Search

Abstract The transition from the swimming larval stage to the settlement stage represents a significant node in the marine sponge developmental process. Previous research has shown that the outer membrane vesicles (OMVs) from the bacterial species Tenacibaculum mesophilum associated with the sponge Tedania sp. influence larval settlement: low concentrations of OMVs increase the attachment rate, whereas high concentrations decrease the attachment rate. Here, by comparing the transcriptomes of sponge larvae in filtered seawater (FSW group) and in FSW supplemented with OMVs (FSW-OMV group), the results indicated that bacterial OMVs affected larval settlement by modulating the expression levels of apoptosis-inducing factor (AIF) in the host. Subsequently, quantitative real-time PCR revealed a decrease in aif expression near the time of settlement (SE) compared to that in the control group. RNA interference (RNAi) was used to target the aif gene, and the rate of larval settlement was significantly reduced, confirming the inhibitory effect of high concentrations of OMVs. Moreover, small RNA (sRNA) sequencing of OMVs revealed the existence of abundant AIF-sRNAs of 30 nt, further suggesting that one pathway for the involvement of sponge-associated bacteria in host development is the transport of OMVs and the direct function of cargo loading.

Abstract The buried interface tens of nanometers beneath the solid-liquid junction is crucial for photocarrier extraction, influencing the overall efficiency of photoelectrochemical devices. Precise characterization of the interfacial properties is essential for device optimization but remains challenging. Here, we directly probe the in situ transformation of a Cu x O interlayer at the NiO/n-Si interface by hard X-ray photoelectron spectroscopy. It is found that Cu(I) in the Cu x O interlayer gradually transforms to Cu(II) with air exposure, forming an energetically more favorable interface and improving photoanode’s efficiency. Based on this finding, a reactive e-beam evaporation process is developed for the direct deposition of a CuO interlayer, achieving a half-cell solar-to-hydrogen efficiency of 4.56% for the optimized NiO/CuO/n-Si heterojunction photoanode. Our results highlight the importance of precision characterization of interfacial properties with advanced hard X-ray photoelectron spectroscopy in guiding the design of efficient solar water-splitting devices.

The connectivity of urban river networks plays an important role in cities in many aspects, such as urban water safety, water quality (WQ), and aquatic ecological balance. This study focuses on the river network and the Majiawan Wetland in the Chaoyang District of Beijing by establishing a two-dimensional hydrological WQ model employing various water allocation schemes between the river network and the wetland. Water circulation and WQ are the main indexes, and the effects of different scenarios on improving water circulation and WQ are simulated and compared. This study demonstrates that the addition of water replenishment at the intersection of river network and internal slow-water zones of the wetland (Scheme 2) has greater effectiveness in improving both hydrology and WQ compared to two other schemes. The water area of the Majiawan Wetland has expanded, and water velocity has increased. Using chemical oxygen demand, total nitrogen, and total phosphorus as the index values for determining the water class, the WQ of about 20% of the wetland area was reached Water Class II (domestic drinking water), with Water Class III (general industrial water) accounting for the other 80%. This study provides valuable evaluation and reference for similar areas of urban river network connectivity. HIGHLIGHTS This study established a comprehensive hydrological and water quality model for the urban river network-wetlands system.; We simulated and analyzed the water cycle allocation schemes of the urban river network-wetlands from the water allocation, water quality index changes and environmental impact evaluation, by using the established mathematical model.; The research results would offer valuable insights for optimizing water resource allocation and improving water quality in the study area and similar water systems.;

Abstract Falls can cause serious health problems in the elderly. China is gradually entering a moderately aging society. In rural areas of China, the elderly are at a higher risk of falling. This study aims to explore and analyze the factors affecting the fall risk of elderly people in rural areas of China, and provide theoretical basis for reducing the fall risk of elderly people. M County, Anhui Province, China was selected as the survey site by the typical field sampling method, and the elderly people in rural areas were selected as the research objects. A total of 1187 people were investigated. Mann–Whitney U test and Kruskal–Wallis H test were used for univariate analysis, and multiple linear regression was used for multivariate analysis. Chronic diseases, multimorbidity, daily living ability, mental health, working status and family doctors are the factors that influence falls among elderly people in rural areas of China (P

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues’ diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

Abstract Introduction This study aimed to validate the effectiveness, safety and feasibility of water‐filtered infrared A radiation (WIRA) whole‐body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real‐world clinical application prospects. Methods This open‐label single‐arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole‐body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. Results Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow‐up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune‐related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune‐activated cells. Conclusions HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

IntroductionThe prevention and mitigation of intestinal immune challenge is crucial for poultry production. This study investigated the effects of dietary Macleaya cordata extract (MCE) supplementation on the prevention of intestinal injury in broiler chickens challenged with lipopolysaccharide (LPS).MethodsA total of 256 one-day-old male Arbor Acres broilers were randomly divided into 4 treatment groups using a 2×2 factorial design with 2 MCE supplemental levels (0 and 400 mg/kg) and 2 LPS challenge levels (0 and 1 mg/kg body weight). The experiment lasted for 21 d.Results and discussionThe results showed that MCE supplementation increased the average daily feed intake during days 0-14. MCE supplementation and LPS challenge have an interaction on the average daily gain during days 15-21. MCE supplementation significantly alleviated the decreased average daily gain of broiler chickens induced by LPS. MCE supplementation increased the total antioxidant capacity and the activity of catalase and reduced the level of malondialdehyde in jejunal mucosa. MCE addition elevated the villus height and the ratio of villus height to crypt depth of the ileum. MCE supplementation decreased the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the jejunum. MCE addition mitigated LPS-induced mRNA up-expression of pro-inflammatory factors IL-1β and IL-17 in the jejunum. MCE supplementation increased the abundance of probiotic bacteria (such as Lactobacillus and Blautia) and reduced the abundance of pathogenic bacteria (such as Actinobacteriota, Peptostretococcaceae, and Rhodococcus), leading to alterations in gut microbiota composition. MCE addition altered several metabolic pathways such as Amino acid metabolism, Nucleotide metabolism, Energy metabolism, Carbohydrate metabolism, and Lipid metabolism in broilers. In these pathways, MCE supplementation increased the levels of L-aspartic acid, L-Glutamate, L-serine, etc., and reduced the levels of phosphatidylcholine, phosphatidylethanolamine, thromboxane B2, 13-(S)-HODPE, etc. In conclusion, dietary supplementation of 400 mg/kg MCE effectively improved the growth performance and intestinal function in LPS-challenged broiler chickens, probably due to the modulation of gut microbiota and plasma metabolites.

