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Redox reaction is a core chemical concept. However, its abstract nature makes it very difficult for students. Students' conceptual structure reflects their mastery of concepts, which helps teachers implement targeted educational strategies. This study aimed to explore the conceptual structures of redox reaction held by students (grades 10 to 12) by employing MDS and HCA. A total of 606 students participated, with 195 students in 10th grade, 202 in 11th grade, and 209 in 12th grade. The results indicated that three-dimensional solutions were appropriate for the conceptual structures of 10th and 12th graders, while 11th graders demonstrated two-dimensional solutions. All students grouped the 15 concepts related to redox reaction into two large clusters: metrology and the redox reaction process. Moreover, both 10th and 12th graders further subdivided the 15 concepts into four subclusters: metrology, oxidation process, reduction process, and chemical reaction. Students' conceptual structures were rational across all three grades. The conceptual structures of 10th and 12th graders were more refined than those of 11th graders, and there was no significant difference between the conceptual structures of 10th and 12th graders. 11th graders learned about electrochemistry and tended to confuse concepts related to redox reaction with those related to electrochemistry.

With the increase of the proportion of hot delivery and hot charging in pipeline steel continuous casting slab， the cut continuous casting slab are prone to quality defects due to the coupling effect of phase transformation， thermal stress， and temperature， resulting in huge economic losses.This article takes X70 pipeline steel as the research object，by comprehensively considering the nonlinear changes of material thermal properties parameters with temperature and the setting of boundary conditions， the ABAQUS finite element analysis software is used to conduct thermal coupling numerical simulation analysis on the cooling process of X70 pipeline steel 4 500 mm × 2 300 mm × 300 mm continuous casting slab. The conclusion shows that the average heat dissipation rate of the center of gravity of the slab is 0.076 ℃/s， the surface center is 0.084 ℃/s， and the temperature difference between the surface and the center is between 100 ℃ and 210 ℃， which gradually decreases over time. The stress value at the edge of the slab is 25 MPa， and the thermal stress within 300 mm of the edge is roughly the same， within 200 MPa. Considering the changes in temperature field， the cutting time to the heating furnace should be shortened as much as possible， or insulation measures should be added to prevent quality defects caused by excessive thermal stress.

Abstract Aim This pre-post intervention study aimed to assess the relationship between baseline dietary quality and the efficacy of a dietitian-guided weight reduction program, which has not been thoroughly documented to date. Methods Ninety-two consecutive obese or overweight patients visiting a tertiary center clinic for weight reduction were enrolled in this study. Participants received a dietitian-guided weight reduction education program aimed at reducing daily caloric intake by 500 kcal and improving adherence to the Mediterranean diet for 3 months. Baseline dietary quality was assessed using the 14-item Taiwanese Mediterranean Diet Adherence Screener (T-MEDAS), where a higher T-MEDAS score reflects greater adherence to the Mediterranean diet. Additional covariates, including dietary behaviors, lifestyle factors, and comorbidities were also recorded. The primary outcome was the percentage of weight reduction at 3 months, analyzed using restricted cubic spline models and generalized estimating equations (GEE) to account for the correlation between weight change and the baseline T-MEDAS scores. Results Thirty-nine participants were excluded due to major illnesses, use of anti-obesity medications, or loss to follow-up. Among the remaining 53 participants (mean age 41.2 ± 12.8 years, 56.6% female), the average weight reduction was 3.9 ± 3.3% from a baseline weight of 98.5 ± 12.8 kg. Participants who did not achieve a weight reduction of more than 5% had higher baseline T-MEDAS scores compared to those who did (5.4 ± 1.7 vs. 4.1 ± 1.8, p = 0.026). A restricted cubic spline model, adjusted for covariates including age, gender, diabetes mellitus (DM), dyslipidemia, and smoking, revealed a significant inverse relationship between higher baseline T-MEDAS scores and weight loss. After controlling for various confounders, GEE analysis demonstrated that higher baseline T-MEDAS scores were significantly associated with less weight loss (beta: -4.1, 95% CI: -5.6 to -2.6, p

Abstract Tropical cyclones have a big impact on flood risk, and understanding how their activity interacts with population exposure under climate change is critical. Here we investigate spatiotemporal changes in flood risk using numerical models together with historical observations and future projections of tropical cyclone tracks. We find that tropical cyclone-related flood risk shifts from the Mekong Delta to the eastern lower Mekong Basin, driven by the interaction between tropical cyclones and population exposure. Historically, extreme precipitation from tropical cyclones increased flood risk in about 14% and decreased in 7% of the basin. Future tropical cyclones may increase flood risk in about 7% and reduce in nearly 18% of the basin. Moreover, population exposure growth has historically increased flood risk in 3% of the basin and is projected to result in a 1% increase. These findings highlight the complex interactions of tropical cyclone hazards and socioeconomic factors influencing flood risk.

Abstract Background Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). Methods Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. Results Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. Conclusions The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia.

