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The second International Conference on RNA Nanotechnology and Therapeutics was held on the 3-5 April in Lexington, (KY, USA). The focus of the conference was on leveraging the unique chemical and biological properties of RNA to promote transformative advances in medicine. The conference convened more than 200 researchers from 15 countries and many disciplines, roughly double the participants of the first conference. While many presentations focused on the design, assembly and characterization of RNA nanoparticles and their uses for in vivo and in vitro sensing, diagnosis and therapy, others covered a variety of relevant areas of RNA biology and chemistry.

Medicinal chemistry is an integrated discipline that primarily concerns the design, discovery, synthesis, identification, and interpretation of biologically active compounds at the molecular level. To assist undergraduates in understanding the core subjects of medicinal chemistry, we introduced a closed-loop education mode combining fundamentals of theoretical and experimental aspects in an undergraduate medicinal chemistry experimental course. Since the "Antibiotics" chapter is an important component in our medicinal chemistry lecture course, the topic "design, synthesis and biological evaluation of [beta]-lactamase inhibitors" was selected to train the students' experimental skills and especially the ability to expand on their acquired learning. The whole course schemes, including course introduction, molecular design, chemical synthesis, biochemical testing, docking simulation, student presentation, and academic writing, were described. The [beta]-lactamase inhibitory activities of synthesized benzoxaborole compounds were discussed on the basis of experimental and computational results. The education experiences regarding course process assessment, teaching management, and student self-evaluation were also summarized. These practices will be useful to solidify medicinal chemistry knowledge, train experimental skills, and improve scientific research ability for undergraduates.

Abstract Biomass pyrolysis greatly impacts climates, ecosystem dynamics, air quality, human health, global carbon and nitrogen cycle. The emissions of nitrogen-containing compounds from biomass pyrolysis highly depend on the protein nitrogen existing in biomass. However, the quantitative kinetic information, including the rate constant and apparent activation energy of individual amino acid induced by pyrolysis are still yet to be well-constrained. Towards this, we performed a series of controlled pyrolysis experiments where 18 equimolar free amino acids standard mixtures were pyrolyzed under ambient oxygen at temperatures between 160 and 240 °C. Additionally, straw samples were pyrolyzed to understand the mechanism of combined amino acids in protein liberation to free amino acids during pyrolytic processes. Our observations indicated that an increase in heating duration and temperature promote the degradation of free amino acids. Further, the heating stability of the 18 examined amino acids varied, which could be related to the length and functional groups present in their side chains. Our result shows that the degradation processes of all examined 18 amino acids followed irreversible first-order reaction kinetics in air within the given temperature range, with their activation energy ranging from 88.5 to 137.44 kJ mol−1. The distinct distribution patterns of both combined and free amino acids in aerosol samples from straw pyrolytic processes were obtained. The kinetic information of amino acids garnered herein helps to elucidate the transformation mechanisms of nitrogenous compounds during biomass burning.

Abstract Endometriosis is a chronic inflammatory disease and an estrogen-dependent disease, so dietary factors that can modulate estrogen activity may be clinically important. Dietary fiber, widely distributed in vegetables and fruits, is closely associated with a plant-based diet. Therefore, this study aims to analyze and explore the relationship between dietary fiber intake and the risk of endometriosis providing insights for future clinical significance and treatment approaches. This cross-sectional study obtained data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 for women aged 20–54 years. A total of 2840 subjects were finally included for analysis, 2599 (91.51%) in the non-endometriosis group and 241 (8.49%) in the endometriosis group. The study used dietary fibre intake as exposure variable and endometriosis risk as outcome variable. Through the use of multiple regression modelling, subgroup analyses, smoothed curve fitting, and threshold effect tests, we uncovered a significant link between exposure and outcome. In Model 2 (Multiple regression equation model after adjusting all confounding variables), after adjusting for confounders, dietary fiber intake was negatively associated with the likelihood of developing endometriosis(OR = 0.588, 95% CI = 0.360–0.959, p = 0.041). In subgroup analyses stratified by age, race, BMI, educational level, hypertension, diabetes,and hyperlipidemia, significant interactions were visualised from smoothed fitted curves. In the cross-sectional study, a connection was observed between a higher intake of dietary fiber and a decreased risk of endometriosis.

Abstract Background: Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. Results: In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. Conclusions: In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC.

