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Abstract To address immune escape, multi-specific CAR-T-cell strategies use natural ligands that specifically bind multiple receptors on malignant cells. In this context, we propose a split CAR design comprising a universal receptor expressed on T cells and ligand-based switch molecules, which preserves the natural trimeric structure of ligands like APRIL and BAFF. Following optimization of the hinges and switch labeling sites, the split-design CAR-T cells ensure the native conformation of ligands, facilitating the optimal formation of immune synapses between target cancer cells and CAR-T cells. Our CAR-T-cell strategy demonstrates antitumor activities against various B-cell malignancy models in female mice, potentially preventing immune escape following conventional CAR-T-cell therapies in the case of antigen loss or switching. This ligand-based split CAR design introduces an idea for optimizing CAR recognition, enhancing efficacy and potentially improving safety in clinical translation, and may be broadly applicable to cellular therapies based on natural receptors or ligands.

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm. For sperm morphology, we used the BlendMask segmentation method to segment individual sperm. SegNet was used to separate the head, midpiece, and principal piece comments from each sperm. Experienced in vivo sperm physicians confirmed a morphological accuracy percentage of 90.82%. A total of 1272 samples were collected from multiple tertiary hospitals for validation of the system, which were also evaluated by physicians. The results of our system were highly consistent with those of manual microscopy. This study realized the automated detection of progressive motility and morphology of sperm simultaneously, which is crucial for selection of morphologically normal and motile sperm for intracytoplasmic sperm injection.

Abstract Objective In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. Methods This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. Results 702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). Conclusions LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Microwave (MW)‐driven strategies could potentially offer transmissivity through obstacles, selective energization, wave‐focusing, and nonmechanical steering via phased‐array technologies, which have unique application prospects in confined environments. Implementing multidegree of freedom (MDOF) control is the key to developing motion strategies for advanced MW‐driven robots. However, the use of MWs for MDOF control of robots has so far remained a challenge. This article first presents examples of wireless driving and controlling millimeter‐scale peristaltic pipeline robots (diameter, 4 mm; length, 30 mm; weight, 0.39 g) utilizing multifrequency MWs in complex nonmetal channel environments. Herein, shape memory alloy springs combined with passive wires, whose length depends on the frequencies of MWs, are adopted to form selectively controlled robot components, and silicon rubber replica technology is utilized to achieve miniaturization of the robot. The monopole antenna model is developed for the actuator, and its structure is refined using antenna theory. This allows the successfully achievement of MDOF control of the robot at several MW frequencies (2.4, 4, and 5.9 GHz). Powered by MWs from outside the pipe, the pipeline robot achieves horizontal, vertical, and curved motions in a pipe with a diameter of 5 mm.

Abstract Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry‐based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.

Background Dexamethasone in conjunction with type 3 serotonin receptor antagonists are being used to the prevention and treatment of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting in clinic. The present study aimed to investigates the stability of ramosetron with dexamethasone in infusions, with the goal of enhancing the safety and clinical applicability of their combined use. Methods Ramosetron hydrochloride (3.0 μg/mL) combining with dexamethasone (0.05, 0.1, 0.2 mg/mL) were prepared with 0.9% sodium chloride injection and then packaged in polyolefin bags or glass bottles. The stability were investigated kept in the dark at refrigeration for 14 days and at room temperature for 48 h. Results The concentration of both drugs maintained at least 97% in the various solutions for both storage conditions with light protection. In the light exposure conditions, as the extension of storage time, the concentration of both drugs had declined. All antiemetic mixture solutions remained clear and no changes in color, turbidity, precipitation, and the pH remained stable. The insoluble particles were in line with Chinese Pharmacopoeia. Conclusion Our findings suggest that combinations of ramosetron hydrochloride with dexamethasone sodium phosphate in 0.9% sodium chloride injection remain stable for 14 days at 4°C and 48 h at 25°C when protected from light.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Abstract Background Tumor-associated macrophages (TAMs) significantly influence the progression, metastasis, and recurrence of esophageal squamous cell carcinoma (ESCC). The aberrant expression of long noncoding RNAs (lncRNAs) in ESCC has been established, yet the role of lncRNAs in TAM reprogramming during ESCC progression remains largely unexplored. Methods ESCC TAM-related lncRNAs were identified by intersecting differentially expressed lncRNAs with immune-related lncRNAs and performing immune cell infiltration analysis. The expression profile and clinical relevance of LINC00330 were examined using the TCGA database and clinical samples. The LINC00330 overexpression and interference sequences were constructed to evaluate the effect of LINC00330 on ESCC progression. Single-cell sequencing data, CIBERSORTx, and GEPIA were utilized to analyze immune cell infiltration within the ESCC tumor microenvironment and to assess the correlation between LINC00330 and TAM infiltration. ESCC-macrophage coculture experiments were conducted to investigate the influence of LINC00330 on TAM reprogramming and its subsequent effect on ESCC progression. The interaction between LINC00330 and C–C motif ligand 2 (CCL2) was confirmed through transcriptomic sequencing, subcellular localization analysis, RNA pulldown, silver staining, RNA immunoprecipitation, and other experiments. Results LINC00330 is significantly downregulated in ESCC tissues and strongly associated with poor patient outcomes. Overexpression of LINC00330 inhibits ESCC progression, including proliferation, invasion, epithelial–mesenchymal transition, and tumorigenicity in vivo. LINC00330 promotes TAM reprogramming, and LINC00330-mediated TAM reprogramming inhibits ESCC progression. LINC00330 binds to the CCL2 protein and inhibits the expression of CCL2 and downstream signaling pathways. CCL2 is critical for LINC00330-mediated TAM reprogramming and ESCC progression. Conclusions LINC00330 inhibited ESCC progression by disrupting the CCL2/CCR2 axis and its downstream signaling pathways in an autocrine fashion; and by impeding CCL2-mediated TAM reprogramming in a paracrine manner. The new mechanism of TAM reprogramming mediated by the LINC00330/CCL2 axis may provide potential strategies for targeted and immunocombination therapies for patients with ESCC. Graphical Abstract

Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.

