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Abstract Background We aimed to gain insight into the response mechanism of alfalfa (Medicago sativa) to drought stress by recognizing and analyzing drought-responsive genes in the roots of different root types of alfalfa. The rhizomatous-rooted M. sativa cv.‘Qingshui’ (QS), tap-rooted M. sativa cv.‘Longdong’ (LD), and creeping-rooted M. varia cv. ‘Gongnong No. 4’ (GN) were used to analyze the transcriptome information and physiological characteristics of the root systems of the cultivars under simulated drought stress using PEG-6000. Results It was found that aridity caused a significant increase in the content of osmotic stress substances and antioxidant enzyme activity. The content of malondialdehyde (MDA) in QS was lower than that in LD and GN under moisture stress, indicating a stronger accumulation capacity of osmotic regulatory substances. Based on sequencing results, 14,475, 9336, and 9243 upregulated DEGs from QS, LD, and GN were annotated into 26, 29, and 28 transcription factor families, respectively. QS showed more DEGs than LD and GN. KEGG enrichment analysis identified that DEGs were significantly enriched in metabolic pathways such as amino acid biosynthesis, phenylpropanoid biosynthesis, plant hormone signaling transduction, and MAPK pathways. This suggests a strong correlation between these pathways and drought stress. The results also show that genes associated with ABA hormone signaling (MS. gene93372, MS. gene072046, and MS. gene012975) are crucial for plant’s adaptation to drought stress. Conclusions These genes, such as serine/threonine protein kinases and abscisic acid receptors, play a crucial role in plant hormone signaling and MAPK pathways. They could serve as potential candidate genes for drought resistance research in alfalfa, providing a molecular foundation for studying drought resistance. Graphical Abstract

Objective: To reveal the distribution characteristics and demographic factors of traditional Chinese medicine (TCM) constitution among elderly individuals in China. Methods: Elderly individuals from seven regions in China were selected as samples in this study using a multistage cluster random sampling method. The basic information questionnaire and Constitution in Chinese Medicine Questionnaire (Elderly Edition) were used. Descriptive statistical analysis, chi-squared tests, and binary logistic regression analysis were used. Results: The single balanced constitution (BC) accounted for 23.9%. The results of the major TCM constitution types showed that BC (43.2%) accounted for the largest proportion and unbalanced constitutions ranged from 0.9% to 15.7%. East China region (odds ratio [OR] = 2.097; 95% confidence interval [CI], 1.912 to 2.301), married status (OR = 1.341; 95% CI, 1.235 to 1.457), and managers (OR = 1.254; 95% CI, 1.044 to 1.505) were significantly associated with BC. Age >70 years was associated with qi-deficiency constitution and blood stasis constitution (BSC). Female sex was significantly associated with yang-deficiency constitution (OR = 1.646; 95% CI, 1.52 to 1.782). Southwest region was significantly associated with phlegm-dampness constitution (OR = 1.809; 95% CI, 1.569 to 2.086). North China region was significantly associated with inherited special constitution (OR = 2.521; 95% CI, 1.569 to 4.05). South China region (OR = 2.741; 95% CI, 1.997 to 1.3.763), Central China region (OR = 8.889; 95% CI, 6.676 to 11.835), senior middle school education (OR = 2.442; 95% CI, 1.932 to 3.088), and managers (OR = 1.804; 95% CI, 1.21 to 2.69) were significantly associated with BSC. Conclusions: This study defined the distribution characteristics and demographic factors of TCM constitution in the elderly population. Adjusting and improving unbalanced constitutions, which are correlated with diseases, can help promote healthy aging through the scientific management of these demographic factors.

Abstract Background Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. Results We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. Conclusion Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

Abstract 5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-β-galactosidase (SA-β-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

To predict renewable energy sources such as solar power in microgrids more accurately, a hybrid power prediction method is presented in this paper. First, the self-attention mechanism is introduced based on a bidirectional gated recurrent neural network (BiGRU) to explore the time-series characteristics of solar power output and consider the influence of different time nodes on the prediction results. Subsequently, an improved quantum particle swarm optimization (QPSO) algorithm is proposed to optimize the hyperparameters of the combined prediction model. The final proposed LQPSO-BiGRU-self-attention hybrid model can predict solar power more effectively. In addition, considering the coordinated utilization of various energy sources such as electricity, hydrogen, and renewable energy, a multi-objective optimization model that considers both economic and environmental costs was constructed. A two-stage adaptive multi- objective quantum particle swarm optimization algorithm aided by a Lévy flight, named MO-LQPSO, was proposed for the comprehensive optimal scheduling of a multi-energy microgrid system. This algorithm effectively balances the global and local search capabilities and enhances the solution of complex nonlinear problems. The effectiveness and superiority of the proposed scheme are verified through comparative simulations.

Abstract Background Presently, the majority of investigations primarily evaluate the correlation between triglyceride-glucose index (TyGI) with lung diseases, such as asthma. However, they did not delve into the correlation between TyGI and inflammatory responses related to the disease. Few studies have explored the association between TyGI and blood eosinophil count (BEOC). Thus, National Health and Nutrition Examination Survey (NHANES) data were used in this study to evaluate the correlation between TyGI and BEOC in individuals with asthma. Methods This study investigated 3902 individuals with asthma. Linear regression analysis was performed to investigate the association between TyGI and BEOC in patients with asthma. Subsequently, the GAM and threshold effect models were used to validate the presence of either a nonlinear or linear association between TyGI and BEOC. Finally, stratified analyses were conducted to ascertain the correlations between different subgroups. Results Four linear regression models confirmed a positive linear correlation between TyGI and BEOC in patients with asthma. In Model D, which controlled for all covariates, BEOC increased by 12.44 cells/uL for every extra unit of TyGI. The GAM and threshold effect models further verified the positive linear correlation between TyGI and BEOC. The XGBoost model indicated that the six most significant variables influencing BEOC, in order of relative importance, were age, cholesterol level, body mass index (BMI), poverty-to-income ratio (PIR), BNEUC, and TyGI. Conclusions In patients with asthma, the study discovered a linear positive correlation between TyGI and BEOC. This indicates a potential connection between TyGI and alterations in the immune status of individuals with asthma, which may help detect abnormalities in a timely manner and provide a reference for clinical decision-making. This study offers fresh insights for the future exploration of the management and treatment of asthma.

Paris polyphylla is an important traditional medicinal plant of the Himalayan region. It is extensively used for the production of natural steroidal saponins and flavonoids. Although seed dormancy of wild plants can be broken to be artificially maintained and regenerated through micropropagation in the laboratory, the success of secondary metabolite production in higher quantities and the synthesis of superior plant metabolites have been very limited. In this study, we present differential metabolic profiling of P. polyphylla plants maintained for 8 years in natural and greenhouse conditions. Untargeted profiling of the metabolites through ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), followed by statistical analysis, identified secondary metabolites that were enriched in the naturally occurring plant roots compared with the greenhouse plant roots. A multivariate statistical analysis revealed the differential distribution of the compounds between the two groups. Overall, we identified 1,182 secondary metabolites, with 116 metabolites being differentially upregulated and 256 metabolites being downregulated. Moreover, 810 metabolites showed no significant variation under both growing conditions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the naturally forest-grown P. polyphylla plants were significantly enriched in steroidal saponins, lipids, vitamins, flavonoids, and flavonols. An analysis of the top 10 differentially upregulated secondary metabolites indicated a significantly enriched quantity of spirost-5-en-3,12-diol and kaempferol synthesis pathways, which are known to reduce the effect of free radicals scavengers inside the cell. In addition, veratramine alkaloids were also enriched under natural conditions. Our findings indicated that naturally maintained P. polyphylla plants are suitable for the extraction of medicinally important compounds. Our study established a causal relationship between the metabolic composition of the roots and their natural growth condition. This study highlighted the importance of environmental conditions in the biosynthesis of secondary metabolites of plants.

