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Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract According to external pressure theory and reputation theory, reputation-oriented enterprises will experience external pressure as societal attention increases, and enhanced ESG performance can mitigate information asymmetry and boost reputation, thereby signaling to customers the company’s commitment to sustainable development. Based on the data of A-share listed firms in China, this paper manually compiles the detailed information of corporate customers, and explores the relationship between firm’s ESG performance and customer stability using a two-way fixed-effects model. The results show that: (1) Firms with ESG advantages can enhance customer stability, and the higher the ESG score, the more significant the improvement in customer stability; (2) The mechanism test indicates that firms’ ESG performance improves customer stability by strengthening internal and external regulation as well as enhancing corporate reputation; (3) The heterogeneity analysis indicates that in high governance level and small-sized firms, the effect of firms’ ESG performance on customer stability is more significant, and in the ESG sub-test, environmental and social responsibility have a more significant impact on customer stability. This paper provides implications for improving firms’ social responsibility and stabilizing the supply chain.

BackgroundThe senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear.ObjectiveTo explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethodsThis study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO2 suspension (100 mg·mL−1). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L−1 and 1125 mmol·L−1). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO2. The in vitro experimental groups were ① SiO2 induction groups: control group, 50 μg·mL−1 SiO2 group, 100 μg·mL−1 SiO2 group, and 200 μg·mL−1 SiO2 group, and ② oxamate treatment groups: control group, SiO2 group (100 μg·mL−1), low-dose oxamate (25 mmol·L−1) treatment group, and high-dose oxamate (50 mmol·L−1) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting.ResultsCompared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO2-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO2-induced group (P＜0.05). Compared with the SiO2 group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05).ConclusionLactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Abstract Currently, flexible capacitive sensors have a wide range of application scenarios in the field of wearable electronic devices. In order to detect more subtle joint movements of the human body, a method of fabricating stacked capacitive sensors is demonstrated. An ultrathin dielectric elastomer film of about 110 μm by the “secondary calendering” method was prepared. The shape of the electrode layers was designed, printed the electrode materials on the dielectric elastomer film by screen-printing, realized the stacked-layer technology, and connected each sensor unit in parallel by the electrode columns formed inside. A 12-layer flexible capacitive sensor with an initial capacitance of 10.2nF, good resolution (1% strain), high sensitivity (1.09) and stability under 10,000 cycles is fabricated. The sensor fabricated in this paper can recognize the motion at various joints of the human body, such as elbow and knee joints. This paper provides a new method for fabrication of stacked flexible capacitive sensors, which opens up new applications in flexible sensors, wearable electronic devices and human-computer interaction.

Abstract This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

Abstract Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.

Abstract Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Abstract Femoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.

Abstract Rapeseed (Brassica napus L.), accounts for nearly 16% of vegetable oil, is the world’s second produced oilseed. However, pod shattering has caused significant yield loses in rapeseed production, particularly during mechanical harvesting. The GH28 genes can promote pod shattering by changing the structure of the pod cell wall in Arabidopsis. However, the role of the GH28 gene family in rapeseed was largely unknown. Therefore, a genome-wide comprehensive analysis was conducted to classify the role of GH28 gene family on rapeseed pod shattering. A total of 37 BnaGH28 genes in the rapeseed genome were identified. These BnaGH28s can be divided into five groups (Group A-E), based on phylogenetic and synteny analysis. Protein property, gene structure, conserved motif, cis-acting element, and gene expression profile of BnaGH28 genes in the same group were similar. Specially, the expression level of genes in group A-D was gradually decreased, but increased in group E with the development of silique. Among eleven higher expressed genes in group E, two BnaGH28 genes (BnaA07T0199500ZS and BnaC06T0206500ZS) were significantly regulated by IAA or GA treatment. And the significant effects of BnaA07T0199500ZS variation on pod shattering resistance were also demonstrated in present study. These results could open a new window for insight into the role of BnaGH28 genes on pod shattering resistance in rapeseed.

Abstract Objective To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. Methods A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. Results High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract Background EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal T cells to these antigens on pancreatic tumors. Methods EGFR and HER2 T-BsAbs were constructed using the 2 + 2 IgG-[L]-scFv T-BsAbs format bearing two anti-CD3 scFvs attached to the light chains of an IgG to engage T cells while retaining bivalent binding to tumor antigens with both Fab arms. A Fab arm exchange strategy was used to generate EGFRxHER2 heterodimeric T-BsAb carrying one Fab specific for EGFR and one for HER2. EGFR and HER2 T-BsAbs were also heterodimerized with a CD33 control T-BsAb to generate ‘tumor-monovalent’ EGFRxCD33 and HER2xCD33 T-BsAbs. T-BsAb avidity for tumor cells was studied by flow cytometry, cytotoxicity by T-cell mediated 51Chromium release, and in vivo efficacy against cell line-derived xenografts (CDX) or patient-derived xenografts (PDX). Tumor infiltration by T cells transduced with luciferase reporter was quantified by bioluminescence. Results The EGFRxEGFR, HER2xHER2, and EGFRxHER2 T-BsAbs demonstrated high avidity and T cell-mediated cytotoxicity against human pancreatic ductal adenocarcinoma (PDAC) cell lines in vitro with EC50s in the picomolar range (0.17pM to 18pM). They were highly efficient in driving human polyclonal T cells into subcutaneous PDAC xenografts and mediated potent T cell-mediated anti-tumor effects. Both EGFRxCD33 and HER2xCD33 tumor-monovalent T-BsAbs displayed substantially reduced avidity by SPR when compared to homodimeric EGFRxEGFR or HER2xHER2 T-BsAbs (∼150-fold and ∼6000-fold respectively), tumor binding by FACS (8.0-fold and 63.6-fold), and T-cell mediated cytotoxicity (7.7-fold and 47.2-fold), while showing no efficacy against CDX or PDX. However, if either EGFR or HER2 was removed from SW1990 by CRISPR-mediated knockout, the in vivo efficacy of heterodimeric EGFRxHER2 T-BsAb was lost. Conclusion EGFR and HER2 were useful targets for driving T cell infiltration and tumor ablation. Two arm Fab binding to either one or both targets was critical for robust anti-tumor effect in vivo. By engaging both targets, EGFRxHER2 heterodimeric T-BsAb exhibited potent anti-tumor effects if CDX or PDX were EGFR+HER2+ double-positive with the potential to spare single-positive normal tissue.