Death receptor-mediated extrinsic apoptosis system had been developed as a promising therapeutic strategy in clinical oncology, such as TRAIL therapy. However, multiple studies have demonstrated that TRAIL resistance is the biggest problem for disappointing clinical trials despite preclinical success. Targeting cellular FLICE inhibitory protein (cFLIP) is one strategy of combinatorial therapies to overcome resistance to DR-mediated apoptosis due to its negative regulator of extrinsic apoptosis. E × 527 (Selisistat) is a specific inhibitor of SIRT1 activity with safe and well tolerance in clinical trials. Here, we show that E × 527 could strengthen significantly activation of rhFasL-mediated apoptotic signaling pathway and increased apoptotic rate of T leukemia cells with high expression of cFLIP. Mechanically, Inhibition of SIRT1 by E × 527 increased polyubiquitination level of cFLIP via increasing acetylation of Ku70, which could promote proteosomal degradation of cFLIP protein. It implied that combinatorial therapies of E × 527 plus TRAIL may have a potential as a novel clinical application for TRAIL-resistant hematologic malignancies.

Abstract Acquired bronchobiliary fistula (ABBF) is very rare among the complications that occur in patients with hepatocellular carcinoma (HCC) after treatment. Although surgery and drainage have been the main methods for treating ABBF for a long time, they are not entirely suitable for patients with refractory ABBF resulting from HCC therapy. In this study, we present four cases of ABBF caused by HCC treatment, who were treated using selective bronchial occlusion (SBO). Among the 4 patients with ABBF treated with SBO, 3 cases successfully blocked ABBF with SBO, and the treatment success rate was 75%. All successfully treated patients reported disappearance of symptoms of bilioptysis and cough was alleviated. No life‐threatening adverse reactions were reported following SBO intervention, and no deaths occurred. We believe that the use of video bronchoscopy to place a self‐made silicone plug in the bronchus to treat refractory ABBF is a feasible palliative treatment, which can significantly improve the condition of ABBF patients.

ABSTRACT Prevotella copri is the dominant species of the Prevotella genus in the gut, which is genomically heterogeneous and difficult to isolate; hence, scarce research was carried out for this species. This study aimed to investigate the effect of P. copri on hyperglycemia. Thirty-nine strains were isolated from healthy individuals, and three strains (HF2123, HF1478, and HF2130) that had the highest glucose consumption were selected to evaluate the effects of P. copri supplementation on hyperglycemia. Microbiomics and non-target metabolomics were used to uncover the underlying mechanisms. Oral administration of P. copri in diabetic db/db mice increased the expression and secretion of glucagon-like peptide-1 (GLP-1), significantly improved hyperglycemia, insulin resistance, and lipid accumulation, and alleviated the pathological morphology in the pancreas, liver, and colon. P. copri changed the composition of the gut microbiota of diabetic db/db mice, which was characterized by increasing the ratio of Bacteroidetes to Firmicutes and increasing the relative abundance of genera Bacteroides, Akkermansia, and Faecalibacterium. After intervention with P. copri, fecal metabolic profiling showed that fumaric acid and homocysteine contents decreased, and glutamine contents increased. Furthermore, amino acid metabolism and cAMP/PKA signaling pathways were enriched. Our findings indicate that P. copri improved glucose metabolism abnormalities in diabetic db/db mice. Especially, one of the P. copri strains, HF2130, has shown superior performance in improving hyperglycemia, which may have the potential as a probiotic against hyperglycemia.IMPORTANCEAs a core member of the human intestinal ecosystem, Prevotelal copri has been associated with glucose metabolic homeostasis in previous studies. However, these results have often been derived from metagenomic studies, and the experimental studies have been based solely on the type of strain DSM 18205T. Therefore, more experimental evidence from additional isolates is needed to validate the results according to their high genomic heterogeneity. In this study, we isolated different branches of strains and demonstrated that P. copri could improve the metabolic profile of hyperglycemic mice by modulating microbial activity. This finding supports the causal contribution of P. copri in host glucose metabolism.

AimTo determine the efficacy and safety of pharmacogenomics (PGx)-guided antidepressant prescribing in patients with depression through an umbrella review and updated meta-analysis.MethodsA comprehensive systematic search was conducted on PsycINFO, PubMed, Embase and the Cochrane databases. The pooled effect sizes of randomized controlled trials (RCTs) were expressed as mean differences for continuous data and risk ratios for noncontinuous data.ResultsPatients who received PGx-guided medications were 41% to 78% more likely to achieve remission and 20% to 49% more likely to respond to antidepressants than patients receiving treatment-as-usual (TAU).ConclusionPGx-guided antidepressant prescribing improves the treatment of depression. However, the significance and magnitude of the benefit varies widely between studies and different PGx testing panels.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022321324.

Quality silicate fertilizers should be in great demand, and yet the production has been limited due to strict regulations on heavy metals, despite many raw materials and activation methods being used. In the chemical deashing of coals for the production of ultraclean coals, the silica gels of high purity were precipitated with little heavy metals from the acid deashing solutions, which could be used to produce quality silicate fertilizers by pulping with CaO or MgO under mild conditions. By varying the Ca/Si molar ratios, silicate fertilizers with different chemical compositions were prepared, and the active silica contents were measured and validated by ICP and colorimetric methods. For the curve of the active silica contents versus the Ca/Si molar ratios, four regions could be clearly marked with unique patterns, and quality silicate fertilizers occurred with the Ca/Si molar ratios from ∼1.10 to ∼3.50. The pH values of the silicate fertilizers could also be divided into the same four regions with respect to the Ca/Si molar ratios, and the highest active silica content occurred at the pH value of ∼11.30 with the Ca/Si molar ratio of ∼1.50. With the XRD investigations of the silicate fertilizers selected from the four regions, the water-insoluble 1.5CaO·SiO2•xH2O was identified as the contributor of active silica in the silicate fertilizers. By replacing full or part of CaO with MgO in the preparation of silicate fertilizers, the silica gels were found to preferably react with CaO, and the active silica contents grew with the increase of CaO. By referring to the model silicate fertilizers prepared in this work by varying the (Ca + Mg)/Si molar ratios, 1.5CaO·SiO2•xH2O was also identified as the dominant in one commercial slag silicate fertilizer. Silicate fertilizers by silica gels can be helpful for secondary pollution elimination and cost reduction of coal deashing.

Probiotic Bacillus strains can solve the problems of single flavor and long fermentation time of fermented products caused by the lack of certain functional genes and insufficient metabolism ability of fermenter strains (Lactobacillus and Bifidobacterium) at the present stage. There is a lack of systematic evaluation and review of probiotic Bacillus as food fermentation agents. In this paper, it is observed that probiotic Bacillus strains are involved to varying degrees in liquid-state, semi-solid state, and solid-state fermentation and are widely present in solid-state fermented foods. Probiotic Bacillus strains not only produce abundant proteases and lipases, but also effective antifungal lipopeptides and extracellular polymers, thus enhancing the flavor, nutritional value and safety of fermented foods. Bacillus with probiotic qualities is an underutilized group of probiotic food fermentation agents, which give a potential for the development of fermentation technology in the food business and the integration of ancient traditional fermentation techniques.