ABSTRACT Toxoplasma gondii bradyzoites play a critical role in pathology due to their long-term persistence in intermediate hosts and their potential to reactivate, resulting in severe diseases in immunocompromised individuals. Currently, there is no effective treatment for eliminating bradyzoites. Hence, better in vitro models of T. gondii bradyzoite development would facilitate identification of therapeutic targets for bradyzoites. Herein, we characterized a natural isolate of T. gondii, called Tg68, which showed slower in vitro replication of tachyzoites, and permissive bradyzoite development under stress conditions in vitro. Transcriptional analysis revealed constitutive expression in Tg68 tachyzoites of the key regulators of bradyzoite development including BFD1, BFD2, and several AP2 factors. Consistent with this finding, Tg68 tachyzoites expressed high levels of bradyzoite-specific genes including BAG1, ENO1, and LDH2. Moreover, after stress-induced differentiation, Tg68 bradyzoites exhibited gene expression profiles of mature bradyzoites, even at early time points. These data suggest that Tg68 tachyzoites exist in a pre-bradyzoite stage primed to readily develop into mature bradyzoites under stress conditions in vitro. Tg68 presents a novel model for differentiation in vitro that will serve as a useful tool for the investigation of bradyzoite biology and the development of therapeutics.IMPORTANCEToxoplasma gondii is a widespread protozoan that chronically infects ~30% of the world’s population. T. gondii can differentiate between the fast-growing life stage that causes acute infection and the slow-growing stage that persists in the host for extended periods of time. The slow-growing stage cannot be eliminated by the host immune response or currently known antiparasitic drugs. Studies on the slow-growing stage have been limited due to the limitations of in vivo experiments and the challenges of in vitro manipulation. Here, we characterize a natural isolate of T. gondii, which constitutively expresses factors that drive development and that is permissive to convert to the slow-growing stage under stress conditions in vitro. The strain presents a novel in vitro model for studying the chronic phase of toxoplasmosis and identifying new therapeutic treatments for chronic infections.

ABSTRACT: The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

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Streptococcus suis (S. suis) is an important swine bacterial pathogen and causes human infections, leading to a wide range of diseases. However, the role of 5’-nucleotidases in its virulence remains to be fully elucidated. Herein, we identified four cell wall-anchored 5’-nucleotidases (Snts) within S. suis, named SntA, SntB, SntC, and SntD, each displaying similar domains yet exhibiting low sequence homology. The malachite green reagent and HPLC assays demonstrated that these recombinant enzymes are capable of hydrolysing ATP, ADP, and AMP into adenosine (Ado), with the hierarchy of catalytic efficiency being SntC>SntB>SntA>SntD. Moreover, comprehensive enzymatic activity assays illustrated slight variances in substrate specificity, pH tolerance, and metal ion requirements, yet highlighted a conserved substrate-binding pocket, His–Asp catalytic dyad, metal, and phosphate-binding sites across Snts, with the exception of SntA. Through bactericidal assays and murine infection assays involving in site-mutagenesis strains, it was demonstrated that SntB and SntC collaboratively enhance bacterial survivability within whole blood and polymorphonuclear leukocytes (PMNs) via the Ado-A2aR pathway in vitro, and within murine blood and organs in vivo. This suggests a direct correlation between enzymatic activity and enhancement of bacterial survival and virulence. Collectively, S. suis 5’-nucleotidases additively contribute to the generation of adenosine, influencing susceptibility within blood and PMNs, and enhancing survival within blood and organs in vivo. This elucidation of their integral functions in the pathogenic process of S. suis not only enhances our comprehension of bacterial virulence mechanisms, but also illuminates new avenues for therapeutic intervention aimed at curbing S. suis infections.

ABSTRACTFine-scale population estimation (FPE) is crucial for urban management. After training, the bottom-up FPE models can be applied independently of census data. However, given the lack of real fine-scale population data, the existing bottom-up methods typically apply models trained on coarse-grained census data to FPE directly, causing estimation bias induced by scale effects. Traffic analysis zones (TAZs) balance geo-semantics and fine granularity, but their potential as population analysis units has not been fully exploited. Hence, we developed a weakly-supervised TAZ-scale bottom-up population estimation method (WSTP). Specifically, to mitigate scale effects, the weakly-supervised training procedure involves fine-scale feature input, model prediction, spatial aggregation, and coarse-scale supervision is designed to ensure that WSTP consistently focuses on FPE throughout the training and prediction phases. To enable weakly-supervised training using census data, we treated TAZs as graph nodes and designed a Spatial Aggregation Layer to aggregate TAZ-scale population predictions into communities. Given the diverse distribution patterns across age groups, we decomposed the FPE task by age groups. The experiments showed that WSTP significantly outperformed the baselines with R2 values of 0.821 and 0.785 at the community and TAZ scales, respectively, indicating that WSTP can mitigate scale effects and produce high-resolution, accurate population data.

ABSTRACTStreptococcus suis (S. suis), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in S. suis pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in S. suis, SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the ΔsspA-1, ΔsspA-1, and ΔsspA-1/2 mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and in vivo colonization compared to the parental strain SC-19. Critical insights from the murine and Galleria mellonella larva infection models further underscore the significance of sspA-1 in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in S. suis immune evasion and the pathogenesis.

Summary: Myeloablative pre-conditioning facilitates the differentiation of transplanted hematopoietic stem and progenitor cells (HSPCs). However, the factors in the stress environment that regulate HSPC behavior remain elusive. Here, we investigated the mechanisms that shaped the cell fates of transplanted murine multipotent progenitors (MPPs) expressing the Fms-related receptor tyrosine kinase 3 gene (Flt3). Using lineage tracing, clonal analysis, and single-cell RNA sequencing (RNA-seq), we showed that the myeloablative environment increased lymphoid priming of Flt3+ MPPs and that their efficient B cell output required intact interleukin 1 (IL-1) signaling. The Flt3+ MPPs with short-term exposure to IL-1β underwent a myeloid-biased to lymphoid-biased cell fate switch and produced more lymphoid-biased progeny with a stronger B lymphopoiesis capacity in vitro. Correspondingly, a brief exposure to IL-1β facilitated the B cell output of transplanted Flt3+ MPPs in vivo. Together, our study demonstrated an unrecognized function of IL-1β in promoting B lymphopoiesis and highlighted a latent effect of IL-1β in regulating MPP cell fate dynamics.

Background: Clear cell renal cell carcinoma (ccRCC) is a serious threat to human life. It is very important to clarify the pathogenesis of ccRCC. In this study we evaluated the clinical value of HADH and explored its role and mechanism in the malignant progression of ccRCC. Methods: HADH expression and its relationship with prognosis were analyzed using bioinformatics database. RT-PCR, Western blot and immunohistochemistry were used to examine the expression of HADH in ccRCC tissues and tissue microarrays. To examine the cell proliferation, apoptosis, migration and invasion ability, ccRCC cells with HADH overexpressed were constructed. Xenograft experiments were performed to determine the role of HADH. Non-target metabolomics was applied to explore the potential metabolic pathway by which HADH inhibited ccRCC progression. Plasmid pcDNA3.1-NRF2 was used to confirm whether HADH inhibited the process of ccRCC cells through NRF2-related glutathione (GSH) synthesis. Results: Bioinformatics database analysis showed that HADH expression was significantly decreased in ccRCC tissues, and its low expression predicted a poor prognosis. Both ccRCC tissues and tissue microarrays exhibited a significantly decreased HADH level compared with adjacent normal renal tissues. HADH overexpression inhibited the malignant behaviors of ccRCC cells. Furthermore, HADH overexpression attenuated GSH synthesis and induced oxidative stress damage. Exogenously increased NRF2 effectively attenuated the inhibitive effect of HADH overexpression on ccRCC cells. Conclusion: Our data revealed that HADH suppressed the malignant behaviors of ccRCC cells by attenuating GSH synthesis through inhibition of NRF2 nuclear translocation, and HADH might be a novel therapeutic target for ccRCC treatment.

