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The purpose of this study was to explore the influence of educational choice on the intention to enter the examination, and the mediating role of career decision-making self-efficacy. A total of 1391 freshmen from six higher vocational colleges in Guangdong Province of China were investigated with Education Choices Scale, Career Decision-Making Self-Efficacy Scale and Willingness to Apply Scale. The results showed that educational choice and career decision-making self-efficacy had significant effects on the willingness to apply. Career decision-making self-efficacy plays a mediating role in the significant positive impact of educational choice on the willingness to apply. Therefore, China's educational institutions and policy makers should focus on cultivating vocational students' career decision-making self-efficacy and improving their confidence and ability in career decision-making. To help students better understand their interests, values, and career goals, and to help students better understand the career fields they face professionally.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P

Abstract Pathogenesis of periodontitis is marked by microbiota dysbiosis and disrupted host responses. Porphyromonas gingivalis is a keystone pathogen of periodontitis which expresses various crucial virulence factors. This study aimed to clarify the role and mechanisms of P. gingivalis tryptophan-indole metabolic pathway in the pathogenesis of periodontitis. This study showed that periodontitis patients exhibited elevated tryptophan metabolism and salivary pathogen abundance. Tryptophanase gene-deficiency altered proteome and metabolome of P. gingivalis , inhibited P. gingivalis virulent factors expression, biofilm growth, hemin utilization, cell adhesion/invasion and pro-inflammation ability. Tryptophan-indole pathway of P. gingivalis stimulated periodontitis biofilm formation and induced oral microbiota dysbiosis. In periodontitis mice, this pathway of P. gingivalis aggravated alveolar bone loss and gingival tissue destruction, causing oral and gut microbiota dysbiosis. This study indicates that the tryptophan-indole pathway serves as a significant regulator of P. gingivalis virulence and oral microbiota dysbiosis, which is also associated with gut dysbiosis.

Abstract Background There is a significant association between work values and burnout. However, most studies have tended to focus on a single influencing factor or rely only on total scale scores to assess nurses’ work values, lacking a comprehensive consideration of differences within groups of nurses. As a result, the specific relationship between different work value patterns and burnout has not been clarified. Objective This study aimed to identify Chinese nurses’ patterns of work values, analyze the sociodemographic differences between these patterns, and explore the associations between these patterns and burnout. Design Cross-sectional study. Methods A total of 550 nurses were recruited for this study via convenience sampling, 505 of whom completed the survey. A pattern of nurses’ work values was identified through a latent profile analysis of 30 items on the nurses’ work values scale. The relationships between nurses’ work value patterns and sociodemographic variables were subsequently explored via bivariate analysis and multiple logistic regression analyses. Moreover, ANOVA was used to assess the associations between different latent profile work value patterns and nurse burnout. Results A total of three nurse work value patterns were identified: demand support (16.6%, n = 84), intrinsically driven (42.2%, n = 213), and overall identification (41.2%, n = 208). Age and marital status, such as being married, were the main predictors of demand support patterns. In contrast, years of working experience, a higher education level (a bachelor’s or master’s degree), and having a career establishment were predictors of intrinsically driven and overall identification patterns. In addition, the analyses revealed significant differences in burnout among nurses with different work value patterns. Conclusion This study provides new perspectives for understanding the work motivation and stressors of the nurse population, revealing significant differences in coping with burnout among nurses with different work value patterns. This finding not only provides an important reference for subsequent research but also provides a strong basis for developing interventions for nurse burnout. Clinical trial number Not applicable.

Abstract Aberrant RNA alternative splicing in cancer generates varied novel isoforms and protein variants that facilitate cancer progression. Here, we employed the advanced long-read full-length transcriptome sequencing on gallbladder normal tissues, tumors, and cell lines to establish a comprehensive full-length gallbladder transcriptomic atlas. It is of note that receptor tyrosine kinases were one of the most dynamic components with highly variable transcript, with Erb-B2 receptor tyrosine kinase 2 (ERBB2) as a prime representative. A novel transcript, designated ERBB2 i14e, was identified for encoding a novel functional protein, and its protein expression was elevated in gallbladder cancer and strongly associated with worse prognosis. With the regulation of splicing factors ESRP1/2, ERBB2 i14e was alternatively spliced from intron 14 and the encoded i14e peptide was proved to facilitate the interaction with ERBB3 and downstream signaling activation of AKT. ERBB2 i14e was inducible and its expression attenuated anti-ERBB2 treatment efficacy in tumor xenografts. Further studies with patient derived xenografts models validated that ERBB2 i14e blockage with antisense oligonucleotide enhanced the tumor sensitivity to trastuzumab and its drug conjugates. Overall, this study provides a gallbladder specific long-read transcriptome profile and discovers a novel mechanism of trastuzumab resistance, thus ultimately devising strategies to improve trastuzumab therapy.