Abstract Background Peutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS. Case presentation Here, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive “cosmos pattern” resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a “quick-up and slow-down” pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC. Conclusions Multimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.

Abstract Background Quercus aliena is a major montane tree species of subtropical and temperate forests in China, with important ecological and economic value. In order to reveal the species’ population dynamics, genetic diversity, genetic structure, and association with mountain habitats during the evolutionary process, we re-sequenced the genomes of 72 Q. aliena individuals. Results The whole chloroplast and nuclear genomes were used for this study. Phylogenetic analysis using the chloroplast genome dataset supported four clades of Q. aliena, while the nuclear dataset supported three major clades. Sex-biased dispersal had a critical role in causing discordance between the chloroplast and nuclear genomes. Population structure analysis showed two groups in Q. aliena. The effective population size sharply declined 1 Mya, coinciding with the Poyang Glaciation in Eastern China. Using genotype–climate association analyses, we found a positive correlation between allele frequency variation in SNPs and temperature, suggesting the species has the capacity to adapt to changing temperatures. Conclusion Overall, this study illustrates the genetic divergence, genomic variation, and evolutionary processes behind the demographic history of Q. aliena.

BackgroundThe accumulation of inorganic arsenic in the liver can lead to liver fibrosis. Solute carrier family 7 member 11 (SLC7A11) and cyclin dependent kinase inhibitor 1A (CDKN1A) are ferroptosis related genes that are abnormally expressed in liver and fibrosis diseases, but their impacts on inorganic arsenic induced liver fibrosis has not been reported yet. ObjectiveTo explore the effect of different doses of sodium arsenite on the migration ability of human hepatic stellate (LX-2) cells and the changes in DNA methylation and expression of SLC7A11 and CDKN1A in LX-2 cell activation induced by sodium arsenite. MethodsLX-2 cells were treated with different doses of sodium arsenite for 24 h. The experiment set up four groups: control group (0 μmol·L−1), low-dose group (5 μmol·L−1), medium-dose group (10 μmol·L−1), and high-dose group (15 μm·L−1). Possible morphological changes of LX-2 cells were observed under an inverted microscope in each group. Cell migration and movement were determined by cell scratch assay. Mitochondrial morphology was observed in the control and the high-dose groups under a transmission electron microscope (TEM). Fe2+ fluorescence intensity was detected with a FerroOrange fluorescence probe. Differentially methylated sites were screened using the Illumina 850 K methylation chip. Ferroptosis related markers (SLC7A11 & CDKN1A) and hepatic stellate cell activation related markers [transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Collagen Ⅲ)] were detected by real-time fluorescence quantitative PCR and Western blot. ResultsWith the increase of exposure dose, the cells retracted tentacles and gradually became round, and the healing of cell scratches gradually deteriorated. Destruction of mitochondrial membrane integrity and mitochondrial crista fracture in some cells were observed under a TEM in the high-dose group. Laser confocal microscopy showed that the fluorescence intensity of Fe2+ gradually increased with the increase of exposure dose. The results of methylation chip displayed that compared with the control group, high methylation was found in the high-dose group at the cg22659014 site in the promoter region of SLC7A11, and at the cg17964532 site in the promoter region of CDKN1A. With the increase of exposure dose, the mRNA and protein expression levels of SLC7A11 decreased (P0.05), and its protein expression levels in the low-, medium-, and high-dose groups were higher than that in the control group (P

Background: Stroke is a major cause of death globally and the leading cause in China. Excessive fluoride exposure has been linked to cardiovascular conditions related to stroke risk factors such as hypertension, atherosclerosis, dyslipidemia, and cardiomyopathy. However, evidence supporting the association between fluoride exposure and stroke risk is limited. Methods: We constructed an ecological study in Changwu Town, Heilongjiang Province, China, a typical endemic fluorosis area caused by excessive fluoride exposure from drinking water. We collected demographic data, stroke prevalence, and mortality information from 2017 to 2021. Fluoride exposure data were obtained from the national monitoring project on endemic fluorosis. Water fluoride concentrations were measured using the standardized methods. Trend changes in stroke rates were assessed using annual percentage change (APC). Differences in stroke rates among fluoride exposure groups were analyzed using chi-square tests. Results: From 2017 to 2021, the all-ages and age-standardized stroke prevalence rates of permanent residents in Changwu Town increased year by year, while the all-ages and age-standardized mortality rates did not change significantly. The prevalence rates of stroke were significantly higher in endemic fluorosis areas compared to non-endemic areas (p < 0.001). Stratifying the population into tertile groups based on the water fluoride cumulative exposure index (WFCEI) revealed statistically significant differences in stroke prevalence rates (p < 0.001), showing a dose–response relationship with the WFCEI. However, the all-ages and age-standardized mortality rates of stroke were not found to be related to fluoride exposure. Conclusions: Long-term excessive fluoride exposure from drinking water may increase the risk of stroke prevalence, indicating fluoride overexposure as a potential risk factor for stroke.

Photocatalysis technology, as an efficient and safe environmentally friendly purification technique, has garnered significant attention and interest. Traditional TiO2 photocatalytic materials still face limitations in practical applications, hindering their widespread adoption. The research prepared TiO2/Cu films with different Cu contents using a magnetron sputtering multi-target co-deposition technique. The incorporation of Cu significantly enhances the antibacterial properties and visible light response of the films. The effects of different Cu contents on the microstructure, surface morphology, wettability, antibacterial properties, and visible light response of the films were investigated using an X-ray diffractometer, X-ray photoelectron spectrometer, field emission scanning electron microscope, confocal laser scanning microscope, Ultraviolet–visible spectrophotometer, and contact angle goniometer. The results showed that the prepared TiO2/Cu films were mainly composed of the rutile TiO2 phase and face-center cubic Cu phase. The introduction of Cu affected the crystal orientation of TiO2 and refined the grain size of the films. With the increase in Cu content, the surface roughness of the films first decreased and then increased. The water contact angle of the films first increased and then decreased, and the film exhibited optimal hydrophobicity when the Cu target power was 10 W. The TiO2/Cu films showed good antibacterial properties against Escherichia coli and Staphylococcus aureus. The introduction of Cu shifted the absorption edge of the films to the red region, significantly narrowed the band gap width to 2.5 eV, and broadened the light response range of the films to the visible light region.

