, using the empirical likelihood method. Moreover, the asymptotic null distribution of the proposed empirical likelihood statistic was investigated. Simulation studies based on different settings were considered, and the results showed that the power of test statistics is significant. In the end, the Chinese stock market was investigated to demonstrate the significance of the proposed method.

In order to investigate the influence of X-ray irradiation dose on the germination and storage quality of coloured potatoes, this study took the coloured potatoes Yellow Rose 3, Purple Rose 3, Red Rose 5 and common potatoes as test materials, and treated them with 5 MeV electron-beam rotary target X-rays at 0, 100, 300 and 500 Gy. The treated potatoes were stored at room temperature (20±2) ℃ with a relative humidity of 80%~90%. In order to study the influence of X-ray irradiation on the appearance, nutritional quality and fresh-keeping effects of potatoes, parameter changes of germination rate, weight loss rate, hardness, VC content, dry matter content and respiration intensity during the storage period were analyzed. The results showed that X-ray irradiation treatment reduced the respiratory intensity of potatoes in the mid to late storage period and decreased the weight loss, hardness decline and loss of VC content during storage. Compared with control group, 100 Gy irradiation treated Yellow Rose 3, Purple Rose 3, Red Rose 5 and common potatoes reduced the weight loss rate by 12.76%, 5.31%, 6.05% and 1.43%, respectively, the degree of decrease in hardness at the end of the storage period compared with the beginning of storage period was reduced by 12.98%, 6.40%, 8.34% and 7.13%, respectively, and the rate of loss of VC content was reduced by 17.71%, 22.80%, 13.52% and 14.65%, respectively. Four varieties of potatoes did not sprout even after storage for more than 240 days after receiving different doses of X-rays. A low dose of 100 Gy of X-ray irradiation treatment could achieve an optimal sprout inhibition effect. Moreover, it delayed weight loss and hardness decline more effectively than 300 and 500 Gy. This dose could be recommended as the dose for irradiation preservation of coloured and ordinary potatoes in industrial applications. This research provides a theoretical basis and technical guidance for the application of X-ray irradiation technology in the storage and preservation of coloured potatoes.

Abstract Objective This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. Methods Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. Results CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. Conclusion CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.

Aiming at the deficiencies presented by the traditional methods of highway project investment evaluation, the proposed highway investment evaluation method was based on system dynamics. First, we constructed an evaluation index system from profitability, solvency, and risk resistance and clarified the positive and negative causality within the investment evaluation system of highway projects; second, we determined the boundaries of the system dynamics model and divided it into six sub-systems, namely, income, cash flow, investment evaluation, profit, cost, investment and financing, and liabilities; and then, we established the system dynamics model of highway investment evaluation based on the sub-systems. The model made up for the limitations of the traditional discounted cash flow method; finally, taking the China's Yunnan Province an Expressway project as an example, using VENSIM software simulation, we get the evaluation results of the system dynamics model and make a comparative analysis with the discounted cash flow method, which showed that the calculation inaccuracies of the NPV and other financial indicators were in a reasonable range, and the evaluation method had strong operability and practicability. The system dynamics investment evaluation model provided a systematic, intuitive, whole-process investment evaluation method, which provided a theoretical basis for the analysis and decision-making of the investment effect of highway projects.

Abstract KDM6A (lysine demethylase 6A) has been reported to undergo inactivating mutations in colorectal cancer, but its function in the progression of colorectal cancer has not been evaluated using animal models of colorectal cancer. In this study, we found that knocking out KDM6A expression in mouse intestinal epithelium increased the length of villus and crypt, promoting the development of AOM (azoxymethane)/DSS (dextran sulfate sodium salt)-induced colorectal cancer. On the other hand, knocking down KDM6A expression promoted the growth of colorectal cancer cells. In molecular mechanism studies, we found that KDM6A interacts with HIF-1α; knocking down KDM6A promotes the binding of HIF-1α to the LDHA promoter, thereby promoting LDHA expression and lactate production, enhancing glycolysis. Knocking down LDHA reversed the malignant phenotype caused by KDM6A expression loss. In summary, this study using animal models revealed that KDM6A loss promotes the progression of colorectal cancer through reprogramming the metabolism of the colorectal cancer cells, suggesting that restoring the function of KDM6A is likely to be one of the strategies for colorectal cancer treatment.