Abstract This study focused on the relationships among gut microbiota, plasma protein ratios, and tuberculosis. Given the unclear causal relationship between gut microbiota and tuberculosis and the scarcity of research on relevant plasma protein ratios in tuberculosis, Mendelian randomization analysis (MR) was employed for in-depth exploration. By analyzing the GWAS data of individuals with European ancestry (the FinnGen dataset included 409,568 controls and 2613 cases), using the two-sample MR method, we focused on evaluating the impact of immunocyte-mediated gut microbiota on tuberculosis and the associations between 2821 plasma protein-to-protein ratios and tuberculosis. Particularly, the mediation effect was emphasized in the exploration. The results showed that 19 gut microbiotas were associated with tuberculosis. An7 indirectly affected tuberculosis through immunocyte (CD4 on CM CD4+), with a masking effect ratio of 0.008, demonstrating immune cells’ mediating role in the association between gut microbiota and tuberculosis. Meanwhile, the MR analysis revealed that 127 plasma protein-to-protein ratios were associated with tuberculosis. In conclusion, this study not only confirmed the impact of immunocyte-mediated gut microbiota on tuberculosis and clarified the mediating mechanism therein but also identified plasma protein-to-protein ratios related to tuberculosis, providing novel and valuable ideas for diagnosing and treating tuberculosis.

Abstract Background This study aimed to explore the clinical and pathological features of patients with diabetic kidney disease (DKD), with and without non-diabetic kidney disease (NDKD), through a retrospective analysis. The objective was to provide clinical insights for accurate identification. Methods A retrospective analysis of 235 patients admitted to the Department of Nephrology at Hangzhou Hospital of Traditional Chinese Medicine was conducted between July 2014 and December 2022. These patients underwent renal biopsy and received a pathology-based diagnosis of DKD. They were categorized into the DKD alone group (93 cases) and the DKD + NDKD group (142 cases). Results In the DKD alone group, gender distribution was even, with ages mainly between 50 and 59 years, and a disease duration of less than 5 years, primarily presenting nodular diabetic glomerulosclerosis. In contrast, the DKD + NDKD group had a higher male incidence, a wider age range, longer disease duration, and prevalent diffuse diabetic glomerulosclerosis. Acute and chronic tubulointerstitial lesions and IgA nephropathy were the predominant types of combined NDKD, accounting for 40.14% and 35.21%, respectively. Clinical correlation analysis revealed associations between glomerular grading, tubulointerstitial lesions, renal arteriolar vitelliform lesions, renal vascular atherosclerosis, and clinical parameters such as 24-hour urine protein, hemoglobin, and urinary specific gravity. Multifactorial logistic regression analysis identified independent factors affecting DKD + NDKD, including body mass index, blood creatinine level, microscopic erythrocyte grade, urinary immunoglobulin G/creatinine ratio, and serum immunoglobulin A. Conclusion The research underscores distinctions in age, gender distribution, disease duration, and renal pathology between DKD alone and DKD + NDKD groups. Additionally, significant discriminative factors including BMI, blood creatinine level, microscopic erythrocyte grade, UIgG/urine creatinine ratio, and serum IgA levels help differentiate DKD from NDKD, thereby enabling personalized treatment approaches. Furthermore, the study highlights the role of RASi as the most commonly used drug in the treatment of both DKD and NDKD, with emerging drugs such as SGLT2 inhibitors showing promising renal protective effects.