Abstract Background Sorafenib is a standard therapeutic agent for advanced hepatocellular carcinoma (HCC). However, its efficacy is moderate, as the survival of patients is prolonged for only a few months, and the response rate is low. The mechanism of low efficacy remains unclear. In this study, we investigated the effect of Toll-like receptor 3 (TLR3) on the effects of sorafenib on HCC. Methods Polyinosinic-polycytidylic acid [poly(I: C)] was used as a double-stranded RNA analog and TLR3 agonist in subsequent experiments. After orthotopic implantation of HCC tumors in BALBc nu/nu or C57BL/6 mice, survival time, tumor growth, and metastasis in the abdomen and lungs were analyzed. Flow cytometry and cytotoxicity assays were used to analyze NK cells isolated from the spleen or peripheral blood. ELISA was used to detect the expression of plasma interferon (IFN)-γ and monocyte chemoattractant protein (MCP)-1. In addition, the expression of phosphorylated-extracellular regulated kinase 1/2 (pERK1/2), phosphorylated-protein kinase B (pAKT), ERK1/2 and AKT was analyzed by Western blotting. Results Sorafenib reduced the number and activity of NK cells in tumor-bearing mice and simultaneously decreased the levels of MCP-1 and IFN-γ in the plasma. The combination of sorafenib and poly(I: C) synergistically inhibited tumor growth and metastasis in tumor xenograft mice and prolonged survival. Poly(I: C) not only exerts a direct inhibitory effect on tumor growth and metastasis by targeting the TLR3 receptor on tumor cells but also facilitates the proliferation and activation of NK cells, indirectly impeding tumor progression. Mechanistically, poly(I: C) decreased the sorafenib-induced inhibition of ERK phosphorylation and increased the phosphorylation of IκB in NK cells, thereby enhancing NK cell function. Conclusion Activation of TLR3 can enhance the antitumor effect of sorafenib on HCC. The combination of a TLR3 activator and sorafenib may be a new strategy for the treatment of HCC.

Abstract Focal adhesions (FAs) strengthen their link with the actin cytoskeleton to resist force. Talin-vinculin association could reinforce actin anchoring to FAs by controlling actin polymerization. However, the actin polymerization activity of the talin-vinculin complex is not known because it requires the reconstitution of the mechanical and biochemical activation steps that control the association of talin and vinculin. By combining kinetic and binding assays with single actin filament observations in TIRF microscopy, we show that the association of talin and vinculin mutants, mimicking mechanically stretched talin and activated vinculin, triggers a sequential mechanism in which filaments are nucleated, capped and released to elongate. In agreement with these observations, FRAP experiments in cells co-expressing the same constitutive mutants of talin and vinculin revealed accelerated growth of stress fibers. Our findings suggest a versatile mechanism for the regulation of actin assembly in FAs subjected to various combinations of biochemical and mechanical cues.

Abstract The Southeastern Siberia (SES) region has recently experienced increasingly extensive wildfires in spring, which have threatened its large carbon sequestration capacity from vast forests and peatlands. However, the underlying mechanisms propelling the increased fires and their potential responses to future climate change remain unclear. Here, by using reanalysis data and climate model output together with a deep learning model, we explore the relationship between positive-phase North Atlantic Tripole (NAT) sea-surface temperature anomalies and SES wildfire increases and project the future trend in SES wildfire intensities under climate change. We found that the positive-phase April NAT enhances the Siberian anticyclone, causing increased temperatures and snowmelt via strengthened transport of warm-air advection into the SES region. The latter process heightens the exposure of local high-density peatlands to favorable conditions for fire ignition and leads to more intensive wildfire incidents. We further demonstrate that the projected NAT variations can drive interdecadal changes in future April SES wildfires. With future phase shifting of NAT modes under global warming, the regionally averaged burned area in SES could be increased by 47–62% under different warming scenarios from 1982–2014 to 2015–2100. Our findings reveal the climate-driven escalation of future wildfires in SES in the context of global warming and call for active and urgent fire management strategies to mitigate the fire risk.

Abstract Phytochrome interacting factors (PIFs) serve as crucial regulators in the light signal transduction pathway and also mediate light signals to regulate secondary metabolite synthesis in plants. However, the regulator role of PIFs in secondary metabolites often varies among different plants. Isorhynchophylline (IRN), an iconic secondary metabolite of Uncaria rhynchophylla, holds significant medicinal value. Low light induces the synthesis of IRN in previous research, but PIFs in U. rhynchophylla have not been studied to date. Building on this, we identified a PIF protein, UrPIF3, which possesses the typical conserved domains of the PIFs and is localized in the nucleus. Moreover, the expression level of UrPIF3 is consistently positively correlated with the expression of two key enzyme genes (UrSGD and UrSTR) in the IRN biosynthesis pathway, regardless of whether under low light or restoring light conditions. Yeast one-hybrid and dual-luciferase assays further demonstrated that UrPIF3 can directly upregulate UrSGD. Conversely, silencing UrPIF3 inhibits IRN synthesis, and significantly reduces the expression levels of UrSGD and UrSTR. In summary, our results suggest that under low light conditions, UrPIF3 can directly upregulate UrSGD and indirectly upregulate UrSTR, thereby promoting the synthesis of IRN.