Abstract Background and purpose Effective evaluation of rotator cuff tear residual tendon quality is the key to surgical repair. However, until now, the evaluation of rotator cuff tissue by ultrasonic shear wave elasticity (SWE) has been controversial. This prospective study analyzed the association between preoperative SWE and arthroscopic residual tendon quality scores. Methods The shear wave velocity (SWV) of the deltoid muscle, the supraspinatus tendon, and the supraspinatus muscle were measured in full-thickness rotator cuff tear patients. Tendon quality was scored according to tear size, tendon margin, tendon thickness, and footprint coverage during arthroscopy. The arthroscopic scores were used as the gold standard, and the SWV ratio of tendon and muscle (supraspinatus tendon/deltoid and supraspinatus muscle/deltoid) were calculated and correlated with the arthroscopic scores. Result Eighty-nine patients (129 shoulders) were enrolled, including 89 operation shoulders and 40 control shoulders. In the group of operation shoulders, both the SWV ratios of tendon (SWV-RT) and the SWV ratio of muscle (SWV-RM) were negatively correlated with arthroscopic scores (The correlation coefficient (R) ranged from -0.722 to -0.884 and -0.569 to -0.689). The SWV-RT and SWV-RM of the operation shoulders were significantly lower than that of the control shoulders (p

As a key material for lithium metal batteries (LMBs), lithium metal is one of the most promising anode materials to break the bottleneck of battery energy density and a commonly used active material for reference electrodes. Although lithium anodes are regarded as the holy grail of lithium batteries, decades of exploration have not led to the successful commercialization of LMBs, due mainly to the challenges related to the inherent properties of lithium metal. To pave the way for further investigation, herein, a comprehensive review focusing on the fundamental science of lithium are provided. Firstly, the natures of lithium atoms and their isotopes, lithium clusters and lithium crystals are revisited, especially their structural and energetic properties. Subsequently, the electrochemical properties of lithium metal are reviewed. Numerous important concepts and scientific questions, including the electronic structure of lithium, influence of high pressure and low temperature on the properties of lithium, factors influencing lithium deposition, generation of lithium dendrites, and electrode potential of lithium in different electrolytes, are explained and analyzed in detail. Approaches to improve the performance of lithium anodes and thoughtfulness about the electrode potential in lithium battery research are proposed.

Abstract Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real‐time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self‐adaptive hyperthermia supramolecular cascade nano‐reactor ACFDG is constructed via one‐step supramolecular self‐assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS‐inflammatory cascade through catalytic cascade reactions, up‐regulate the expression of heat shock proteins (HSPs) under near‐infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real‐time non‐invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano‐reactor combined with PA imaging for real‐time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

The influence of the sub-nano Ni3P and Cu3P phases on the microstructure, mechanical properties, and strengthening mechanism of Cu–20Pb–5Sn-xP (x = 0,0.05,0.1,0.3,0.5) alloy were discussed under the addition of P to obtain a new Pb–Sn bronze alloy applying for bimetallic cylinder block. The results showed that the tensile strength and hardness of the Pb–Sn bronze alloy increase with the P contents, while the elongation increased first and then decreased. The main strengthen mechanism was that sub-nano Ni3P and Cu3P phases dispersed in the matrix, hindering the movement of dislocations during deformation. Additionally, the grain refinement also contributed to the improvement of mechanical properties. The Ni3P phase is easier to form than the Cu3P phase. And it is easier to combine with the matrix and more stable. The Ni3P and Cu3P phases were studied by using different characterization techniques, such as OM, SEM, EDS, XRD, TEM and First-principles, Phase diagram calculation method. When P is added to the alloy, the Ni3P phase first appears in the alloy, and when the P content increases to more than 0.3 wt%, the Cu3P phase begins to appear. This is because the Ni3P phase is easier to form than the Cu3P phase and is more stable. Only after part of P reacts with Ni dissolved in copper to form Ni3P, the remaining P and Cu can form Cu3P.

The contamination of arsenic (As) in aqueous environments has drawn widespread attention, and iron compounds may largely alter the migration ability of As. However, the stability of As(III) in Fe-As system with the intervention of organic matter (OM) remains unclear. Herein, we had explored the co-precipitation and co-oxidation processes of As-Fe system by using batch experiments combined with Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) in this research. The precipitation quantity of As(III) increased (28.85–92.41 %) when the As/Fe ratio decreased, and increased (24.20–64.20 %) with pH increased. The main active substance for oxidizing As(III) was H2O2, which was produced in the As-Fe system. FTIR and XPS revealed that As(III) was first oxidized in neutral, and then absorbed and enteredthe interior of Fe(OH)3 colloids. But under alkaline conditions, As(III) was adsorbed by Fe (Oxyhydr) oxides firstly, and then oxidized. The intervention of OM would inhibit the redistribution process of As(III) in aqueous environments. Functional groups and unsaturation of the carbon chain were the dominant factors that affected the precipitation and oxidation processes of As(III), respectively. Co-existing ions (especially PO43-) also signally affected the precipitation quantity of As(Ⅲ) in the system and, when coexisting with OM, could exacerbate this process. The influence of co-existing ions on the redistributive process of As(III) in the As-Fe system with/without OM were as follows: PO43- > SO42- > mixed ions > SiO32-. Moreover, high concentration of OM and PO43- might lead to morphological alterations of As, acting as a threat to aqueous environments. In summary, the present findings were to further understand and appreciate the changes of As toxicity in the aqueous environments. Particularly, the coexistence of OM and As can potentially increase the risk to drinking water safety.