Abstract Background As depressed patients often fail to seek help and obtain treatment on time for reasons such as stigma and lack of treatment resources, research on self-management for depressed patients is crucial. This study aimed to explore the factors influencing self-management in depression patients from the perspectives of both patients and psychiatric nurses. Methods Six depression patients and twelve psychiatric nurses were chosen for semi-structured interviews through a purposive sampling method from a tertiary Grade A psychiatric hospital in Shandong Province, China. The group of depressed patients included in the study had a male to female sex ratio of 1:1 with a mean age of 46years. The psychiatric nurse group had a male to female ratio of 1:2 with a mean age of 42.42 years. We used descriptive qualitative research techniques. Nvivo 12.0 software was used for the data management and analysis using thematic analysis. Results The factors influencing the self-management of depression patients were summarized into three themes and eight sub-themes: disease impact (symptoms, stigma), the degree of symptom control (medication adherence, depression’s cognitive status, its treatment and rehabilitation as well as additional factors), and support (self-efficacy, external support). Conclusions This study found that multiple factors influence the self-management of depression patients, including disease impact, the degree of symptom control, and support. In addition to helping patients integrate social resources and seek social support, medical staff should also pay attention to changes in the patient’s condition and disease control. Moreover, they should help patients increase their self-efficacy and enhance their self-management abilities through health education and other means. Clinical trial number Not applicable.

Abstract Background Due to the lack of effective treatment options, the prognosis of patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor. Although chimeric antigen receptor (CAR)-T-cell therapy has shown promising effects in acute lymphoblastic leukemia (ALL) and lymphoma, its application in R/R AML is limited by “off-target” effects, which lead to severe bone marrow suppression and limit its clinical application. CAR-natural killer (NK) cells not only exhibit antitumor effects but also demonstrate increased safety and universality. We have developed a new CAR construct that targets CD33 and modified NK cells, specifically eliminating AML cells while reducing severe side effects on stem cells. Methods The CD33-targeting domain was selected by CAR-T cells, and this optimized CAR construct was subsequently transduced into umbilical cord-derived NK cells via a retroviral vector. Preclinical efficacy and safety studies were conducted both in vitro and in vivo. Ten eligible patients with R/R AML aged 18–65 years who received one or more infusions of anti-CD33 CAR-NK cells following the preconditioning regimen were enrolled. We assessed the response rates and treatment-related side effects post-infusion, while also documenting the long-term efficacy of the therapy. Results The CD33 sequence was selected on the basis of its antitumor efficacy and safety in CAR-T-cell studies conducted both in vitro and in vivo. CD33 CAR-NK cells demonstrated efficacy comparable to that of CD33 CAR-T cells but showed limited toxicity to hematopoietic stem cells (HSCs). Ten patients, with a median of five prior lines of treatment, completed the efficacy evaluation (range, 3–8). No grade 3–4 adverse events were observed, except bone marrow suppression, which was relieved within one month. No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) were reported following CAR-NK cell infusion. Only one patient experienced grade 2 cytokine release syndrome (CRS) and presented with persistent fever. By day 28, six of ten patients had achieved minimal residual disease (MRD)-negative complete remission. Conclusions Our preclinical and clinical data demonstrated the primary efficacy and safety of CD33 CAR-NK cells for patients with R/R AML. Expanded samples and longer follow-up periods are needed to provide further efficacy data. Trial registration NCT05008575 ( https://clinicaltrials.gov/study/NCT05008575 ).

Abstract Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cys redox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteins modified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved in immunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasing with age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cys modifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signaling pathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidative stress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. This work decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulators of oxidative stress and redox signaling.

Abstract Background Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications. Methods Here, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications. Results We observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08–0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18–7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19–0.85); HR = 2.52, 95% CI (1.14–5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42–11.44); HR = 0.18, 95% CI (0.07–0.43), respectively). Conclusions Our findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients.

Abstract. Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.

With thermoplastic polyurethane (TPU) limit spring extruder head as the research object, the relevant material parameters of the constitutive equation of raw TPU were obtained by the rheological property test. Numerical simulation of the flow process of TPU in the extrusion runner was carried out based on the software Polyflow, and in the meanwhile, a second-order regression model of standard deviation of velocity (Sd) at the exit of the forming section was established by response surface method, and the influence law of extrusion runner structure on the melt flow uniformity of TPU was explored. The results showed that after optimization the structure parameters of extrusion runner were as follows: the length of the forming section of 165 mm, the expansion angle of 25°, and the number of diverter shuttles of 6. After optimization the predicted value of Sd at the exit of the forming section of extrusion runner was 0.531 m/s and was only 0.188% different from the actual value of Sd(0.532 m/s), which indicated that the model was more accurate, and the model could be used for the prediction and optimization of the structure parameters of extrusion runner.