ObjectiveThe aim of this study was to understand the psychological insulin resistance status among Chinese patients with type 2 diabetes and investigate its associated factors in these patients.MethodsA multi-stage stratified random sampling was performed to randomly select patients with type 2 diabetes from the eastern, central, and western regions in Shandong Province, China, and 660 valid questionnaires were collected. Psychological insulin resistance was assessed by the scale of My Opinion on Insulin (MOI). Factors associated with psychological insulin resistance were examined in a binary logistic model.ResultsFour-fifths of the patients with type 2 diabetes (82.1%) had psychological insulin resistance. Being female (OR = 1.770, 95% CI: 1.063–2.950, p < 0.05), having a monthly income of greater than 4,000 Renminbi (approximately $1,540) (OR = 0.444, 95% CI: 0.216–0.915, p < 0.05), living with type 2 diabetes for 11 years or more (OR = 0.387, 95% CI: 0.238–0.630, p < 0.05), self-rated poor health (OR = 1.706, 95% CI: 1.092–2.664, p < 0.05), and moderate discrimination against type 2 diabetes (OR = 1.924, 95% CI: 1.166–3.175, p < 0.05) were associated with psychological insulin resistance.ConclusionsThe prevalence of psychological insulin resistance among Chinese patients with type 2 diabetes is relatively high. Approaches are needed to address the issue of psychological insulin resistance of type 2 diabetes.

In this study, high-throughput sequencing and metabolomics analysis were conducted to analyze the microbial and metabolites of dry-cured Sanchuan ham, Laowo ham, Nuodeng ham, and Heqing ham that have fermented for two years produced from western Yunnan China. Results showed that at the genus level, the dominant bacteria in the four types of ham were Halomonas and Staphylococcus, while the dominant fungi were Aspergillus and Yamadazyma. A total 422 different metabolites were identified in four types of ham, mainly amino acids, peptides, fatty acids, and their structural analogs, which were involved in pantothenate and coenzyme A biosynthesis, caffeine, and tyrosine metabolism. The dominant microorganisms of the four types of ham were mainly related to the metabolism of fatty acids and amino acids. This research enhances the identification degree of these four types of dry-cured ham and provides a theoretical basis for developing innovative and distinctive ham products.

The flame propagation processes of MgH2 dust clouds with four different particle sizes were recorded by a high-speed camera. The dynamic flame temperature distributions of MgH2 dust clouds were reconstructed by the two-color pyrometer technique, and the chemical composition of solid combustion residues were analyzed. The experimental results showed that the average flame propagation velocities of 23 μm, 40 μm, 60 μm and 103 μm MgH2 dust clouds in the stable propagation stage were 3.7 m/s, 2.8 m/s, 2.1 m/s and 0.9 m/s, respectively. The dust clouds with smaller particle sizes had faster flame propagation velocity and stronger oscillation intensity, and their flame temperature distributions were more even and the temperature gradients were smaller. The flame structures of MgH2 dust clouds were significantly affected by the particle sinking velocity, and the combustion processes were accompanied by micro-explosion of particles. The falling velocities of 23 μm and 40 μm MgH2 particles were 2.24 cm/s and 6.71 cm/s, respectively. While the falling velocities of 60 μm and 103 μm MgH2 particles were as high as 15.07 cm/s and 44.42 cm/s, respectively, leading to a more rapid downward development and irregular shape of the flame. Furthermore, the dehydrogenation reaction had a significant effect on the combustion performance of MgH2 dust. The combustion of H2 enhanced the ignition and combustion characteristics of MgH2 dust, resulting in a much higher explosion power than the pure Mg dust. The micro-structure characteristics and combustion residues composition analysis of MgH2 dust indicated that the combustion control mechanism of MgH2 dust flame was mainly the heterogeneous reaction, which was affected by the dehydrogenation reaction.

Abstract Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

Abstract This ecological study examined the individual and joint impacts of natural–human factors on the spatial patterns of maternal and child health status in China at the provincial scale in 2020. We considered natural factors (forest coverage, average temperature, and total sulfur dioxide and particulate matter emissions) and human factors (economic development, urbanization, healthcare access, and education level). We combined maternal, infant, and under-five mortality rates into a composite maternal and child health index using the entropy method. The spatial autocorrelation analysis of this index highlighted distinct health patterns across provinces, whereas the geodetector method assessed the effects of natural–human factors on the patterns. A notable east–central–west stepwise decline in health status was observed. Global Moran’s I showed positive spatial clustering, with high–high clustering areas in the Yangtze River Delta and low–low clustering areas in western regions. Factor detection identified eight significant natural–human factors impacting maternal and child health, with total sulfur dioxide emission density having the greatest impact. The interaction between average schooling years and total sulfur dioxide emission notably affected maternal and child health patterns. The study concludes that natural–human factors critically affect the spatial distribution of maternal and child health.

Abstract Plants usually produce defence metabolites in non-active forms to minimize the risk of harm to themselves and spatiotemporally activate these defence metabolites upon pathogen attack. This so-called two-component system plays a decisive role in the chemical defence of various plants. Here, we discovered that Panax notoginseng, a valuable medicinal plant, has evolved a two-component chemical defence system composed of a chloroplast-localized β-glucosidase, denominated PnGH1, and its substrates 20(S)-protopanaxadiol ginsenosides. The β-glucosidase and its substrates are spatially separated in cells under physiological conditions, and ginsenoside hydrolysis is therefore activated only upon chloroplast disruption, which is caused by the induced exoenzymes of pathogenic fungi upon exposure to plant leaves. This activation of PnGH1-mediated hydrolysis results in the production of a series of less-polar ginsenosides by selective hydrolysis of an outer glucose at the C-3 site, with a broader spectrum and more potent antifungal activity in vitro and in vivo than the precursor molecules. Furthermore, such β-glucosidase-mediated hydrolysis upon fungal infection was also found in the congeneric species P. quinquefolium and P. ginseng. Our findings reveal a two-component chemical defence system in Panax species and offer insights for developing botanical pesticides for disease management in Panax species.

