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Abstract Mobile genetic elements (MGEs) enable bacteria to acquire novel genes and traits. However, the functions of cargo genes within MGEs remain poorly understood. The cadmium resistance operon cadDX is present in many gram-positive bacteria. Although cadDX has been reported to be involved in metal detoxification, its regulatory mechanisms and functions in bacterial pathogenesis are poorly understood. This study revealed that cadDX contributes to cadmium resistance, oxidative stress resistance, and virulence in Streptococcus suis, an important zoonotic pathogen in pigs and humans. CadX represses cadD expression by binding to the cadDX promoter. Notably, cadX responds to H2O2 stress through an additional promoter within the cadDX operon, mitigating the harmful effect of excessive cadD expression during oxidative stress. cadDX resides within an 11 K integrative and mobilizable element that can autonomously form circular structures. Moreover, cadDX is found in diverse MGEs, accounting for its widespread distribution across various bacteria, especially among pathogenic streptococci. Transferring cadDX into another zoonotic pathogen, Streptococcus agalactiae, results in similar phenotypes, including resistance to cadmium and oxidative stresses and increased virulence of S. agalactiae in mice. The new functions and regulatory mechanisms of cadDX shed light on the importance of the cadDX system in driving evolutionary adaptations and survival strategies across diverse gram-positive bacteria.

High-performance grinding wheels are critical tools for precision surface generation. In precision grinding processes, the coolant supply at the wheel-workpiece interface is critical for reducing grinding temperature and detrimental friction. For better lubrication and chip removal performance, the cavities or pores need to be generated throughout the grinding wheel. The ideal morphology of pores in grinding wheels should be inter-connected and capable of providing sufficient coolant. Conventional grinding wheel design and fabrication methods can only passively generate closed circular pores by using pore-forming agents. Increasing the percentage of pores in this way generally leads to an uncontrollable reduction in mechanical strength, while the closed pores are insufficient in cooling performance. In this paper, the grinding wheels with triply periodic minimal surface lattice structure are designed and fabricated, which achieves the regulable and inter-connected internal structure of grinding wheels. Meanwhile, to balance the relationship between the structural properties and performance indicators of porous grinding wheels, an optimal design method for the porous structure of grinding wheels is proposed. Finally, the grinding performance of the novel grinding wheels in comparison to electroplated diamond grinding wheels is investigated in terms of grinding force, specific grinding energy and ground surface roughness.

Abstract The neighborhood effect has become an important framework with which to study the mechanisms that maintain the coexistence of tree species. Phylogenetic relatedness among neighboring plants directly affects species coexistence and the maintenance of tree diversity. And some studies have reported that seedling performance is negatively correlated with phylogenetic relatedness, which termed phylogenetic negative density dependence. Soil-borne fungal pathogens affected seedling performance of phylogenetically related host species, i.e., phylogenetic Janzen–Connell effect. Seedlings may be particularly vulnerable to habitat and neighbor characteristics. Although previous studies have demonstrated the influence of neighborhood effects, phylogenetic relatedness, and habitat filtering on seedling survival, growth, and mortality, the effect of variation in these factors on seedling abundance remains unclear. To address this question, we used a 4-ha (200 m × 200 m) and monitored four-year (2020–2023) seedling dataset from a mid-montane humid evergreen broad-leaved subtropical forest in the Gaoligong Mountains, Yunnan, Southwestern China, and which consisted of 916 seedlings belonging to 56 species. The results of generalized linear mixed models showed no significant effect of conspecific adult neighbors on seedling abundance at any of the intervals evaluated. In contrast, we found evidence of phylogenetic distance density dependence in the forests of the Gaoligong Mountains. Specifically, there was a significant positive effect of the relative average phylogenetic distance between heterospecific adult neighbors and focal seedlings on focal seedling abundance in 2020; however, the relative average phylogenetic distance between heterospecific seedling neighbors and focal seedlings had a significant negative effect on seedling abundance over the four-year period (2020–2023). Among the habitat factors, only light (canopy opening) had a negative effect on seedling abundance in all four years. Light resources may be a limiting factor for seedlings, and determine seedling dynamics in subtropical forests. Overall, our results demonstrated that phylogenetic density dependence and habitat filtering affected subtropical seedling abundance. Our findings provide new evidence of the impact of phylogenetic density dependence on seedling abundance in a subtropical mid-montane humid evergreen broad-leaved forest and highlight the need to incorporate the neighborhood effect, phylogenetic relatedness, and habitat factors in models assessing seedling abundance.

Objective To investigate the serological characteristics and gene mutation mechanism of RhD variant blood donors in Zhengzhou. Methods From January 2023 to December 2023, 1 619 RhD-negative blood donors sent to our laboratory were selected for the study, and RhD negative confirmation test and RhCE phenotype detection were applied by tube method and microcolumn gel indirect antiglobulin test method. RHD gene amplification and Sanger sequencing were used to detect RhD variant sample genotypes. Results A total of 69 cases of RhD variants were detected in the RhD negative confirmation test, with a proportion of 4.26%(69/1 619).The RhCE phenotypes were ccEe, Ccee, CcEe and CCee.There were 17 genotypes and 15 phenotypes of the D variant.The RHD*weak partial 15 allele was the most frequent(33 cases), with a frequency of 47.83%(33/69), and the main phenotype was the ccEe. This was followed by the RHD*DVI.3 allele in 20 cases with a frequency of 28.99%(20/69) and the predominant phenotype was Ccee. The RHD*weak partial 15/RHD*01EL.01 heterozygote was found in 3 cases with a frequency of 4.35%(3/69), all with the CcEe phenotype. Other rare genotypes were present in 13 cases with a frequency of 18.84%(13/69). Antibody screening was positive in 3 cases with a frequency of 4.35%(3/69). Two cases of female blood donors, both with history of pregnancy and childbirth, were identified as anti-D; one case of male donor was anti-M. Conclusion The RHD*weak partial 15 genotype was the most common among the RhD variants in blood donors in Zhengzhou, followed by the RHD*DVI.3 genotype. It plays an important role in guaranteeing the safety of blood supply and guiding precision transfusion.