Genetic algorithm (GA) and particle swarm optimization (PSO) were used to optimize the back propagation（BP） neural network to establish the prediction model of Mooney viscosity of ethylene-propylene-diene monomer (EPDM) compound, and the error of the prediction results was compared and analyzed. The results showed that the predicted va-lues of the BP neural network model optimized by the two algorithms all maintained a high degree of fit and correlation with the measured values. Compared with the single BP neural network, the accuracy of the GA-BP neural network prediction model increased by 58.9% and the accuracy of the PSO-BP model increased by 3.57%, which indicated that the prediction accuracy of the prediction model optimized by the two algorithms, especially the BP neural network prediction model optimized by GA, improved significantly Mooney viscosity of EPDM compound.

Abstract Objective The aim of this study was to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of patients with immunoglobulin A nephropathy (IgAN). Methods A retrospective analysis of clinicopathological data from 774 patients with primary IgAN at Hangzhou Hospital of Traditional Chinese Medicine between January 1, 2016, and December 31, 2018, was conducted. Patients were categorized into end-event and non-end-event groups according to whether they reached the renal composite endpoint, defined as a ≥ 50% decline in eGFR or progression to end-stage renal disease (ESRD). Risk factors for adverse renal outcomes were evaluated via univariate and multivariate Cox regression models. Patients were further divided into three groups on the basis of IgM deposition levels in the glomerular mesangial area: IgM-negative, low (IF

Abstract Background This study evaluates the effectiveness of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, typically applied to singleton pregnancies, in managing gestational diabetes mellitus (GDM) in twin pregnancies. Focusing on a Chinese cohort, it contrasts the clinical outcomes and complications in twin pregnancies with and without GDM. Methods We conducted a retrospective cohort study at our hospital from January 2019 to December 2021, including all twin deliveries except those before 28 weeks of gestation, with prior diabetes, or unknown GDM status. GDM was diagnosed using a 75 g oral glucose tolerance test based on the IADPSG criteria, and management involved dietary or insulin interventions. We assessed outcomes such as hypertensive disorders (gestational hypertension, preeclampsia, and eclampsia), membrane rupture, preterm birth, small for gestational age (SGA), large for gestational age (LGA), and neonatal intensive care unit (NICU) admissions. Results Among 1003 twin pregnancies, 21.7% had GDM, with 11.5% receiving insulin. GDM was associated with older maternal age, higher BMI, and a family history of diabetes. Pregnant women with GDM had lower weekly weight gain (0.44 kg/week vs. 0.58 kg/week, p

Abstract Background Influenza is a major cause of morbidity and mortality. Influenza A virus (IAV) is one of the most important pathogens causing influenza and often causes global pandemics due to its tendency to mutate. We aim to use epidemiology based on wastewater and respiratory specimens to understand the occurrence of influenza A virus infections in Taiyuan City. Methods A retrospective epidemiology surveillance was carried out at the First Hospital of Shanxi Medical University (FHSMU) and five wastewater treatment plants (WTPs) in Taiyuan city from 2023 to 2024. Reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect influenza A viruses in wastewater and respiratory specimens. High-throughput whole genome sequencing was performed on 17 strains obtained in this study, and subsequent analyses included characterization, phylogenetic construction, amino acid mutation analysis, and antigenic structural variability assessment. Results 520 wastewater samples and 1,203 throat swab samples were collected. We detected RNA concentration from pH1N1 and H3N2 viruses in wastewater and got 17 genome sequences (5 of pH1N1 and 12 of H3N2) in respiratory specimens. Whole-genome sequencing showed co-prevalence of pH1N1 viruses in the branches of 6B.1 A.5a.2a.1 and H3N2 viruses in the branches of 3 C.2a1b.2a.2a.3a.a in Taiyuan from 2023 to 2024. Moreover, a HA mutation (N138D), predicted to be of high phenotypic consequence, was found in 8 Taiyuan H3N2 sequences. Conclusion This study highlights the predominant presence of pH1N1 and H3N2 strains in Taiyuan. The analysis also identified amino acid site variations in the HA antigenic epitopes in H3N2 strains, which may contribute to immune escape.

Abstract To explore the formula for calculating the haemoglobin glycation index (HGI) in an appropriate Chinese population. Evaluating the applicability of the HGI calculation formula proposed by Hempe et al. in the Chinese population; according to the data from CHARLS 2011, 10,587 self-reported nondiabetics aged 20 years and older were selected as the study subjects, regression equations were constructed to fit the linear relationship between HbA1c and FPG in the population, and the profile characteristics of the resultant population were analysed. The standardized HGI formula put forth by Hempe and colleagues has been found unsuitable for application to the Chinese population. Leveraging CHARLS dataset, we derive a novel HGI calculation formula tailored to the Chinese demographic: HGI = Measured HbA1c-Predicted HbA1c, where Predicted HbA1c = 0.011×FPG + 4.032. We found statistically significant differences in HGI among obese individuals; those with higher waist circumference, total cholesterol levels, LDL levels, diastolic blood pressure and those with lower HDL levels. The HGI calculation formula proposed using CHARLS data is more applicable to the Chinese population and can be used as a standardised HGI to Chinese.