Foodborne spores are ubiquitous with extremely strong resistance, and pose a serious threat to food safety and human health. Therefore, rapid, sensitive, and selective detection of spores are crucial. In this study, a fluorescent probe was developed based on lanthanide ion (Eu3+)-labeled nano-silver-modified graphene oxide (GO-AgNPs-Eu3+) for the detection of 2,6-dipicolinic acid (DPA), a biomarker unique to spores, to allow quantitative spores detection. The GO-AgNPs-Eu3+ nano-fluorescent probe was loaded onto a polyvinylidene fluoride microfiltration membrane, and a smartphone-assisted portable GO-AgNPs-Eu3+ nanoparticles-based paper visual sensor was designed for rapid on-site quantitative and real-time online detection of spores. The results indicated that the developed probe achieved equilibrium binding with DPA within 5 min, and enhanced fluorescence emission through antenna effect. The fluorescence detection presented a good linear relationship in the DPA concentration range of 0–45 μM, with a DPA detection limit of 4.62 nM and spore detection limit of 104 cfu/mL. The developed sensor showed a change in fluorescence from blue to red with increasing DPA concentration, and this color change was quantitatively detected through smartphone RGB variations, with a detection limit of 13.1 μM for DPA and 6.3 cfu/mL for Bacillus subtilis spores. Subsequently, the sensitivity and selectivity of the developed sensor were verified using actual milk and water samples spiked with B. subtilis spores. The results of this study provided objective technological support for rapid detection of spores, which is important for reducing the occurrence of foodborne diseases and improving food safety.

The p-type Te-free Cu3SbSe4 with famatinite structure is a potential candidate for thermoelectric materials due to the low cost and eco-friendly constituent elements. However, its strong bipolar effect and high lattice thermal conductivity (κlat) are the main challenges for its performance enhancement. Herein, we report a new strategy to enhance its figure of merit zT ∼0.86 at 673 K for Cu3Sb0.95Fe0.05Se2.8S1.2 via band structure tuning and hierarchical architecture. Firstly, S substituted Se atoms in lattice can widen the band gap to alleviate the bipolar effect. Secondly, Fe doping in Sb site significantly increases the density of states, thus increasing the carrier effective mass, and obtaining a remarkably high Seebeck coefficient of ∼560 μV/K at 300 K. Moreover, the induced hierarchical architecture defects resulting in a minimum κlat of ∼0.48 W·m−1·K−1 at 673 K. Consequently, the improved Seebeck coefficient combined with low thermal conductivity leads to an enhanced zT.

Adding high melting point nano-particles to the weld seam is an effective method to improve the thermal crack sensitivity and mechanical properties of aluminum alloy fusion welded joints, and a reasonable heat treatment process will further improve the mechanical properties of the welded joints. In this work, effects of heat treatment on the microstructure and mechanical properties of spray formed 7055 aluminum alloy TIG welded joints reinforced by ZrB2/Al3(Sc, Zr) particles were investigation. The results revealed that the precipitates in S1-SZ7 and S1-Z7 weld seams were η´ phase, and the precipitates in the S1-SZ7 weld seam were smaller, more abundant and dispersed than that in the S1-Z7 weld seam. As a result, the mechanical properties of the S1-SZ7 welded joint were better than those of the S1-Z7 welded joint. Fine grain strengthening, dispersion strengthening, and precipitation strengthening were the reasons for the improvement of mechanical properties of S1-SZ7 welded joints. With the extension of the secondary aging time, the η´ phases in the SZ7 weld seam transformed into η phase, and the precipitated phases gradually became coarse. The mechanical properties of S1-SZ7, S2-SZ7, and S3-SZ7 welded joints gradually decreased.

Adding nano ceramic particles to the weld seam is an effective way to improve the strength of the spray formed 7055 aluminum alloy welded joint. However, nano ceramic particles are prone to agglomeration, and the agglomerated nano ceramic particles in welded joint can cause stress concentration and brittle fracture of the specimen. In order to improve the aggregation of nano ZrB2 ceramic particles in the weld seam and further improve the mechanical properties of spray formed 7055 aluminum alloy TIG welded joint, Sc/ZrB2-7055 (SZ7) and ZrB2-7055 (Z7) welded joints were prepared in this study. Compared to the Z7 weld seam with coarse grains and severe aggregation of ZrB2 particles, the SZ7 weld seam has fine grains, and the distribution of ZrB2, Al3(Sc, Zr), and Sc modified ZrB2 particles in the weld seam was more uniform. The tensile strength and elongation of Z7 welded joints were 281 MPa and 2.0%, while the tensile strength and elongation of SZ7 welded joints were 320 MPa and 4.9%. The tensile strength and elongation values of SZ7 welded joints have increased by 13.8% and 145% respectively compared to Z7 welded joints. Sc elements formed a rich Sc layer on the surface of ZrB2 particles, which passivated the sharp corners of ZrB2 particles and increased the wettability between ZrB2 particles and Al liquid, resulting in uniform distribution of ZrB2 particles in the weld seams. Fine grain strengthening, dispersion strengthening, and dislocation strengthening are the main reasons for improving the mechanical properties of SZ7 welded joints.

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. Methods This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson’s Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. Discussion In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. Trial registration ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

Background The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population.Methods RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m2), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4–6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform.Results Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity.Conclusions Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients.Trial registration number ChiCTR2100045104.

Using Nafion212 membrane and TEOS solution as raw materials, Nafion212/SiO2 composite membranes were prepared. In the in situ sol-gel reaction process, a series of Nafion/SiO2 composite membranes were prepared by varying the reaction temperature and reaction time. The effects of different modification schemes on Nafion/SiO2 composite membranes were studied using SEM, EDS, TEM, TGA, XRD, and mechanical tensile experiments, among other methods. The results show that Nafion/SiO2 composite membranes prepared at 3°C exhibit a well-separated phase structure and excellent water retention properties, with a water uptake of 29.23% and a swelling ratio of 24.25%. These membranes also demonstrate outstanding physical and chemical performance, with a maximum tensile stress of 13.6 MPa and an elongation at a break of 270%. At 110°C, the proton conductivity of the Nafion/SiO2 composite membrane reaches 0.172 S/cm, meeting the requirements for high-temperature proton exchange membrane fuel cells.

Objective This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).Methods A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I2 was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.Results The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.Conclusions Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did’ not include results on other adverse events.