A suitable irrigation pattern is of great significance for reducing greenhouse gas emissions. In this study, field experiments and a denitrification-decomposition (DNDC) model were used to study the global warming potential based on CH4, N2O and CO2 fluxes under flooding irrigation and controlled irrigation in paddy fields in the Erhai Lake basin. The results showed that the average value of CH4 flux under controlled irrigation was lower than that under flooding irrigation, with a reduction range of 43.21% to 48.88%, however, the average value of the N2O and CO2 fluxes from paddy field under controlled irrigation were higher than those under flooding irrigation. Controlled irrigation patterns can significantly reduce the global warming potential in paddy fields based on CH4, N2O and CO2 fluxes. Controlled irrigation can effectively reduce the global warming potential per unit yield. For water management in the Erhai Lake basin, it is recommended the controlled irrigation treatment of soil moisture with an upper limit of 100% and a lower limit of 75-85% with irrigation, and a maximum surface water depth of 150-200 mm lasting for five days after precipitation from the jointing-booting stage to the milk stage.

The effect of germination degree (shoot length) on the content of nutritional and bioactive components, antioxidant activity was investigated in tartary buckwheat whole grain powder (TBWGP). The findings demonstrated that as germination degree increased, the absolute contents of total starch, protein and fat fractions as well as the ratio of straight-chain starch to total starch in TBWGP decreased, and the content of dietary fiber (IDF, SDF, TDF) elevated (P

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Background This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. Methods In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. Results According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P 0.05). Conclusions The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

Abstract The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.

In order to study the effects of reverse transcriptase inhibitors, protease inhibitors and flavonoids on two target cells infected by HIV in a heterogeneous environment, an HIV mathematical model at the cellular level was established. Research shows that infected cells can be categorized into immature infected cells, latent infected cells, and mature infected cells based on the infection process. The basic reproduction number $ R_{0} $ was established, and it is proved that $ R_{0} $ serves as a threshold parameter: When $ R_{0} < 1 $, the disease-free steady state is globally asymptotically stable, and the disease is extinct; when $ R_{0} > 1 $, the solution of the system is uniformly persistent, and the virus exists. Considering the huge advantages of drug intervention in controlling HIV infection, the optimal control problem was proposed under the condition that the constant diffusion coefficient is positive, so as to minimize the total number of HIV-infected cells and the cost of drug treatment. To illustrate our theoretical results, we performed numerical simulations in which the model parameters were obtained with reference to some medical studies. The results showed that: (1) as $ R_{0} $ increases, the risk of HIV transmission increases; (2) pharmacological interventions are important in early treatment of HIV spread and control of viral load in the body; (3) the treatment process must consider the heterogeneity of medication, otherwise it will not be conducive to suppressing the spread of the virus and will increase costs.

Objective To analyze the application of serological test results in the diagnosis and treatment of anti-M-induced hemolytic disease of the fetus and newborn(HDFN), and to explore HDFN prevention strategies. Methods The serological test results of 12 cases of HDFN caused by anti-M diagnosed in our laboratory from January 2017 to December 2023 were retrospectively analyzed, including blood group identification of mothers and children, serum total bilirubin/hemoglobin/antibody titer test, and three hemolysis tests in newborns. Clinical data of the children and mothers were collected, including pregnancy history, blood transfusion history, prenatal antibody testing, history of intrauterine blood transfusion and gestational week of delivery, and the prognosis of the children was followed up. Results All 12 cases of fetal neonatal hemolytic disease due to anti-M were RhD+ MN phenotype newborn born to RhD+ NN mother, with maternal- fetal incompatiblility in MN blood groups. In the ABO blood group system, ABO incompatibility between mother and child accounted for 41.7%(5/12).None of the mothers had a history of blood transfusion, and the median titer of the test at 4℃ was 32, and the median titer at 37℃ was 4. The mothers of 3 cases had a history of multiple intrauterine blood transfusions, with an incidence of 25%(3/12). One case had an abnormal first pregnancy, with an incidence of 8.3%(1/12), and seven cases had an abnormal pregnancy with a miscarriage, with an incidence of abnormal pregnancy and birth history of 58.3%(7/12). There were 6 cases of premature labor, with an incidence of 50%(6/12). The mothers in three cases underwent regular obstetric examination and the specificity of the antibodies was determined, accounting for 25%(3/12). Twelve children had free antibodies with a median titer of 6 at 4℃ and 2 at 37℃. Two children had anti-M antibodies that were not reactive at 37℃, with a negative rate of 16.7%(2/12). The positive rate of DAT and elution test was respectively 8.3%(1/12) and 16.7%(2/12) in the children. The median minimum hemoglobin value was 75 g/L, and all 12 children received blood transfusions. The median peak total bilirubin value was 157.5 μmol/L, and none of them reached the threshold for blood exchange. The rate of delayed anemia was 16.7%(2/12), the postnatal mortality rate was 8.3%(1/12), and 11 children was free of growth and neurodevelopmental delay in prognosis. Conclusion Anti-M can cause severe HDFN, which can also occur in primigravida. The intensity of antibody titer does not correlate with the severity of the disease, and it is prone to cause delayed anemia, which should be monitored regularly according to the serological characteristics of anti-M and clinical symptoms, and should be treated timely.

This is an article in the field of mining engineering. Fly ash is not only a large amount of solid waste discharged from coal-fired power plants, but also a potential secondary resource. At present, although the resource utilization of fly ash covers a wide range of fields, the high value utilization rate is low. The main chemical components of fly ash are silicon and alumina. Making full use of aluminum and silicon resources is one of the important ways to improve its resource utilization. In this article, the application of fly ash in the extraction of metallurgical grade alumina, preparation of non-metallurgical grade alumina, silica, silica aerogels, silicon-aluminum composites and other high value-added products are reviewed. The existing problems of high value utilization are analyzed and the future development trend is pointed out.

Abstract Background Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. Methods We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. Results We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. Conclusions These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.