Abstract Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the “first responders” in the context of cancer development. In this literature review, we provide an updated understanding of NK cell development, functions, and their applications in disease therapy. Furthermore, we explore the rationale for utilizing engineered NK cell therapies, such as CAR-NK cells, and discuss the differences between CAR-T and CAR-NK cells. We also provide insights into the key elements and strategies involved in CAR design for engineered NK cells. In addition, we highlight the challenges currently encountered and discuss the future directions in NK cell research and utilization, including pre-clinical investigations and ongoing clinical trials. Based on the outstanding antitumor potential of NK cells, it is highly likely that they will lead to groundbreaking advancements in cancer treatment in the future.

The development of China’s superhard industry in the first half of 2023 is analyzed according to statistical data, as well as the import & export data of customs and the national macroeconomic indicators. It is found that the industry falls short of development expectations due to the structural adjustment of the manufacturing industry. The main indicators, including the total industrial output value, the sales revenue, the total profit and the export delivery, all in a negative growth, especially the total profit who decreases 39.5% year-on-year. Against the backdrop of relative weak global markets, the export destinations are increasingly concentrated due to the rapid development of emerging economies. For example, the markets in the Middle East and Russia hava shown higher vitality. It is suggested that the companies take active decisions and explore emerging markets for breakthroughs in products and vitality in development.

Black tea is highly favored by consumers worldwide, with enzymatic reactions being recognized as a pivotal factor influencing tea quality. The role of microorganisms in shaping the composition of black tea has emerged as a focus of research due to their involvement in enzyme catalysis and metabolic processes. In this study, full-length amplicon sequencing combined with qPCR more accurately reflected microbial profile, and Pantoea, Pseudomonas, Paucibacter, and Cladosporium were identified as the main microbial genera. Moreover, by comprehensively analyzing color, aroma, and taste components over time in black tea samples, correlations were established between the dominant genus and various quality factors. Notably, peroxidase activity levels, total soluble sugar content, and tea pigments concentration exhibited significant associations with the dominant genus. Consequently, this microbiological perspective facilitated the exploration of driving factors for improving black tea quality while establishing a theoretical foundation for quality control in industrial production.

Abstract Background Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in‐depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies. Methods We integrated single‐cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three‐dimensional bioprinting technique, canonical ex vivo co‐culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME. Results This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte‐mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2‐phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand‐receptor‐based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications. Conclusions Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA. Key points Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA.

Summary: Many Gram-negative bacteria use type Ⅲ secretion system (T3SS) to inject effector proteins and subvert host signaling pathways, facilitating the growth, survival, and virulence. Notably, some bacteria harbor multiple distinct T3SSs with different functions. An extraordinary T3SS, the Escherichia coli Type III Secretion System 2 (ETT2), is widespread among Escherichia coli (E. coli) strains. Since many ETT2 carry genetic mutations or deletions, it is thought to be nonfunctional. However, increasing studies highlight ETT2 contributes to E. coli pathogenesis. Here, we present a comprehensive overview of genetic distribution and characterization of ETT2. Subsequently, we outline its functional potential, contending that an intact ETT2 may retain the capacity to translocate effector proteins and manipulate the host’s innate immune response. Given the potential zoonotic implications associated with ETT2-carrying bacteria, further investigations into the structure, function and regulation of ETT2 are imperative for comprehensive understanding of E. coli pathogenicity and the development of effective control strategies.

Freeway traffic volume is strongly correlated with the intensity of regional socioeconomic spatial interactions and the road network structure. Although existing studies have proposed indicators of betweenness centrality (BC) integrated into regional spatial interactions, the socio-economic drivers of freeway traffic volume formation have been neglected. More importantly, existing studies have not established a non-linear response relationship among BC, city socio-economic spatial interactions, and road traffic volume, which severely limits the comprehensive quantification of the role of freeway traffic flow drivers. Therefore, this study proposes a freeway traffic volume inference method that integrates spatial interaction to enhance BC. First, the socioeconomic factors of the origin and destination cities are incorporated into the BC indicator to create an enhanced betweenness centrality indicator (ODBC), which quantifies the strength of spatial interactions between cities. Second, a machine learning approach is used to develop the non-linear response relationship between ODBC and freeway traffic flow to accurately infer traffic volume. Finally, utilizing the SHapley additive explanation approach, the role vectors of intercity freeway traffic volume drivers are quantified. Experiments conducted on data from freeway toll stations demonstrate that the proposed method surpasses the baseline method based on BC and weighted by BC considering only the potential destination or origin city attractiveness, with an improvement in R2 of 14%, 4.2%, and 4%, and a maximum reduction in RMSE of 40%, 24.5%, and 26%. The proposed method yields higher accuracy for unknown road segments and is easily interpretable.

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto’s thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient’s condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.

IntroductionClostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear.MethodsIn vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms.Results and discussionThe results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1β, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-β (TGF-β), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Summary: Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.