AbstractAims Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD). The identification of risk factors involved in the progression of DKD to ESKD is expected to result in early detection and appropriate intervention and improve prognosis. This study aimed to explore whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with kidney outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.Methods Patients with biopsy-proven DKD who were followed up at West China Hospital over 12 months were enrolled. The kidney outcome was defined as progression to ESKD. The cutoff value of plasma NT-proBNP concentration was calculated by using receiver operating characteristic (ROC) curve analysis. The influence of NT-proBNP levels on kidney outcome in patients with DKD was assessed using Cox regression analysis.Results A total of 30 (24.5%) patients reached ESKD during a median follow-up of 24.1 months. The baseline serum NT-proBNP level had a significant correlation with baseline proteinuria, kidney function, glomerular lesions, interstitial fibrosis tubular atrophy (IFTA), and arteriolar hyalinosis. Multivariate Cox regression analysis indicated that increased NT-proBNP level was significantly associated with a higher risk of progression to ESKD (HR 6.43; 95% CI (1.65–25.10, p = 0.007), and each 1 SD increase in LG (NT-proBNP) was also associated with a higher risk (HR 2.43; 95% CI 1.94–5.29, p = 0.047) of an adverse kidney outcome after adjusting for confounding factors.Conclusions A higher level of plasma NT-proBNP predicts kidney prognosis in patients with biopsy-proven DKD. This warrants further investigation into the potential mechanisms.

Semi-hydrogenation of acetylene to ethylene over metal oxide-supported Au nanoparticles is an interesting topic. Here, a hydrotalcite-based MMgAlOx (M=Cu, Ni, and Co) composite oxide was exploited by introducing different Cu, Ni, and Co dopants with unique properties, and then used as support to obtain Au/MMgAlOx catalysts via a modified deposition–precipitation method. XRD, BET, ICP-OES, TEM, Raman, XPS, and TPD were employed to investigate their physic-chemical properties and catalytic performances for the semi-hydrogenation of acetylene to ethylene. Generally, the catalytic activity of the Cu-modified Au/CuMgAlOx catalyst was higher than that of the other modified catalysts. The TOR for Au/CuMgAlOx was 0.0598 h−1, which was 30 times higher than that of Au/MgAl2O4. The SEM and XRD results showed no significant difference in structure or morphology after introducing the dopants. These dopants had an unfavorable effect on the Au particle size, as confirmed by the TEM studies. Accordingly, the effects on catalytic performance of the M dopant of the obtained Au/MMgAlOx catalyst were improved. Results of Raman, NH3-TPD, and CO2-TPD confirmed that the Au/CuMgAlOx catalyst had more basic sites, which is beneficial for less coking on the catalyst surface after the reaction. XPS analysis showed that gold nanoparticles exhibited a partially oxidized state at the edges and surfaces of CuMgAlOx. Besides an increased proportion of basic sites on Au/CuMgAlOx catalysts, the charge transfer from nanogold to the Cu-doped matrix support probably played a positive role in the selective hydrogenation of acetylene. The stability and deactivation of Au/CuMgAlOx catalysts were also discussed and a possible reaction mechanism was proposed.

Past studies have shown that spontaneous electroencephalography indicators—namely, the theta/beta power ratio and alpha oscillation—may measure individuals’ attentional control processes. However, there is lack of research distinguishing these differences. This study investigated whether the theta/beta power ratio and alpha oscillation were separately related to the objective and subjective criteria of attentional control in eyes-open and eyes-closed conditions. The results showed two main findings: (1) In the eyes-open condition, the theta/beta power ratio at the Fz and Pz electrode sites were significantly negatively correlated with the attentional control scale score; the alpha power at the Pz electrode site was significantly negatively correlated with flanker RT interference effect; (2) In the eyes-closed condition, the alpha power at the Cz and Pz electrode sites were significantly positively correlated with flanker P3d. In summary, this study showed that the eyes-open spontaneous theta/beta power ratio may reflect individuals’ beliefs in their attentional control ability, and the alpha oscillation may be related to individuals’ attentional control ability.

Background and Aims: While there is a recognised role of optimising lifestyle (diet and physical activity) in the management of infertility, factors influencing the lifestyle behaviours of people with infertility are not well understood. The aim of this study was to describe the barriers and facilitators to achieving or prescribing a healthy lifestyle in the management of infertility from the perspectives of couples and health professionals. Method: Ovid MEDLINE(R), PsycINFO, EMBASE, EBM Reviews, and CINAHL Plus were searched for quantitative and qualitative primary studies (12[Formula: see text] September 2022) that explored barriers and enablers to lifestyle behaviours for infertility management. Data were analysed by inductive thematic analysis with themes mapped to the Theoretical Domains Framework (TDF) and the Capability, Opportunity, Motivation and Behaviour model. Results: After screening 10703 citations and 82 full texts, there were 23 included studies (13 quantitative, 8 mixed-methods and 2 qualitative) with 18 studies including women with infertility, 10 men with infertility and 6 health professionals. From the perspectives of people with infertility, themes related to capability (e.g., strategies for behaviour change), opportunity (e.g., limited time, resources and money) and motivation (e.g., interplay between lifestyle and emotional state); themes mapped to 8 TDF domains. From the perspectives of health professionals, themes related to capability (e.g., identification of patients appropriate for lifestyle intervention), opportunity (e.g., time constraints and organisational factors) and motivation (e.g., professional responsibility); themes mapped to 6 TDF domains. Conclusion: Several interacting factors influence lifestyle behaviours in couples with infertility which can be targeted for optimisation of future interventions. There is a need for more qualitative research to gain insights into the perspectives of couples with infertility and health professionals for further exploration of the complex and interacting factors which shape lifestyle during the stressful journey of infertility and fertility treatment.