Abstract Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor β1 (TGF-β1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-β1 promoted cell proliferation. The HA + TGF-β1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-β1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-β1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-β1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-β1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue.

Abstract Purpose To evaluate the safety and efficacy of intravitreal dexamethasone implantation during phacoemulsification and intraocular lens implantation in pediatric uveitis. Methods A retrospective analysis was conducted on pediatric uveitis patients undergoing phacoemulsification and intraocular lens implantation with intravitreal dexamethasone implantation. Patients with a minimum follow-up of 6 months were included. Primary outcome measures included ocular inflammation, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and worsening of uveitis. Results 36 eyes of 28 patients were ultimately included in this study. The mean preoperative BCVA was 1.00 (0.40–1.50) LogMAR. BCVA significantly improved to 0.40 (0.20–0.54) LogMAR at 1 month postoperatively (P = 0.006), further improving to 0.30 (0.20–0.40) LogMAR at 3 months postoperatively (P = 0.001). BCVA remained stable at 0.30 (0.20–0.70) LogMAR at 6 months postoperatively (P = 0.005). Mean IOP showed no statistically significant difference during the follow-up period of three to six months after surgery. Eight children experienced recurrence of ocular inflammation during the 6-month follow-up period. No cases of worsening macular edema, glaucoma, or elevated IOP were observed in any patient. Conclusion Intravitreal dexamethasone implantation during phacoemulsification and intraocular lens implantation is a safe and effective method for preventing and treating postoperative inflammation in children with uveitis.

Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins, providing a robust form of cytolysis. Meanwhile, along with the thorough research, a great deal of evidence has demonstrated the dual effects of pyroptosis in host defense and inflammatory diseases. More importantly, the recent identification of abundant gasdermin-like proteins in bacteria and fungi suggests an ancient origin of pyroptosis-based regulated cell death in the life evolution. In this review, we bring a general overview of pyroptosis pathways focusing on gasdermin structural biology, regulatory mechanisms, and recent progress in induction and inhibition strategies for disease treatment. We look forward to providing an insightful perspective for readers to comprehend the frame and challenges of the pyroptosis field, and to accelerating its clinical application.

Abstract The propagation of Bloch waves in one dimensional phononic crystal consisting of dielectric elastic solids is studied with consideration of the strain gradient, inertial gradient and flexoelectric effects. The transfer matrixes for single layer and one-cell of phononic structure are derived based on the constitutive equations and the governing equations of dielectric elastic solids. The dispersion equation for Bloch waves is obtained by the application of periodic conditions for the generalized displacements and tractions considered within strain gradient theory of electro-elasticity. Based on the numerical solution of the derived dispersion equation, the influences of the micro-stiffness length scale, micro-inertial length scale and flexoelectric coefficients on the dispersion and the bandgap are discussed.

Abstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. Methods The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. Results In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. Conclusions The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Introduction: Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China. Methods: We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022, to January 8, 2023. The non-contrast-enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient’s clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality. Results: This study included a total of 858 HD patients, of which 660 were infected with COVID-19. The mean age was (55.61 ± 14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level, and calcium were independent risk factors for disease severity, while platelets, urea nitrogen, serum chlorine and creatinine were identified as independent protective factors. Furthermore, total iron-binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p < 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes. Conclusion: The majority of HD patients are susceptible to COVID-19. Demographic, clinical features, and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Abstract Background and aim China has used traditional Chinese medicine (TCM) to treat diseases for more than 2000 years. Traditionally, TCMs in medicine cabinets are arranged alphabetically or on the basis of experience, but this arrangement greatly affects dispensing efficiency. However, owing to the unique properties and qualities of TCM, very few automatic approaches or systems have specifically addressed TCM dispensing problems. Therefore, it is necessary to establish a method of optimizing the traditional Chinese medicine placement scheme (TCMPS) via computer algorithms to improve the work efficiency of pharmacists. Methods A prescription dataset from a hospital in 2022 was obtained, and the association rule algorithm (ARA) was used to calculate the frequency of use for each type of TCM and the associations between different types of TCMs. On the basis of these association and frequency data, the optimal TCMPS was calculated using the simulated annealing algorithm (SAA) and then verified using the prescription dataset from 2023. Results A total of 10,601 prescriptions were collected in 2022, involving 360 different TCMs, and each prescription contained an average of 9.485 TCMs, with Danggui (3628) being the most frequently used. When the threshold of support was set to 0.05 and the confidence was set to 0.8, 78 couplet medicines used in orthopedics clinics were found through ARA. When the threshold value of support was set to 0, the confidence was set to 0, and the rule length was 2, a total of 129,240 rules were obtained, indicating support between all pairwise TCMs. The TCMPS, calculated using SAA, had a correlation sum of 14.183 and a distance sum of 3.292. The TCMPS was verified using a prescription dataset from 2023 and theoretically improved the dispensing efficiency of pharmacists by approximately 50%. Conclusions In this study, the ARA and SAA were successfully applied to pharmacies for the first time, and the optimal TCMPS was calculated. This approach not only significantly improves the dispensing efficiency of pharmacists and reduces patient waiting time but also enhances the quality of medical services and patient satisfaction, and provides a valuable reference for the development of smart medicine.