Abstract Background Sexually transmitted and blood-borne infections (STBBIs) is a major public health concern in China. This study assessed the overall trends in STBBIs to improve the comprehensive understanding of the burden of STBBIs and provide evidence for their prevention and control. Methods Data for the period from 2005 to 2021 were analyzed across China on infections with hepatitis B or C; syphilis; gonorrhea; and HIV infection. Trends, annual percent change (APC), and average annual percent change (AAPC) in diagnosis rate was analyzed using joinpoint regression models for the five STBBIs together or individually. Results From 2005 to 2021, the overall diagnosis rate of all five STBBIs increased, with an AAPC of 1.3% [95% confidence interval (CI) -0.5% to 3.1%]. Diagnosis rates of HIV, syphilis and hepatitis C increased individually, but it decreased for infections of hepatitis B and gonorrhea. Joinpoint analysis identified four phases in diagnosis rate of hepatitis C; three phases in diagnosis rate of hepatitis B, HIV infection, and syphilis; two in diagnosis rate of gonorrhea infection. Conclusion Despite national efforts to prevent and control STBBIs, their overall diagnosis rate has continued to rise in China, and they remain an important public health challenge. Further efforts should be made to educate the general population about STBBIs, particularly HIV. Interventions targeting vulnerable groups should be adopted and their efficacy monitored through regular analysis of trends.

Abstract Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

Background: For locally advanced rectal cancer (LARC), accurate response evaluation is necessary to select complete responders after neoadjuvant therapy (NAT) for a watch-and-wait (W&W) strategy. Algorithms based on deep learning have shown great value in medical image analyses. Here we used deep learning algorithms of endoscopic images for the assessment of NAT response in LARC. Method: 214 LARC patients were retrospectively included in the study. After NAT, these patients underwent total mesorectal excision (TME) surgery. Among them, 51 (23.8%) of the patients achieved a pathological complete response (pCR). 160 patients from Shanghai Changzheng Hospital were regarded as primary dataset, and the other 54 patients from Zhejiang Cancer Hospital were regarded as validation dataset. ResNet-18 and DenseNet-121 were applied to train the models based on endoscopic images after NAT. Deep learning models were valid in the validation dataset and compared to manual method. Results: The performances were comparable in AUC between deep learning models and manual method. For mean metrics, sensitivity (0.750 vs. 0.417) and AUC (0.716 vs. 0.601) in ResNet-18 deep learning model were higher than those in the manual method. The deep learning models were able to identify the endoscopic features associated with NAT response by the heatmaps. A diagnostic flow diagram which integrated the deep learning model to assist the clinicians in making decisions for W&W strategy was constructed. Conclusions: We created deep learning models using endoscopic features for assessment of NAT in LARC. The deep learning models achieved modest accuracies and performed comparably to manual method.

Elucidating the water utilization strategy of trees during forest succession is a prerequisite for predicting the direction of forest succession. However, the water utilization characteristics of trees in forests across a successional gradient remain unclear. Here, we utilized the hydrogen and oxygen stable isotopes combined with the Bayesian mixed model (MixSIAR) to analyze the water utilization of dominant trees (Pinus massoniana, Castanea henryi, and Schima superba) in forests along a successional gradient in the Dinghushan Biosphere Reserve of China. Furthermore, we determined the primary factor affecting the water utilization of various trees based on variation partitioning analysis and a random forest model. Our results illustrated that in the early-successional forest, the water utilization ratios from shallow soil layers by P. massoniana were significantly lower than that in the mid-successional forest (51.3%–61.7% vs. 75.3%–81.4%), while its water utilization ratios from deep soil layers exhibited the opposite pattern (26.1%–30.1% vs. 9.0%–15.0%). Similarly, the ratios of water utilization from shallow soil layers by C. henryi (18.9%–29.5% vs. 32.4%–45.9%) and S. superba (10.0%–25.7% vs. 29.2%–66.4%) in the mid-successional forest were relatively lower than in the late-successional forest, whereas their water utilization ratios from deep soil layers showed the contrary tendency. Moreover, our results demonstrated that the diverse water utilization of each tree in different successional forests was mainly attributed to their distinct plant properties. Our findings highlight the increased percentage of water utilization of trees from shallow soil layers with forest succession, providing new insights for predicting the direction of forest succession under changing environments.

Bacterial outer membrane vesicles (OMVs) contain a variety of chemical compounds and play significant roles in maintaining symbiotic relationships in a changing ocean, but little is known about their function, particularly in sponge larval development. During the growth of sponge Tedania sp., OMVs from Bacteroidetes species significantly promoted larval settlement, and Tenacibaculum mesophilum SP-7-OMVs were selected as a representative strain for further investigation. According to OMVs metabolomics, larval settlement might be connected to organic acids and derivatives. The multiomics analysis of the T. mesophilum genome, SP-7-OMVs metabolome, and larval transcriptome revealed 47 shared KEGG pathways. Among the number of candidate metabolites, arginine was chosen for its greater ability to increase the settlement rate and its role as the principal substrate for nitric oxide (NO) synthesis of sponge larvae. In summary, these results demonstrated that sponge-associated bacteria might utilize OMVs and their cargo to support host development and make up for host metabolic pathway deficiencies. This study enhances our fundamental knowledge of OMVs in interactions between metazoan hosts and microorganisms that are crucial in the coevolution of marine ecosystems and the complex marine environment.

Clostridium perfringens α toxin is generated by all types of C. perfringens and is closely related to necrotic enteritis in poultry. This study was conducted to investigate the effects of α toxin on immune function, antioxidant capacity, intestinal health and the underlying mechanisms in broiler chickens. A total of 144 twenty-day-old broiler chickens were randomly assigned to four treatments. On d 21, the birds were intraperitoneally injected with PBS (control group) or α toxin at 0.025, 0.1 or 0.4 U/kg of body weight. Samples were collected at 3 h and 24 h post injection (p.i.). Results showed that α toxin challenge linearly decreased the average daily gain during the 3 days after infection and decreased plasma IgA and IgM levels 3 h p.i. Plasma diamine oxidase and d-lactate levels were linearly elevated by α toxin challenge at 3 h p.i. and 24 h p.i. Alpha toxin challenge linearly decreased plasma and jejunal mucosal catalase, glutathione peroxidase and total superoxide dismutase activities at 3 h p.i. and linearly decreased glutathione peroxidase and total superoxide dismutase activities at 24 h p.i. The ileal villus height to crypt depth ratio decreased linearly with increasing α toxin levels at 3 h p.i. and 24 h p.i. Alpha toxin challenge linearly elevated jejunal IL-1β, IL-6, IL-8 and tumor necrosis factor α mRNA expression at 3 h p.i. Additionally, α toxin challenge linearly reduced the jejunal claudin-1, claudin-3 and zonula occludens 1 mRNA expression at 3 h p.i. and the claudin-3, occludin and zonula occludens 1 mRNA expression at 24 h p.i. What's more, α toxin linearly increased the jejunal PLCγ1, AMPKα1 and ATG5 mRNA expression and linearly decreased the mTOR mRNA expression. In conclusion, C. perfringens α toxin challenge decreased body weight gain, impaired immune function, antioxidant capacity and intestinal health, and induced PLCγ1/AMPK/mTOR pathway-mediated autophagy. The recommended intraperitoneal injection dose for moderate injury was 0.1 U/kg of body weight and the recommended sampling time was 3 h p.i. in broiler chickens.