Arsenic (As) is a widespread global pollutant, and there is significant controversy surrounding its complex relationship with obesity, primarily focused on short-term exposure. Recognizing the prolonged nature of dietary arsenic exposure, this study involved feeding mice with arsenic-contained food for 14 months. The results showed that mice exposed to arsenic developed a non-alcoholic fatty liver condition, characterized by a light-yellow hue on the liver surface and various pathological alterations in the liver cells, including enlarged nuclei, cellular necrosis, inflammatory infiltration, dysfunctional mitochondria, and endoplasmic reticulum disorganization. There were also disruptions in biochemistry indices, with a significant increase in total cholesterol (TC) level and a decrease in high-density lipoprotein (HDL) level. However, some contradictory observations occurred, such as a significant decrease in body weight, triglyceride (TG) level, and the numbers of lipid droplets. Several genes related to lipid metabolism were tested, and a model was used to explain these discrepancies. Besides, examinations of the colon revealed compromised intestinal barrier function and signs of inflammation. Fecal 16S rRNA sequencing and pseudo-targeted metabolomics revealed disruptions in internal homeostasis, such as modules, nodes, connections, and lipid-related KEGG pathways. Fecal targeted metabolomics analyses of short-chain fatty acids (SCFAs) and bile acids (BAs) demonstrated a significant upregulation in three primary bile acids (CA, CDCA, TCDCA), four secondary bile acids (TUDCA, DCA, LCA, GUDCA), and total SCFAs level. Oxidative stress and inflammation were also evident. Additionally, based on correlation analysis and mediation analysis, it was assumed that changes in the microbiota (e.g., Dubosiella) can impact the liver metabolites (e.g., TGs) through alterations in fecal metabolites (e.g., LPCs). These findings provide a theoretical reference for the long-term effect of arsenic exposure on liver lipid metabolism.

The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.

Chronic predator stress (CPS) is an important and ecologically relevant tool for inducing anhedonia in animals, but the neural circuits underlying the associated neurobiological changes remain to be identified. Using cell-type-specific manipulations, we found that corticotropin-releasing hormone (CRH) neurons in the medial subthalamic nucleus (mSTN) enhance struggle behaviors in inescapable situations and lead to anhedonia, predominately through projections to the external globus pallidus (GPe). Recordings of in vivo neuronal activity revealed that CPS distorted mSTN-CRH neuronal responsivity to negative and positive stimuli, which may underlie CPS-induced behavioral despair and anhedonia. Furthermore, we discovered presynaptic inputs from the bed nucleus of the stria terminalis (BNST) to mSTN-CRH neurons projecting to the GPe that were enhanced following CPS, and these inputs may mediate such behaviors. This study identifies a neurocircuitry that co-regulates escape response and anhedonia in response to predator stress. This new understanding of the neural basis of defensive behavior in response to predator stress will likely benefit our understanding of neuropsychiatric diseases.

IntroductionHemorrhagic Fever with Renal Syndrome (HFRS) is the most commonly diagnosed zoonosis in Asia. Despite taking various preventive measures, HFRS remains prevalent across multiple regions in China. This study aims to investigate the impact of climatic and environmental factors on the prevalence of HFRS in Anhui Province, China, utilizing satellite and reanalysis data.MethodsWe collect monthly HFRS data from Anhui Province spanning 2005 to 2019 and integrated MODIS satellite datasets and ERA5 reanalysis data, including variables such as precipitation, temperature, humidity, solar radiation, aerosol optical depth (AOD), and Normalized Difference Vegetation Index (NDVI). Continuous wavelet transform, Spearman correlation analysis, and Poisson regression analysis are employed to assess the association between climatic and environmental factors and HFRS cases.ResultsOur findings reveal that HFRS cases predominantly occur during the spring and winter seasons, with the highest peak intensity observed in a 9-year cycle. Notably, the monthly average relative humidity exhibits a Spearman correlation coefficient of 0.404 at a 4-month lag, taking precedence over other contributing factors. Poisson regression analysis elucidates that NDVI at a 2-month lag, mean temperature (T) and solar radiation (SR) at a 4-month lag, precipitation (P), relative humidity (RH), and AOD at a 5-month lag exhibit the most robust explanatory power for HFRS occurrence. Moreover, the developed predictive model exhibiting commendable accuracy.DiscussionThis study provides key evidence for understanding how climatic and environmental factors influence the transmission of HFRS at the provincial scale. Insights from this research are critical for formulating effective preventive strategies and serving as a resource for HFRS prevention and control efforts.

Prokaryotes play a crucial role in marine ecosystem health and drive biogeochemical processes. The northern Ninety East Ridge (NER) of the Indian Ocean, a pivotal yet understudied area for these cycles, has been the focus of our study. We employed high-throughput 16S rRNA gene sequencing to analyze 35 water samples from five stations along the ridge, categorized into three depth- and dissolved oxygen-level-based groups. Our approach uncovered a clear stratification of microbial communities, with key bioindicators such as Prochlorococcus MIT9313, Sva0996 marine group, and Candidatus Actinomarina in the upper layer; Ketobacter, Pseudophaeobacter, Nitrospina, and SAR324 clade in the middle layer; and Methylobacterium-Methylorubrum, Sphingomonas, Sphingobium, and Erythrobacter in the deep layer. Methylobacterium-Methylorubrum emerged as the most abundant bacterial genus, while Nitrosopumilaceae predominated among archaeal communities. The spatial and depth-wise distribution patterns revealed that Ketobacter was unique to the northern NER, whereas Methylobacterium-Methylorubrum, UBA10353, SAR324 clade, SAR406, Sva0996_marine_group, Candidatus Actinomarina were ubiquitous across various marine regions, exhibiting niche differentiation at the OTU level. Environmental factors, especially dissolved oxygen (DO), silicate, nitrate, and salinity, significantly influence community structure. These findings not only reveal the novelty and adaptability of the microbial ecosystem in the northern NER but also contribute to the broader understanding of marine microbial diversity and its response to environmental heterogeneity.

SUMMARY: The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 μM) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 μM curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h·ug/L) and a higher Cmax values (9.94 vs. 7.61 μg/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol.