BackgroundThis study aimed to explore the mechanism of action of DiWuYangGan (DWYG) capsule in improving Immunological non-responder (INR) by analyzing the active ingredients of DWYG.MethodsThe study employed a randomized, controlled, double-blind, single-simulation method. Patients were randomly divided into control and trial groups and treated with the primal highly effective antiretroviral therapy. To demonstrate the effect of DWYG on INR, patients in the control group were administered simulated DWYG, whereas patients in the trial group were administered DWYG capsules (ChiCTR1900024673). The chemical composition of DWYG was analyzed using ultra-performance liquid chromatography-high-resolution mass spectrometry. Potential targets of DWYG in the treatment of INR were identified and predicted using network pharmacology and molecular docking. The molecular mechanisms underlying the effects of DWYG were validated using a peripheral blood monocyte model.ResultsThe CD4:CD8 ratio in the trial group was significantly higher than that in the control group (p < 0.01). A total of 210 DWYG compounds were identified and network pharmacology revealed 182 potential therapeutic targets for DWYG and INR. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the toll-like receptor signaling pathway is one of the key pathways. This study demonstrated that DWYG reduced the expression level of TLR4 and the levels of IL-2, IL-10, and TNF-α, which are important cytokines involved in the immune response.ConclusionThe efficacy of DWYG in the treatment of INR confirmed the potential practical components of DWYG. Moreover, the results of network pharmacology and experimental validation showed that DWYG could restore the immune function of acquired immune deficiency syndrome patients by inhibiting the expression of TLR4 and related signaling pathways and the overactivation of immune function.Clinical Trial Registration:https://www.chictr.org.cn/index.html, identifier ChiCTR1900024673.

ABSTRACT: This study aimed to investigate the effects of baicalin and chlorogenic acid (BC) on growth performance, intestinal barrier function, antioxidant capacity, intestinal microbiota, and mucosal metabolism in broilers. A total of 720 twenty-one-day-old broilers were randomly allocated into 3 groups, with 6 replicates per group and 40 chickens per replicate. They were fed a basal diet (Con group) or a basal diet supplemented with 250 or 400 mg/kg BC (BC250 and BC400 groups) for 40 consecutive days. The results revealed that 250 mg/kg BC significantly increased 60-d body weight and average daily gain during 39 to 60 d (P < 0.05). Furthermore, Supplementation with 250 mg/kg BC improved the antioxidant capacity and immunity of broilers, as evidenced by increased (P < 0.05) superoxide dismutase and decreased (P < 0.05) malondialdehyde levels in serum and ileum, as well as increased (P < 0.05) immunoglobulin G levels. Supplementation with 250 mg/kg BC enhanced intestinal development by improving intestinal morphology and promoting the proliferation of intestinal crypts. Moreover, Supplementation with 250 mg/kg BC improved (P < 0.05) intestinal permeability, up-regulated (P < 0.05) the expression of tight junction-related genes (Occludin and ZO-1), and down-regulated (P < 0.05) the expression of pro-inflammatory genes (IL-2, IL-8, and IFN-γ). 16S rRNA sequencing revealed significant enrichment of Microbacteriaceae, Micromonosporaceae, Anaerovoracaceae, and Coriobacteriaceae in the BC250 group. Metabolomics showed that 250 mg/kg BC up-regulated the lysosome, foxo signaling pathway, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and oxidative phosphorylation pathways, while down-regulating the biosynthesis of cofactors pathway. In conclusion, supplementing diets with 250 mg/kg BC is recommended to modulate intestinal microbiota, mucosal metabolism, and antioxidant capacity, thereby improving broiler growth performance and intestinal health.

Background Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients.