Abstract Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

Background/purpose: The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exhibits diverse and complicated functions in cancer progression. Despite reports suggesting both tumor-suppressive and oncogenic effects in various cancers, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study aimed to investigate the association between NEAT1 expression levels and survival outcomes in HNSCC patients. Materials and methods: Paired tissue samples of tumor and non-cancerous matching tissues (NCMT) from 92 HNSCC patients were collected. NEAT1 expression was analyzed using RT-qPCR. Clinical characteristics, treatment received, and survival rates of the patients were assessed to determine the correlation with NEAT1 expression and explore its association with alcohol, betel quid, and cigarette use. Additionally, we examined the effect of arecoline on NEAT1 expression in normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). Results: The study revealed a significant downregulation of NEAT1 expression in oral cancer tissues compared to NCMT. Meanwhile, arecoline increased NEAT1 expression in NHOK and NHOF cells. However, patients with downregulated NEAT1 expression exhibited higher overall survival rates, particularly in those who did not receive chemotherapy or radiotherapy. Conclusion: NEAT1 expression levels are associated with survival outcomes in HNSCC patients, with upregulated expression indicating a worse prognosis, suggesting this lncRNA might contribute to cancer aggressiveness, especially in the absence of active treatment. These findings indicate NEAT1 may serve as a potential prognostic biomarker in HNSCC, but further research is required to elucidate its role in cancer progression and its potential as a therapeutic target.

With the rapid development of the electronics industry, the demand for dielectric materials with high permittivities, low losses, and excellent electrical breakdown strengths prepared via low-temperature fabrication techniques is increasing. Herein, we propose a one-step cold sintering process route to improve the comprehensive performance of BaTiO3−based ceramics by integrating polyetherimide (PEI). Dense BaTiO3–PEI nanocomposites can be prepared via a cold sintering process at 250 °C using Ba(OH)2∙8H2O and H2TiO3 as the transient liquid phase. The grain growth of BaTiO3 is inhibited, and thin PEI layers less than 10 nm in size are located at the grain boundaries. The dissolution‒precipitation process triggered by the transient liquid phase and viscous flow assisted by PEI dominates the cold sintering mechanism of the (1−x)BaTiO3–xPEI nanocomposites. The dielectric properties are stable over a broad temperature range up to 200 °C. Compared with BaTiO3, 80% BaTiO3–20% PEI has superior performance, with a relative permittivity of 163 and a low dielectric loss of 0.014, and the electrical breakdown strength is increased by 80.65% compared with BaTiO3. Overall, the cold sintering process provides a potential way to develop dielectric nanocomposites with excellent comprehensive performance.

ObjectiveTo understand the current status of sleep chronotype, sleep duration, and depression among adolescents in Chongqing municipality, and explore the relationship between sleep chronotype, sleep duration, and depression. MethodsFrom December 2021 to January 2022, a total of 4 427 middle and high school students in Chongqing were selected using stratified cluster sampling. The reduced Morningness-Eveningness Questionnaire (rMEQ) and Patient Health Questionnaire-9 (PHQ-9) were used to assess the current status of adolescent sleep chronotype and depression. Chi-square tests were used to analyze the relationship between different demographic characteristics, sleep, and depression. Binary logistic regression models were used to explore the relationship between sleep chronotype, sleep duration, and depression. ResultsThe incidence of depressive symptoms among adolescents was 19.90%. The proportions of morning type (M-type), intermediate type (N-type), and evening type (E-type) sleep chronotypes were 17.44%, 62.16%, and 20.40%, respectively. Insufficient sleep accounted for 75.18%. Adolescents who were female, had poor family economic status, had heavy academic burden, had intermediate or evening sleep chronotypes, and had insufficient sleep were at higher risk of developing depressive symptoms. ConclusionIntermediate type, evening type, and insufficient sleep are risk factors for the occurrence of depression among adolescents in Chongqing municipality. Early intervention in adolescent sleep can reduce the risk of depression.