Summary: Indole-3-propionic acid (IPA) is known to be a microbe-derived compound with a similar structure to the phytohormone auxin (indole-3-acetic acid, IAA). Previous studies reported that IPA exhibited auxin-like bioactivities in plants. However, the underlying molecular mechanism is not totally understood. Here, we revealed that IPA modulated lateral root (LR) development via auxin signaling in the model plant Arabidopsis thaliana. Genetic analysis indicated that deficiency of the TIR1/AFB-Aux/IAA-ARF auxin signaling pathway abolished the effects of IPA on regulating LR development. Further biochemical, transcriptomic profiling and cell biological analyses revealed that IPA directly bound to the TIR1/AFB-Aux/IAA coreceptor complex and thus activated downstream gene expression. Therefore, our work revealed that IPA is a potential signaling molecule that modulates plant growth and development by targeting the TIR1/AFB-Aux/IAA-mediated auxin signaling pathway, providing potential insights into root growth regulation in plants.

BackgroundPresently, numerous studies have indicated that protein consumption and levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. However, there have been few investigations into the correlation between protein consumption, serum albumin, and asthma.MethodsOur analysis incorporated 2509 asthmatics from the 2011–2018 NHANES dataset. The investigation employed three linear regression models and XGBoost model to investigate the potential link between protein intake, serum albumin levels, and blood eosinophil counts (BEOC) in patients with asthma. The trend test, generalized additive model (GAM), and threshold effect model were utilized to validate this correlation. As well, we undertook stratified analyses to look at the correlation of serum albumin with BEOC among distinct populations.ResultsIn the univariable regression model, which did not account for any covariates, we observed a positive correlation between protein intake and BEOC. However, univariable and multivariable regression analyses all suggested a negative connection of serum albumin with BEOC in asthma populations. In Model C, which took into account all possible factors, BEOC dropped by 2.82 cells/uL for every unit increase in serum albumin (g/L). Additionally, the GAM and threshold effect model validated that serum albumin and BEOC showed an inverted U-shaped correlation.ConclusionOur investigation discovered there was no independent link between asthmatics’ protein intake and BEOC. However, we observed an inverted U-shaped relationship between serum albumin levels and BEOC, suggesting a possible relationship between the overall nutritional status of asthmatics and immune system changes. Our findings provide new directions for future research in the field of asthma management and therapy.

BackgroundPulmonary alveolar microlithiasis (PAM) is a rare disease whose clinical and imaging manifestations are non-specific, characterized by the deposition of microliths, which primarily consist of calcium and phosphorus, within the alveoli. In the cases of PAM, patients combined with calcification of other organs such as gastric mucosal calcification are less common.Case presentationA 59-year-old woman was admitted to our hospital due to cough producing white, foamy sputum, accompanied by dyspnea and fever for 20 days. The CT scan showed diffuse ground-glass opacities and calcification of the gastric mucosa. Lung tissue biopsy revealed the presence of calcification and granulomatous foreign bodies in the interstitium and alveolar cavity. In the later stages, she developed painful skin petechiae. For this patient, the diagnosis of PAM, gastric mucosal calcification, and purpura fulminans was made. However, the genetic test results hinted that the patient and her son had a heterozygous mutation in the FBN1 gene, but her daughter's genetic test results were normal. Although the patient received anti-infection treatment, steroids, and oxygen therapy, her condition did not improve.ConclusionWe reported a rare case of PAM combined with calcification of other organs and purpura fulminans. Treatment of steroids did not show any benefit. The causative mechanism and effective treatment of this disease remain unclear. More treatments need to be explored.

Purpose: To explore the mechanism by which Remazolam affects the phenotype and function of astrocytes to improve traumatic brain injury (TBI). Methods: The oxygen -glucose deprivation/recovery (OGD/R) cell model was constructed to simulate the pathological state of astrocytes in a TBI environment. The viability of astrocytes was measured by CCK-8, and the cytoskeleton changes were observed by Phalloidin- TRITC staining. The expressions of differentiation markers, Cx43 and phosphorylated Cx43 (P-Cx43) of A1/A2 astrocytes were detected by Western blot, and the complement C3 and S100A10 of A1/A2 astrocytes were detected by ELISA. The TBI rat model was established. The water content of brain tissue was measured by dry-wet specific gravity method, the pathological morphology of brain tissue in cortical injury area was observed by HE staining method, ROS was detected by fluorescence quantitative method, Cx43 expression was detected by immunohistochemistry method, and the differentiation markers of A1/A2 astrocytes were detected by immunofluorescence. Results: In the TBI environment, astrocytes showed decreased cell viability, blurred skeleton, and increased expression of Cx43. In TBI rats, the water content of brain tissue increased, the brain tissue in the cortex injury area was seriously damaged, ROS and Cx43 expression were significantly increased, and mainly distributed in A2 astrocytes. Remazolam can reverse the above results after the intervention. Conclusion: Remazolam affects the phenotype and function of astrocytes to improve TBI via regulating Cx43, and plays a role in protecting the neurological function of TBI rats.

Information on the population distribution at the building scale can help governments make supplemental decisions to address complex urban management issues. However, the discontinuity and strong spatial heterogeneity of research units at the building scale make it challenging to fuse multi-source geographic data, which causes significant errors in population estimation. To address this problem, this study proposes a method for population estimation at the building scale based on Dual-Environment Feature Fusion (DEFF). The dual environments of buildings were constructed by splitting the physical boundaries and extracting features suitable for the dual-environment scale from multi-source geographic data to describe the complex environmental features of buildings. Meanwhile, Data Quality Weighting based Technique for Order of Preference by Similarity to Ideal Solution (DQW-TOPSIS) method was proposed to assign appropriate weights to the features of the external environment for better feature fusion. Finally, a regression model was established using dual-environment features for building-scale population estimation. The experimental areas chosen for this study were Jianghan and Wuchang Districts, both located in Wuhan City, China. The estimated results of the DEFF were compared with those of the ablation experiments, as well as three publicly accessible population datasets, specifically LandScan, WorldPop, and GHS-POP, at the community scale. The evaluation results showed that DEFF had an [Formula: see text] of approximately 0.8, Mean Absolute Error (MAE) of approximately 1200, Root Mean Square Error (RMSE) of approximately 1700, and both Mean Absolute Percentage Error (MAPE) and Symmetric Mean Absolute Percentage Error (SMAPE) of approximately 26%, indicating an improved performance and verifying the validity of the proposed method for fine-scale population estimation.