Porcine epidemic diarrhea (PED) is a highly contagious swine intestinal disease caused by PED virus (PEDV). Vaccination is a promising strategy to prevent and control PED. Previous studies have confirmed that glycosylation could regulate the immunogenicity of viral antigens. In this study, we constructed three recombinant PEDVs which removed the glycosylation sites in RBD. Viral infection assays revealed that similar replication characteristics between the recombinant viruses and parental PEDV. Although animal challenging study demonstrated that the glycosylation sites in RBD do not affect the pathogenicity of PEDV, we found that removing the glycosylation sites on the RBD regions could promote the IgG and neutralization titer in vivo, suggesting deglycosylation in RBD could enhance the immunogenicity of PEDV. These findings demonstrated that removal of the glycosylation sites in RBD is a promising method to develop PEDV vaccines.

ABSTRACT The cAMP receptor proteins (CRPs) play a critical role in bacterial environmental adaptation by regulating global gene expression levels via cAMP binding. Here, we report the structure of DdrI, a CRP family protein from Deinococcus radiodurans. Combined with biochemical, kinetic, and molecular dynamics simulations analyses, our results indicate that DdrI adopts a DNA-binding conformation in the absence of cAMP and can form stable complexes with the target DNA sequence of classical CRPs. Further analysis revealed that the high-affinity cAMP binding pocket of DdrI is partially filled with Tyr113-Arg55-Glu65 sidechains, mimicking the anti-cAMP-mediated allosteric transition. Moreover, the second syn-cAMP binding site of DdrI at the protein-DNA interface is more negatively charged compared to that of classical CRPs, and manganese ions can enhance its DNA binding affinity. DdrI can also bind to a target sequence that mimics another transcription factor, DdrO, suggesting potential cross-talk between these two transcription factors. These findings reveal a class of CRPs that are independent of cAMP activation and provide valuable insights into the environmental adaptation mechanisms of D. radiodurans.IMPORTANCEBacteria need to respond to environmental changes at the gene transcriptional level, which is critical for their evolution, virulence, and industrial applications. The cAMP receptor protein (CRP) of Escherichia coli (ecCRP) senses changes in intracellular cAMP levels and is a classic example of allosteric effects in textbooks. However, the structures and biochemical activities of CRPs are not generally conserved and there exist different mechanisms. In this study, we found that the proposed CRP from Deinococcus radiodurans, DdrI, exhibited DNA binding ability independent of cAMP binding and adopted an apo structure resembling the activated CRP. Manganese can enhance the DNA binding of DdrI while allowing some degree of freedom for its target sequence. These results suggest that CRPs can evolve to become a class of cAMP-independent global regulators, enabling bacteria to adapt to different environments according to their characteristics. The first-discovered CRP family member, ecCRP (or CAP) may well not be typical of the family and be very different to the ancestral CRP-family transcription factor.

BackgroundTo explore the relationship between body mass index (BMI), age, sex, and blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP) in children during COVID-19, providing reference for the prevention and screening of hypertension in children.MethodsThis study adopted a large-scale cross-sectional design to investigate the association between BMI and blood pressure in 7-17-year-old students in City N, China, during COVID-19. Thirty-six primary and secondary schools in City N were sampled using a stratified cluster sampling method. A total of 11,433 students aged 7–17 years in City N, China, were selected for blood pressure (Diastolic blood pressure, DBP, Systolic blood pressure, SBP), height, and weight, Resting heart rate (RHR), chest circumference, measurements, and the study was written using the STROBE checklist. Data analysis was conducted using SPSS 26.0, calculating the mean and standard deviation of BMI and blood pressure for male and female students in different age groups. Regression analysis was employed to explore the impact of BMI, age, and sex on SBP and DBP, and predictive models were established. The model fit was evaluated using the model R2.ResultsThe study included 11,287 primary and secondary school students, comprising 5,649 boys and 5,638 girls. It was found that with increasing age, BMI and blood pressure of boys and girls generally increased. There were significant differences in blood pressure levels between boys and girls in different age groups. In regression models, LC, Age, BMI, and chest circumference show significant positive linear relationships with SBP and DBP in adolescents, while RHR exhibits a negative linear relationship with SBP. These factors were individually incorporated into a stratified regression model, significantly enhancing the model’s explanatory power. After including factors such as Age, Gender, and BMI, the adjusted R2 value showed a significant improvement, with Age and BMI identified as key predictive factors for SBP and DBP. The robustness and predictive accuracy of the model were further examined through K-fold cross-validation and independent sample validation methods. The validation results indicate that the model has a high accuracy and explanatory power in predicting blood pressure in children of different weight levels, especially among obese children, where the prediction accuracy is highest.ConclusionDuring COVID-19, age, sex, and BMI significantly influence blood pressure in children aged 7–17 years, and predictive models for SBP and DBP were established. This model helps predict blood pressure in children and reduce the risk of cardiovascular diseases. Confirmation of factors such as sex, age, and BMI provide a basis for personalized health plans for children, especially during large-scale infectious diseases, providing guidance for addressing health challenges and promoting the health and well-being of children.