Abstract Stem cells have the potential to replace damaged or defective cells and assist in the development of treatments for neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease. iPS cells derived from patient-specific somatic cells are not only ethically acceptable, but they also avoid complications relating to immune rejection. Currently, researchers are developing stem cell-based therapies for PD using induced pluripotent stem (iPS) cells. iPS cells can differentiate into cells from any of the three germ layers, including neural stem cells (NSCs). Transplantation of neural stem cells (NSCs) is an emerging therapy for treating neurological disorders by restoring neuronal function. Nevertheless, there are still challenges associated with the quality and source of neural stem cells. This issue can be addressed by genetically edited iPS cells. In this study, shRNA was used to knock down the expression of mutant α-synuclein (SNCA) in iPS cells that were generated from SNCA A53T transgenic mice, and these iPS cells were differentiated to NSCs. After injecting these NSCs into SNCA A53T mice, the therapeutic effects of these cells were evaluated. We found that the transplantation of neural stem cells produced from SNCA A53T iPS cells with knocking down SNCA not only improved SNCA A53T mice coordination abilities, balance abilities, and locomotor activities but also significantly prolonged their lifespans. The results of this study suggest an innovative therapeutic approach that combines stem cell therapy and gene therapy for the treatment of Parkinson’s disease.

Abstract Background Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is acknowledged as an independent risk factor (IRF) for atherosclerotic cardiovascular disease. Nevertheless, studies on the impact of LDL-C on microvasculature are still scarce. The retina, abundant in microvasculature, can now be examined for microvascular alterations through the novel, non-invasive, and quantitative optical coherence tomography angiography (OCTA) technique. Methods In this cross-sectional study, 243 patients from the geriatric department were recruited (between December 2022 and December 2023). Individuals were classified into four groups based on their LDL-C levels: Group 1 (≤ 1.8 mmol/L), Group 2 (> 1.8 mmol/L to ≤ 2.6 mmol/L), Group 3 (> 2.6 mmol/L to ≤ 3.4 mmol/L), and Group 4 (> 3.4 mmol/L). The OCTA results including retinal vessel density (VD), foveal avascular zone (FAZ) area, macula thickness, and retinal nerve fiber layer (RNFL) thickness were contrasted across these groups. T-tests, analysis of variance, Welch’s tests, or rank-sum tests were employed for statistical comparisons. In cases where significant differences between groups were found, post-hoc multiple comparisons or rank-sum tests were performed for pairwise group comparisons. Spearman’s correlation coefficient was employed to perform bivariate correlation analysis to evaluate the relationship between LDL-C levels and various OCTA measurements. Multivariable regression analysis was used to evaluate the association between LDL-C levels and various OCTA measurements. Linear regression analysis or mixed-effects linear models were applied. Results It was discovered that individuals with LDL-C levels exceeding 2.6 mmol/L (Groups 3 and 4) exhibited reduced VD in the retina, encompassing both the optic disc and macular regions, compared to those with LDL-C levels at or below 2.6 mmol/L (Groups 1 and 2). A negative correlation among LDL-C levels and retinal VD was identified, with r values spanning from − 0.228 to -0.385. Further regression analysis presented β values between − 0.954 and − 2.378. Additionally, no notable disparities were detected among the groups regarding FAZ area, macular thickness, and RNFL thickness. Conclusions The outcomes of this study suggest that elevated LDL-C levels constitute an IRF for decreased VD across the entire retina. Trial registration NCT05644548, December 1, 2022.

The release of ChatGPT has triggered global attention on artificial intelligence (AI), and AI for science is thus becoming a hot topic in the scientific community. When we think about unleashing the power of AI to accelerate scientific research, the question coming to our mind first is whether there is a continuous supply of highly available data at a sufficiently large scale.

Abstract Vigorous CD8+ T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the “rejection” of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8+ T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens. Here, we review the newly discovered methods to enhance the function of CD8+ T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells. We also discuss how to participate in the epigenetic changes of CD8+ T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.

Abstract Background Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. Methods Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. Results Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8–9.7) vs. 9.0 (8.5–9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. Conclusions Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.

Abstract The last glacial maximum (LGM) is widely acknowledged as the most recent cold period representing maximum global ice conditions. However, substantial warming is observed over Northern Hemisphere. Here, we show that the LGM climate shifted from very cold to fairly warm, followed by less cold conditions in the early Heinrich Stadial 1 (HS1) phases. Our synthesis of accurate AMS 14C dates refines the exact timing of Laurentide Ice Sheet (LIS) advances during the early LGM/HS1, constraining the chronology of the LIS decay during the late LGM. The summertime soil temperatures near ice fronts were found to increase by 1.3 °C from the early to late LGM and to decrease by 0.5 °C to the early HS1 phases, consistent with the cold-warm-cool climate patterns. The early/late LGM and early HS1 climates are found to be characterized by frequent cold/warm summers and cold winters since the world’s largest LIS began to decay.