Objective. To retrospectively evaluate the efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) through a follow-up study of continuous postoperative surveillance and large-sample data. Methods. The efficacy of ultrasound-guided RFA was evaluated by measuring the tumor volume reduction rate (VRR), tumor disappearance rate, and disease progression in 358 patients with low-risk unifocal PTMC who underwent ultrasound-guided RFA at Hangzhou Weja Hospital, while the safety was evaluated by measuring their complications. Results. The VRR was −745.69 ± 1012.69 (%), −150.35 ± 395.5 (%), 46.47 ± 138.74 (%), 92.95 ± 27.88 (%), 97.78 ± 10.99 (%), and 99.27 ± 3.82 (%), respectively, at 1, 3, 6, 12, 18, and 24 months after RFA. The corresponding tumor disappearance rate was 1.68%, 9.78%, 43.85%, 82.68%, 92.59%, and 95.63%, respectively. No local recurrence, new tumors, lymph node metastasis, distant metastasis, and deaths caused by recurrent/metastatic PTMC were found at the last follow-up. Except for 3 cases (0.84%) with thickening or hoarseness of voice and 3 cases (0.84%) with coughing during drinking water, no other complications were found. Conclusions. Ultrasound-guided RFA has good efficacy and safety for the treatment of low-risk unifocal PTMC and can be promoted for use in patients who meet the required indications.

A better understanding of financial contagion and systemically important financial institutions (SIFIs) is essential for the prevention and control of systemic financial risk. Considering the ripple effect of financial contagion, we integrate the relevant spatiotemporal information that affects financial contagion and propose to use the ripple-spreading network to simulate the dynamic process of risk contagion in China’s financial system. In addition, we introduce the smooth-transition vector autoregression (STVAR) model to identify “high” and “low” systemic risk regimes and set the relevant parameters of the ripple-spreading network on this basis. The results show that risk ripples spread much faster in high than in low systemic risk regimes. However, systemic shocks can also trigger large-scale risk contagion in the financial system even in a low systemic risk regime as the risk ripple continues. In addition, whether the financial system is in a high or low systemic risk regime, the risk ripples from a contagion source (i.e., a real estate company) spread first to the real estate sector and the banking sector. The network centrality results of the heterogeneous ripple-spreading network indicate that most securities and banks and some real estate companies have the highest systemic importance, followed by the insurance, and finally the diversified financial institutions. Our study provides a new perspective on the regulatory practice of systemic financial risk and reminds regulators to focus not only on large institutions but also on institutions with strong ripple capacity.

A survey on main economic indicators of Chinese superhard industry is conducted to reflect its development. Considering China’s macroeconomic data and the import and export trade of superhard commodities, the development situation of Chinese superhard industry is concluded. It is found that the overall development of the industry is benign, with 23.8% increase in operating revenue and 52.8% increase in operating profit, which are the highest in the past decade. The sales profit margin has reached 23.7, obviously higher than the average one of national enterprises above designated size. As with the imports and exports, the superhard industry has lower increase rates than the national average, more manifesting an internal circulation.

Hilbert$ ' $s 16th problem is extensively studied in mathematics and its applications. Arnold proposed a weakened version focusing on differential equations. While significant progress has been made for Hamiltonian systems, less attention has been given to integrable non-Hamiltonian systems. In recent years, investigating quadratic reversible systems in integrable non-Hamiltonian systems has gained widespread attention and shown promising advancements. In this academic context, our study is based on qualitative analysis theory. It explores the upper bound of the number of zeros of Abelian integrals for a specific class of quadratic reversible systems under perturbations with polynomial degrees of n. The Picard-Fuchs equation method and the Riccati equation method are employed in our investigation. The research findings indicate that when the degree of the perturbing polynomial is n ($ n\geq5 $), the upper bound for the number of zeros of Abelian integrals is determined to be $ 7n-12 $. To achieve this, we first numerically transform the Hamiltonian function of the quadratic reversible system into a standard form. By applying a combination of the Picard-Fuchs equation method and the Riccati equation method, we derive the representation of the Abelian integrals. Using relevant theorems, we estimate the upper bound for the number of zeros of the Abelian integrals, which consequently provides an upper bound for the number of limit cycles in the system. The research results demonstrate that when the perturbation polynomial degree is high or equal to n, the Picard-Fuchs equation method and the Riccati equation method can be applied to estimate the upper bound of the number of zeros of the Abelian integrals.

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.

The archetypal symbols of Mazu’s statues and pictorial art are the mapping of a religious concept, a way of belief, and some programmed behaviours and rituals. They are also emotional imagery used to arouse the cultural awareness of international Chinese, inspire them to help and trust each other, to encourage and to comfort each other, to share weal and woe, and to always forge ahead. From the perspectives of historical memory, visual signs, and cultural identity, this paper explores the construction of archetypal symbols for the statues and images of Mazu. In addition, this paper generalizes the foundation and methods of this construction by analyzing the artistic forms and characteristics of the surviving Mazu images and statues and comparing the rules and regulations for making statues of other religions. Moreover, we consider the function of artistic signs that refer to and symbolize broader religious concepts and beliefs. The purpose of this work is to make the image of Mazu more visually present and strengthen cultural identity.