ChaCha is a well-known stream cipher that has been used in many network protocols and software. In this paper, we study the security of reduced round ChaCha. First, by considering the differential-linear hull effect, we improve the correlation of a four-round differential-linear distinguisher proposed at FSE 2023 by providing other intermediate linear masks. Then, based on the four-round differential-linear distinguisher and the PNB method, by using the assignment 100 ··· 00 for consecutive PNBs, higher backward correlation is obtained and improved key recovery attacks of 7-round and 7.25-round ChaCha are obtained with time complexity 2189.7 and 2223.9, which improve the previously best-known attacks by 217.1 and 214.44, respectively. Finally, we consider the equivalence of the security between (R + 0.25)-round and (R + 0.5)⊕-round ChaCha, and show that (R + 0.25)-round and (R + 0.5)⊕-round ChaCha provide the same security against chosen(known) plaintext attacks. As a result, improved differential-linear cryptanalysis of 7.5⊕-round ChaCha can also be obtained similarly to that of 7.25-round ChaCha, which improves the previously best-known attack by 219.

IntroductionTravel satisfaction as experienced by rural residents is closely related to personal physical and mental health, as well as rural economic conditions. An improved rural road environment can be expected to enhance villagers’ satisfaction with regards to visits to markets, but to date this has not been established empirically.MethodsIn this study, a questionnaire was designed to obtain local residents’ evaluations of road environment characteristics for periodic market travel. And we use an Oprobit regression model and Importance-Performance Map Analysis (IPMA) to explore the heterogeneity of the 14 key elements of the “home-to-market” road environment impact on villagers’ satisfaction under different modes of travel.ResultsThe results of the study reveal that villagers expressed dissatisfaction with the current lack of sidewalks and non-motorized paths, and except for road traffic disturbances and road deterioration, which did not significantly affect mode of travel, other factors proved significant. Significantly, bus services are associated with a significant positive effect on walking, non-motorized and bus travel satisfaction, while distance travel also affects walking, non-motorized and motorized travel satisfaction. It is worth noting that greening and service facilities negatively affect motorized travel satisfaction. In summary, road width, sidewalks, bus service, and road deterioration, are among the elements most in need of urgent improvement for all modes of travel.DiscussionThe characteristics of the road environment that influence satisfaction with travel to the periodic market vary by travel mode, and this study is hoped to provide data support and optimization recommendations for the improvement of the rural road environment in China and other countries.

Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.

Lotus (Nelumbo nucifera Gaertn.) seed, a traditional Chinese herbal medicine, exhibits good hypoglycemic activities. However, the bioactive components that are responsible for the biological effects and their underlying mechanisms remain obscure. This study aimed to identify the bioactive components of lotus seed skin phenolic-rich extract (LSSE) and investigate their α-glucosidase inhibitory activity. In vivo study showed that LSSE could significantly decrease the fasting blood glucose levels and the area under the curves with dose-dependent manners in diabetes mellitus mice. And the α-glucosidase activity was decreased by 39.4% after intervention with LSSE. The results also demonstrated that LSSE possessed up to 77.53% rat intestinal maltase inhibitory activity and general sucrase and isomaltase inhibitory activity. A total of 38 phenolic compounds were first quantified in LSSE. Molecular docking analysis further revealed that the bioactive components in LSSE bind with α-glucosidase by hydrogen bonding Van der Waals and hydrophobic interactions. These results indicate the potential use of LSSE for natural hypoglycemic functional foods.

Abstract Background The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. Methods Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. Results The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). Conclusion The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Abstract Bacteria have evolved various response systems to adapt to environmental stress. A protease-based derepression mechanism in response to DNA damage was characterized in Deinococcus, which is controlled by the specific cleavage of repressor DdrO by metallopeptidase PprI (also called IrrE). Despite the efforts to document the biochemical, physiological, and downstream regulation of PprI-DdrO, the upstream regulatory signal activating this system remains unclear. Here, we show that single-stranded DNA physically interacts with PprI protease, which enhances the PprI-DdrO interactions as well as the DdrO cleavage in a length-dependent manner both in vivo and in vitro. Structures of PprI, in its apo and complexed forms with single-stranded DNA, reveal two DNA-binding interfaces shaping the cleavage site. Moreover, we show that the dynamic monomer-dimer equilibrium of PprI is also important for its cleavage activity. Our data provide evidence that single-stranded DNA could serve as the signal for DNA damage sensing in the metalloprotease/repressor system in bacteria. These results also shed light on the survival and acquired drug resistance of certain bacteria under antimicrobial stress through a SOS-independent pathway.

Abstract Traditional methods for developing new materials are no longer sufficient to meet the needs of the human energy transition. Machine learning (ML) artificial intelligence (AI) and advancements have caused materials scientists to realize that using AI/ML to accelerate the development of new materials for batteries is a powerful potential tool. Although the use of certain fixed properties of materials as descriptors to act as a bridge between the two separate disciplines of AI and materials chemistry has been widely investigated, many of the descriptors lack universality and accuracy due to a lack of understanding of the mechanisms by which AI/ML operates. Therefore, understanding the underlying operational mechanisms and learning logic of AI/ML has become mandatory for materials scientists to develop more accurate descriptors. To address those challenges, this paper reviews previous work on AI, machine learning and materials descriptors and introduces the basic logic of AI and machine learning to help materials developers understand their operational mechanisms. Meanwhile, the paper also compares the accuracy of different descriptors and their advantages and disadvantages and highlights the great potential value of accurate descriptors in AI/machine learning applications for battery research, as well as the challenges of developing accurate material descriptors. Graphical Abstract

Highlights The poly(1,3-dioxolane) (PDOL) electrolyte demonstrates promising potential for practical application due to its advantages in in-situ polymerization process, high ionic conductivity, and long cycle life. This review focuses on the polymerization mechanism, composite innovation, and application of PDOL electrolytes. This review provides a comprehensive summary of the challenges associated with the PDOL electrolyte and makes forward-looking recommendations.