Abstract Due to the influence of construction quality, engineering geology and hydrological environment, defects such as dehollowing and insufficient compaction can occur in tunnels. Aiming at the problems of complex detection model, poor real-time performance and low accuracy of the current tunnel lining defect detection methods, the study proposes a lightweight defect detection algorithm of tunnel lining based on knowledge distillation. Firstly, a high-precision teacher model based on yolov5s was constructed by constructing a C3CSFM module that combines residual structure and attention mechanism, a MDFPN network structure with multi-scale feature fusion and a reweighted RWNMS re-screening mechanism. Secondly, in the distillation process, the feature and output dimension results are fused to improve the detection accuracy, and the mask feature relationship is learned in the space and channel dimension to improve the real-time detection. Tests on the tunnel lining radar defect image dataset showed that the number of parameters of the improved model was reduced from 16.03 MB to 3.20 MB, a reduction of 80%, and the average accuracy was improved from 83.4 to 86.5%, an increase of 3.1%. On the basis of maintaining the structure and detection performance of the model, the lightweight degree of the model is greatly improved, and the high-precision and real-time detection of tunnel lining defects is realized.

Abstract Due to the polycrystalline cubic boron nitride tool has the characteristics of high hardness, brittleness, etc., it is easy to break the tool or produce defects in the laser cutting process, which affects the cutting performance of the tool. Traditional defect detection methods can no longer meet the needs of modern manufacturing. Aiming at the problems of low accuracy and poor real-time detection of surface defects on laser-cutting polycrystalline cubic boron nitride tools, this study proposes the surface defect detection model of laser cutting polycrystalline cubic boron nitride tool based on asymptotic fusion strategy, which fills the gap in the field. In the backbone network, the C3SE module is constructed by modeling the correlation between feature channels to improve the model’s focus on key features in order to enhance the feature extraction and processing capability of the backbone network; In the neck network, adaptive spatial fusion operation and direct interaction of non-adjacent layers are utilized for multi-scale information fusion, and the asymptotic feature pyramid network for object detection (AFPN) is used instead of the FPN structure to improve the detection performance; In the head network, a soft suppression mechanism is introduced to reduce the overlapping frame score using a decay function, thus improving the detection accuracy. The experimental results based on the self-constructed laser-cutting polycrystalline cubic boron nitride tool surface defects dataset show that the average accuracy of the AFFS-YOLO model is improved by 5.6% compared with that of the YOLOv5 model, reaching 86.1%, and the detection effect is better than that of the original network and other classical target detection networks.

Abstract We aim to evaluate the prevalence of steatotic liver disease (SLD) in United States (US) adolescents and explore whether metabolic dysfunction-associated steatotic liver disease (MASLD) can identify individuals with clinically significant fibrosis (CSF) in this study. The prevalence of SLD and its categories, including MASLD, metabolic dysfunction and alcohol associated liver disease (MetALD), alcohol related liver disease (ALD) and other SLD were determined. Weighted multivariable logistic regression analysis was conducted to evaluate the association between MASLD and CSF in adolescents with SLD. Among the total 1,446 US adolescents, SLD was present in 291 (20.1%) of individuals, including 260 (17.9%) for MASLD, 9 (0.6%) for MetALD and 5 (0.3%) for ALD. Only 58 (4%) had CSF. Patients with SLD showed a higher prevalence of CSF (9.6% vs. 2.6%, p

Objective To investigate short-term clinical efficacy of autologous leukocyte-poor platelet-rich plasma(LP-PRP) treatment of knee osteoarthritis(KOA). Methods 85 cases of patients with Keligren Lawrence grade Ⅰ-Ⅲ knee osteoarthritis in Peking University First Hospital Taiyuan Hospital (Taiyuan Central Hospital) from 2022 to 2023 were collected for autologous LP-PRP collection and quality assessment using a blood component separator, and all patients were treated with autologous LP-PRP. The degree and function of knee pain were assessed by visual analog scale(VAS) and knee arthritis index scale(WOMAC) at 1, 3 and 6 months after injection. Knee MRI was performed after 6 months of treatment, and the MRI imaging changes before and after treatment were compared. Different influencing factors in the treatment results were grouped and analyzed, mainly including platelet concentration in LP-PRP and K-L grading of knee joint. According to the platelet concentration in LP-PRP, it was divided into three grades, which are low concentration[(1 000)×109/L]; According to the K-L grade of the knee joint, the severity of knee osteoarthritis was divided into three grades: Ⅰ、Ⅱ、Ⅲ. Results The VAS and WOMAC scores at 1, 3 and 6 months after LP-PRP treatment were significantly lower than those before treatment, and the difference was statistically significant (P