During the period preceding the vegetation growing season (GS), temperature emerges as the pivotal factor determining phenology in northern terrestrial ecosystems. Despite extensive research on the impact of daily mean temperature (Tmean) during the preseason period, the influence of diurnal temperature range (DTR) on vegetation photosynthetic phenology (i.e., the impact of the plant photosynthetic cycle on seasonal time scale) has largely been neglected. Using a long-term vegetation photosynthetic phenology dataset and historical climate data, we examine vegetation photosynthetic phenology dynamics and responses to climate change across the mid–high latitudes of the Northern Hemisphere from 2001 to 2020. Our data reveal an advancing trend in the start of the GS (SOS) by −0.15 days per year (days yr−1), affecting 72.1% of the studied area. This is particularly pronounced in western Canada, Alaska, eastern Asia, and latitudes north of 60°N. Conversely, the end of the GS (EOS) displays a delaying trend of 0.17 days yr−1, impacting 62.4% of the studied area, especially northern North America and northern Eurasia. The collective influence of an earlier SOS and a delayed EOS has resulted in the notably prolonged length of the GS (LOS) by 0.32 days yr−1 in the last two decades, affecting 70.9% of the studied area, with Eurasia and western North America being particularly noteworthy. Partial correlation coefficients of the SOS with preseason Tmean, DTR, and accumulated precipitation exhibited negative values in 98.4%, 93.0%, and 39.2% of the study area, respectively. However, there were distinct regional variations in the influence of climate factors on the EOS. The partial correlation coefficients of the EOS with preseason Tmean, DTR, and precipitation were positive in 58.6%, 50.1%, and 36.3% of the region, respectively. Our findings unveil the intricate mechanisms influencing vegetation photosynthetic phenology, holding crucial significance in understanding the dynamics of carbon sequestration within terrestrial ecosystems amidst climate change.

In order to study the bactericidal mechanism of slightly acidic electrolyzed water (SAEW) against Salmonella enteritidis, the effects of SAEW on cell membrane permeability, cell membrane integrity, reactive oxygen species (ROS), and intracellular ATP of Salmonella enteritidis were studied. The results showed that 2.04 lg (CFU/g) of Salmonella enteritidis on the surface of eggshells was inactivated after the SAEW treatment at the available chlorine concentration of 10 mg/L for 1 min. Moreover, relative to the control group, the conductivity of bacterial suspension of Salmonella enteritidis was increased from 13.78±0.13 ms/cm to 16.32±0.10 ms/cm (P

Tunnels in karst areas are prone to collapse during construction. There are many analyses on the mechanism of tunnel collapse in mechanical aspects, but the mechanism of tunnel collapse in karst weak fracture zones and other strata were seldom examined. In order to ensure the safety, economy and feasibility of tunnel construction, it is necessary to master the mechanism of collapse in the tunnel construction. Relying on a tunnel project in a karst broken stratum in Guizhou, where the collapse phenomenon occurred during the excavation process, the monitoring data of the tunnel are examined, and the construction principle of the BP neural network is used to invert the stratum parameters of the tunnel. The inversion soil mechanical parameters are input into different construction models constructed by using the FLAC3D finite element software, and the collapse failure mechanism and risk of typical sections are judged and analyzed. The results show that the construction method has a great influence on the stability of the tunnel excavation, and for the tunnel with the surrounding rock grade V , the three-step seven-step method and the single-side wall pilot pit method are safer for construction, and the tunnel collapse has no relationship with the simultaneous excavation of the tunnel in both directions. The predicted value of the tunnel vault displacement obtained by the inversion is 2.3 cm, and the predicted value of the surface displacement is 1.2 cm. The deviation from the monitoring data is about 13%, and the inversion result has certain reliability. The research results are of important guiding significance for the construction of tunnels and highways in weak and broken strata in karst areas.

Objective(s): To explore the effects and mechanism of three types of fresh Rehmannia glutinosa, namely Beijing No. 3 (BJ3H), Huaizhong No. 1 (HZ1H), and Taisheng (TS) on lipopolysaccharide (LPS)-induced acute kidney injury in the sepsis (S-AKI) mice model through the estrogen receptor pathway.Materials and Methods: BALB/c mice were randomly divided into control (CON), model (LPS), astragalus injection (ASI), BJ3H, HZ1H, TS water extract groups, the estrogen receptor antagonist ICI182,780 groups were added to each group. The antagonist groups received an intraperitoneal injection of ICI 0.5 hr before administration and an intraperitoneal injection of LPS 3 days after administration. The kidney pathology, function, inflammatory factors, immune cells, levels of reactive oxygen species (ROS), apoptosis, and the protein expression levels of TLR4/NF-κB/NLRP3 signaling pathway in the mice kidneys were detected.Results: ASI, BJ3H, HZ1H, and TS improved LPS-induced renal pathology in S-AKI mice, reduced the kidney and serum levels of inflammatory factors, positive rates of macrophages and neutrophils, levels of ROS and apoptosis, and the relative expression levels of TLR4, MyD88, NF-κB p-p65/NF-κB p65, and NLRP3 proteins in the kidney. In addition, they increased the positive rate of dendritic cells (DCs) in the mice kidneys. The overall effect of HZ1H was superior to that of ASI, BJ3H, and TS. However, after adding ICI, the regulatory effects of drugs were inhibited.Conclusion: The three types of fresh R. glutinosa may completely or partially affect the TLR4/NF-κB/NLRP3 signaling pathway through the estrogen receptor pathway to exert a protective effect on S-AKI.