Time Domain Coding Metasurface (TDCM) is an emerging technology enabling dynamic modulation of electromagnetic waves. In response to the control characteristics of this technology, this paper presents a radar jamming method based on TDCM intrapulse and interpulse coding optimization. First, optimization models are established in fast and slow time domains. By optimizing intrapulse and interpulse phase coding, the energy redistribution of targets is achieved, thereby generating deceptive interference on the range-Doppler two-dimensional plot. Subsequently, a genetic algorithm is employed to solve this discrete optimization problem. Furthermore, this paper analyzes the effect of various modulation factors on interference effectiveness in terms of TDCM coding strategies, providing guidance for achieving optimal strategies for deceptive interference.

Abstract Rapeseed (Brassica napus L.) with short or no dormancy period are easy to germinate before harvest (pre-harvest sprouting, PHS). PHS has seriously decreased seed weight and oil content in B. napus. Short-chain dehydrogenase/ reductase (SDR) genes have been found to related to seed dormancy by promoting ABA biosynthesis in rice and Arabidopsis. In order to clarify whether SDR genes are the key factor of seed dormancy in B. napus, homology sequence blast, protein physicochemical properties, conserved motif, gene structure, cis-acting element, gene expression and variation analysis were conducted in present study. Results shown that 142 BnaSDR genes, unevenly distributed on 19 chromosomes, have been identified in B. napus genome. Among them, four BnaSDR gene clusters present in chromosome A04、A05、C03、C04 were also identified. These 142 BnaSDR genes were divided into four subfamilies on phylogenetic tree. Members of the same subgroup have similar protein characters, conserved motifs, gene structure, cis-acting elements and tissue expression profiles. Specially, the expression levels of genes in subgroup A, B and C were gradually decreased, but increased in subgroup D with the development of seeds. Among seven higher expressed genes in group D, six BnaSDR genes were significantly higher expressed in weak dormancy line than that in nondormancy line. And the significant effects of BnaC01T0313900ZS and BnaC03T0300500ZS variation on seed dormancy were also demonstrated in present study. These findings provide a key information for investigating the function of BnaSDRs on seed dormancy in B. napus.

Abstract Over the long history of evolution, nature has developed a variety of biological systems with switchable recognition functions, such as the ion transmissibility of biological membranes, which can switch their ion selectivities in response to diverse stimuli. However, developing a method in an artificial host-guest system for switchable recognition of specific guests upon the change of external stimuli is a fundamental challenge in chemistry because the order in the host-guest affinity of a given system hardly varies along with environmental conditions. Herein, we report temperature-responsive recognition of two similar gaseous guests, CO2 and C2H2, with selectivities switched by temperature change by a diffusion-regulatory mechanism, which is realized by a dynamic porous crystal featuring ultrasmall pore apertures with flip-flop locally-motive organic moiety. The dynamic local motion regulates the diffusion process of CO2 and C2H2 and amplifies their rate differences, allowing the crystal to selectively adsorb CO2 at low temperatures and C2H2 at high temperatures with separation factors of 498 (CO2/C2H2) and 181 (C2H2/CO2), respectively.

Abstract Background Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes a heavy burden on individuals, families and society. Previous studies on MDD predominantly focused on neurons and employed bulk homogenates of brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development and MDD at the single-cell resolution level. Methods Here, we present the use of a guided regularized random forest (GRRF) algorithm to explore single-nucleus RNA sequencing profiles (GSE144136) of the OL at four developmental stages, which contains dorsolateral prefrontal cortex of 17 healthy controls (HC) and 17 MDD cases, generated by Nagy C et al. We prioritized and ordered differentially expressed genes (DEGs) based on Nagy et al., which could predominantly discriminate cells in the four developmental stages and two adjacent developmental stages of the OL. We further screened top-ranked genes that distinguished between HC and MDD in four developmental stages. Moreover, we estimated the performance of the GRRF model via the area under the curve value. Additionally, we validated the pivotal candidate gene Malat1 in animal models. Results We found that, among the four developmental stages, the onset development of OL (OPC2) possesses the best predictive power for distinguishing HC and MDD, and long noncoding RNA MALAT1 has top-ranked importance value in candidate genes of four developmental stages. In addition, results of fluorescence in situ hybridization assay showed that Malat1 plays a critical role in the occurrence of depression. Conclusions Our work elucidates the mechanism of MDD from the perspective of OL development at the single-cell resolution level and provides novel insight into the occurrence of depression.

Abstract Backgroud Laparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis. Methods We retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox’s multivariate proportional hazard analysis. Results Visual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P

Objective The ability of D‐dimer to diagnose periprosthetic joint infection (PJI) before revision hip or knee arthroplasty is still controversial, and the differences in diagnostic ability between serum‐ or plasma‐based assays of D‐dimer and fibrin (fibrinogen) degradation product (FDP) are uncertain. The prospective parallel study was performed to determine the ability of D‐dimer to diagnose PJI before revision hip or knee arthroplasty, and the differences in diagnostic ability between serum‐ or plasma‐based assays of D‐dimer and FDP. Methods Patients undergoing knee or hip arthroplasty at our institution were prospectively enrolled into the following groups: those without inflammatory diseases who were undergoing primary arthroplasty (“Prim” group), those with inflammatory arthritis who were undergoing primary arthroplasty (“Prim/Inflam”), those undergoing revision arthroplasty because of aseptic failure (“Rev/Asept”), or those undergoing revision arthroplasty because of PJI (“Rev/PJI”). The ability of preoperative levels of D‐dimer or FDP in serum or plasma to diagnose PJI in each group was assessed using areas under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators. The diagnostic performance of these assays was compared with that of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results In the final analysis, Prim included 42 patients; Prim/Inflam, 40; Rev./Asept, 62; and Rev./PJI, 47. D‐dimer assays led to AUCs of 0.635 in serum and 0.573 in plasma, compared to 0.593 and 0.607 for FDP. Even in combination with CRP or ESR, these assays failed to perform as well as the combination of CRP and ESR for diagnosing PJI. Conclusion Levels of D‐dimer or FDP in serum or plasma, whether used alone or together with CRP or ESR, are unreliable for diagnosing PJI before revision arthroplasty.