IntroductionThe accurate extraction of navigation paths is crucial for the automated navigation of agricultural robots. Navigation line extraction in complex environments such as Panax notoginseng shade house can be challenging due to factors including similar colors between the fork rows and soil, and the shadows cast by shade nets.MethodsIn this paper, we propose a new method for navigation line extraction based on deep learning and least squares (DL-LS) algorithms. We improve the YOLOv5s algorithm by introducing MobileNetv3 and ECANet. The trained model detects the seven-fork roots in the effective area between rows and uses the root point substitution method to determine the coordinates of the localization base points of the seven-fork root points. The seven-fork column lines on both sides of the plant monopoly are fitted using the least squares method.ResultsThe experimental results indicate that Im-YOLOv5s achieves higher detection performance than other detection models. Through these improvements, Im-YOLOv5s achieves a mAP (mean Average Precision) of 94.9%. Compared to YOLOv5s, Im-YOLOv5s improves the average accuracy and frame rate by 1.9% and 27.7%, respectively, and the weight size is reduced by 47.9%. The results also reveal the ability of DL-LS to accurately extract seven-fork row lines, with a maximum deviation of the navigation baseline row direction of 1.64°, meeting the requirements of robot navigation line extraction.DiscussionThe results shows that compared to existing models, this model is more effective in detecting the seven-fork roots in images, and the computational complexity of the model is smaller. Our proposed method provides a basis for the intelligent mechanization of Panax notoginseng planting.

BackgroundIntracranial metastasis that failed standard systematic treatment is common in advanced non-small cell lung cancer (NSCLC), contributing significantly to morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with whole-brain radiotherapy (WBRT) for NSCLC with brain metastases (BMs) that progressed or developed after at least one line of prior treatment and compare the outcomes with that of the contemporary institutional control.MethodsNSCLC patients with multiple BMs that progressed or developed after at least one line of prior systematic treatment and treated with WBRT subsequently between 2019 and 2021 were selected retrospectively for analysis. Based on whether concurrent anlotinib had been used in combination with WBRT, the cases were divided into the anlotinib group and control group. The primary endpoints were intracranial progression-free survival (iPFS) and safety.ResultsA total of 76 patients met the inclusion criteria of the study. Of the 76 patients, 34 received concurrent WBRT and anlotinib followed by anlotinib maintenance and 42 were treated with WBRT alone or in combination with other systemic agents at the physicians’ discretion. The median follow-up for the entire cohort was 21 months. The median iPFS for the anlotinib and control group was 6.7 months (95% CI, 4.6–9.9) and 5.3 months (95% CI, 4.0–6.5), respectively (log-rank P = 0.04). There was no difference in overall survival between the two groups (log-rank P = 0.38). In the anlotinib group, treatment-related adverse events were reported in 15 patients (44.1%), with acute or late grade 3–5 adverse events identified in 14.7% of patients (n = 5).ConclusionsWBRT plus anlotinib, as a convenient chemo-free regimen, may represent an overall safe and effective procedure in advanced NSCLC with multiple BMs that progressed or developed after standard systematic treatment.

Germline variations in the DNA polymerase genes, POLE and POLD1, can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In this report, we present the case of a 22-year-old female patient who had been diagnosed with gastrointestinal polyposis, breast fibroadenoma, multiple primary colorectal cancers, and glioblastoma (grade IV) within a span of 4 years. Next-generation sequencing analysis revealed a germline variant in POLD1 (c.1816C>A; p.L606M). In silico analysis using protein functional predicting software, including SIFT, Polyphen, GERP++, and CADD, further confirmed the pathogenicity of POLD1 p.L606M (classified as ACMG grade Class 4). In line with polymerase deficiency, both rectal cancer and glioblastoma tissues exhibited a high tumor mutation burden, with 16.9 muts/Mb and 347.1 muts/Mb, respectively. Interestingly, the patient has no family history of cancer, and gene examination of both parents confirms that this is a de novo germline variant. Therefore, molecular screening for POLD1 may be necessary for patients with such a cancer spectrum, regardless of their family history.

Cold chain meat has become the main force of meat consumption in China due to its unique taste and rich nutrition. However, there are serious regulatory blind spots throughout the cold chain process, making it difficult to monitor the freshness quality and shelf life of cold chain meat in real time. Therefore, in this study, the dominant spoilage microorganism prediction model for cold chain meat was parsed to predict the logarithmic value of the dominant spoilage microorganism in real time based on temperature information, which was compared with the freshness quality threshold to derive real-time quality information. This paper proposes to develop the system with ASP.NET three-tier architecture as the development framework and .NET Framework 4.6.2 as the development environment. Combining MySQL 5.7.31 application database, Vue 2.6 and Apache ECharts front-end technology development a intelligent monitoring system for cold chain meat freshness. The system has five core application modules: multi-role login module, big data visualization and analysis module, product information management module, product freshness quality and shelf life real-time monitoring and warning module, and system setting module, to monitor the freshness quality and shelf life of cold chain meat products at all stages, real time. The development of this system can realize the real-time supervision of the quality of cold chain meat products in the whole industrial chain of processing, storage, transportation and sales, timely detect product abnormalities, provide technical support for food enterprises, and provide food safety assurance for consumers.

Objective: The aim of this paper was to study the effect of wheat protein on the quality of low-NaCl pork sausage and find the suitable range of wheat protein under different NaCl conditions. Methods: By single factor experiment, 0~50% KCl substitution levels and 0~8% wheat protein adding levels were applied. The texture, color, yield and water-holding capacity of products were determined. And then all the data were processed by means of variance analysis, correlation analysis, principal component analysis and regression analysis to study the effects of wheat protein on the quality of low-NaCl products, discuss the relationship between the quality indexes, establish the comprehensive quality evaluation model and find the optimum addition of wheat protein under different KCl substitution levels with the established model. Results: When KCl substituted level was 20%~30%, 6%~8% wheat protein significantly increased the product yield and water-holding capacity. The comprehensive quality evaluation model of low-NaCl pork sausage controlled by wheat protein was established: Y4=0.342×(0.127×Z1+0.169×Z2+...−0.110×Z10−0.108×Z11)+0.230×(0.328×Z10−0.185×Z2+...+0.115×Z10+0.249×Z11)+0.146×(−0.088×Z1+0.315×Z2+...+0.367×Z10+0.308×Z11). The optimum condition of wheat protein regulating low-NaCl pork sausage was 40% KCl substitution, and wheat protein addition was 6%. Conclusion: Construction of the prediction model of wheat protein addition to the quality of smoked and cooked sausage by multivariate analysis methods could guide the actual production and control the product quality.