Abstract Wheat (Triticum aestivum L.) is one of the most significant crops and the backbone of food security worldwide. However, low wheat production remains a substantial concern in global agricultural systems. It can be attributed to several factors, including adverse climatic conditions, plant disease and poor soil quality. Recent efforts have explored bioinoculant applications as a promising approach to enhance wheat yield, trying to mitigate constraints essential for future wheat production and global food security. This study tested talc powder, wheat biochar, sugarcane bagasse biochar, and farmyard manure as carriers with two endophytic bacterial strains, Burkholderia phytofirmans PsJN and Bacillus spp. MN54 was applied to three wheat varieties (Ujala-16, Zincol-16, and Fathejang-16). The data was recorded at the seedling and maturity growth stages of plants. A pot experiment revealed significant improvements in plant growth following bioinoculant application compared to controls. Notably, the combination of sugarcane bagasse biochar with Bacillus sp. MN54 exhibited the most pronounced effects, promoting internodal length, spike length, tiller number per plant, grain yield per plant, and spikelets per spike. Additionally, talc powder with Bacillus sp. MN54 increased peduncle length, tiller number per plant, and spike length in Fathejang-16. These findings offer valuable insights into optimizing bioinoculant formulations for improved agricultural practices, adapting to climate change, and contributing to ensuring global food security.

In order to solve the problems of high content of higher alcohols in traditional Xiaoqu Huangjiu and easy occurrence of drinker's "headache", Saccharomyces cerevisiae with low-yield higher alcohols, Saccharomycopsis fibuligera, and Wickerhamomyces anomalus were mixed to prepare compound yeast agents. Using Huangjiu fermented with traditional Xiaoqu as control group, the physicochemical indexes, volatile flavor substances and sensory quality of Huangjiu fermented with compound yeast agents were investigated. The results showed that comparing with the control droup, the alcohol content (13.66%vol) of Huangjiu fermented with compound yeast agents had no significant difference, but the total sugar content (301.54 g/L) was increased by 7.5%. 5 volatile flavor compounds were increased, namely ethyl isovalerate, 3-(methylthio) propionaldehyde, furfural, 5-methylfurfural and 2,3-butanedione. The total ester content (247.49 mg/L) was increased by 5 times, the total higher alcohol content (420.09 mg/L) was decreased by 15.9%, the bitter amino acid content was decreased by 33.1%, and the sensory score (75 points) was increased by 17%.

Abstract The detection of gravitational waves has ushered in a new era of observing the universe. Quantum resource advantages offer significant enhancements to the sensitivity of gravitational wave observatories. While squeezed states for ground-based gravitational wave detection have received marked attention, the generation of squeezed states suitable for mid-to-low-frequency detection has remained unexplored. To address the gap in squeezed state optical fields at ultra-low frequencies, we report on the first direct observation of a squeezed vacuum field until Fourier frequency of 4 millihertz with the quantum noise reduction of up to 8.0 dB, by the employment of a multiple noise suppression scheme. Our work provides quantum resources for future gravitational wave observatories, facilitating the development of quantum precision measurement.

Abstract The asymmetric Büchner reaction and related arene cyclopropanations represent one type of the powerful methods for enantioselective dearomatization. However, examples of asymmetric Büchner reactions via a non-diazo approach are quite scarce, and the related arene cyclopropanation based on alkynes has not been reported. Herein, we disclose an asymmetric Büchner reaction and the related arene cyclopropanation by copper-catalyzed controllable cyclization of N-propargyl ynamides via vinyl cation intermediates, leading to chiral tricycle-fused cycloheptatrienes and benzonorcaradienes in high yields and enantioselectivities. Importantly, this protocol represents an asymmetric arene cyclopropanation reaction of alkynes and an asymmetric Büchner reaction based on vinyl cations.