Abstract Background The Hubei Province in China reported its last indigenous malaria case in September 2012, but imported malaria cases, particularly those related to Plasmodium vivax and Plasmodium falciparum, threaten Hubei’s malaria-free status. This study investigated the epidemiological changes in P. vivax and P. falciparum malaria in this province to provide scientific evidence for preventing malaria resurgence. Methods The prevalence, demographic characteristics, seasonal features, and geographical distribution of malaria were assessed using surveillance data and were compared across three stages: control stage (2005–2009) and elimination stages I (2010–2014) and II (2015–2019). Results In 2005–2019, 8483 malaria cases were reported, including 5599 indigenous P. vivax cases, 275 imported P. vivax cases, 866 imported P. falciparum cases, and 1743 other cases. Imported P. falciparum cases accounted for 0.07% of all cases reported in 2005, but increased to 78.81% in 2019. Most imported P. vivax and P. falciparum malaria occurred among males, aged 21–60 years, during elimination stages I and II. The number of regions affected by imported P. falciparum and P. vivax increased markedly in Hubei from the control stage to elimination stage II. Overall, 1125 imported P. vivax and P. falciparum cases were detected from 47 other nations. Eight imported cases were detected from other provinces in China. From the control stage to elimination stage II, the number of cases of malaria imported from African countries increased, and that of cases imported from Southeast Asian countries decreased. Conclusions Although Hubei has achieved malaria elimination, it faces challenges in maintaining this status. Hence, imported malaria surveillance need to be strengthened to reduce the risk of malaria re-introduction.

Future offshore wind engineering raises demands on higher reliability, better power generating performance, as well as lower manufacturing and transportation cost. This paper presents a direct-driven permanent magnet generator (DDPMG) with modular fractional-slot concentrated winding (MFSCW), to meet the large-scale, low-cost and high-reliability requirements of offshore wind power applications. The corresponding pole–slot combination method and electromagnetic characteristics analysis for this novel generator are proposed and performed in detail, including the winding coefficient analysis, magnetomotive force (MMF) harmonic analysis, cogging torque analysis, finite element simulations and generator parameter optimization. After finite element simulations, a 3.3 MW prototype MFSCW-DDPMG is developed to validate the proposed scheme. The results provide a complete and feasible scheme of pole–slot​ combination and electromagnetic design for future MFSCW-DDPMG engineering applications.

Edible mushroom products, encompassing both cultivated and wild varieties, are highly favored by consumers due to their rich nutritional profiles, including significant levels of proteins and amino acids. These mushrooms have extensive applications across the food, pharmaceutical, and cosmetic industries, making the edible mushroom industry a vital component of global poverty alleviation efforts. Taking China as an example, the country produces over 45 million tons of edible mushrooms annually, accounting for 94.01% of the world’s total production, thereby establishing itself as the leading global producer of edible mushrooms. However, alongside the rapid expansion of this industry, concerns have emerged regarding counterfeit products and incidents of poisoning resulting from the consumption of toxic wild mushrooms. As follows, to advance the development and integrity of the mushroom production and processing industry: (1) This study presents the situation of counterfeit edible mushrooms and elucidates the factors contributing to the production of fraudulent products from both subjective and non-subjective perspectives. (2) We provide a detailed introduction to 22 varieties of freshly cultivated edible mushrooms and commonly encountered wild edible mushrooms in the Chinese consumer market, proposing the application of DNA barcoding, environmental DNA analysis, and other technologies for the future authentication of counterfeit mushroom products. (3) Concurrently, we present an overview of mushroom poisoning incidents in China from 2010 to 2023, emphasizing the challenges in mitigating the risks associated with wild mushroom consumption and preventing food poisoning, thereby necessitating heightened consumer caution. (4) Finally, we offer four recommendations aimed at ensuring the healthy, stable, and sustainable growth of the edible mushroom industry.

Medicago sativa is a high-quality legume forage that is widely cultivated around the world. However, low phosphorus (LP) stress is one of the main limiting factors for its yield and quality. Currently, it is unclear how various alfalfa root types respond to LP stress. Thus, the creeping-rooted M. varia ‘Gannong No. 4’ (or GN), tap-rooted M. sativa ‘Longdong’ (or LD), and rhizomatous-rooted M. sativa ‘Qingshui’ (or QS) were selected to detect changes in growth, metabolites, phytohormones, and organic acids after 34 days of LP stress treatment (0.01 mmol·L−1 KH2PO4). We observed LP stress significantly inhibited plant growth, and 123, 73, and 42 considerably upregulated differential metabolites were categorized into 33, 26, and 20 metabolic pathways in GN, LD, and QS under LP stress, respectively. Amino acids, plant growth regulators, and organic acids are the main metabolites. After 34 d of LP treatment, the plant height, total surface area, leaf length, ground biomass, leaf width, total volume, leaf area, and ZT content of different root types of alfalfa significantly decreased, while the contents of malic acid, citric acid, oxalic acid, IAA, ABA, and GA3 significantly increased. The plant height, leaf length, leaf width, leaf area, total surface area, total volume, ground biomass, root biomass, the number of different metabolites, and the contents of malic, citric, and oxalic acid, and IAA of GN were significantly higher than those of QS and LD under LP stress. From this point of view, GN was more tolerant than LD and QS under the LP condition.

Photocured resin materials are widely used in various fields, such as 3D printing, medical applications, and dentistry. However, the strength, wear resistance, and antibacterial properties of photocured resin are relatively limited, rendering it susceptible to potential failures. In this recent study, photocured composite resins incorporating titanium-doped hydroxyapatite (Ti-HAp) were fabricated to investigate their mechanical and biological properties. It was found that the hardness and wear resistance increased with the addition of an appropriate amount of hydroxyapatite (HAp). Specifically, the 6wt%HAp resin demonstrated superior hardness. Compared with the 6wt%HAp resin, the acid resistance and wear resistance improved when an appropriate amount of Ti-HAp was added. Notably, the resin containing 0.56%Ti-HAp demonstrated superior wear resistance. Additionally, the antibacterial performance improved with higher titanium (Ti) content, showcasing a 71.9% improvement in the resin containing 1.37%Ti-HAp compared with the 6wt%HAp resin, alongside commendable remineralization capabilities. In summary, the Ti-HAp composite resin showed enhanced mechanical and biological properties, meeting clinical standards in terms of mechanical and antibacterial properties.

In recent years, China’s new energy storage application on a large scale has shown a good development trend; a variety of energy storage technologies are widely used in renewable energy development, consumption, integrated intelligent energy systems, distribution grids, and microgrids; and substantial progress has been made in the research and development of technology and equipment, construction of demonstration projects, exploration of business models, and construction of standard systems. Up to now, a unified statistical index system and evaluation method standard for new energy storage has not yet been formed domestically or even internationally. The work takes the status quo of the new power system construction of the Hebei South Network as the research object and carries out research on the new energy storage statistical index system and evaluation method. It constructs a new energy storage power station statistical index system centered on five primary indexes: energy efficiency index, reliability index, regulation index, economic index, and environmental protection index; proposes Analytic Hierarchy Process (AHP)–coefficient of variation combination assignment method; and evaluates the development level of the new energy storage power station by adopting a comprehensive evaluation model based on the object element topology method. The new energy storage statistical index system and evaluation method are designed to provide a scientific index system and evaluation method for comprehensively monitoring, assessing and measuring the comprehensive performance and effect of new energy storage power plants in the process of operation and development, and optimizing the operation strategy of new energy storage power plants as well as the development and promotion of energy storage technology.

Ganoderma lucidum polysaccharides (G. PS) have been recognized for their immune-modulating properties. In this study, we investigated the impact of G. PS in a sepsis mouse model, exploring its effects on survival, inflammatory cytokines, Treg cell differentiation, bacterial load, organ dysfunction, and related pathways. We also probed the role of macrophages through chlorphosphon-liposome pretreatment. Using the cecal ligation and puncture (CLP) model, we categorized mice into normal, PBS, and G. PS injection groups. G. PS significantly enhanced septic mouse survival, regulated inflammatory cytokines (TNF-α, IL-17A, IL-6, IL-10), and promoted CD4+Foxp3+ Treg cell differentiation in spleens. Additionally, G. PS reduced bacterial load, mitigated organ damage, and suppressed the NF-κB pathway. In vitro, G. PS facilitated CD4+ T cell differentiation into Treg cells via the p-STAT5 pathway. Chlorphosphon-liposome pretreatment heightened septic mortality, bacterial load, biochemical markers, and organ damage, emphasizing macrophages' involvement. G. PS demonstrated significant protective effects in septic mice by modulating inflammatory responses, enhancing Treg cell differentiation, diminishing bacterial load, and inhibiting inflammatory pathways. These findings illuminate the therapeutic potential of G. PS in sepsis treatment.