Abstract Background Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms. Objective To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment. Methods A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users. Results Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent. Conclusions Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

BackgroundSilicosis is one of the most serious occupational diseases in China, requiring new treatment targets and therapies. The effects and mechanisms of integrated stress response inhibitors (ISRIB) on silicosis are still unknown. ObjectiveTo observe the effects of ISRIB on silicosis fibrosis and its possible mechanisms. Methods The study was divided into two parts: in vivo and in vitro experiments. For the in vivo part, 40 SPF grade male C57BL/6J mice were randomly divided into four groups: control group, ISRIB group, silicotic model group, and ISRIB treatment group, with 10 mice in each group. A silicotic mouse model was established by using a single tracheal infusion of 50 μL 200 mg·mL−1 SiO2 suspension. After one week of perfusion with SiO2 (the control group and the ISRIB group were perfused with an equal amount of sodium chloride solution), the ISRIB group and the ISRIB treatment group were intraperitoneally injected with 200 μL 2.5 mg·kg−1 ISRIB for four weeks, and mice of other groups were injected with equal amounts of sodium chloride solution. A micro-CT instrument was used to observe the lung field clarity and lung texture of each group; hematoxylin eosin (HE) staining was used to observe the histopathology morphology of the lung and the formation of silicon nodules; Van Gieson (VG) staining was used to observe the deposition of collagen in silicotic nodules; immunofluorescence assay was used to detect the expression and localization of p-protein kinase RNA-like ER kinase (PERK) in lung tissue; immunoblotting was used to detect the expression of collagen I (Col I) and endoplasmic reticulum stress signal related proteins p-PERK, p-inositol-requiring enzyme-1α (p-IRE-1α), p-eukaryotic initiation factor 2α (p-eIF-2α), activating transcription factor 4 (ATF4), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). For the in vitro part, mouse alveolar macrophages MH-S cells were cultured in vitro and divided into a control group, an ISRIB (1 μg·mL−1) group, a SiO2 induction group (100 μg·mL−1), and an ISRIB treatment group (1 μg·mL−1 ISRIB treatment for 1 h, followed by 100 μg·mL−1 SiO2 induction). Immunofluorescence assay was used to detect the expression of p-PERK in MH-S cells; immunoblotting was used to determine expressions of endoplasmic reticulum stress signal related proteins p-PERK, p-IRE-1α, p-eIF-2α, and ATF4. ResultsThe CT images showed that the lung markings of the silicotic model group mice were thickened, and several high-density shadows of varying sizes were observed in the lung field, mainly distributed around the bronchi. Compared with the silicotic model group, the ISRIB treatment group showed a decrease in the number and volume of high-density shadows. The HE staining results showed that lung tissues in the silicotic model group lost their normal structure, with the formation of silicon nodules, around which were thickened alveoli around the silicon nodules, and infiltration of inflammatory cells; the area and number of silicon nodules in the ISRIB treatment group were significantly reduced, and the range of silicon nodules was limited. The results of VG staining showed that the proportion of collagen fiber area in the lung tissue of the silicotic model group was 21.47%±2.59%, and it decreased to 9.34%±1.06% in the ISRIB treatment group, with a statistically significant difference (P

Abstract Background As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. Results The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. Conclusions In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.

Abstract Gaining continuous trust from mobile banking customers is a critical step in retaining customers for their usage of the provided services. The current study aims to investigate how customers’ continuous trust is formed at the continuous-use stage. Online survey responses from 450 frequent mobile banking users are collected. The data were analysed using structural equation modelling (SEM) based on a proposed model that predicts trust. The findings successfully validated the model and its reduced form. Based on the model, customers’ continuous trust can be predicted by mobile banking apps’ perceived ease of use, privacy assurance and security features, organisation reputation, customer support, and customers’ previous experience. Furthermore, the interactive relationships among these proposed factors are proposed and validated in the model. By studying trust in mobile banking past the initial adoption stage, we provide evidence to support the theoretical framework of investigating mobile banking continuous trust from the three constructs—mobile app (perceived ease of use, privacy assurance, security features), organisation (reputation, customer support), and customer (prior experience).