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Water rights trading within a market economy has emerged as an effective solution for enhancing water use efficiency and addressing water scarcity. However, the development of a pricing mechanism that accounts for the spatial heterogeneity of water resources remains a critical challenge. This study proposes an “initial-engineering-end use” quasi-market pricing mechanism based on empirical research of cross-regional water rights trading in Pingxiang, Jiangxi, China. The mechanism comprises three stages, each designed to address specific risks. To support these stages, data from field studies is used to calibrate three unique pricing models: the stochastic differential game, incomplete contract theory, and the Nash-bargaining model. We analyze the interactions among equilibrium water prices across these stages to explore the cascade effects. In Pingxiang, the local government has successfully adopted and implemented this mechanism. Empirical results and practical applications reveal several key findings. (1) A comparative analysis of national governance across different countries indicates that the quasi-market pricing mechanism effectively determines end use water prices in China. (2) Initial corporate and government investments mitigate trading risks and enhance stability. (3) Overlooking ecosystem service value leads to the undervaluation of initial and end use water prices. (4) Practical applications of the proposed mechanism in Inner Mongolia, China, and the Murray-Darling Basin, Australia, demonstrate that end use water prices are generally higher in water-scarce regions. Overall, this study provides a practical and adaptable approach for pricing cross-regional water rights trading, applicable to both water-rich and water-scarce regions globally.

Two-dimensional (2D) MoTe2 shows great potential for future semiconductor devices, but the lab-to-fab transition is still in its preliminary stage due to the constraints in the crystal growth level. Currently, the chemical vapor deposition growth of 2D MoTe2 primarily relies on the tellurization process of Mo-source precursor (MSP). However, the target product 2H-MoTe2 from Mo precursor suffers from long growth time and suboptimal crystal quality, and MoOx precursor confronts the dilemma of unclear growth mechanism and inconsistent growth products. Here, we developed magnetron-sputtered MoO3 film for fast and high-mobility 2H-MoTe2 growth. The solid-to-solid phase transition growth mechanism of 2D MoTe2 from Mo and MoOx precursor was first experimentally unified, and the effect mechanism of MSPs on 2D MoTe2 growth was systematically elucidated. Compared with Mo and MoO2, the MoO3 precursor has the least Mo-unit lattice deformation and exhibits the optimal crystal quality of growth products. Meanwhile, the lowest Gibbs free energy change of the chemical reaction results in an impressive 2H-MoTe2 growth rate of 8.07 μm/min. The constructed 2H-MoTe2 field-effect transistor array from MoO3 precursor showcases record-high hole mobility of 85 cm2·V-1·s-1, competitive on-off ratio of 3×104, and outstanding uniformity. This scalable method not only offers efficiency but also aligns with industry standards, making it a promising guideline for diverse 2D material preparation towards real-world applications.

Atrogin-1, a muscle-specific ubiquitin ligase, is integral to the regulation of protein degradation and plays a pivotal role in the targeted degradation of critical muscle signaling proteins, which can lead to skeletal muscle dysfunction. High salt stress is known to induce muscle atrophy and alter the physical and chemical properties of muscle in cultured fish. Conversely, an optimal salinity level can enhance muscle quality. The Russian sturgeon (Acipenser gueldenstaedtii), an anadromous species of significant economic value, is potentially adaptable to brackish water environments, yet the underlying regulatory mechanisms remain elusive. To elucidate the regulatory mechanism of Atrogin-1 in response to high salt stress in Russian sturgeon, we conducted cDNA cloning and expression analysis. The cDNA encoding the Russian sturgeon protein Atrogin-1 was successfully cloned, comprising 1472 bp and encoding 353 amino acid residues (with an open reading frame of 1062 bp). Utilizing the sequence of Russian sturgeon atrogin-1, we designed novel primers and a specific anti-peptide antibody for our study, confirming that atrogin-1 is selectively expressed in skeletal muscle and heart tissues. The sturgeons were then allocated into four experimental groups for salt stress exposure; one control group was maintained in freshwater, while the others were subjected to salinities of 8 ‰, 16 ‰, and 24 ‰, respectively. Quantitative PCR (qPCR) and western blot analysis were employed to assess Atrogin-1 expression levels under high salt stress. A significant upregulation of atrogin-1 mRNA was observed at salinities of 16 ‰ and 24 ‰ compared to the control group. Similarly, protein expression levels of Atrogin-1 were markedly elevated under the same salinity conditions. Our findings indicate that the modulation of Atrogin-1 expression is a sensitive indicator of the response to high salt stress. This research is anticipated to inform aquaculture practices and shed light on the selection of germplasm resources for the development of salt-tolerant Russian sturgeon strains.