IntroductionDiabetic nephropathy (DN) presents a significant therapeutic challenge, compounded by complex pathophysiological mechanisms. Recent studies suggest Exendin-4 (Ex-4) as a potential ameliorative agent for DN, albeit with unclear mechanisms. This research investigates the effects and underlying mechanisms of Ex-4-enriched exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) on DN, focusing on their renoprotective properties and interactions with gut microbiota.MethodExosomes from hUCMSCs (hUCMSCs-Exo) were loaded with Ex-4 via electroporation. A streptozotocin (STZ) -induced DN mouse model was employed to assess the therapeutic impact of these engineered exosomes. The study further explored immune cell dynamics, mainly CD4+ regulatory T (Treg) cells, using bioinformatics, flow cytometry, and the influence of gut microbiota through antibiotic treatment and specific bacterial reintroduction.ResultsTreatment with hUCMSCs-Exo@Ex-4 significantly improved key DN markers, including blood glucose and proteinuria, alleviating kidney damage. A notable decrease in natural Treg cell infiltration in DN was observed, while Ex-4-loaded exosomes promoted CD4+ Treg cell induction. The therapeutic benefits of hUCMSCs-Exo@Ex-4 were diminished upon CD4+ Treg cell depletion, underscoring their role in this context. Notably, CD4+ Treg cell induction correlated with the presence of Prevotella species, and disruption of gut microbiota adversely affected these cells and the therapeutic efficacy of the treatment. However, the reintroduction of Prevotella strains counteracted these adverse effects.DiscussionThis study elucidates a novel therapeutic mechanism of Ex-4-loaded hUCMSCs exosomes in DN, highlighting the induction of CD4+ Treg cells mediated by specific gut microbiota components. These findings underscore the potential of leveraging gut microbiota and immune cell interplay in developing effective DN treatments.

Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.

Carbendazim (methyl benzimidazol-2-ylcarbamate, CBZ) is a systemic benzimidazole carbamate fungicide and can be used to control a wide range of fungal diseases caused by Ascomycetes, Basidiomycetes and Deuteromycetes. It is widely used in horticulture, forestry, agriculture, preservation and gardening due to its broad spectrum and leads to its accumulation in soil and water environmental systems, which may eventually pose a potential threat to non-target organisms through the ecological chain. Therefore, the removal of carbendazim residues from the environment is an urgent problem. Currently, a number of physical and chemical treatments are effective in degrading carbendazim. As a green and efficient strategy, microbial technology has the potential to degrade carbendazim into non-toxic and environmentally acceptable metabolites, which in turn can dissipate carbendazim from the contaminated environment. To date, a number of carbendazim-degrading microbes have been isolated and reported, including, but not limited to, Bacillus, Pseudomonas, Rhodococcus, Sphingomonas, and Aeromonas. Notably, the common degradation property shared by all strains was their ability to hydrolyze carbendazim to 2-aminobenzimidazole (2-AB). The complete mineralization of the degradation products is mainly dependent on the cleavage of the imidazole and benzene rings. Additionally, the currently reported genes for carbendazim degradation are MheI and CbmA, which are responsible for breaking the ester and amide bonds, respectively. This paper reviews the toxicity, microbial degradation of carbendazim, and bioremediation techniques for carbendazim-contaminated environments. This not only summarizes and enriches the theoretical basis of microbial degradation of carbendazim, but also provides practical guidance for bioremediation of carbendazim-contaminated residues in the environment.

Biochar has demonstrated potential for stabilising high yields and sequestering carbon in dryland farmland, but it is unclear whether biochar affects the carbon sequestration capacity and carbon balance of annual farmland ecosystems. For this purpose, we conducted a plot control trial in salinised farmland in 2019-2021, where we set three treatments, control, and two biochar rates, 0 (CK), 15 (B15), and 30 t/ha (B30). The results showed that biochar application decreased soil organic carbon stocks in the early part of the experiment (first freeze and freeze period); these increased in the later part, and overall, the biochar treatments increased soil organic carbon storage by 3-6% compared with the control. Compared with the control (CK), biochar inhibited the total soil respiration rate and microbial respiration rate significantly (P < 0.05) during the crop growing period compared with the freeze-thaw period. After two years of freeze-thaw cycling, biochar application increased sunflower plant carbon sequestration and net primary productivity and suppressed total soil microbial respiration, thereby increasing net ecosystem productivity. Therefore, the application of biochar is conducive to carbon sequestration in farmland ecosystems and presents a carbon sink effect, thus being a good choice for improving the soil carbon pool and reducing emissions in the northern dry zone.

Abstract Background The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals, integrating emotional information, and regulating related behaviors. The cells in the LHb are predominantly glutamatergic and have heterogeneous functions in response to different stimuli. The circuitry connections of the LHb glutamatergic neurons play a crucial role in integrating a wide range of events. However, the circuitry connections of LHb glutamatergic neurons in both sexes have not been thoroughly investigated. Methods In this study, we injected Cre-dependent retrograde trace virus and anterograde synaptophysin-labeling virus into the LHb of adult male and female Vglut2-ires-Cre mice, respectively. We then quantitatively analyzed the input and output of the LHb glutamatergic connections in both the ipsilateral and contralateral whole brain. Results Our findings showed that the inputs to LHbvGlut2 neurons come from more than 30 brain subregions, including the cortex, striatum, pallidum, thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum with no significant differences between males and females. The outputs of LHbvGlut2 neurons targeted eight large brain regions, primarily focusing on the midbrain and pons nuclei, with distinct features in presynaptic bouton across different brain subregions. While correlation and cluster analysis revealed differences in input and collateral projection features, the input-output connection pattern of LHbvGlut2 neurons in both sexes was highly similar. Conclusions This study provides a systematic and comprehensive analysis of the input and output connections of LHbvGlut2 neurons in male and female mice, shedding light on the anatomical architecture of these specific cell types in the mouse LHb. This structural understanding can help guide further investigations into the complex functions of the LHb.

Abstract Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI− based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.

ABSTRACTThis study prepared ultralow electron-loss perovskites with spinel-like structures via a solid-state reaction. The (Mg0.95Co0.05)2(Ti0.95Sn0.05)O4 (MCTS) ceramic exhibited approximate values for ultrahigh quality factor, permittivity, and negative temperature coefficient (τf) of 310,000 GHz, 14.25, and −48.1 ppm/oC, respectively. To bring the τf closer to zero, a trace amount of (Ca0.95Sr0.05)(Ti0.97Sn0.03)O3 (CSTS) perovskite was added to MCTS during ceramic manufacturing. CSTS exhibited a permittivity of 92 and a large positive τf value of 810 ppm/°C. A 0.92MCTS–0.08CSTS hybrid ceramic sintered at 1325°C achieved remarkable microwave dielectric properties of εr ~18.42, Q×f ~ 237,000 GHz and τf ~3.72 ppm/°C. This mixed ceramic has significant potential for applications in manufacturing microwave devices.