Abstract This study investigated the performance of ultrasonography in diagnosing deep soft-tissue tumors and tumor-like lesions in children with histological results. Demographic information and ultrasound characteristics of benign and malignant masses were statistically analyzed. Three radiologists (Radiologists 1, 2, and 3) independently reviewed the ultrasonography studies while being blinded to the medical history and other imaging findings. The 82 lesions included in the study were histopathologically classified as malignant (n = 25) or benign (n = 57). No statistically significant differences were observed between the benign and malignant subgroups regarding age (p = 0.059), sex (p = 1.0), disease course (p = 0.812), presence or absence of symptoms (p = 0.534), maximum diameter (p = 0.359), margin (p = 1.0), calcification (p = 0.057), or blood Adler type (p = 0.563). However, statistically significant differences were observed between the benign and malignant subgroups in terms of isolated or Multiple occurrences (p

Summary: Cardiovascular diseases (CVDs) and metabolic disorders (MDs) have surfaced as formidable challenges to global health, significantly imperiling human well-being. Recently, microneedles (MNs) have garnered substantial interest within the realms of CVD and MD research. Offering a departure from conventional diagnostic and therapeutic methodologies, MNs present a non-invasive, safe, and user-friendly modality for both monitoring and treatment, thereby marking substantial strides and attaining pivotal achievements in this avant-garde domain, while also unfurling promising avenues for future inquiry. This thorough review encapsulates the latest developments in employing MNs for both the surveillance and management of CVDs and MDs. Initially, it succinctly outlines the foundational principles and approaches of MNs in disease surveillance and therapy. Subsequently, it delves into the pioneering utilizations of MNs in the surveillance and management of CVDs and MDs. Ultimately, this discourse synthesizes and concludes the primary findings of this investigation, additionally prognosticating on the trajectory of MN technology.

Osteoarthritis (OA) is a common degenerative joint disease in the elderly, while oxidative stress-induced chondrocyte degeneration plays a key role in the pathologic progression of OA. One possible reason is that the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which acts as the intracellular defense factor against oxidative stress, is significantly inhibited in chondrocytes. Spinosin (SPI) is a potent Nrf2 agonist, but its effect on OA is still unknown. In this study, we found that SPI can alleviate tert-Butyl hydroperoxide (TBHP)-induced extracellular matrix degradation of chondrocytes. Additionally, SPI can effectively activate Nrf2, heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) in chondrocytes under the TBHP environment. When Nrf2 was silenced by siRNA, the cartilage protective effect of SPI was also weakened. Finally, SPI showed good alleviative effects on OA in mice. Thus, SPI can ameliorate oxidative stress-induced chondrocyte dysfunction and exhibit a chondroprotective effect through activating the Nrf2/HO-1 pathway, which may provide a novel and promising option for the treatment of OA.

ABSTRACTInoculation with plant growth-promoting rhizobacteria (PGPR) strains has promoted plant growth and decreased nitrous oxide (N₂O) emissions from agricultural soils simultaneously. However, limited PGPR strains can mitigate N₂O emissions from agricultural soils, and the microbial ecological mechanisms underlying N₂O mitigation after inoculation are poorly understood. In greenhouse pot experiments, the effects of inoculation with Stutzerimonas stutzeri NRCB010 and NRCB025 on tomato growth and N₂O emissions were investigated in two vegetable agricultural soils with contrasting textures. Inoculation with NRCB010 and NRCB025 significantly promoted tomato growth in both soils. Moreover, inoculation with NRCB010 decreased the N₂O emissions from the fine- and coarse-textured soils by 38.7% and 52.2%, respectively, and inoculation with NRCB025 decreased the N₂O emissions from the coarse-textured soil by 76.6%. Inoculation with NRCB010 and NRCB025 decreased N₂O emissions mainly by altering soil microbial community composition and the abundance of nitrogen-cycle functional genes. The N₂O-mitigating effect might be partially explained by a decrease in the (amoA + amoB)/(nosZI + nosZII) and (nirS + nirK)/(nosZI + nosZII) ratios, respectively. Soil pH and organic matter were key variables that explain the variation in abundance of N-cycle functional genes and subsequent N₂O emission. Moreover, the N₂O-mitigating effect varied depending on soil textures and individual strain after inoculation. This study provides insights into developing biofertilizers with plant growth-promoting and N₂O-mitigating effects.IMPORTANCEPlant growth-promoting rhizobacteria (PGPR) have been applied to mitigate nitrous oxide (N₂O) emissions from agricultural soils, but the microbial ecological mechanisms underlying N₂O mitigation are poorly understood. That is why only limited PGPR strains can mitigate N₂O emissions from agricultural soils. Therefore, it is of substantial significance to reveal soil ecological mechanisms of PGPR strains to achieve efficient and reliable N₂O-mitigating effect after inoculation. Inoculation with Stutzerimonas stutzeri strains decreased N₂O emissions from two soils with contrasting textures probably by altering soil microbial community composition and gene abundance involved in nitrification and denitrification. Our findings provide detailed insight into soil ecological mechanisms of PGPR strains to mitigate N₂O emissions from vegetable agricultural soils.

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.

As an aftermath of the Fukushima nuclear accident and its implications for public acceptance of nuclear energy, the nuclear industry has begun to seriously rethink and improve the safety strategies of nuclear power plants. The beyond-design-basis external events, such as the earthquake and tsunami in Fukushima nuclear accident, may lead to an extreme accident which may lead to the failure of the traditional strategies. In the recent decade, the concept of FLEX strategies has been accepted in the nuclear engineering community and attracted a large number of researchers to investigate it for nuclear accident mitigation. The development of FLEX strategies is divided into two steps. One is an uncertainty study of system response, especially the safety injection system. The other is training and testing of machine learning (ML)-based FLEX strategies and to verify the effectiveness of ML algorithms in the development of FLEX strategies for nuclear power plants. This paper focuses on first step uncertainty study of the nuclear accidents by using statistical algorithm to generate a database of incidents and system responses. The conclusion of this paper is useful for analyzing the characteristic of typical nuclear accidents and benefits to the FLEX strategy development, which will be focused on in the near future.