Abstract Aquaculture generates less greenhouse gas emissions compared to other agriculture practices due to its limited land‐use changes, improved feed conversion rates, and reduced methane emissions from animals' digestive systems. The aquaculture carbon emissions come from various production stages, including feed production, farm operations, processing, transportation, and so forth. This review illustrates the theories, calculation methods, and practical applications of the carbon footprint in fisheries and aquaculture, as well as the challenges and strategies for emission reduction. The factors influencing the carbon footprint of fishing and manufacturing aquaculture are also discussed. Further research should focus on refining carbon footprint assessment techniques, promoting green technologies and sustainable aquaculture practices. Managing aquaculture's carbon footprint though is crucial for mitigating environmental impacts and supporting sustainable development.

ABSTRACT Gut microbiota crucially affects metabolism and health. Hycleus cichorii Linnaeus has been listed as a medicinal insect in the Pharmacopeia of the People's Republic of China due to the presence of cantharidin, which has a curative effect on many cancers and skin diseases. In order to analyze the effects of dietary habits and gender on the diversity and composition of gut microbiota in H. cichorii and provide a basis for an artificial diet, in this study, the full‐length 16S rRNA sequencing technology was used to analyze the gut microbiota of 35 H. cichorii adults, including wild female adults (WFA), wild male adults (WMA), female adults fed with luffa flowers (LFA), male adults fed with luffa flowers (LMA), female adults fed with artificial diet (AFA), and male adults fed with artificial diet (AMA). The results displayed that the major bacterial phyla present in the gut microbiota of the H. cichorii were Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, Teneriicutes, and Actinobacteria. The major bacterial genera were Lactococcus, Lactobacillus, Enterococcus, Ralstonia, Sebaldella, Dysgonomonas, Spiroplasma, Weissella, Klebsiella, and Serratia. Food habits had a significant effect on the diversity and composition of gut microbiota in H. cichorii, whereas gender did not exhibit a remarkable impact on the diversity and composition of gut microbiota. The artificially fed group of H. cichorii had more beneficial microorganisms in the intestine and higher food utilization efficiency. These results provide a basis for subsequent examination of gut microbiota in H. cichorii or other Coleoptera insects, as well as the artificial rearing of blister beetles.

Echo training represents the primary mechanism through which rain bands precipitate extreme rainfall events. This study employed a combination of observational data and ERA5 reanalysis data to examine two instances of “echo training” that occurred following the landfall of typhoons Soudelor (2015, Process 1) and Fitow (2013, Process 2) in China. The findings indicate notable differences in the environmental background, characteristics, and the organization of convective rainbands between these two “echo training” processes. During Process 1, a well-developed convective system accompanied by a deeper boundary layer convergence between the cold pool and the easterly flow is observed. The presence of baroclinic structures permits the uplift of warm and humid air from the ocean that facilitated by the solenoidal term. During this period, the dispersion queues on both sides of the rainband contributed to the strengthening of convection and enabled convective cells to traverse the length of the rainband for an extended duration. In Process 2, the comparative wind between the easterly flow and the weak cold pool resulted in relatively shallow convergence, while the warm rain process dominated. The continuous generation of new cells occurred at the eastern boundary of the rainband, while dissipation occurred at the western boundary, resulting in persistent heavy rainfall for the covered area.

We prove that for a GNS-symmetric quantum Markov semigroup, the complete modified logarithmic Sobolev constant is bounded by the inverse of its complete positivity mixing time. For classical Markov semigroups, this gives a short proof that every sub-Laplacian of a Hörmander system on a compact manifold satisfies a modified log-Sobolev inequality uniformly for scalar and matrix-valued functions. For quantum Markov semigroups, we show that the complete modified logarithmic Sobolev constant is comparable to the spectral gap up to the logarithm of the dimension. Such estimates are asymptotically tight for a quantum birth-death process. Our results, along with the consequence of concentration inequalities, are applicable to GNS-symmetric semigroups on general von Neumann algebras.