The cable-driven parallel robots have the advantages of fast moving speed, large workspace and strong dynamic load carrying capacity, so they are employed to perform the pick-and-place operation of the target gangues quickly and accurately. However, due to the flexibility and the unidirectional characteristics of the cables, the cables must be kept in tension all the time, which makes the control of the robots face great challenges. At the same time, the dynamic impact, uncertainty of dynamic parameters, external interference and other factors caused by the process of the pick-and-place the target gangues will inevitably affect the motion accuracy of the end-grab of the robot, and even lead to the failure of the sorting of target gangues. Therefore, a robust adaptive fuzzy control strategy, which can ensure the motion accuracy of the end-grab of the cable-driven gangue sorting robots, is presented to overcome the disturbances of dynamic parameters and the influences of external interference in the process of picking and placing the gangues. Based on Lyapunov stability theory, the stability of the proposed control strategy is proved. The simulation analysis of the proposed control strategy is carried out through a spatial spiral trajectory and practical pick-and-place trajectory for the robot. The results show that the end-grab of the robot has a good tracking effect on the predetermined trajectory, and the maximum position tracking error and root mean square error are 2×10−2 m and 8.9867×10−4 m, respectively; and furthermore, the cable tensions are smooth and continuous, which satisfies the constraint conditions of the cable tensions. It is proved that the proposed robust adaptive fuzzy control strategy in this paper is effective and reliable for the trajectory tracking control of the cable-driven gangue sorting robots. This study can lay a good theoretical foundation for the further application of the cable-driven gangue sorting robots.

Abstract In order to improve the reliability and performance of photovoltaic systems, a fault diagnosis method for photovoltaic modules based on infrared images and improved MobileNet‐V3 is proposed. Firstly, the defect images of open‐source photovoltaic modules and their existing problems are analysed; based on the existing problems, image enhancement and data enhancement are performed on the infrared defect images of photovoltaic modules, so that the infrared images meet the requirements of image availability and sample quantity. Finally, the basic MobileNet‐V3 network is improved to realize fault classification of photovoltaic modules. The experimental results show that, compared with the traditional CNN and the basic MobileNet V3, the proposed fault classification method not only has high accuracy and fast diagnosis speed, but also has a high recognition rate for various fault categories, which has good practicability and application value.

Abstract Kagome metals AV3Sb5 (A = K, Cs, Rb) provide a rich platform for intertwined orders, where evidence for time-reversal symmetry breaking, likely due to the long-sought loop currents, has emerged in STM and muon spin relaxation experiments. An isotropic component in the spontaneous optical rotation has also been reported and was interpreted as the magneto-optic Kerr effect. Intriguingly, the observed rotations differ by five orders of magnitude between different wavelengths and samples, suggesting more intricate physics. Here we report optical rotation and polar Kerr measurements in CsV3Sb5 crystals at the same wavelength. We observe large isotropic components of 1 milliradian in the optical rotation that do not respond to applied magnetic fields, while the spontaneous Kerr signal is less than 20 nanoradians. Our results prove unambiguously that the reported isotropic rotation is not from time-reversal symmetry breaking but represents the long-sought specular optical rotation and indicates a new intertwined order.

Abstract Objective To investigate the epidemiological characteristics of syphilis cases detected among entry-exit personnel at Shanghai ports from 2014 to 2022 and the changing trend of the syphilis epidemic in the region so as to provide data support for the scientific and effective prevention and control of syphilis at ports. Methods From January 2014 to December 2022, the subjects of syphilis screening at Shanghai port were selected. Physical examination and serological testing were used to confirm syphilis. All the data used were downloaded from the HIS system of Shanghai International Travel Healthcare Center. Descriptive epidemiology was used to analyze the characteristics of the detected cases, and the linear trend Chi-square test was used to analyze the trend between groups. Results From 2014 to 2022, a total of 918 cases of syphilis were detected among entry-exit personnel at Shanghai port, with a total detection rate of 154.68/100 000. The detection rate was the highest in 2015 and the lowest in 2022, showing a downward trend year by year since 2015. 54.36% of syphilis patients from East Asia were detected. Syphilis cases were reported in all age groups; most cases were under 39 years old, accounting for 36.06%. The syphilis detection rate in males was significantly higher than in females (79.63% vs. 20.4%). The main way of transmission was sexual transmission, accounting for 60.89%, among which male-to-male transmission was the primary way (22.36%). Conclusion The detection rate of syphilis among entry-exit personnel at Shanghai port has been decreasing continuously in recent years. Targeted health intervention should be carried out according to the monitoring results.

Abstract Cancers are a group of heterogeneous diseases characterized by the acquisition of functional capabilities during the transition from a normal to a neoplastic state. Powerful experimental and computational tools can be applied to elucidate the mechanisms of occurrence, progression, metastasis, and drug resistance; however, challenges remain. Bulk RNA sequencing techniques only reflect the average gene expression in a sample, making it difficult to understand tumor heterogeneity and the tumor microenvironment. The emergence and development of single-cell RNA sequencing (scRNA-seq) technologies have provided opportunities to understand subtle changes in tumor biology by identifying distinct cell subpopulations, dissecting the tumor microenvironment, and characterizing cellular genomic mutations. Recently, scRNA-seq technology has been increasingly used in cancer studies to explore tumor heterogeneity and the tumor microenvironment, which has increased the understanding of tumorigenesis and evolution. This review summarizes the basic processes and development of scRNA-seq technologies and their increasing applications in cancer research and clinical practice.

The Pearl River Estuary (PRE) is one of the world’s most urbanized subtropical coastal systems. It presents a typical environmental gradient suitable for studying estuarine phytoplankton communities’ dynamics and photosynthetic physiology. In September 2018, the maximum photochemical quantum yield (Fv/Fm) of phytoplankton in different salinity habitats of PRE (oceanic, estuarine, and freshwater zones) was studied, revealing a complex correlation with the environment. Fv/Fm of phytoplankton ranged from 0.16 to 0.45, with taxa in the upper Lingdingyang found to be more stressed. Community composition and structure were analyzed using 18S rRNA, accompanied by a pigment analysis utilized as a supplementary method. Nonmetric multidimensional scaling analysis indicated differences in the phytoplankton spatial distribution along the estuarine gradients. Specificity-occupancy plots identified different specialist taxa for each salinity habitat. Dinophyta and Haptophyta were the predominant taxa in oceanic areas, while Chlorophyta and Cryptophyta dominated freshwater. Bacillariophyta prevailed across all salinity gradients. Canonical correlation analysis and Mantel tests revealed that temperature, salinity, and elevated nutrient levels (i.e., NO3−-N, PO43−-P, and SiO32−-Si) associated with anthropogenic activities significantly influenced the heterogeneity of community structure. The spatial distribution of phytoplankton, along with in situ photosynthetic characteristics, serves as a foundational basis to access estuarine primary productivity, as well as community function and ecosystem health.