Abstract Background The 9th edition of the TNM Classification for lung cancer delineates M1c into two subcategories: M1c1 (Multiple extrathoracic lesions within a single organ system) and M1c2 (Multiple extrathoracic lesions involving multiple organ systems). Existing research indicates that patients with lung cancer in stage M1c1 exhibit superior overall survival compared to those in stage M1c2. The primary frontline therapy for patients with advanced non‐small cell lung cancer (NSCLC), lacking driver gene mutations, involves the use of immune checkpoint inhibitors (ICIs) combined with chemotherapy. Nevertheless, a dearth of evidence exists regarding potential survival disparities between NSCLC patients with M1c1 and M1c2 undergoing first‐line immune‐chemotherapy, and reliable biomarkers for predicting treatment outcomes are elusive. Serum metabolic profiles may elucidate distinct prognostic mechanisms, necessitating the identification of divergent metabolites in M1c1 and M1c2 undergoing combination therapy. This study seeks to scrutinize survival discrepancies between various metastatic patterns (M1c1 and M1c2) and pinpoint metabolites associated with treatment outcomes in NSCLC patients undergoing first‐line ICIs combined with chemotherapy. Method In this study, 33 NSCLC patients lacking driver gene mutations diagnosed with M1c1, and 22 similarly diagnosed with M1c2 according to the 9th edition of TNM Classification, were enrolled. These patients received first‐line PD‐1 inhibitor plus chemotherapy. The relationship between metastatic patterns and progression‐free survival (PFS) in patients undergoing combination therapy was analyzed using univariate and multivariate Cox regression models. Serum samples were obtained from all patients before treatment initiation for untargeted metabolomics analysis, aiming to identify differential metabolites. Results In the univariate analysis of PFS, NSCLC patients in M1c1 receiving first‐line PD‐1 inhibitor plus chemotherapy exhibited an extended PFS (HR = 0.49, 95% CI, 0.27–0.88, p = 0.017). In multivariate PFS analyses, these M1c1 patients receiving first‐line PD‐1 inhibitor plus chemotherapy also demonstrated prolonged PFS (HR = 0.45, 95% CI, 0.22–0.92, p = 0.028). The serum metabolic profiles of M1c1 and M1c2 undergoing first‐line PD‐1 inhibitors plus chemotherapy displayed notable distinctions. In comparison to M1c1 patients, M1c2 patients exhibited alterations in various pathways pretreatment, including platelet activation, linoleic acid metabolism, and the VEGF signaling pathway. Diminished levels of lipid‐associated metabolites (diacylglycerol, sphingomyelin) were correlated with adverse outcomes. Conclusion NSCLC patients in M1c1, devoid of driver gene mutations, receiving first‐line PD‐1 inhibitors combined with chemotherapy, experienced superior outcomes compared to M1c2 patients. Moreover, metabolomic profiles strongly correlated with the prognosis of these patients, and M1c2 patients with unfavorable outcomes manifested distinct changes in metabolic pathways before treatment. These changes predominantly involved alterations in lipid metabolism, such as decreased diacylglycerol and sphingomyelin, which may impact tumor migration and invasion.

Abstract Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A−1 T−1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

The paper assesses the moderating role of firm age in the relationship between financial constraints, as measured by the KZ index, and the WW index on three alternative measures of firm growth (Asset growth, ROA, and ROE) in the ASEAN–6 region. This study employs a sample of ASEAN–6 listed firms over the period 2009–2019 using Fixed Effects and the System GMM model. Firm age is found to interact positively with financial constraints in their effects on firm growth. The negative impact of financial constraints on firm growth is less severe with older age firms.

Abstract Nonlinear transport enabled by symmetry breaking in quantum materials has aroused considerable interest in condensed matter physics and interdisciplinary electronics. However, achieving a nonlinear optical response in centrosymmetric Dirac semimetals via defect engineering has remained a challenge. Here, we observe the helicity dependent terahertz emission in Dirac semimetal PtTe2 thin films via the circular photogalvanic effect under normal incidence. This is activated by a controllable out-of-plane Te-vacancy defect gradient, which we unambiguously evidence with electron ptychography. The defect gradient lowers the symmetry, which not only induces the band spin splitting but also generates the giant Berry curvature dipole responsible for the circular photogalvanic effect. We demonstrate that the THz emission can be manipulated by the Te-vacancy defect concentration. Furthermore, the temperature evolution of the THz emission features a minimum in the THz amplitude due to carrier compensation. Our work provides a universal strategy for symmetry breaking in centrosymmetric Dirac materials for efficient nonlinear transport.