We aimed to determine the utility of biopsy data and anemia for the prediction of renal outcomes in Chinese patients with type 2 diabetes. In total, 441 Chinese patients with type 2 diabetes and biopsy-confirmed diabetic nephropathy (DN) were enrolled in a retrospective study. Their renal pathology was assessed using the Renal Pathology Society system. Cox proportional hazards models were used to estimate hazard ratios (HRs) for end-stage renal disease (ESRD), and immunofluorescence staining was used to assess the expression of hypoxia-inducible factor (HIF)-α in patients’ kidneys. We found that glomerular pathology classification was an independent pathological predictor of low hemoglobin concentration, according to linear and logistic regression analyses. Each 1 g/dL decrease in baseline hemoglobin concentration was associated with a 42% higher risk of an adverse renal outcome, after adjustment for clinical and pathologic covariates. In patients with severe glomerular lesions, the risk of progression to ESRD was significantly higher if mild or moderate/severe anemia was present, but in patients with mild glomerular lesions, the risk was only significantly higher in those with moderate or severe anemia than in the absence of anemia. Harrell’s C Concordance was improved, but the Akaike information criterion was worsened by adding the glomerular pathology classification to the use of anemia status and clinical data. Immunofluorescence staining revealed that renal HIF-1α and HIF-2α expression was significantly higher in classes II–IV than class I. Thus, the addition of glomerular pathology classification increases the value of anemia status for the prediction of the progression to ESRD.

Aims Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM).Methods Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD.Results There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD.Conclusion Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model.HighlightsWhat is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention.What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP.What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.

In this study, the facile synthesis method of Bi2−xZrxO2Se (x = 0, 0.02, 0.04, and 0.06) ceramics using a combining the high-energy ball milling and cold pressing was reported. The effects of zirconium (Zr) doping on the microstructure and thermoelectric properties of Bi2O2Se were systematically investigated. The results indicate that the powder samples were synthesized as a single phase with no impurities. With increasing Zr content, conductivity increased from 13.49 S to 34.91 S cm−1 at 773 K. The thermal conductivity of Bi1.98Zr0.02O2Se was also reduced to 0.51 W m−1 K−1. The maximum power factor (PF) value of the Bi1.96Zr0.04O2Se sample was 186 μW m−1 K−2 at 773 K. A peak ZT of around 0.27 was achieved for the Bi1.96Zr0.04O2Se sample, which is approximately 2.4 times greater than that of un-doped one (∼0.11). The results indicate that Zr-doping significantly improves the thermoelectric properties of the Bi2O2Se system.

Reasonable design of a kind of non-noble metal catalyst with high catalytic performance, good stability and low cost is of great significance to realize the overall water splitting. Herein, a bottom-up method is proposed to synthesize NiFe layered double hydroxides (NiFe LDHs) coated sulfide/phosphide heterostructure on the nickel foam (Ni3S2-NixPy/NF@NiFe LDH) through hydrothermal method combined with electrodeposition. Low overpotentials of only 248 and 298 mV are required to achieve the current densities of 50 and 100 mA cm−2 for OER. Meanwhile, the HER performance only needs 137 mV at a current density of 10 mA cm−2.

Through composition design and structural regulation, low electronegativity selenium and phosphorus were doped into NiCo LDH nanosheets to prepare phosphorus and selenium co-doped nickel–cobalt layered double hydroxide electrodes (P, Se-NiCo LDH), which can enhance the availability of active sites, significantly improve the conductivity and promote the reaction kinetics. Prepared it as a positive cathode of supercapacitor ultrahigh energy density (61.23 Wh kg−1) and power density (16496.5 W kg−1) can be obtained. Rate performance of the hybrid supercapacitor can be maintained 50.9% at 20 A g−1. Both excellent rate performance and energy density may promote the wider application of supercapacitors.

IntroductionTicks and fleas, as blood-sucking arthropods, carry and transmit various zoonotic diseases. In the natural plague foci of China, monitoring of Yersinia pestis has been continuously conducted in Marmota himalayana and other host animals, whereas other pathogens carried by vectors are rarely concerned in the Qinghai-Tibet Plateau.MethodsIn this study, we investigated the microbiota of ticks and fleas sampling from M. himalayana in the Qinghai-Tibet Plateau, China by metataxonomics combined with metagenomic methods.ResultsBy metataxonomic approach based on full-length 16S rDNA amplicon sequencing and operational phylogenetic unit (OPU) analyses, we described the microbiota community of ticks and fleas at the species level, annotated 1,250 OPUs in ticks, including 556 known species and 492 potentially new species, accounting for 48.50% and 41.71% of the total reads in ticks, respectively. A total of 689 OPUs were detected in fleas, consisting of 277 known species (40.62% of the total reads in fleas) and 294 potentially new species (56.88%). At the dominant species categories, we detected the Anaplasma phagocytophilum (OPU 421) and potentially pathogenic new species of Wolbachia, Ehrlichia, Rickettsia, and Bartonella. Using shotgun sequencing, we obtained 10 metagenomic assembled genomes (MAGs) from vector samples, including a known species (Providencia heimbachae DFT2), and six new species affliated to four known genera, i.e., Wolbachia, Mumia, Bartonella, and Anaplasma. By the phylogenetic analyses based on full-length 16S rRNA genes and core genes, we identified that ticks harbored pathogenic A. phagocytophilum. Moreover, these potentially pathogenic novel species were more closely related to Ehrlichia muris, Ehrlichia muris subsp. eauclairensis, Bartonella rochalimae, and Rickettsia limoniae, respectively. The OPU 422 Ehrlichia sp1 was most related to Ehrlichia muris and Ehrlichia muris subsp. eauclairensis. The OPU 230 Bartonella sp1 and Bartonella spp. (DTF8 and DTF9) was clustered with Bartonella rochalimae. The OPU 427 Rickettsia sp1 was clustered with Rickettsia limoniae.DiscussionThe findings of the study have advanced our understanding of the potential pathogen groups of vectors in marmot (Marmota himalayana) in the Qinghai-Tibet Plateau.

The emulsifying capacity of bovine bone protein extracted using high-pressure hot water (HBBP) has been determined to be good. Nevertheless, given that HBBP is a blend of peptides with a broad range of molecular weights, the distinction in emulsifying capacity between polypeptide components with high and low molecular weights is unclear. Therefore, in this study, HBBP was separated into three molecular weight components of 10–30 kDa (HBBP 1), 5–10 kDa (HBBP 2), and

BackgroundObesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD).MethodsA total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD.ResultsThere are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel–Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99–4.88] in the MHO group, 2.16 (95% CI 1.20–3.88) in the MUNO group, and 2.31 (95% CI 1.27–4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88–1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10–2.60).ConclusionObesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.