Abstract Background Colorectal cancer (CRC) is one of the most prevalent diagnosed malignancies and one of the leading causes of cancer-related deaths worldwide. 5-Fluorouracil (5-FU) and its combination regimen are commonly used as primary chemotherapeutic agents for advanced CRC. Intestinal mucositis is one of the most frequent side effects of 5-FU. Artesunate (Arte) is derived from the wormwood plant Artemisia annua. Arte is not only effective against malaria but also diabetes, atherosclerosis, inflammation, and other conditions. The mechanism by which 5-FU damages the intestinal tract is unclear, and there is no standard treatment for diarrhea caused by 5-FU. Therefore, it is critical to discover novel and promising therapeutic drugs for 5-FU side effect treatment. Methods The morphology and expression of genes and proteins associated with the aging of HUVECs, HIECs, and intestinal tissues were compared to the those of the control group. The cell lines and tissues were evaluated by SA-β-Gal staining, Western blotting, and RT‒qPCR. HIEC and HCT116 cell viability was assessed in vitro by a CCK-8 assay and in vivo by a subcutaneous tumor mouse assay. Tumor cell proliferation and apoptosis was evaluated by immunohistochemistry. Results Here, we report that Arte alleviates the adverse side effects caused by 5-FU in intestinal tissue, and that 5-FU-induced intestinal damage is associated with drug-induced chemical inflammation and an increase in the proportion of senescent cells. Arte decreases the ratio of SA-β-Gal-positive cells and downregulated the expression of aging-related proteins (p53, p16) and aging-related genes (p53, p21). Mechanistically, Arte relieves intestinal injury by inhibiting mTOR expression, which is associated with the regulation of aging. Moreover, Arte suppresses the p38MAPK and NF-κB signaling pathways, which are related to inflammation regulation. In addition, the combined therapy of Arte plus 5-FU significantly decreases cancer cell viability in vitro. Arte and 5-FU synergistically reduce the growth of colorectal cancer (CRC) xenografts in vivo. Conclusions Overall, our findings point to the crucial treatment effect of Arte on inflammation, intestinal cell senescence, and CRC cell proliferation and offer a new option for CRC treatment.

Abstract Background The global battle against malaria is facing formidable challenges, particularly in controlling Plasmodium vivax and Plasmodium ovale, whose cases have not been reduced as effectively as Plasmodium falciparum because of their relapse. This study investigates the current situation and underlying factors contributing to relapse or recrudescence of imported cases of P. vivax and P. ovale, and seeks to provide a reference for reducing relapse or recrudescence in malaria-free areas and offers a scientific basis for designing strategies to prevent imported re-transmission. Methods This study analysed imported P. vivax and P. ovale in Anhui, Zhejiang, Henan, Hubei, and Guangxi provinces during 2014–2021 by retrospective analysis. A case–control study was conducted on patients who experienced relapse or recrudescence. Results From 2014 to 2021, 306 cases of P.vivax and 896 cases of P.ovale were included in the study, while 75 cases had relapse or recrudescence, including 49 cases of P. ovale (65.33%) and 26 cases of P. vivax (34.67%). Within less than 5 weeks after returning to the country, 122 cases of P. vivax (39.87%, 122/306) and 265 cases of P. ovale (29.58%, 265/896) occurred. Within less than 53 weeks, the ratio of P. vivax was 94.77% (290/306), and that of P. ovale was 89.96% (806/896). Among the cases experiencing relapse or recrudescence, only 1 case of P. vivax (1/26 3.85%) and 3 cases of P. ovale (3/49 6.12%) occurred within less than 5 weeks after the first onset, whereas 21 cases of P. vivax (21/26 80.77%) and 42 cases of P. ovale (42/49 85.71%) occurred within less than 53 weeks after the first onset. The difference in relapse or recrudescence due to different drugs and medication regimens and medical activities at various levels of medical institutions was statistically significant. Conclusion In areas where malaria has been eliminated, routine health screening in a scientific time frame for people returning from at-risk areas can effectively improve the efficiency of preventing re-transmission, thereby reducing prevention costs and disease burden. Preventing patients from self-treating and strengthening medication regulations in health facilities are key measures to reduce relapse or recrudescence.

Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta-analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma-glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high-risk subjects.

Background. An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic occurred throughout China from December 2022 to January 2023, and the vast majority of those infected individuals were mild. The symptom characteristics of mildly infected individuals in this epidemic wave of the Omicron variant have not been well described. Methods. We conducted a nationwide survey of symptomatic characteristics of nonhospitalized individuals with mild Omicron infection through a WeChat app. Results. Respondents (68.6% female) were aged 18–87 years (42.6 ± 13.1 years), of whom 79.8% were diagnosed by SARS-CoV-2 PCR or antigen test. Of the 19 symptoms predefined in the questionnaire, an average of 7.8 symptoms was reported. The most common symptoms included cough (81.2%), fever (79.9%), fatigue (73.8%), muscle soreness (62.2%), headache (59.2%), and phlegm (55.1%). Painful swallowing was present in 38.3% of the participants and was one of the most severe symptoms perceived by the participants. Also, we found that young people were more likely to have symptoms such as fever, painful swallowing, and headache compared to the elderly population. 36.9% of respondents graded their symptoms as severe, and the severity of symptoms was higher in young people than in older adults, with fever, cough, painful swallowing, fatigue, and headache being the most severe. In addition, women experienced a significantly higher prevalence of symptoms than men, but there was no significant difference in the severity of most symptoms. The presence of comorbidities did not increase the incidence or severity of symptoms in those with mildly infected individuals. Conclusions. The symptom profile of mild COVID-19 cases in the nationwide Omicron wave in China was markedly different from previous reports, featuring a high incidence of symptoms, multiple symptoms, and heavy symptoms. The symptoms of mild Omicron infection cases are not mild and are more pronounced in young people.

Using creativity to promote recreational services is crucial. Accordingly, creative linguistic landscapes (CLLs) are being used to improve visitors' experiences in some recreational zones. However, relevant research is still in its early stages. Therefore, this study was conducted. It summarized the leisure function categories and function evaluation indicators of CLLs in recreational zones respectively based on image materials and related online reviews. The leisure function outcomes of all CLL types were ranked using the fuzzy PROMETHEE method; based on this ranking, a CLL configuration optimization mode was suggested. The findings reveal the following. (1) Currently, there are mainly nine leisure function types of CLL in practice, although the type structure is severely imbalanced; there are 12 primary corresponding function evaluation indicators, although each of them draws significantly different attention. (2) There are notable variations among the outcomes of different types of functions of CLL: mood adjustment is the most advantageous function of CLL for leisure services, followed by emotional guidance and cognitive building functions; (3) According to the study findings, in the configuration of CLL, which aims at leisure function optimization, the "function focusing and coordinating mode (the superior functions of CLL are focused on and its various functions are coordinated)" should be adopted. The results provide meaningful lessons for the establishment of rational and effective CLL in recreational zones.

Phytosterol organic acid esters are important food resources and the components of biomembrane structure. Due to the lack of extraction and synthesis techniques, more research has been focused on phytosterols, and the research on phytosterol acid esters have encountered a bottleneck, but phytosterol acid esters confer substantial benefits to human health. In this study, stigmasteryl vanillate (VAN), stigmasteryl protocatechuate (PRO) and stigmasteryl sinapate (SIN) were prepared through the Steglich reaction. The processes are promotable and the products reach up to 95% purity. In addition, their stability was evaluated by differential scanning calorimetry and thermogravimetric analysis. HPLC analysis revealed an enhancement in water solubility after esterification with phenolic acid. In an in vitro digestion model, the bioaccessibility of stigmasteryl phenolates was significantly higher than that of stigmasterols (STIs). Regarding the anti-inflammatory properties, VAN, PRO, and SIN exhibit superior effects against TNF-α induced pro-inflammatory responses compared to STI. All stigmasteryl phenolates supplementation increased the ATP production, the basal, and maximal oxygen consumption rate in mitochondrial stress test. Overall, we present a synthesis method for stigmasteryl phenolates. It will contribute to the development and research of phytosterol acid ester analysis, functions and utilization in food. Moreover, the nutrient-stigmasterol hybrids tactic we have constructed is practical and can become a targeted mitochondrial delivery strategy with enhanced anti-inflammatory effects.