Background Esophageal squamous cell carcinoma (ESCC) is a malignant condition in humans. Anoikis-related genes (ARGs) are crucial to cancer progression. Therefore, more studies on the relationship between ARGs and ESCC are warranted.Methods The study acquired ESCC-related transcriptome data from TCGA. Differentially expressed ARGs (DE-ARGs) were obtained by differential analysis and candidates were filtered out by survival analysis. Prognostic genes were determined by Cox and LASSO regression. A risk model was constructed based on prognostic gene expressions. An immune infiltration study was done to explain how these genes contribute to ESCC development. The IC50 test was adopted to assess the clinical response of chemotherapy drugs. Single cell analysis was performed on the GSE145370 dataset. Moreover, the prognostic gene expressions were detected by qRT-PCR.Results 53 DE-ARGs were screened and four candidate genes including PBK, LAMC2, TNFSF10 and KL were obtained. Cox and LASSO regression identified the two prognostic genes, TNFSF10 and PBK. Immuno-infiltration analysis revealed positive associations of PBK with Macrophages M0 cells, and TNFSF10 with Macrophages M1 cells. The IC50 values of predicted drugs, in the case of Tozasertib 1096 and WIKI4 1940, were significantly variant between risk groups. Single cell analysis revealed that TNFSF10 and PBK levels were higher in epithelial cells than in other cells. The prognostic genes expression results by qRT-PCR were compatible with the dataset analysis.Conclusion The study established an ARG prognosis model of ESCC. It provided a reference for the research of ARGs in ESCC.

ABSTRACT: Copy number variation (CNV) is a crucial component of genetic diversity in the genome, serving as the foundation for the genetic architecture and phenotypic variability of complex traits. In this study, we examined CNVs in the Danzhou (DZ) chicken, an indigenous breed exclusive to Hainan Province, China. By employing whole-genome resequencing data from 200 DZ chickens, we conducted a comprehensive genome-wide analysis of CNVs using CNVpytor and performed CNV-based genome-wide association studies (GWAS) on 6 body size traits, including body slope length (BSL), keel length (KeL), tibial length (TiL), tibial circumference (TiC), chest width (ChW), and chest depth (ChD) utilizing linear mixed model methods considering a genomic relationship matrix. We identified a total of 144,265 autosomal CNVs among the 200 individuals, comprising 67,818 deletions and 76,447 duplications. After merging these variants together, we obtained 4,824 distinct copy number variant regions, which accounted for approximately 20% of the chicken autosomal genome. Furthermore, we discovered several significantly associated CNV segments with body size traits located proximal to genes such as IHH, WNT6, WNT10A, LPR4, FZD2, WNT7B, and GNAS that have been extensively implicated in skeletal development and growth processes. These findings enhance our understanding of CNVs in chickens and their potential impact on body size traits by revealing candidate genes involved in the regulation of these traits. This establishes a solid framework for future studies and may prove particularly beneficial for exploring genetic structural variation in chickens.

IntroductionThe detection rate of benign thyroid nodules is increasing every year, with some affected patients experiencing symptoms. Ultrasound-guided thermal ablation can reduce the volume of nodules to alleviate symptoms. As the degree and speed of lesion absorption vary greatly between individuals, an effective model to predict curative effect after ablation is lacking. This study aims to predict the efficacy of ultrasound-guided thermal ablation for benign thyroid nodules using machine learning and explain the characteristics affecting the nodule volume reduction ratio (VRR).DesignProspective studyPatientsThe clinical and ultrasonic characteristics of patients who underwent ultrasound-guided thermal ablation of benign thyroid nodules at our hospital between January 2020 and January 2023 were recorded.MeasurementsSix machine learning models (logistic regression, support vector machine, decision tree, random forest, eXtreme Gradient Boosting [XGBoost], and Light Gradient Boosting Machine [LGBM]) were constructed to predict efficacy; the effectiveness of each model was evaluated, and the optimal model selected. SHapley Additive exPlanations (SHAP) was used to visualize the decision process of the optimal model and analyze the characteristics affecting the VRR.ResultsIn total, 518 benign thyroid nodules were included: 356 in the satisfactory group (VRR ≥70% 1 year after operation) and 162 in the unsatisfactory group. The optimal XGBoost model predicted satisfactory efficacy with 78.9% accuracy, 88.8% precision, 79.8% recall rate, an F1 value of 0.84 F1, and an area under the curve of 0.86. The top five characteristics that affected VRRs were the proportion of solid components < 20%, initial nodule volume, blood flow score, peripheral blood flow pattern, and proportion of solid components 50–80%.ConclusionsThe models, based on interpretable machine learning, predicted the VRR after thermal ablation for benign thyroid nodules, which provided a reference for preoperative treatment decisions.