Floods are the most common natural disaster worldwide and significantly impact human society and ecosystems. Therefore, research on flood risk assessment and zoning is crucial. Constructing polders in river deltas changes flood formation mechanisms and processes, impacting flood risk. This study proposes an integrated flood risk assessment model combining index-based evaluation, the best worst method, the projection pursuit model optimized by CPSGA, game theory, and the hydrological-hydrodynamic model, which was implemented in the Qinhuai River Basin to assess and zoning the flood risk. The results show that the integrated model allows an excellent flood risk assessment under different scenarios. Spatially, the high and highest-risk areas are mainly distributed in the urban areas, concentrated in densely populated and economically developed areas. Compared with the natural stream (without the PFCM), the high and highest risk areas decreased 0.06, 0.04, and 0.58 km2 for 50 %, 30 %, and 3 % frequency flood scales, respectively. The proposed integrated model characterizes the spatial distribution of flood risk, understands the impact of polders on flood risk, and provides a reference for implementing integrated and efficient flood risk management.

Soil salinization poses a significant ecological and environmental challenge both in China and across the globe. Plant growth-promoting rhizobacteria (PGPR) enhance plants’ resilience against biotic and abiotic stresses, thereby playing a vital role in soil improvement and vegetation restoration efforts. PGPR assist plants in thriving under salt stress by modifying plant physiology, enhancing nutrient absorption, and synthesizing plant hormones. However, the mechanisms through which PGPR regulate the contents of carbon (C) and nitrogen (N), and biomass allocation of desert plant in response to salt stress is still unclear. This study explores the impact of PGPR on biomass allocation, C, and N contents of R. soongorica seedlings through a pot experiment. Strains P6, N20, and N21, identified as Enterobacter, were isolated from the rhizosphere of R. soongorica, and they exhibited various beneficial traits such as indole-3-acetic acid (IAA) production, phosphate solubilization, nitrogen fixation, and tolerance to up to 8% NaCl stress. We found that under NaCl stress, R. soongorica seedlings exhibit significant reductions in plant height, basal diameter, and root surface area (P

Neuromedin B (NMB) has potentially great impacts on the development of cardiovascular diseases by promoting hypertensive and sympatho-excitation effects. However, studies regarding the NMB function in paraventricular nucleus (PVN) are lacking. With selective neuromedin B receptor (NMBR) antagonist, BIM-23127, we aim to determine whether the blockade of NMB function in PVN could alleviate central inflammation and attenuate hypertensive responses. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were chronically infused with BIM-23127 in the PVN for 6 weeks. Mean arterial pressure (MAP) was assessed with tail cuff and electrophysiological acquisition systems. PVN tissues were collected to analyze expressions of Fra-LI, inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10, and IL-4), renin-angiotensin system (angiotensin-converting enzyme (ACE), ACE2, and AT1-reporter (AT1-R)) and oxidative stress (reactive oxygen species (ROS), superoxide dismutase (SOD)1, NADPH oxidase (NOX)2, and NOX4). ELISA was used to detect inflammation indices, norepinephrine (NE), and nuclear factor κB (NF-κB) p65 in plasma and PVN tissue homogenate. Compared to WKY, SHR exhibited higher mean arterial pressure (MAP), plasma NE, and pro-inflammatory cytokines (PICs). Higher PVN levels of Fra-LI, PICs, ACE, AT1-R, ROS, NOX2, NOX4, and NF-κB p65, while lower central levels of anti-inflammatory cytokines (AICs), ACE2, and SOD1 were observed in SHR. Administration of BIM-23127 in PVN reversed all these changes in SHR. In SHR, blockade of NMBR in the PVN inhibited sympatho-excitation and attenuated hypertensive response. The attenuation mechanism may involve reducing inflammation and the RAS/ROS/ NF-κB pathways in PVN.

Background: Given the wide application of TNF-α inhibitors for the treatment of rheumatoid arthritis (RA), more active tuberculosis cases have been reported in patients with RA. This meta-analysis was performed to evaluate the risk of active tuberculosis (TB) in RA patients undergoing treatment with TNF-α inhibitors. Methods and Results: Thirty randomized controlled trials (RCTs), comprising 18,640 patients, were included in the meta-analysis after searching PubMed, EMBASE, and Web of Science databases. Overall, there was a higher risk of active TB in patients with RA undergoing treatment with TNF-α inhibitors than in the control group (Peto OR, 2.57; 95%CI, 1.42-4.66; P=0.002). Conclusion: Our meta-analysis showed that RA patients treated with TNF-α inhibitors had a higher risk of developing active TB. Tuberculosis screening should be performed before and during the use of TNF-α inhibitors in these patients.

Abstract Background The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. Materials and methods Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. Results Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. Conclusions Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease.

Abstract Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1αR698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-mediated HIF-1αR698 citrullination and cancer development. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression.

Abstract Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline’s additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures. Graphical Abstract