Abstract Age-related osteoporosis is a prevalent bone metabolic disorder distinguished by an aberration in the equilibrium between bone formation and resorption. The reduction in the stemness of Bone Marrow Mesenchymal Stem Cells (BMSCs) plays a pivotal role in the onset of this ailment. Comprehending the molecular pathways that govern BMSCs stemness is imperative for delineating the etiology of age-related osteoporosis and devising efficacious treatment modalities. The study utilized single-cell RNA sequencing and miRNA sequencing to investigate the cellular heterogeneity and stemness of BMSCs. Through dual-luciferase reporter assays and functional experiments, the regulatory effect of miR-183 on CTNNB1 (β-catenin) was confirmed. Overexpression and knockdown studies were conducted to explore the impact of miR-183 and β-catenin on stemness-related transcription factors Oct4, Nanog, and Sox2. Cell proliferation assays and osteogenic differentiation experiments were carried out to validate the influence of miR-183 and β-catenin on the stemness properties of BMSCs. Single-cell analysis revealed that β-catenin is highly expressed in both high stemness clusters and terminal differentiation clusters of BMSCs. Overexpression of β-catenin upregulated stemness transcription factors, while its suppression had the opposite effect, indicating a dual regulatory role of β-catenin in maintaining BMSCs stemness and promoting bone differentiation. Furthermore, the confluence of miRNA sequencing analyses and predictions from online databases revealed miR-183 as a potential modulator of BMSCs stemness and a novel upstream regulator of β-catenin. The overexpression of miR-183 effectively diminished the stemness characteristics of BMSCs by suppressing β-catenin, whereas the inhibition of miR-183 augmented stemness. These outcomes align with the observed alterations in the expression levels and functional assessments of transcription factors associated with stemness. This study provides evidence for the essential involvement of β-catenin in preserving the stemness of BMSCs, as well as elucidating the molecular mechanism through which miR-183 selectively targets β-catenin to modulate stemness. These results underscore the potential of miR-183 and β-catenin as molecular targets for augmenting the stemness of BMSCs. This strategy is anticipated to facilitate the restoration of bone microarchitecture and facilitate bone tissue regeneration by addressing potential cellular dysfunctions, thereby presenting novel targets and perspectives for the management of age-related osteoporosis.

Abstract The aims of the present stud were to optimize fermentation parameters of seedless wampee wine using response surface methodology (RSM) and evaluate the changes in flavor metabolites during fermentation. Seedless wampee wine of optimal sensory quality was produced using an inoculum concentration of 0.6%, initial sugar levels of 200 g/L, a fermentation temperature of 22 °C, and a fermentation period of 9 days. Then the flavor compound profiles (amino acids, organic acids and volatile aroma compounds) of seedless wampee wine during the fermentation under optimal conditions were analyzed using high performance liquid chromatography (HPLC) and gas chromatography–mass spectrometr (GC-MS). The main fermented phase of fermentation resulted in fluctuations in both total amino acids and organic acids, with stabilization occurring later on. A total of 54 volatile components, including esters, alcohols, terpenes, and acids, were putatively identified. Terpenes were the primary drivers of the flavor characteristics of seedless wampee. The rise of esters and decline of terpenes have the potential to significantly alter the flavor of wine during fermentation. These results would contribute to the further development of seedless wampee wine. Graphical Abstract

Abstract Background Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes. Methods A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data. Results The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA. Conclusion Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development.

Abstract Osteoarthritis (OA) is the most common form of arthritic disease, and phenotypic modification of chondrocytes is an important mechanism that contributes to the loss of cartilage homeostasis. This study identified that Fascin actin-bundling protein 1 (FSCN1) plays a pivotal role in regulating chondrocytes phenotype and maintaining cartilage homeostasis. Proteome-wide screening revealed markedly upregulated FSCN1 protein expression in human OA cartilage. FSCN1 accumulation was confirmed in the superficial layer of OA cartilage from humans and mice, primarily in dedifferentiated-like chondrocytes, associated with enhanced actin stress fiber formation and upregulated type I and III collagens. FSCN1-inducible knockout mice exhibited delayed cartilage degeneration following experimental OA surgery. Mechanistically, FSCN1 promoted actin polymerization and disrupted the inhibition of Decorin on TGF-β1, leading to excessive TGF-β1 production and ALK1/Smad1/5 signaling activation, thus, accelerated chondrocyte dedifferentiation. Intra-articular injection of FSCN1-overexpressing adeno-associated virus exacerbated OA progression in mice, which was mitigated by an ALK1 inhibitor. Moreover, FSCN1 inhibitor NP-G2-044 effectively reduced extracellular matrix degradation in OA mice, cultured human OA chondrocytes, and cartilage explants by suppressing ALK1/Smad1/5 signaling. These findings suggest that targeting FSCN1 represents a promising therapeutic approach for OA.

Abstract Background There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson’s disease (PD). This study aimed to determine whether MetS increases PD risk. Methods To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. Results Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16–1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07–1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02–1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15–1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11–1.26; p = 0.001). Conclusion MetS can contribute to the incidence of Parkinson’s disease, with individual components of MetS demonstrating comparable effects.