Background and PurposeThe risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries.MethodsHindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines.ResultsUnder SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1β, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions.ConclusionLLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

Thirteen previously undescribed lindenane sesquiterpenoid dimers (LSDs), named chlorahololides G–S (1–13), were isolated from the whole plants of Chloranthus holostegius var. shimianensis, along with ten known analogues (14–23). The structures and absolute configurations of compounds 1–13 were elucidated through comprehensive spectroscopic analysis, NMR and electronic circular dichroism (ECD) calculations, and X-ray single-crystal diffraction. Chlorahololide G (1) represents the first instance of LSDs formed via a C-15–C-9′ carbon-carbon single bond, whose plausible biosynthetic pathway was also proposed. Chlorahololides I and J (3 and 4) were deduced to be rare 8,9-seco and 9-deoxy LSDs with C-11–C-7′ carbon-carbon bond, respectively. The inhibitory activity against NLRP3 inflammasome activation was evaluated for all isolates, with six compounds (5, 7, 8, 17, 22, and 23) exhibiting significant effects, and IC50 values ranging from 2.99 to 8.73 µM. Additionally, a preliminary structure-activity relationship analysis regarding their inhibition of NLRP3 inflammasome activation was summarized. Compound 17 exhibited dose-dependent inhibition of nigericin-induced pyroptosis in J774A.1 cells. Molecular docking studies suggested a strong interaction between compound 17 and NLRP3.

Abstract The growth of newly formed particles through new particle formation (NPF) contributes a significant fraction to the cloud condensation nuclei, yet the driving mechanisms remain unclear, especially for polluted environments. To investigate the potential species contributing for nanoparticle growth in environments with significant anthropogenic influences, we measured the hygroscopicity of newly formed particles at 20–40 nm at a rural observational site in the North China Plain during winter 2018. Our results demonstrate that these particles were not very hygroscopic, with the mean hygroscopicity parameter κ of 0.13 ± 0.09. Clear differences in the inferred κ of the growing material responsible for the growth were observed among different events, indicating that even at the same region, the compounds driving particle growth may not be identical. This may be synergistically influenced by the NPF precursors, oxidants and meteorological conditions, suggesting complex mechanisms might co‐exist behind nanoparticle growth in polluted environments.

IntroductionAnti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown.MethodsWe searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition.ResultsTheir median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5μmol/L, IQR:270.0~702.0 vs. 515.8~1231.2μmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2μmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2μmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3 weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

Abstract Atmospheric aerosols not only cause severe haze pollution, but also affect climate through changes in cloud properties. However, during the haze pollution, aerosol‐cloud interactions are not well understood due to a lack of in situ observations. In this study, we conducted simultaneous observations of cloud droplet and particle number size distribution, together with supporting atmospheric parameters, from ground to cloud base in East China using a high‐payload tethered airship. We found that high concentrations of aerosols and cloud condensation nuclei were constrained below cloud, leading to the pronounced “Twomey effect” near the cloud base. The cloud inhibited the pollutants dispersion by reducing surface heat flux and thus deteriorated the near‐surface haze pollution. Satellite retrievals matched well with the in situ observations for low stratus clouds, while were insufficient to quantify aerosol‐cloud interactions for other cases. Our results highlight the importance to combine in situ vertical and satellite observations to quantify the aerosol‐cloud interactions.

Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

[Objective] Slug flow is one of the main gas-liquid two-phase flow regimes. Its fluctuation characteristics not only impact the safe operation of multi-phase pumps and the measurement accuracy of multi-phase flowmeters but also arouse flow-induced vibrations in various pipeline sectors, such as elbows, valves, and places where pipelines are connected in parallel. Therefore, conducting a systematic study on fluctuation frequencies induced by slug flow is of utmost importance for securing the operation safety of these pipelines and associated fittings. [Methods] By leveraging the dynamics model of slug flow and recognizing the inherent continuity wave characteristics of slug flow, a novel continuity wave model was developed. This model employed the Strouhal number to characterize the dimensionless fluctuation frequencies induced by slug flow. Through extensive literature investigations, existing empirical calculation models for fluctuation frequencies induced by slug flow in horizontal pipelines were summarized. Additionally, an experimental study was conducted to examine fluctuation frequencies induced by air-water two-phase slug flow in a 30 m long horizontal pipeline with an inner diameter of 24 mm. Conducting probes were used to measure the fluctuation frequencies within the parameter ranges of 0.23 m/s to 1.85 m/s for superficial liquid velocity and 0.88 m/s to 10.0 m/s for superficial gas velocity. The experimental data and calculation results based on the new model were taken to compare with the prediction results obtained using 12 different empirical formulas proposed by various scholars. [Results] Analysis of the experimental data revealed that the fluctuation frequencies induced by continuity waves in slug flow increased with rising superficial liquid velocities, approximating a linear trend. At low superficial liquid velocities, the fluctuation frequency initially decreased and subsequently increased with the increase of superficial gas velocities. However, the influence of superficial gas velocities on slug frequencies became less noticeable at high superficial liquid velocities. The proposed model had an average relative error of approximately -15%, lower than the mean level observed in the empirical formulas, and the root-mean-square relative error was the lowest, approximately 26%. [Conclusion] Error analysis demonstrates that the prediction results of fluctuation frequencies induced by slug flow obtained from the proposed continuity wave model align more closely with the experimental data compared to those obtained from existing empirical formulas, exhibiting a greater degree of scattering.

With the widespread adoption of electronic health records, the amount of stored medical data has been increasing. Clinical data, often in the form of semi-structured or unstructured electronic medical records (EMRs), contains rich patient information. However, due to the use of natural language by physicians when composing these records, the effectiveness of traditional methods such as dictionaries, rule matching, and machine learning in the extraction of information from these unstructured texts falls short of clinical standards. In this paper, a novel deep-learning-based natural language extraction method is proposed to overcome current shortcomings in data governance and Gensini score automatic calculation in coronary angiography. A pre-trained model called bidirectional encoder representation from transformers (BERT) with strong text feature representation capabilities is employed as the feature representation layer. It is combined with bidirectional long short-term memory (BiLSTM) and conditional random field (CRF) models to extract both global and local features from the text. The study included an evaluation of the model on a dataset from a hospital in China and it was compared with another model to validate its practical advantages. Hence, the BiLSTM-CRF model was employed to automatically extract relevant coronary angiogram information from EMR texts. The achieved F1 score was 91.19, which is approximately 0.87 higher than the BERT-BiLSTM-CRF model.

Abstract Background Bovine viral diarrhea (BVD) is an acute febrile infectious disease caused by the bovine viral diarrhea virus (BVDV), which has brought huge economic losses to the world's cattle industry. At present, commercial inactivated BVDV vaccines may cause some adverse reactions during use. This study aims to develop a safer and more efficient inactivated BVDV vaccine. Methods Here, we described the generation and preclinical efficacy of a hydrogen peroxide (H2O2) inactivated BVDV type 1 vaccine in mice, and administered it separately with commercial vaccine (formaldehyde inactivated) in mice to study its efficacy. Results The BVDV type 1 IgG, IFN- γ, IL-4 and neutralizing antibody in the serum of the H2O2 inactivated vaccine group can be maintained in mice for 70 days. The IgG level reached its maximum value of 0.67 on the 42nd day, significantly higher than the commercial formaldehyde inactivated BVDV type 1 vaccine. IFN- γ and IL-4 reached their maximum values on the 28th day after immunization, at 123.16 pg/ml and 143.80 pg/ml, respectively, slightly higher than commercial vaccines, but the effect was not significant. At the same time the BVDV—1 neutralizing antibody titer reached a maximum of 12 Nu on the 42nd day post vaccination. Conclusions The H2O2 inactivated BVDV vaccine has good safety and immunogenicity, which provides a potential solution for the further development of an efficient and safe BVDV vaccine.