Abstract Background and objective Mental health imbalance are the main cause of anxiety, depression and happiness reduction in the older. Self-assessment living standard and sleep quality are both influencing factors of mental health. Meantime, self-assessment living standard has an impact on sleep quality. But there’s no research on the relationship between the three, we conducted this study to explore the relationship between self-assessment living standard and mental health and the mediating role of sleep quality among the older in rural areas of China. Methods Using typical field sampling method, M County, Anhui Province was selected as the investigation site, and a total of 1223 respondents were selected. With the help of questionnaires enclosing respondents’ sociodemographics information, 12 Items General Health Questionnaire (GHQ-12) and Pittsburgh Sleep Quality Scale (PSQI), face-to-face interviews were used to collect data. Bootstrap test was used for data analysis. Results The results showed that the age of the respondents ranged from 60 to 99 years, with an average age of (66.53 ± 6.77) years, the proportion of the older with a tendency to mental health problems was 24.7%. Most of the older people’s self-assessment living standard was normal (average score was 2.89 ± 0.726), accounting for 59.3% of the total. The average sleep quality score was (6.97 ± 4.066), and 2.5% of the respondents reported serious sleep problems. older with low self- assessment living standards were more likely to report a higher propensity for psychological problems (β = 0.420, P

Abstract Injectable hydrogels have attracted increasing attention for promoting systemic antitumor immune response through the co‐delivery of chemotherapeutics and immunomodulators. However, the biosafety and bioactivity of conventional hydrogel depots are often impaired by insufficient possibilities for post‐gelling injection and means for biofunction integration. Here, an unprecedented injectable stimuli‐responsive immunomodulatory depot through programming a super‐soft DNA hydrogel adjuvant is reported. This hydrogel system encoded with adenosine triphosphate aptamers can be intratumorally injected in a gel formulation and then undergoes significant molecular conformation change to stimulate the distinct release kinetics of co‐encapsulated therapeutics. In this scenario, doxorubicin is first released to induce immunogenic cell death that intimately works together with the polymerized cytosine‐phosphate‐guanine oligodeoxynucleotide (CpG ODN) in gel scaffold for effectively recruiting and activating dendritic cells. The polymerized CpG ODN not only enhances tumor immunogenicity but minimizes free CpG‐induced splenomegaly. Furthermore, the subsequently released anti‐programmed cell death protein ligand 1 (aPDL1) blocks the corresponding immune inhibitory checkpoint molecule on tumor cells to sensitize antitumor T‐cell immunity. This work thus contributes to the first proof‐of‐concept demonstration of a programmable super‐soft DNA hydrogel system that perfectly matches the synergistic therapeutic modalities based on chemotherapeutic toxicity, in situ vaccination, and immune checkpoint blockade.

Objective The present study investigated the province-level distribution and drivers of infant mortality rate (IMR) in mainland China.Design Ecological analysis based on publicly available data for all 31 provinces in mainland China.Data sources Data on province-level IMRs in 2020 were obtained from the official websites of the healthcare commissions within each province and from the China Health Statistics Yearbook 2021. Data on potential IMR drivers were retrieved from the China Statistical Yearbook 2021.Data analysis GeoDa V.1.12.1 and ArcMap V.10.2 software were used to examine province-level distribution of IMR. Global and local spatial autocorrelations were performed, and Getis-ord G* hotspots and coldspots were identified. Geodetector was used to analyse the individual and joint influence of drivers on IMR.Results IMRs in 2020 varied from 1.91 to 7.60 per 1000 live births across provinces. The following statistically significant drivers with q values >0.5 were identified: health literacy of the population (0.6673), male illiteracy rate (0.6433), proportion of the population older than >65 years (0.6369), per capita government health expenditure (0.6216), forest coverage rate (0.5820), per capita disposable income (0.5785), per capita number of hospitals (0.5592), per capita gross regional product (0.5410) and sulfur dioxide concentration in the atmosphere (0.5158). The following three interactions among these drivers emerged as strongest influences on province-level IMR: proportion of population >65 years ∩ per capita gross regional product (q=0.9653), forest coverage rate ∩ per capita gross regional product (0.9610) and per capita government health expenditure ∩ sulfur dioxide (0.9295).Conclusion IMR in mainland China varies substantially across the country, being generally high-west and low-east. Several factors, on their own and interacting together, contribute to IMR. Policies and programmes to reduce IMR should be formulated according to local conditions and should focus on western provinces of the country.

Objective: This study aims to investigate the level of knowledge, attitude and self-management behaviors of diabetic patients, to explore the mediating role of attitude in the relationship between knowledge and self-management behaviors.Methods: 900 diabetes patients were randomly selected from the eastern, central and western regions of Shandong Province, China, and recovered 863 valid questionnaires. Path analysis was used to examine the mediating role of attitude in the relationship between knowledge and self-management behaviors in patients with diabetes.Results: The mean score (SD) of the diabetes self-management questionnaire (DSMQ) in this study was 35.01 (6.87). The direct effect value of knowledge level on self-management behaviors was 0.357, accounting for 62.09% of the total effect. The indirect effect value of knowledge on self-management behaviors through attitude was 0.218, accounting for 37.91%.Conclusion: Level of knowledge has a significant direct impact on self-management behaviors and an indirect impact on self-management behaviors through attitude. Therefore, it is necessary to strengthen health education on diabetes to improve awareness, ameliorate attitudes toward diabetes, and change self-management behaviors.

The inappropriate use of antibiotics has led to the emergence of multidrug-resistant strains. Bacteriophages (phages) have gained renewed attention as promising alternatives or supplements to antibiotics. In this study, a lytic avian pathogenic Escherichia coli (APEC) phage designated as PEC9 was isolated and purified from chicken farm feces samples. The morphology, genomic information, optimal multiplicity of infection (MOI), one-step growth curve, thermal stability, pH stability, in vitro antibacterial ability and biofilm formation inhibition ability of the phage were determined. Subsequently, the therapeutic effects of the phages were investigated in the mice model. The results showed that PEC9 was a member of the siphovirus-like by electron microscopy observation. Biological characterization revealed that it could lyse two serotypes of E. coli, including O1 (9/20) and O2 (6/20). The optimal multiplicity of infection (MOI) of phage PEC9 was 0.1. Phage PEC9 had a latent period of 20 min and a burst period of 40 min, with an average burst size of 68 plaque-forming units (PFUs)/cell. It maintained good lytic activity at pH 3-11 and 4-50°C and could efficiently inhibit the bacterial planktonic cell growth and biofilm formation, and reduce bacterial counts within the biofilm, when the MOI was 0.01, 0.1, and 1, respectively. Whole-genome sequencing showed that PEC9 was a dsDNA virus with a genome of 44379 bp and GC content of 54.39%. The genome contains 56 putative ORFs and no toxin, virulence, or resistance-related genes were detected. Phylogenetic tree analysis showed that PEC9 is closely related to E. coli phages vB_EcoS_Zar3M, vB_EcoS_PTXU06, SECphi18, ZCEC10, and ZCEC11, but most of these phages exhibit different gene arrangement. The phage PEC9 could successfully protect mice against APEC infection, including improved survival rate, reduced bacterial loads, and organ lesions. To conclude, our results suggest that phage PEC9 may be a promising candidate that can be used as an alternative to antibiotics in the control of APEC infection.