This paper combines augmented learning algorithms and data mining techniques for an intelligent recommendation system for computer course projects to optimize the allocation of learning resources and improve learning efficiency and effectiveness. The research methodology includes an improved association rule mining algorithm and an augmented learning model applying deep Q-network and adaptive reward function. The research results show that the system can effectively mine knowledge point associations and achieve personalized recommendation. In particular, the accuracy of knowledge point associations and the customized level of recommendation are improved by multi-support strategy improvement and knowledge point association correction. Experiments show that on the edX dataset, the recommendation recall reaches 0.347 at k=10 and 0.433 at k=20, significantly better than the traditional recommendation algorithm. This intelligent recommendation system can effectively improve the learning effect of computer course projects, and it has a positive impact on both learning attitude and independent learning ability, especially helping the backward students significantly and reducing the learning differences between classes.

IntroductionAlfalfa (Medicago sativa L.) is the favored premium feed ingredient in animal husbandry production which is in serious jeopardy due to soil moisture shortages. It is largely unknown how different root types of alfalfa respond to arid-induced stress in terms of metabolites and phytohormones.MethodsTherefore, rhizomatous rooted M. sativa ‘Qingshui’ (or QS), tap-rooted M. sativa ‘Longdong’ (or LD), and creeping rooted M. varia ‘Gannong No. 4’ (or GN) were investigated to identify metabolites and phytohormones responses to drought conditions.ResultsWe found 164, 270, and 68 significantly upregulated differential metabolites were categorized into 35, 38, and 34 metabolic pathways in QS, LD, and GN within aridity stress, respectively. Amino acids, organic acids, sugars, and alkaloids were the four categories of primary differential metabolites detected, which include 6-gingerol, salicylic acid (SA), indole-3-acetic acid (IAA), gibberellin A4 (GA4), abscisic acid (ABA), trans-cinnamic acid, sucrose, L-phenylalanine, L-tyrosine, succinic acid, and nicotinic acid and so on, turns out these metabolites are essential for the resistance of three root-type alfalfa to aridity coercing.DiscussionThe plant hormone signal transduction (PST) pathway was dramatically enriched after drought stress. IAA and ABA were significantly accumulated in the metabolites, indicating that they play vital roles in the response of three root types of alfalfa to water stress, and QS and LD exhibit stronger tolerance than GN under drought stress.

Bilirubin-induced liver injury is a severe health issue with inadequate treatment. This study examined whether saffron's Crocin and Crocetin could reduce bile stasis-induced liver injury. This study also investigated how these compounds may affect bile acid metabolism by inhibiting ERK phosphorylation. Network pharmacology analysis and in vitro and in vivo experiments showed that Crocin and Crocetin could affect the ERK signaling pathway, reducing bile acid production and bile stasis-induced liver injury. The study found that Crocin and Crocetin reduced CYP7A1 synthesis by inhibiting ERK signaling pathway phosphorylation and promoting PPARα binding to the promoter. Crocin and Crocetin also increased Mrp3 and Mrp4, which reduced bile acid formation and mitigated bile stasis-induced liver injury. These findings offer new insights into developing novel bile stasis-induced liver injury treatments.

Stereoelectroencephalography (SEEG) offers unique neural data from in-depth brain structures with fine temporal resolutions to better investigate the origin of epileptic brain activities. Although oscillatory patterns from different frequency bands and functional connectivity computed from the SEEG datasets are employed to study the epileptic zones, direct electrical stimulation-evoked electrophysiological recordings of synaptic responses, namely cortical-cortical evoked potentials (CCEPs), from the same SEEG electrodes are not explored for the localization of epileptic zones. Here we proposed a two-stream model with unsupervised learning and graph convolutional network tailored to the SEEG and CCEP datasets in individual patients to perform localization of epileptic zones. We compared our localization results with the clinically marked electrode sites determined for surgical resections. Our model had good classification capability when compared to other state-of-the-art methods. Furthermore, based on our prediction results we performed group-level brain-area mapping analysis for temporal, frontal and parietal epilepsy patients and found that epileptic and non-epileptic brain networks were distinct in patients with different types of focal epilepsy. Our unsupervised data-driven model provides personalized localization analysis for the epileptic zones. The epileptic and non-epileptic brain areas disclosed by the prediction model provide novel insights into the network-level pathological characteristics of epilepsy.

ABSTRACT Listeria monocytogenes is a facultative, intracellular foodborne pathogen widely distributed in nature and is responsible for severe invasive infection in humans and animals with a mortality rate as high as 30%. L. monocytogenes can adapt to various oxidative stresses since it has evolved oxidative modification and regulation mechanisms. The disulfide bond formation protein (Dsb) is required to catalyze the formation of disulfide bonds to promote oxidative folding or modification of proteins involved in bacterial virulence and survival. However, the functions of Lmo1059, a DsbA family protein of L. monocytogenes, remain unknown. In this study, we found that Lmo1059 could efficiently catalyze oxidized glutathione (GSSG) reduction, with the residues Cys36 and Cys39 as the key amino acids for its catalytic activity. Moreover, Lmo1059 plays a critical role in oxidative stress tolerance for L. monocytogenes, and Cys36 is the crucial amino acid to participate in this process. When Lmo1059 was deleted, the adhesion and invasion of L. monocytogenes were reduced while the cell-to-cell spread was increased, suggesting an intricate role of Lmo1059 during bacterial infection. Altogether, these data indicate that the DsbA family protein Lmo1059 is an important participant in the antioxidant stress system and works in concert with other proteins to help protect L. monocytogenes from oxidative stress and establish intracellular infection. IMPORTANCE The adaption and tolerance to various environmental stresses are the fundamental factors for the widespread existence of Listeria monocytogenes. Anti-oxidative stress is the critical mechanism for the survival and pathogenesis of L. monocytogenes. The thioredoxin (Trx) and glutaredoxin (Grx) systems are known to contribute to the anti-oxidative stress of L. monocytogenes, but whether the Dsb system has similar roles remains unknown. This study demonstrated that the DsbA family protein Lmo1059 of L. monocytogenes participates in bacterial oxidative stress tolerance, with Cys36 as the key amino acid of its catalytic activity and anti-oxidative stress ability. It is worth noting that Lmo1059 was involved in the invading and cell-to-cell spread of L. monocytogenes. This study lays a foundation for further understanding the specific mechanisms of oxidative cysteine repair and antioxidant stress regulation of L. monocytogenes, which contributes to an in-depth understanding of the environmental adaptation mechanisms for foodborne bacterial pathogens.