Abstract Background This study aimed to investigate the turnover intention among nurses in eastern China and explore the association between turnover intention and personal characteristics, family factors, and work-related factors. Methods A total of 2504 nurses participated in a cross-sectional survey administered in 26 hospitals in Eastern China from October to November 2017. In December 2021, a survey was conducted on nurses who resigned between December 2017 and November 2021. Results The turnover intention score of in-service nurses was 15 (12–17), and 43% of nurses had a high turnover intention, which was mainly due to the following reasons: age 1 child, low income, involuntary career selection, frequent night shifts, informal employment, part-time, and high job stress are significant factors associated with nurses’ willingness to leave. Government and hospital administrators should consider ways to address these factors to retain nurses in hospitals in eastern China and improve the quality of nursing services.

Objective To analyze the serological characteristics and molecular mechanism of a novel B subtype allele 803delC. Methods ABO blood group was detected by serological method. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect ABO blood group genes. The coding region of exon 1-7 of ABO gene was detected by Sanger sequencing to determine the mutation site. Results Serological identification of patients was with forward O-type and reverse B-type. The result of PCR-SSP genotyping was A/O. There was A gene, which was not consistent with serological results. Further Sanger double-strand sequencing revealed that the C-base was deleted at position 803 of exon 7 on the basis of ABO*B. 01/ABO*O. 01.01. The mutation eventually leads to the amino acid substitution of p. Ala268Gly and p. Phe269Ser and the production of new open reading frame starting at position 269, with the new open reading frame No.20 amino acid being stop codon, resulted in the termination of B gene expression. Further single-strand sequencing of the ABO gene revealed that the mutation was located in the ABO*B. 01 gene. The mutation was submitted to the NCBI database with the number OR343908. Conclusion A new ABO allele leading to B variant has been found in Chinese population. Genetic detection can be used to identify the ambiguous blood group with discrepancy between forward and reverse blood grouping.

Objective To reveal the sources and ecological risks of heavy metals in a typical lead-zinc mining area in Hebei Province, 156 soil samples were collected around a zinc mining area in Hebei Province through a systematic field sampling method. Methods The sources of heavy metals in the area were analysed via principal component analysis(PCA) and a positive matrix factorization(PMF) model. The risk assessment was carried out according to the index of geoaccumulation method and potential ecological risk index method. Results The results show that the mean values of Cr, Ni, Cu, Zn, As, Cd, Pb and Hg are 53.6, 25.7, 62.7, 692, 10.6, 1.75, 142, 0.129 mg/kg, respectively. Except for Cr, Ni and As, the other 5 elements present at different pollution levels. Above the background values of the soils in Hebei Province, the coefficient of variation of Hg, Cd, Zn, Pb and Cu is more than 1.75, and the coefficient of variation of As exceeds 0.5, indicating the high variability of these 6 elements. The results of the source analysis reveal that the main sources of soil heavy metals include mining activities, natural sources, agricultural activities, and gold smelting. Zn, Cd and Pb were mainly derived from mining activities; Cr and Ni were influenced by natural parent materials and were derived from natural sources; Cu was mainly derived from agricultural activities and mining activities; As was controlled by natural sources, mining activities and agricultural activities; and Hg was originated from mainly gold smelting and mining activities. The combination of PCA and the PMF model to corroborate each other facilitates the reliability of the heavy metal source analysis results. Conclusion There is anthropogenic Hg and Cd contamination in this area, as indicated by the high geoaccumulation indices and potential ecological risk indices. In addition, the ecological risk in general was found to be very high, and attention needs to be given to and management work to be carried out.

Abstract Purpose The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer. Methods Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI. Results SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p

Low rate distributed denial of service attack (LR-DDoS) is a special type of distributed denial of service (DDoS) attack, which uses the vulnerability of HTTP protocol to send HTTP requests to applications or servers at a slow speed, resulting in long-term occupation of server threads and affecting the normal access of legitimate users. Since LR-DDoS attacks do not need to send flooding or a large number of HTTP requests, it is difficult for traditional intrusion detection methods to detect such attacks, especially when HTTP traffic is encrypted. To overcome the above problems, we proposed an encrypted LR-DDoS attack detection and mitigation method based on the multi-granularity feature fusion (MFFLR-DDoS) for software defined networking (SDN). This method analyzes the encrypted session flow from the time sequence of packets and the spatiality of session flow and uses different deep learning methods to extract features, to obtain more effective features for abnormal traffic detection. In addition, we used the advantages of SDN architecture to perform real-time defense against LR-DDoS attacks by the way of SDN controller issuing flow rules. The experimental results showed that the MFFLR-DDoS model had a higher detection rate than advanced methods, and could mitigate LR-DDoS attack traffic online and in real-time.

Abstract To explore the effect of a combination of Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) with modularization teaching in the context of clinical instruction in trauma care. A total of 244 nursing students who participated in clinical practice in orthopaedic wards from March 2020 to April 2022 were divided into two groups that received the same trauma care teaching content. The control group (n = 119) used the traditional teaching approach, and the experimental group (n = 125) utilized a combination of TeamSTEPPS with a modularization teaching model. A questionnaire was used to assess students’ theoretical knowledge, practical skills, self-concepts and professional benefits after one month with the goal of determining their end-of-course performance. The theoretical knowledge scores obtained by the control group and the experimental group were 89.56 ± 4.06 and 91.62 ± 2.84, respectively, and these results were statistically significant (P

Abstract Background Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. Methods This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. Results A total of 1022 patients with a mean age of 66 (60–88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, ‘distress/feeling upset’ (MDASI 5) appears to be a structurally important node in all three networks, and ‘I lost interest in my own appearance’ (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). Conclusion The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. Trial registration Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