Abstract Background Nephronophthisis (NPHP) is a genetically heterogeneous disease that can lead to end‐stage renal disease (ESRD) in children. The TTC21B variant is associated with NPHP12 and mainly characterized by cystic kidney disease, skeletal malformation, liver fibrosis, and retinopathy. Affected patients range from children to adults. Some patients experience ESRD in infancy or early childhood, but clinical reports on neonatal patients are rare. We report a case of NPHP12 in a premature infant and analyze its genetic etiology. Methods Trio‐whole exome sequencing analysis was performed on the patient and her parents; bioinformatics software was used to predict and analyze the hazards of the variants. Sanger sequencing was performed to verify variants. We calculated the free energy between mutant IFT139 and the IFT121‐IFT122‐IFT43 complex structure using molecular dynamics (MD). Finally, the clinical and genetic characteristics of patients with hotspot variant Cys518Arg were reviewed. Results Genetic analysis revealed compound‐heterozyous TTC21B variants in the patient, c.497delA (p.Lys166fs*36) and c.1552T>C (p.Cys518Arg). Her father and mother had heterozygous c.497delA (p.Lys166fs*36) and heterozygous c.1552T>C (p.Cys518Arg), respectively. Cys518Arg represents a hotspot variant, and the MD calculation results show that this can reduce the structural stability of the IFT121‐IFT122‐IFT139‐IFT43 complex structure. A literature review showed that Cys518Arg might lead to the early occurrence of ESRD. Conclusions Compound‐heterozygous TTC21B variants underlie the phenotype in this patient. Thus, Cys518Arg may be a hotspot variant in the Chinese population. Genetic testing should be recommended for NPHP in neonates and early infants.

Abstract Background The association between major depressive disorder (MDD) and irritable bowel syndrome (IBS) has been found in observational research; however, the causative relationship between MDD and IBS remains uncertain. Using the two‐sample Mendelian randomization (MR) approach, we attempted to examine the causal effect of MDD on IBS. Methods Independent genetic variants for MDD identified by Howard et al. based on a genome‐wide meta‐analysis were selected for this study. Gene‐Outcome associations for IBS were gathered from UK Biobank and FinnGen databases. The MR analysis included inverse variance weighted (IVW), MR‐Egger regression, weighted median, weighted mode, and MR‐PRESSO sensitivity analyses. Results FinnGen database subjected to inverse variance weighted (IVW) analysis revealed that MDD may be a risk factor for the development of IBS (OR = 1.356, 95% CI: 1.125–1.632, p = 0.0013). The same finding was reached in UK Biobank for IVW (OR = 1.011, 95% CI: 1.006–1.015, p = 3.18 × 10−7), MR‐Egger progression (OR = 1.030, 95% CI: 1.008–1.051, p = 0.007), and weighted median (OR = 1.011, 95% CI: 1.005–1.016, p = 0.0001). Conclusion Our findings supported a causal relationship between MDD and IBS, which may have implications for the clinical management of IBS in individuals with MDD.

The uncanny valley (UV) effect captures the observation that artificial entities with near-human appearances tend to create feelings of eeriness. Researchers have proposed many hypotheses to explain the UV effect, but the visual processing mechanisms of the UV have yet to be fully understood. In the present study, we examined if the UV effect is as accessible in brief stimulus exposures compared to long stimulus exposures (Experiment 1). Forty-one participants, aged 21–31, rated each human-robot face presented for either a brief (50 ms) or long duration (3 s) in terms of attractiveness, eeriness, and humanness (UV indices) in a 7-point Likert scale. We found that brief and long exposures to stimuli generated a similar UV effect. This suggests that the UV effect is accessible at early visual processing. We then examined the effect of exposure duration on the categorisation of visual stimuli in Experiment 2. Thirty-three participants, aged 21–31, categorised faces as either human or robot in a two-alternative forced choice task. Their response accuracy and variance were recorded. We found that brief stimulus exposures generated significantly higher response variation and errors than the long exposure condition. This indicated that participants were more uncertain in categorising faces in the brief exposure condition due to insufficient time. Further comparisons between Experiment 1 and 2 revealed that the eeriest faces were not the hardest to categorise. Overall, these findings indicate (1) that both the UV effect and categorical uncertainty can be elicited through brief stimulus exposure, but (2) that categorical uncertainty is unlikely to cause the UV effect. These findings provide insights towards the perception of robotic faces and implications for the design of robots, androids, avatars, and artificial intelligence agents.

This study aims to investigate the influencing factors and Acquired Immune Deficiency Syndrome (AIDS) related knowledge among high-risk male population in Chongqing. A total of 388 men who had sex with their fellow men (MSM) and volunteered for counseling or human immunodeficiency virus (HIV) testing in Chongqing were divided into two groups identified as: aware group (n = 299) and unaware group (n = 89). According to the study subjects, the MSM sentinel surveillance questionnaire of the Chinese Center for Disease Control and Prevention was utilized to investigate their AIDS awareness demographic and behavioral characteristics. Univariate analysis was also applied to analyze the influencing factors of their AIDS knowledge. Binary multivariate logistic analysis was further used to screen the independent risk factors of AIDS inadequate knowledge, leading to the use of regression analysis model. Furthermore, hosmer and lemeshow were employed to test the goodness and fitness of the regression analysis model. Finally, SPSS was used to draw receiver operating characteristic (ROC) curves to evaluate the predictive value of the regression analysis model. Among 388 respondents, 299 participants were aware while 89 participants were unaware of AIDS-related knowledge with an overall awareness rate of 77.06%; univariate and multivariate logistic regression analysis showed that education (high school and below) and household registration (other places) were risk factors for AIDS-related knowledge in high-risk male groups in Chongqing. In addition, a probability model predicted high incidence of AIDS in high-risk male groups in Chongqing because of inadequate AIDS knowledge: P = 1/[1 + exp (1.429 − 1.169X2 − 0.969X3)]. The overall level of awareness of AIDS-related knowledge among high-risk male groups in Chongqing was not high because of low education levels (high school or below) and foreign household registration.