BackgroundThe coronavirus disease 2019 (COVID-19) has been spreading astonishingly and caused catastrophic losses worldwide. The high mortality of severe COVID-19 patients is an serious problem that needs to be solved urgently. However, the biomarkers and fundamental pathological mechanisms of severe COVID-19 are poorly understood. The aims of this study was to explore key genes related to inflammasome in severe COVID-19 and their potential molecular mechanisms using random forest and artificial neural network modeling.MethodsDifferentially expressed genes (DEGs) in severe COVID-19 were screened from GSE151764 and GSE183533 via comprehensive transcriptome Meta-analysis. Protein-protein interaction (PPI) networks and functional analyses were conducted to identify molecular mechanisms related to DEGs or DEGs associated with inflammasome (IADEGs), respectively. Five the most important IADEGs in severe COVID-19 were explored using random forest. Then, we put these five IADEGs into an artificial neural network to construct a novel diagnostic model for severe COVID-19 and verified its diagnostic efficacy in GSE205099.ResultsUsing combining P value < 0.05, we obtained 192 DEGs, 40 of which are IADEGs. The GO enrichment analysis results indicated that 192 DEGs were mainly involved in T cell activation, MHC protein complex and immune receptor activity. The KEGG enrichment analysis results indicated that 192 GEGs were mainly involved in Th17 cell differentiation, IL-17 signaling pathway, mTOR signaling pathway and NOD-like receptor signaling pathway. In addition, the top GO terms of 40 IADEGs were involved in T cell activation, immune response-activating signal transduction, external side of plasma membrane and phosphatase binding. The KEGG enrichment analysis results indicated that IADEGs were mainly involved in FoxO signaling pathway, Toll-like receptor, JAK-STAT signaling pathway and Apoptosis. Then, five important IADEGs (AXL, MKI67, CDKN3, BCL2 and PTGS2) for severe COVID-19 were screened by random forest analysis. By building an artificial neural network model, we found that the AUC values of 5 important IADEGs were 0.972 and 0.844 in the train group (GSE151764 and GSE183533) and test group (GSE205099), respectively.ConclusionThe five genes related to inflammasome, including AXL, MKI67, CDKN3, BCL2 and PTGS2, are important for severe COVID-19 patients, and these molecules are related to the activation of NLRP3 inflammasome. Furthermore, AXL, MKI67, CDKN3, BCL2 and PTGS2 as a marker combination could be used as potential markers to identify severe COVID-19 patients.

【Objective】The study was carried out to explore the dynamic changes of leaf nutrients and soil nutrients of Carya cathayensis in different seasons of the year, and provide basis for fertilization, management and transformation of low yield forest of C. cathayensis economic forest and control of rocky desertification in karst area.【Method】Twenty C. cathayensis were selected from 10 walnut orchards in Huanjiang County to collect leaves and soil. Leaf nutrients (total carbon, total nitrogen, total phosphorus, total potassium, calcium, iron, zinc and boron) and soil physical and chemical properties (organic matter, total nitrogen, total phosphorus, total potassium, available nitrogen, available phosphorus, rapid potassium, available boron, available iron, available zinc and available calcium) were determined, and the seasonal dynamics of leaves and soil nutrients were analyzed.【Result】With the growth of C. cathayensis, the content of nitrogen in leaves gradually decreased to 13.59 g/kg, while the contents of boron and calcium gradually increased. Iron content decreased first and then increased, while phosphorus content was the opposite. The calcium content in July and October was about twice that in April (13.54 g/kg). The contents of exchangeable calcium and available boron in the forest soil increased first and then decreased, and the content of total potassium gradually increased to 8.84 g/kg. The effective zinc content in April (8.46 mg/kg) was 6.9 times that in October. There were obvious seasonal changes in leaf nutrients. Except for organic matter and available nitrogen, other nutrients in soil had obvious seasonal changes. Correlation analysis showed that there was a significant negative correlation between leaf nitrogen and soil available zinc, a very significant negative correlation between leaf phosphorus and soil available nitrogen, and a significant negative correlation between leaf iron and soil available phosphorus.【Conclusion】The application of potassium fertilizer should be strengthened at the flowering stage of C. cathayensis; attention should be paid to the application of nitrogen and potassium fertilizers to improve the availability of macro elements during the fruit growth period; phosphorus fertilizer and trace element fertilizers such as calcium and boron should be supplemented during the fruit ripening period.

Nsun4-mediated m5C and Mettl3-mediated m6A are found to be required for Sox9-regulated chondrogenic differentiation, whereby Nsun4 and Mettl3 interact with each other and recruit Ythdf2 and eEF1a-1 to form a complex at the 3’UTR of Sox9.

Abstract Background Haemophilus influenzae was the most aggressive pathogen and formed a major cause of bacterial meningitis and pneumonia in young children and infants, which need medical emergency requiring immediate diagnosis and treatment. However, From isolation to identification of H. influenzae, the traditional diagnose strategy was time-consuming and expensive. Therefore, the establishment of a convenient, highly sensitive, and stable detection system is urgent and critical. Results In this study, we used a combined method to detect H. influenzae. Six specific primers were designed on the basis of outer membrane protein P6 gene sequence of H. influenzae. The reaction condition such as the optimum temperature was 65℃, and the optimum reaction time was 30 min, respectively. Through the loop-mediated isothermal amplification (LAMP) in combination with nanoparticle-based lateral flow biosensor (LFB), the sensitivity of LAMP-LFB showed 100 fg was the lowest genomic DNA templates concentration in the pure cultures. Meanwhile, the specificity of H. influenzae-LAMP-LFB assay showed the exclusive positive results, which were detected in H. influenzae templates. In 55 clinical sputum samples, 22 samples were positive with LAMP-LFB method, which was in accordance with the traditional culture and Polymerase Chain Reaction (PCR) method. The accuracy in diagnosing H. influenzae with LAMP-LFB could reach 100%, compared to culture and PCR method, indicating the LAMP-LFB had more advantages in target pathogen detection. Conclusions Taken together, LAMP-LFB could be used as an effective diagnostic approach for H. influenzae in the conditions of basic and clinical labs, which would allow clinicians to make better informed decisions regarding patient treatment without delay.

With the development of cloud computing technology in remote sensing data processing, container cloud technology was applied to remote sensing data processing, remote sensing intelligent processing algorithm image was deployed and storage services were distributed in the computing cluster, shielding complex environmental dependence problems.And management through configuration files was processed forming an overall technical route from development to deployment, which provides an efficient and reliable new scheme for the integration of remote sensing intelligent processing algorithms.Taking several typical remote sensing intelligent algorithms as examples, the efficiency of the scheme in the integrated development and deployment was proved, and the feasibility of the new cloud mode of remote sensing intelligent technology was explored.