Abstract Background N-acetylcysteine (NAC) reduces the cytotoxicity and genotoxicity induced by monomers leached from dental composite resins. Herein, we investigated the effects of methacrylate-based resin cement used in dental implant restoration on apoptosis and genotoxicity, as well as the antiapoptotic and antigenotoxic capabilities of its component, NAC. Methods The antioxidant NAC (0.1 or 1 wt.%) was experimentally incorporated into the methacrylate-based dental resin cement Premier®. The Premier® + NAC (0.1 or 1 wt.%) mixture was subsequently immersed into Dulbecco’s modified Eagle’s medium for 72 h, and used to treat human gingival fibroblasts (HGFs). The viability of HGFs was determined using the XTT assay. The formation of deoxyribonucleic acid (DNA) double-strand breaks (DNA-DSBs) was determined using a γ-H2AX assay. Reactive oxygen species (ROS), apoptosis, necrosis, and cell cycles were detected and analyzed using flow cytometry. Results The eluate of Premier® significantly inhibited HGF proliferation in vitro by promoting a G1-phase cell cycle arrest, resulting in cell apoptosis. Significant ROS production and DNA-DSB induction were also found in HGFs exposed to the eluate. Incorporating NAC (1 wt.%) into Premier® was found to reduce cell cytotoxicity, the percentage of G1-phase cells, cell apoptosis, ROS production, and DNA-DSB induction. Conclusion Incorporating NAC (1 wt.%) into methacrylate-based resin cement Premier® decreases the cell cytotoxicity, ROS production, and DNA-DSBs associated with resin use, and further offers protective effects against the early stages of cell apoptosis and G1-phase cell cycle arrest in HGFs. Overall, our in vitro results indicate that the addition of NAC into methacrylate-based resin cements may have clinically beneficial effects on the cytotoxicity and genotoxicity of these materials.

Objective: The aim was to investigate the ability of superb microvascular imaging (SMI) to improve the differential diagnosis of mummified thyroid nodules (MTNs) and papillary thyroid carcinomas (PTCs) using the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). Materials and methods: We enrolled 110 cases of MTNs and 110 cases of PTCs confirmed by fine needle aspiration (FNA) or surgery. Conventional ultrasound (US) and the quantity of microvessels detected by SMI were analyzed for all nodules. Thyroid nodules were initially categorized by ACR-TIRADS based on US imaging features and then reclassified based on ACR-TIRADS combined with SMI blood-flow grade (SMI-TIRADS). We compared the diagnostic performances of ACR-TIRADS and SMI-TIRADS by receiver operating characteristic curve, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). Results: US-detected margin, shape, and echogenic foci differed between MTNs and PTCs (P < 0.05). The SMI blood-flow grade was significantly greater in PTCs compared with MTNs (Χ2 = 158.78, P < 0.05). There was no significant difference in ACR-TIRADS indicators between MTNs and PTCs (Χ2 = 1.585, P = 0.453); however, reclassification by SMI-TIRADS showed significant differences between the groups (Χ2 = 129.521, P < 0.001). The area under the curve was significantly lower for ACR-TIRADS compared with SMI-TIRADS (0.517 vs 0.887, P < 0.05). SMI-TIRADS had significantly higher diagnostic value for distinguishing MTNs and PTCs than ACR-TIRADS (sensitivity: 91.82% vs 74.55%, P < 0.05; specificity: 84.55% vs 21.82%, P < 0.05; accuracy: 88.18% vs 48.18%, P < 0.05; PPV: 85.59% vs 48.81%, P < 0.05; and NPV: 91.18% vs 46.15%, P < 0.05). Conclusion: The detection of microvascular flow and large vessels in thyroid nodules by SMI resulted in high diagnostic specificity and sensitivity. ACR-TIRADS combined with SMI could effectively distinguish between MTNs and PTCs, to avoid unnecessary FNA or surgical excision.

In order to study the difference effects of wheat bran dietary fiber (WBDF) and raw wheat bran (RWB) on the quality of steamed bread, WBDF was prepared by complex enzyme hydrolysis (moderate temperature α-amylase, cellulase, and alkaline protease), the sensory quality, textural property, in vitro starch digestibility and microstructure of steamed bread with different WBDF and RWB addition level were determined by millet replacement method, colorimeter, texture analyzer, in vitro simulated total starch hydrolysis method and SEM. The different effects between WBDF and RWB on the quality and property of steamed bread were compared under the same total dietary fiber content in the mixed flour. The results showed that both WBDF and RWB could affect the quality of steamed bread, but they could also inhibit the in vitro digestion of starch in steamed bread. When the total dietary fiber content was same, the steamed bread in WBDF group had larger specific volume, deeper color, rounder and plumper appearance, less separation of skin and pulp, higher bulkiness, lower internal structure density, better texture (low hardness, high springiness, low chewiness, and high resilience), more continuous and smooth microstructure, besides the damage of gluten network was lower than that of the steamed bread of RWB group. RWB had a slightly more ability to inhibit starch digestion than WBDF. The results suggested that compared with raw wheat bran, the relatively pure wheat bran dietary fiber was a more potential form of dietary fiber supplement under the condition of achieving the same dietary fiber supplement requirements, which was more conducive to developing good quality high-fiber wheat products.

Phase transformation is a crucial factor that determines the quality and deformation of components in laser-directed energy deposition (L-DED). Owing to the limitations of in situ observation methods, there is a lack of effective means to study the complete phase transformation and their impacts on deformation during the deposition process. In this study, multilayer heterogeneous deposition was investigated with the high-carbon high-speed steel by modelling the coupled phase transformation-thermomechanical physics. The methodology was proposed to identify the specific phase transformations by iteratively comparing the whole deformation history between digital image correlation (DIC) measurements and simulations. Besides the thermo-mechanical coupling effect and basic volumetric phase transformation, carbon partitioning between precipitated carbides and matrix was manifested, which also resulted in a rise of the Ms point by 208.4 °C and a reduction of the transformation rate by 73.2%. Additionally, an increase of 13.8% in energy absorption could be attributed to the surface oxidation of the deposited layer. The model predictions exhibited good consistency with the DIC in-situ measurement data, indicating that the deformation history contained sufficient information on the phase transformations. Based on the proposed transformation-thermomechanical coupling model, it helps to understand the complete phase transformation during deposition.