In the domain of medical image segmentation, the nnUNet framework is highly respected for its excellent performance and wide range of applications. However, the inherent bias of locality and weight sharing introduced by the continuous convolutional operations currently used limits the network’s performance in modeling long-term dependencies. Furthermore, in the process of implementing residual links, certain limitations are encountered due to the substantial semantic discrepancy between the encoder’s output feature maps and the decoder’s. These limitations are seen in the direct application of skip connections for feature fusion and gradient propagation, which are known to impact the model’s convergence speed and overall performance. In this paper, a novel framework is presented, namely Multi-Attention nnUNet (MulA-nnUNet), which utilizes nnUNet as the foundational network structure and integrates two key attention mechanisms: large kernel convolutional attention (LKA) and pixel attention (PA). LKA is embedded within the deep encoder, maintaining the effectiveness of shallow feature extraction and enhancing the deep neural networks’ ability to understand long-range spatial dependencies. At the same time, the semantic distinction between the encoder and decoder’s output map of features is decreased by the PA module, which helps to improve the effect of skip connection feature fusion. The complexity of the model is reduced by replacing the standard convolutions in the encoder and decoder layers with depthwise separable convolutions (DS), which have fewer parameters. The effectiveness of the proposed framework is confirmed by a set of ablation experiments and comparison experiments with current state-of-the-art models on the computed tomography (CT) subset of the multimodal abdominal multi-organ segmentation dataset (AMOS), which includes 500 CT scans, with 350 scans for training, 75 for validation, and 75 for testing. MulA-nnUNet shows improvements of 1.1% in mean dice similarity coefficient (mDSC) and 1.52% in mean intersection over union (mIoU), while the baseline model requires 5 times the floating point operations (FLOPs) and over 7 times the parameters (Params). Additionally, it demonstrates superior accuracy in segmenting organs such as the liver, stomach, aorta, and pancreas, thereby enhancing the accuracy of 3D abdominal multi-organ image segmentation.

Urban day-to-day travel system is a complex nonlinear system, its current status depends not only on the status of the whole urban transportation system at the previous point in time, but also on the travel decision made by each traveler. Moreover, information environment generated by various intelligent terminals like smart phones, has even increased the complexity of urban day-to-day travel system, for micro level route choice decision made by each traveler can be affected by macro level road traffic flow information at any time, and micro route choice behavior can generate new macro traffic information. Nowadays, there is a lack of macro-micro integrated models to explain urban day-to-day travel system, especially its development in information environment. In this paper, complex system dynamics has been proposed and used to explain urban day-to-day travel system in a macro-micro integrated way. The main contribution of this paper is twofold: in micro level, each traveler in urban day-to-day travel system in information environment is endowed with unique physical properties, and the time correlation effect of individual travelers is described; in macro level, the traffic flow fluctuations under the influence of individual micro decisions, the stylized facts of urban day-to-day travel has been deduced, and an effective description of urban day-to-day travel phenomena has been formed.

Vehicle path planning is one of the effective ways to relieve the huge traffic flow pressure of modern urban transportation system, and it is also an important way to realize carbon emission reduction and to build green transportation system as well as smart city. At present, the artificial intelligence (AI) algorithms with reinforcement learning (RL) as the mainstream have achieved great success in the field of vehicle path planning. However, RL only conducts policy learning based on the evaluation feedback of the environment, whereas imitation learning (IL) can obtain more direct feedback from expert decision data, and then obtain a decision model close to the expert level by comparing with RL. At present, there are very few vehicle path planning algorithms based on IL, and they are often hindered by the compounding error and sample complexity dilemma, resulting in poor path planning effectiveness. In order to overcome these problems, in this paper, a mixed generative adversarial IL (MixGAIL) algorithm has been proposed, which effectively integrates the transition aware adversarial IL (TAIL) and generative adversarial IL (GAIL) based on minimum-distance functions (MIMIC-MD) methods under the framework of GAIL. In order to overcome the optimization dilemma of non-convex and non-smooth objective function after the integration, the proposed MixGAIL uses mixed policy gradient actor-critic model with random escape term and filter optimization (MPGACEF), and pioneers the noise projected subgradient descent method with momentum (MNPSGD) for global optimization. Experiments have shown that by learning expert decision data, MixGAIL has better vehicle path planning performance and faster iteration speed than classic IL algorithms such as behavioral cloning (BC), dataset aggregation (DAgger), feature expectation matching (FEM), game theoretical appraisal learning (GTAL), TAIL, and MIMIC-MD, and is closer to expert level.

We consider a scenario where an unmanned aerial vehicle (UAV), a typical unmanned aerial system (UAS), transmits confidential data to a moving ground target in the presence of multiple eavesdroppers. Multiple friendly reconfigurable intelligent surfaces (RISs) help to secure the UAV-target communication and improve the energy efficiency of the UAV. We formulate an optimization problem to minimize the energy consumption of the UAV, subject to the mobility constraint of the UAV and that the achievable secrecy rate at the target is over a given threshold. We present an online planning method following the framework of model predictive control (MPC) to jointly optimize the motion of the UAV and the configurations of the RISs. The effectiveness of the proposed method is validated via computer simulations.