Objective This study aimed to identify and characterize a novel endo-β-glucanase, IDSGLUC9-4, from the rumen metatranscriptome of Hu sheep. Methods A novel endo-β-glucanase, IDSGLUC9-4, was heterologously expressed in Escherichia coli and biochemically characterized. The optimal temperature and pH of recombinant IDSGLUC9-4 were determined. Subsequently, substrate specificity of the enzyme was assessed using mixed-linked glucans including barley β-glucan and Icelandic moss lichenan. Thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), matrix assisted laser desorption ionization time of flight mass spectrometry analyses were conducted to determine the products released from polysaccharides and cello-oligosaccharides substrates. Results The recombinant IDSGLUC9-4 exhibited temperature and pH optima of 40°C and pH 6.0, respectively. It exclusively hydrolyzed mixed-linked glucans, with significant activity observed for barley β-glucan (109.59±3.61 μmol/mg min) and Icelandic moss lichenan (35.35±1.55 μmol/mg min). TLC and HPLC analyses revealed that IDSGLUC9-4 primarily released cellobiose, cellotriose, and cellotetraose from polysaccharide substrates. Furthermore, after 48 h of reaction, IDSGLUC9-4 removed most of the glucose, indicating transglycosylation activity alongside its endo-glucanase activity. Conclusion The recombinant IDSGLUC9-4 was a relatively acid-resistant, mesophilic endo-glucanase (EC 3.2.1.4) that hydrolyzed glucan-like substrates, generating predominantly G3 and G4 oligosaccharides, and which appeared to have glycosylation activity. These findings provided insights into the substrate specificity and product profiles of rumen-derived GH9 glucanases and contributed to the expanding knowledge of cellulolytic enzymes and novel herbivore rumen enzymes in general.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by Allokutzneria and Kibdelosporangium were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

There is a growing interest in leveraging LiDAR-generated forest Aboveground Biomass (LG-AGB) data as a reference to retrieve AGB from satellite observations. However, the biases arising from the upscaling process and the impact of the sampling strategy on model accuracy still need to be resolved. In this study, we first corrected the bias arising from upscaling the LG-AGB map to match the spatial resolution of Landsat observations. Subsequently, the stratified random sampling method was used to select training samples from the corrected LG-AGB map (cLG-AGB) for the Random Forest (RF) regression model. The RF model features were extracted from the Landsat observations and auxiliary data. The impact of strata numbers on model accuracy was explored during the sampling process. Finally, independent validation was conducted using in situ measurements. The results indicated that: (1) about 68% of the biases can be corrected in the up-scale transformation; (2) compared to no stratification, a three-strata model achieved a 6.5% improvement in AGB estimation accuracy while requiring a 37.8% reduction in sample size; (3) the black locust forest had a low saturation point at 60.52 ± 4.46 Mg/ha AGB and 72.4% AGB values were underestimated and the remaining were overestimated. In summary, our study provides a framework to harmonize near-surface LiDAR and satellite data for AGB estimation in plantation forest ecosystems with small patch sizes and fragmented distribution.

Prior research has documented that mindfulness is negatively associated with aggressive behaviors. Recently, studies have examined mediating psychological constructs that account for the relationships between mindfulness and cyberbullying perpetration. The purpose of the current study was to examine the longitudinal relationship between mindfulness and cyberbullying behaviors through the mediating variables of self-esteem and empathy. This study used a two-wave longitudinal design. The final sample consisted of 661 Chinese junior high school students. Participants completed four self-report questionnaires including mindfulness, self-esteem, empathy, and cyberbullying perpetration. Structural equation modeling revealed that mindfulness was significantly related to cyberbullying perpetration over time. Self-esteem and empathy significantly mediated the relationship between mindfulness and cyberbullying. Future research may focus on the potential mechanisms linking mindfulness and other protective factors with cyberbullying perpetration to facilitate the development and use of cyberbullying interventions.

In low- and middle-income countries, urbanization has spurred the expansion of peri-urban communities, or urban communities of formerly rural residents with low socioeconomic status. The growth of these communities offers researchers an opportunity to measure the associations between the level of urbanization and the home language environment (HLE) among otherwise similar populations. Data were collected in 2019 using Language Environment Analysis observational assessment technology from 158 peri-urban and rural households with Han Chinese children (92 males, 66 females) aged 18-24 months in China. Peri-urban children scored lower than rural children in measures of the HLE and language development. In both samples, child age, gender, maternal employment, and sibling number were positively correlated with the HLE, which was in turn correlated with language development.