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students’ enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university’s official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students’ exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Abstract Density dependence and habitat filtering have been proposed to aid in understanding community assembly and species coexistence. Phylogenetic relatedness between neighbors was used as a proxy for assessing the degree of ecological similarity among species. There are different conclusions regarding the neighborhood effect in previous studies with different phylogenetic indices or at different spatiotemporal scales. However, the effects of density dependence, neighbor phylogenetic relatedness, and habitat filtering on seedling survival with different phylogenetic indices or at different temporal and spatial scales are poorly understood. We monitored 916 seedlings representing 56 woody plant species within a 4‐ha forest dynamics plot for 4 years (from 2020 to 2023) in a subtropical mid‐mountain moist evergreen broad‐leaved forest in the Gaoligong Mountains, Southwestern China. Using generalized linear mixed models, we tested whether and how four phylogenetic indices: total phylogenetic distance (TOTPd), average phylogenetic distance (AVEPd), relative average phylogenetic distance (APd′), and relative nearest taxon phylogenetic distance (NTPd′), three temporals (1, 2, and 3 years), and spatial scales (1, 2, and 4 ha) affect the effect of density dependence, phylogenetic density dependence, and habitat filtering on seedling survival. We found evidence of the effect of phylogenetic density dependence in the 4‐ha forest dynamics plot. The effects of density dependence, phylogenetic density dependence, and habitat filtering on seedling survival were influenced by phylogenetic indices and temporal and spatial scales. The effects of phylogenetic density dependence and habitat filtering on seedling survival were more conspicuous only at 1‐year intervals, compared with those at 2‐ and 3‐year intervals. We did not detect any effects of neighborhood or habitat factors on seedling survival at small scales (1 and 2 ha), although these effects were more evident at the largest spatial scale (4 ha). These findings highlight that the effects of local neighborhoods and habitats on seedling survival are affected by phylogenetic indices as well as temporal and spatial scales. Our study suggested that phylogenetic index APd′, shortest time scale (1 year), and largest spatial scales (4 ha) were suitable for neighborhood studies in a mid‐mountain moist evergreen broad‐leaved forest in Gaoligong Mountains. Phylogenetic indices and spatiotemporal scales have important impacts on the results of the neighborhood studies.

ABSTRACT Mixotrophy is an important trophic strategy for bacterial survival in the ocean. However, the global relevance and identity of the major mixotrophic taxa remain largely elusive. Here, we combined phylogenetic, metagenomic, and metatranscriptomic analyses to characterize ubiquitous Arcobacteraceae based on our deep-sea in situ incubations and the global data. The phylogenomic tree of Arcobacteraceae is divided into three large clades, among which members of clades A and B are almost all from terrestrial environments, while those of clade C are widely distributed in various marine habitats in addition to some terrestrial origins. All clades harbor genes putatively involved in chitin degradation, sulfide oxidation, hydrogen oxidation, thiosulfate oxidation, denitrification, dissimilatory nitrate reduction to ammonium, microaerophilic respiration, and metal (iron/manganese) reduction. Additionally, in clade C, more unique pathways were retrieved, including thiosulfate disproportionation, ethanol fermentation, methane oxidation, fatty acid oxidation, cobalamin synthesis, and dissimilatory reductions of sulfate, perchlorate, and arsenate. Within this clade, two mixotrophic Candidatus genera represented by UBA6211 and CAIJNA01 harbor genes putatively involved in the reverse tricarboxylic acid pathway for carbon fixation. Moreover, the metatranscriptomic data in deep-sea in situ incubations indicated that the latter genus is a mixotroph that conducts carbon fixation by coupling sulfur oxidation and denitrification and metabolizing organic matter. Furthermore, global metatranscriptomic data confirmed the ubiquitous distribution and global relevance of Arcobacteraceae in the expression of those corresponding genes across all oceanic regions and depths. Overall, these results highlight the contribution of previously unrecognized Arcobacteraceae to carbon, nitrogen, and sulfur cycling in global oceans.IMPORTANCEMarine microorganisms exert a profound influence on global carbon cycling and ecological relationships. Mixotrophy, characterized by the simultaneous utilization of both autotrophic and heterotrophic nutrition, has a significant impact on the global carbon cycling. This report characterizes a group of uncultivated bacteria Arcobacteraceae that thrived on the “hot time” of bulky particulate organic matter and exhibited mixotrophic strategy during the in situ organic mineralization. Compared with clades A and B, more unique metabolic pathways were retrieved in clade C, including the reverse tricarboxylic acid pathway for carbon fixation, thiosulfate disproportionation, methane oxidation, and fatty acid oxidation. Global metatranscriptomic data from the Tara Oceans expeditions confirmed the ubiquitous distribution and extensive transcriptional activity of Arcobacteraceae with the expression of genes putatively involved in carbon fixation, methane oxidation, multiple sulfur compound oxidation, and denitrification across all oceanic regions and depths.

Summary: Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to immune checkpoint inhibitors in non-small cell lung cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use. Here, we constructed high-mesoporous Mn-based nanocarrier loading metformin nanoparticles (Mn-MSN@Met-M NPs) that actively target tumors and respond to release higher concentration of Mn2+ ions and metformin. The NPs significantly enhanced the T cells to kill lung cancer cells with the STK11 mutant. The mechanism shows that enhanced STING pathway activation promotes STING, TBKI, and IRF3 phosphorylation through Mn2+ ions and metformin release from NPs, thus boosting type I interferon production. In vivo, NPs in combination with a PD-1 inhibitor effectively decreased tumor growth. Collectively, we developed a Mn-MSN@Met-M nanoactivator to intensify immune activation for potential cancer immunotherapy.

In contemporary times, tumors have emerged as the primary cause of mortality in the global population. Ongoing research has shed light on the significance of neurotransmitters in the regulation of tumors. It has been established that neurotransmitters play a pivotal role in tumor cell angiogenesis by triggering the transformation of stromal cells into tumor cells, modulating receptors on tumor stem cells, and even inducing immunosuppression. These actions ultimately foster the proliferation and metastasis of tumor cells. Several major neurotransmitters have been found to exert modulatory effects on tumor cells, including the ability to restrict emergency hematopoiesis and bind to receptors on the postsynaptic membrane, thereby inhibiting malignant progression. The abnormal secretion of neurotransmitters is closely associated with tumor progression, suggesting that focusing on neurotransmitters may yield unexpected breakthroughs in tumor therapy. This article presents an analysis and outlook on the potential of targeting neurotransmitters in tumor therapy.