The study of road traffic flow theory utilizes physics and applied mathematics to analyze relevant parameters and their relationships quanlitatively and quantitatively, in order to explore their dynamic changes. The fluid dynamics model used for traffic flow analysis is highly favored by scholars due to its solid mathematical foundation and good simulation results. However, existing models have two main shortcomings: firstly, existing research is mostly limited to non-viscoelastic fluid equation or incompressible non-Newtonian fluid equation, making it difficult to accurately describe the viscosity state and micro cluster properties of the actual traffic flow; secondly, the existing non-Newtonian fluid partial differential equations (PDEs) rely heavily on the finite element method (FEM) for solving, requiring higher computational cost, larger storage space, and more constraint conditions. Thus, in this paper, a traffic flow equation based on compressible non-Newtonian fluid has been constructed, and it has been solved by using physical-informed rational neural network (PIRNN) and noise heavy-ball acceleration gradient descent (NHAGD) to ensure learning and training speed and accuracy. Numerical results indicate that the proposed method can truly reflect the gradual change process in the viscosity of traffic flow, and has better solving performance than traditional FEM and physical-informed neural network (PINN) with activation functions; under the same conditions, the prediction error of the proposed method is also smaller than that of traditional traffic flow models.

To improve the utilisation rate of recycled fine aggregate (RFA), five different replacement rates of RFA were used in this article. Recycled mortar (RM) was used as the research object to test its consistency, compressive strength, flexural strength, chloride ion migration coefficient, and frost resistance. Thermal analysis (TG) and scanning electron microscopy (SEM) were used to analyse the hydration products and microstructure of the mortar. Using RM as the research object, tests were conducted on the consistency, compressive strength, flexural strength, resistance to chloride ion migration coefficient, and frost resistance. TG and SEM were used to analyse the hydration products and microstructure of the mortar. The results showed that the higher the RFA replacement rate, the lower the RM consistency. When the replacement rate is 30%, the RM has better mechanical properties than the natural mortar (NM); when the RFA increases the chloride ion migration coefficient and its replacement rate exceeds 30%, the frost resistance of the RM decreases, and the strength loss rate increases significantly; the TG analysis showed that as the RFA replacement rate increased, the CH content decreased and the CaCO₃ content increased; the SEM analysis shows that the microstructure of the RM is sparse, and the distribution of hydration products is uneven.

This paper considers a time-constrained data collection problem from a network of ground sensors located on uneven terrain by an Unmanned Aerial Vehicle (UAV), a typical Unmanned Aerial System (UAS). The ground sensors harvest renewable energy and are equipped with batteries and data buffers. The ground sensor model takes into account sensor data buffer and battery limitations. An asymptotically globally optimal method of joint UAV 3D trajectory optimization and data transmission schedule is developed. The developed method maximizes the amount of data transmitted to the UAV without losses and too long delays and minimizes the propulsion energy of the UAV. The developed algorithm of optimal trajectory optimization and transmission scheduling is based on dynamic programming. Computer simulations demonstrate the effectiveness of the proposed algorithm.

Ship target detection faces the challenges of complex and changing environments combined with the varied characteristics of ship targets. In practical applications, the complexity of meteorological conditions, uncertainty of lighting, and the diversity of ship target characteristics can affect the accuracy and efficiency of ship target detection algorithms. Most existing target detection methods perform well in conditions of a general scenario but underperform in complex conditions. In this study, a collaborative network for target detection under foggy weather conditions is proposed, aiming to achieve improved accuracy while satisfying the need for real-time detection. First, a collaborative block was designed and SCConv and PCA modules were introduced to enhance the detection of low-quality images. Second, the PAN + FPN structure was adopted to take full advantage of its lightweight and efficient features. Finally, four detection heads were used to enhance the performance. In addition to this, a dataset for foggy ship detection was constructed based on ShipRSImageNet, and the mAP on the dataset reached 48.7%. The detection speed reached 33.3 frames per second (FPS), which is ultimately comparable to YOLOF. It shows that the model proposed has good detection effectiveness for remote sensing ship images during low-contrast foggy days.