Finger joint angle (FJA) estimation, as a dynamic and fine-grained decoding mode, can support intuitive and natural human–machine interactions. This study is pioneering work dedicated to achieving accurate and clinically friendly FJA estimation. In this context, a novel surface electromyography and force myography-based multimodal multistream multilevel fusion network (MMMFNet) is proposed. MMMFNet utilises gate-recurrent units (GRU) networks to capture spatial dependencies among features and adopts a multilevel fusion strategy to extract more comprehensive representations from information sources than a single-level fusion. A cross-stream interaction (CSI) block is added between the GRU networks to focus on important information in the prediction and optimise the learning process and representation capability by facilitating information interaction among branch networks. The experimental results suggest that the MMMFNet has higher estimation accuracy (RMSE: 6.225±0.276 vs. 6.953±0.282, R2: 0.879±0.019 vs 0.846±0.021), shorter training time (4.146±0.074 min vs. 16.536±0.430 min), and lower computational complexity (5.4×106 FLOPs vs 8.8×106 FLOPs) than state-of-the-art fusion methods. Moreover, MMMFNet, which quantifies feature importance using attention weights, is the first explainable multimodal model for hand movement intention decoding. In summary, compared with state-of-the-art methods, MMMFNet can not only estimate FJAs more accurately but is also more clinically friendly.

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

Objective The objective of this study was to test the therapeutic effect of carbon monoxide polyhemoglobin (polyCOHb) in haemorrhagic shock/resuscitation and its underlying mechanisms.Methods 48 rats were divided into two experimental parts, and 36 rats in the first experiment and 12 rats in the second experiment. In the first experimental part, 36 animals were randomly assigned to the following groups: hydroxyethyl starch group (HES group, n = 12), polyhemoglobin group (polyHb group, n = 12), and carbon monoxide polyhemoglobin group (polyCOHb group, n = 12). In the second experimental part, 12 animals were randomly assigned to the following groups: polyHb group (n = 6), and polyCOHb group (n = 6). Then the anaesthetised rats were haemorrhaged by withdrawing 50% of the animal’s blood volume (BV), and resuscitated to the same volume of the animal’s withdrawing BV with HES, polyHb, polyCOHb. In the first experimental part, the 72h survival rates of each groups animals were measured. In the second experimental part, the rats’ mean arterial pressure (MAP), heart rate (HR), blood gas levels and other indicators were dynamically monitored in baseline, haemorrhagic shock (HS), at 0point resuscitation (RS 0h) and after 1 h resuscitation (RS 1h). The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA kits in both groups of rats at RS 1h. Changes in pathological sections were examined by haematoxylin-eosin (HE) staining. Nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) levels were detected by immunohistochemical analysis, while myeloperoxidase (MPO) levels were detected by immunofluorescence. DHE staining was used to determine reactive oxygen species (ROS) levels.Results The 72h survival rates of the polyHb and polyCOHb groups were 50.00% (6/12) and 58.33% (7/12) respectively, which were significantly higher than that of the 8.33% (1/12) in the HES group (p

ABSTRACTThe Global Navigation Satellite System (GNSS) Multipath Reflection (MR) technique utilises the multipath effects of GNSS signals on the sea surface to retrieve tidal variations, playing a crucial role in tidal monitoring. However, traditional GNSS-MR techniques have certain limitations in terms of accuracy and stability due to restrictions in satellite elevation angles and antenna heights. This study proposes a new GNSS-MR sea surface height retrieval method that combines Particle Swarm Optimization (PSO) optimised Support Vector Machine (SVM) with improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN). The method utilises the GNSS multipath interfering signal frequencies (signal-to-noise oscillation term) extracted by ICEEMDAN as input features to the PSO-SVM model to retrieve the sea level height. Using one year of signal-to-noise ratio data from GNSS stations SC02 and TPW2, the stability and accuracy of the proposed method are evaluated under conditions of high satellite elevation angles and without precise GNSS antenna height information. Experimental results demonstrate that the PSO-SVM-ICEEMDAN method is superior to other existing methods in aspects of retrieval stabilities, root mean square errors, consistent tidal patterns, and so on.

AbstractRadiotherapy (RT) is a highly valuable method in cancer therapy, but its therapeutic efficacy is limited by its side effects and tumour radiation resistance. The resistance is mainly induced by hypoxia in the tumour microenvironment (TME). As a nano-oxygen carrier, Haemoglobin-based oxygen carriers (HBOCs) administration is a promising strategy to alleviate tumour hypoxia which may remodel TME to ameliorate radiation resistance and enable RT more effective. In this study, we administered fractionated RT combined with HBOC to treat Miapaca-2 cell and Hela cell xenografts on nude mice. The study found that HBOC relieved hypoxic environment and down-regulate expression of hypoxia-inducible factor-1α (Hif-1α) both in regular (100 mm3) and large (360/400 mm3) tumours. The proliferation and metastasis of tumour tissue also decreased after HBOC application. Nevertheless, in vivo RT combined with HBOC performed more effectively to suppress tumour growth in large tumours than in regular tumours. This is due to more severe hypoxic regions exist in the large solid tumours compared to the regular counterparts, and HBOC administration may be more effective in alleviating hypoxia in large tumours. Thus, HBOC sensitization therapy is more suitable for large solid tumours.