PM2.5 emissions from heavy-duty diesel trucks (HDDTs) have a significant impact on air quality, human health, and climate change, and seriously threaten the UN Sustainable Development Goals. Globally, a series of emission control measures have been implemented to reduce pollution emissions from HDDTs. Current studies assessing the impact of these measures on air quality and human health have mainly used coarse-grained emission data as input to dispersion model, resulting in the inability to capture the spatiotemporal variability of pollutant concentrations and tending to increase the uncertainty of health impact assessment results. In this study, we quantified the impact of pollution control policies for HDDTs in Beijing on PM2.5 concentrations, human health, and economic losses by integrating policy scenario analysis, pollution dispersion simulation, public health impact and economic benefit assessment models, supported by high spatiotemporal resolution emission data from HDDTs. The results show that PM2.5 concentrations from HDDTs exhibit significant spatial aggregation characteristics, with the intensity of aggregation at night being about twice as high as that during the day. The emission hotspots are mainly concentrated in the sixth, fifth and fourth rings and major highways. Compared to the “business as usual” scenario in 2018, the current policy of updating the fuel standard to China VI and the emission standard to China 6 can reduce PM2.5 concentrations by 96.72%, thereby avoiding 612 premature deaths, which is equivalent to obtaining economic benefits of 1.65 billion CNY. This study further emphasizes the importance of high spatiotemporal resolution emission data during traffic dispersion modeling. The results can help improve the understanding of the effectiveness of emission reduction measures for HDDTs from a health benefit perspective.

ABSTRACT: The aim of this work was to investigate the effects of dietary vitamin K3 (VK3) supplementation on production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. A total of one hundred twenty 82-wk-old Wulong geese with similar body weights were randomly divided into 6 groups with 4 replicates and 5 geese each (1 male and 4 female). The geese in the control group were fed a basal diet, and the geese in the treatment groups were fed diets supplemented with different levels of VK3 (2.5, 5.0, 7.5, 10.0, and 12.5 mg/kg) for 11 wk. Dietary VK3 supplementation linearly and quadratically increased feed intake, egg mass, egg weight, and egg production (P < 0.05). Increasing VK3 levels linearly and quadratically increased albumen height, shell thickness and Haugh unit of eggs (P < 0.05). VK3 reduced osteocalcin (OC) and uncarboxylated osteocalcin (ucOC) levels in the serum. Dietary VK3 addition linearly decreased serum malondialdehyde (MDA) levels (P < 0.01). There was linear and quadratic effect in the activity of serum total superoxide dismutase (T-SOD) (P < 0.01), and linear effect in serum total antioxidant capacity (T-AOC) (P < 0.01). In conclusion, dietary VK3 supplementation enhanced the production performance, egg quality, vitamin K-dependent proteins, and antioxidant properties in breeding geese during the laying period. The optimal dose of dietary VK3 supplementation was 10.0 mg/kg.

【Objective】Microorganisms play a key role in the fermentation process of cigar tobacco leaves. In order to better improve the quality of cigar tobacco leaves, it is necessary to screen the dominant strains of cigars and apply them to the fermentation of cigar tobacco leaves. Therefore, it is necessary to optimize and expand the biomass of the dominant strains.【Method】16S sequencing and physiological and biochemical analysis were carried out on a dominant strain ZLX10 screened from cigars to identify the strain. At the same time, the composition of culture medium (carbon source, nitrogen source and inorganic salt) and culture conditions (inoculation amount, liquid content and seed age) were optimized through single factor and orthogonal test to improve its biomass.【Result】Based on 16S rDNA sequence comparison, the sequence homology between strain ZLX10 and Bacillus mojavensis (MT043920.1) reached 99.86%, and the strain had strong ability to degrade polysaccharide and protein macromolecule, which could be identified as Bacillus mojavenis. Through single factor and orthogonal test, the optimal medium formula of strain ZLX10 was obtained as follows: carbon source (sucrose) 50 g/L, nitrogen source (yeast extract) 20 g/L, inorganic salt (MgSO4) 0.25 g/L, and the optimal culture conditions were 1% (V/V) of inoculum, 30 mL/250 mL of liquid content, and 24 h of seed age. The biomass of strain ZLX10 was 1.98 times that before optimization when cultured under the optimal conditions for 24 h.【Conclusion】The biomass of strain ZLX10 can be significantly increased by optimizing the conditions, which provides a basis for artificial inoculation of fermented cigar tobacco leaves.

Under the background of the comprehensive implementation of the National Carbon Peak Carbon Neutralization Action, the superhard material industry energy consumption research was carried out. It aims to promote the superhard material industry to make new contributions to the green, low-carbon and high-quality development of the country. The energy consumption data of superhard material and product enterprises were summarized and analyzed, and the energy consumption of typical products in the inorganic non-metallic field was compared. The results show that from 2019 to 2021, the energy consumption per unit of gross industrial output value of superhard materials is 0.11, 0.10, and 0.08 tce/10 000¥; and that the energy consumption per unit of gross industrial output value of superhard materials products is 0.08, 0.07 and 0.05 tce/10 000¥ respectively. The reduction rate of energy consumption in superhard materials industry is far greater than the reduction percentage of national GDP energy consumption index. Compared with the typical products in the inorganic non-metallic field such as cement, ceramics and ordinary abrasives, the energy consumption in the superhard material industry is at a lower level. Finally, the paper makes suggestions on superhard industry policies and enterprise carbon reduction.