Background: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. Methods: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. Results: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were − 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions. Conclusion: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.

Cynoglossus semilaevis (half-smooth tongue sole) is an important aquaculture species that has a ZW/ZZ sex-determination system (females, ZW; males, ZZ). Some genotypic females may develop phenotypic males, and are known as pseudomales (ZW). These pseudomales can develop mature testes and produce sperm. However, previous studies have shown that pseudomales cannot produce sperms bearing W chromosome (W sperm). In this study, transcriptomic, proteomic, and ubiquitinated proteomic analyses were employed simultaneously to investigate the differences in gonads between pseudomales and normal males. Functional enrichment analysis of the differentially expressed genes/proteins showed that non-coding RNA metabolic processes and RNA degradation were more active in the gonads of pseudomales, and they showed higher levels of ubiquitination compared to males. In addition, most genes/proteins related to sperm morphogenesis expressed downwards in pseudomales. These genes included genes located exclusively on the Z chromosome, such as sperm flagellar protein 2 (spef2), doublesex and mab-3 related transcription factor 1 (dmrt1), doublesex and mab-3 related transcription factor 3 (dmrt3), and cilia- and flagella-associated protein 157 (cfap157). These findings characterized the transcriptional and proteomic profiles of the gonads of pseudomales and males, and suggested that W sperm were absent in pseudomales, possibly due to the disruption of sperm morphogenesis, resulting from W chromosome lacking spermatogenesis-related genes.

Dendritic fibrous nano silica (DFNS) was functionalized through the utilization of graphene oxide (GO) as a long-lasting anchoring agent. Consequently, the LaFeO3 nanoparticles were evenly spread out without clumping over the DFNS/GO. The supramolecular polymerized GO served the dual purpose of preventing the restacking of graphene sheets and functioned as a supplier of nitrogen to create active sites for the bonding of LaFeO3 nanoparticles. The nitrogen content above the extent of the GO films was modified by LaCl3·7 H2O and Fe(NO3)3·9H2O ions to synthesize LaFeO3 nanoparticles. The catalytic properties of DFNS/GO-LaFeO3 was observed in the reaction between CO2 and oxetane and epoxide, leading to the production of the corresponding polycarbonates. The results indicated that DFNS/GO-LaFeO3 significantly enhanced the efficiency of synthesizing poly(propylene carbonate) and poly(trimethylene carbonate) from carbon dioxide. This approach offers substantial benefits, including high economic efficiency. The union reaction of CO2 and highly substituted epoxides sourced from sustainable sources such as discarded vegetable oils and fatty acids resulted in the production of novel cyclic carbonates of bio-origin. This reaction occurred under gentle and solvent-free conditions using DFNS/GO-LaFeO3 as a catalyst. The DFNS/GO-LaFeO3 exhibited a high capacity for CO2 uptake with exceptionally rapid kinetics. The nanoplate morphology of DFNS/GO-LaFeO3 facilitated the formation of a satisfactory outer layer for carbon dioxide uptake at each metal site. Consequently, the nanoplate morphology of DFNS/GO-LaFeO3 ensured systematic carbon dioxide emission, guaranteeing a complete reaction with the entire sheet and enabling rapid CO2 adsorption kinetics.

Abstract Background Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. Patients and Methods We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9), respectively. A multivariable logistic regression model was employed to establish the model structure. Results In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS‐A score, HADS‐D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82–0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. Conclusion This study built an easy‐to‐use, good‐performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Abstract Objectives Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. Methods A multicenter cross‐sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. Results About one‐third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p

Rice body synovitis (RBS) is a rare disease, especially in children. Rheumatoid disorders and tuberculosis are the first two reasons for the formation of the RB. The diagnosis is mainly based on imaging and histopathological features. Herein, we report three cases of RBS in children diagnosed with congenital synovial chondromatosis, tuberculosis (unconfirmed), and ANA -positive juvenile idiopathic arthritis. Clinical features, radiographic findings, pathophysiology, treatment process, and prognosis were reviewed and documented meticulously to enhance cognition in this population and provide some references for clinicians in diagnosing and treating the disease.

The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter “PD-1-CD28-TCR-T” or “CD19 CAR-TCR-T” cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified through transduction with a plasmid encoding the PD-1-CD28-T2A-CD19 CAR) were evaluated in vivo. PD-1-CD28-TCR-T cells showed a formidable anti-tumor ability that was not subject to PD-1/PD-L1 signaling in vivo. CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor abilities both in vitro and in vivo. Three patients with refractory solid tumors received S-TILs infusion. No treatment-related mortality was observed, and none of the patients experienced serious side effects. One patient with melanoma achieved a partial response, and two patients with colon or kidney cancer achieved long-term stable disease following S-TILs therapy. To the best of our knowledge, this is the first study describing the safety and efficacy of the adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer.

This study aims to develop new quaternary ammonium salt-based antimicrobial materials with good biocompatibility, biosafety, and strong antimicrobial properties that promote wound healing in infected wounds. First, four new quaternary ammonium salt antibacterial fibers (QASAF) are constructed: QASAF-C12, QASAF-C14, QASAF-C16, and QASAF-C18, with varying carbon chain lengths of C12, C14, C16, and C18, respectively. Then, their structure is characterized by proton nuclear magnetic resonance (NMR) analysis and their hemolytic and cytotoxic properties are also investigated. QASAFs are then evaluated for in vivo and in vitro antimicrobial performance against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA). Finally, the effect of QASAF on promoting wound healing in infected wounds is evaluated using mouse wound models infected with S. aureus and MRSA. The obtained results suggest that QASAF is non-toxic to cells in the 25–125 µg/mL concentration range, is slightly hemolytic, has good biocompatibility, and has a biosafety profile. QASAF-C18 shows the best antibacterial performance against S. aureus with significant pro-healing effects on infected wounds. QASAF-C12 exhibits the best antibacterial performance against MRSA with significant pro-healing effects. The novel quaternary ammonium-based antimicrobial material provides a reference for developing antimicrobial and biocompatible wound dressings.