Objective: The pathogenesis of leukemia is complex and there are no effective diagnostic and prognostic indicators. Previous studies showed that microRNA-22 (miR-22) has altered expression level in multiple leukemia subtypes, which is associated with the survival outcomes of leukemia. Methods: According to the constituted retrieval strategy, eligible studies were included from January 2010 to November 2022 by searching database. The pooled Risk Ratio (RR) and 95% confidence intervals (CI) were used to study the relationship between miR-22 and survival. Stata12.0 was used for meta-analysis. Differential expression analysis was conducted based on expression profile of miRNA. Results: Four English articles were included containing a total of 215 leukemia patients. Data showed that the pooled RR for overall survival (OS) was 1.558 (95% CI: 1.197-2.028, P

Abstract Attenuated Salmonella Typhimurium is a promising antigen delivery system for live vaccines such as polysaccharides. The length of polysaccharides is a well-known key factor in modulating the immune response induced by glycoconjugates. However, the relationship between the length of Lipopolysaccharide (LPS) O-antigen (OAg) and the immunogenicity of S. Typhimurium remains unclear. In this study, we assessed the effect of OAg length determined by wzz ST on Salmonella colonization, cell membrane permeability, antimicrobial activity, and immunogenicity by comparing the S. Typhimurium wild-type ATCC14028 strain to those with various OAg lengths of the Δwzz ST mutant and Δwzz ST::wzz ECO2. The analysis of the OAg length distribution revealed that, except for the very long OAg, the short OAg length of 2–7 repeat units (RUs) was obtained from the Δwzz ST mutant, the intermediate OAg length of 13–21 RUs was gained from Δwzz ST::wzz ECO2, and the long OAg length of over 20 RUs was gained from the wild-type. In addition, we found that the OAg length affected Salmonella colonization, cell permeability, and antibiotic resistance. Immunization of mice revealed that shortening the OAg length by altering wzz ST had an effect on serum bactericidal ability, complement deposition, and humoral immune response. S. Typhimurium mutant strain Δwzz ST::wzz ECO2 possessed good immunogenicity and was the optimum option for delivering E. coli O2 O-polysaccharides. Furthermore, the attenuated strain ATCC14028 ΔasdΔcrpΔcyaΔrfbPΔwzz ST::wzz ECO2-delivered E. coli O2 OAg gene cluster outperforms the ATCC14028 ΔasdΔcrpΔcyaΔrfbP in terms of IgG eliciting, cytokine expression, and immune protection in chickens. This study sheds light on the role of OAg length in Salmonella characteristics, which may have a potential application in optimizing the efficacy of delivered polysaccharide vaccines.

AIM: To investigate the clinical effect of 25G+pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of patients with proliferative diabetic retinopathy(PDR), and analyze the influence on visual acuity, central foveal thickness(CMT)and serum vascular endothelial growth factor(VEGF)level.METHODS: A retrospective study was conducted from October 2019 to January 2022. A total of 80 patients(87 eyes)with PDR were divided into the two groups according to the treatment method, with 40 patients(45 eyes)treated with 25G+PPV in the control group, and 40 patients(42 eyes)treated with 25G+PPV combined with preoperative intravitreal injection of conbercept in the observation group. The two groups were compared in terms of the best corrected visual acuity(BCVA), intraocular pressure, CMT and serum VEGF level before treatment and at 2wk, 1 and 3mo after treatment. The patients were followed up for 3mo, with postoperative complications and recurrence recorded.RESULTS: The incidence of intraoperative bleeding in the observation group was significantly lower than that in the control group(P0.05). The BCVA and CMT of observation group were lower than those of control group at 1 and 3mo after treatment(P0.05).CONCLUSION: With few complications, 25G+PPV combined with preoperative intravitreal injection of conbercept is effective in the treatment of patients with PDR, which can better promote postoperative vision recovery, improve macular edema, and reduce serum VEGF level.

ABSTRACT Glutathione (GSH) is an essential component of the glutaredoxin (Grx) system, and it is synthesized by the enzyme glutathione synthase GshF in Listeria monocytogenes. GSH plays a crucial role in regulating Listeria virulence by modifying the virulence factors LLO and PrfA. In this study, we investigated the involvement of L. monocytogenes GshF in oxidative tolerance and intracellular infection. Our findings revealed that the deletion of gshF resulted in a significant reduction in bacterial growth in vitro when exposed to diamide and copper ions stress. More importantly, this deletion also impaired the efficiency of invasion and proliferation in macrophages and mice organs. Furthermore, GshF influenced global transcriptional profiles, including carbohydrate and amino acid metabolism, particularly those related to the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) genes lmo1997-lmo2004, under oxidative stress conditions. In the wild-type strain, the transcription of lmo1997-lmo2004 was notably downregulated in response to copper ions and diamide stress compared to normal conditions. However, in the absence of gshF, the transcripts of lmo1997-lmo2004 were upregulated in response to these stress conditions. Notably, the deletion of iiBman (lmo2002) enhanced oxidative stress tolerance to copper ions, whereas overexpression of iiBman reduced this resistance. In conclusion, our study provides the first evidence that L. monocytogenes GshF plays a crucial role in bacterial antioxidation through the regulation of iiBman . IMPORTANCE Listeria monocytogenes has developed various mechanisms to withstand oxidative stress, including the thioredoxin and glutaredoxin systems. However, the specific role of the glutathione synthase GshF, responsible for synthesizing GSH in L. monocytogenes, in oxidative tolerance remains unclear. This study aimed to elucidate the relationship between GshF and oxidative tolerance in L. monocytogenes by examining the efficiency of invasion and proliferation in macrophages and mice organs, as well as analyzing global transcriptional profiles under oxidative stress conditions. The results revealed that GshF plays a significant role in L. monocytogenes’ response to oxidative stress. Notably, GshF acts to suppress the transcription of phosphoenolpyruvate-carbohydrate phosphotransferase system genes lmo1997-lmo2004, among which iiBman (lmo2002) was identified as the most critical gene for resisting oxidative stress. These findings enhance our understanding of how L. monocytogenes adapts to its environment and provide valuable insights for investigating the environmental adaptation mechanisms of other pathogenic bacteria.

ABSTRACT: The H6N2 subtype avian influenza virus (AIV) is commonly detected in the migratory waterfowl reservoirs. Previously, H6N2 AIV was believed to be nonpathogenic to young chickens and could not infect or shed in their respiratory tract under experimental conditions. However, in present study, a highly recombinant strain of duck-derived H6N2 AIV was discovered and isolated for pathogenicity tests. The results revealed that H6N2 could induce seroconversion in chickens and high morbidity of over 86.7%, along with evident upper respiratory tract hemorrhage. Moreover, 5 substitutions were detected in the upper respiratory tract shedding reisolated virus, with a high viral load in the target organs of infected chickens. In contrast, ducks failed to exhibit any symptoms, pathological lesions, or viral shedding, while demonstrated seroconversion and high viral load in the livers. These findings indicate that H6N2 AIV could also show pathogenicity to chickens under experimental conditions, thereby effectively replicating and shedding in chickens. Therefore, the study provides further elucidations on the pathogenicity of H6N2 AIV.

ABSTRACT: The H9N2 subtype of avian influenza virus (H9N2 AIV) has caused significant losses in chicken flocks throughout China. At present, consensus has been reached that field isolates of H9N2 underwent antigenic drift to evolve into distinct groups with significant antigenic divergence from the commercially available vaccines in China. This project continues to monitor the evolution characteristics of H9N2 hemagglutinin (HA) genes in China over the past 3 yr. The results showed that the current circling H9N2 viruses were diversified into h9.4.2.5 subclade, which was genetically distant from commonly used commercial vaccine strains. Compared with vaccine strains or 2014 strains, more than 42.1% of the variable antigenic sites in recent 3 yr' strains have shown significant changes and these stacked changes have caused significant differences in antigenicity. We constructed a recombinant vaccine strain rCQY-GHHA, which uses A/Chicken/China/SichuanCQY/2014 as the framework and A/Chicken/China/SichuanGH/2020 strain, which meets the recent viral antigenic characteristics, as the HA gene donor. The recombinant strain was prepared as an oil-adjuvant inactivated vaccine following an industrial process. The results of the immune protection experiment showed that the rCQY-GHHA vaccine was better than the commercial vaccine strain SS in reducing the morbidity, pathological lesion, virus shedding, and viral load. These results provide a reference for the control of H9N2 AIV in China.