Abstract Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Abstract Pilocytic astrocytoma (PA) is classified as a Grade I benign neuroglial tumor. The extent of surgical resection is a critical factor influencing the prognosis for patients with PA. In prior researches of PA, the extent of surgical resection is generally categorized into GTR, STR and biopsy. In some researches on brain tumor surgeries, the extent of resection also includes GTL. There is no existing research specifically comparing the efficacy of GTR versus GTL in PA treatment. In this study, the data we used are from the SEER database. We categorized the extent of resection into GTL, GTR, STL, STR, biopsy, and no surgery based on SEER classification of surgical procedures, to investigate the impact of extent of resection on PA patient survival. A multivariate logistic regression model was utilized to acquire odds ratios (OR) for different extent of resection. Survival outcomes across different extent of resection (GTL, GTR, STL, STR, biopsy, no surgery) were assessed using Kaplan–Meier survival curve analysis, with curve comparisons conducted via log-rank tests. The impact of various risk factors on survival was assessed using the Cox proportional hazards model. The hazard ratio (HR) was employed to quantify the influence of one or more factors on overall survival throughout the follow-up period. Multivariate Cox analysis revealed that age, tumor location, extent of resection, as well as the application of radiotherapy and chemotherapy, all significantly impacted prognosis. Compared to GTL, GTR did not significantly increase the risk of mortality (HR 1.17; 95% CI 0.73–1.86, p = 0.5). Furthermore, there was no statistically significant difference between the Kaplan–Meier survival curves of the two groups (p = 0.18). We employed propensity score matching (PSM) to balance the differences in baseline characteristics of patients receiving chemotherapy or radiotherapy. A total of 4429 patients were included in this study. Age, diagnosis period, race, tumor size, and tumor location as influential on the extent of resection. Age, tumor location, extent of resection, and application of radiotherapy and chemotherapy influenced the survival of PA patients. The Kaplan–Meier survival curves revealed that the long-term survival rate for GTR is slightly higher than that for GTL. The PSM analysis revealed that the application of radiotherapy and chemotherapy was associated with the reduction of overall survival in PA patients. In conclusion, there was no significant difference in survival between GTR and GTL, so GTR with less damage was preferred. The application of radiotherapy and chemotherapy can reduce overall survival of patients with PA.

Summary Brucellosis, caused by Gram-negative Brucella, spreads in human and animal populations through contact with infected animals and products. Developing a rapid and sensitive detection technology for pathogen is crucial to reduce the risk of this disease transmitting between animal populations and to humans. We produced a monoclonal antibody LPS-6B5, which shows high affinity to LPS and limited cross-reactivity with other bacteria. Based on LPS-6B5, a colloidal gold immunochromatographic assay (GICA) was developed which demonstrates high sensitivity and specificity in detecting cultured B. melitensis, B. abortus and B. suis. The Gold Immunochromatographic Assay (GICA) strips exhibited the most sensitive detection limits, with a value of 7.8125 × 105 CFU/mL for Brucella melitensis, surpassing the sensitivity levels observed for Brucella abortus and Brucella suis. It is also suitable for clinical and field samples, providing a cost-effective and user-friendly alternative to traditional methods.

Abstract The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient’s complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (β = -1.1788, 95% CI: -1.7230 to -0.6345, P-value

Abstract Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

Abstract Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease with a high fatality rate caused by a novel bunyavirus (SFTSV). The role of lipids in viral infections is well-documented; however, the specific alterations in lipid metabolism during SFTSV infection remain elusive. This study aims to elucidate the lipid metabolic dysregulations in the early stages of SFTS patients. Methods This study prospectively collected peripheral blood sera from 11 critical SFTS patients, 37 mild SFTS patients, and 23 healthy controls during the early stages of infection for lipidomics analysis. A systematic bioinformatics analysis was conducted from three aspects integrating lipid differential expressions, lipid differential correlations, and lipid-clinical indices correlations to reveal the serum lipid metabolic dysregulation in SFTSV-infected individuals. Results Our findings reveal significant lipid metabolic dysregulation in SFTS patients. Specifically, compared to healthy controls, SFTS patients exhibited three distinct modes of lipid differential expression: increased levels of lipids including phosphatidylserine (PS), hexosylceramide (HexCer), and triglycerides (TG); decreased levels of lipids including lysophosphatidylcholine (LPC), acylcarnitine (AcCa), and cholesterol esters (ChE); and lipids showing “dual changes” including phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Finally, based on lipid metabolic pathways and literature analysis, we systematically elucidated the potential mechanisms underlying lipid metabolic dysregulation in the early stage of SFTSV infection. Conclusions Our study presents the first global serum lipidome profile and reveals the lipid metabolic dysregulation patterns in the early stage of SFTSV infection. These findings provide a new basis for the diagnosis, treatment, and further investigation of the disease.

Abstract Background Chimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hostile tumor microenvironment (TME). Radiotherapy is commonly used for solid tumors and proved to improve the TME. Therefore, the combination with radiotherapy would be a potential strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors. Methods Glypican-3 (GPC3) was used as a target antigen of CAR-NK cell for hepatocellular carcinoma (HCC). To promote migration towards HCC, CXCR2-armed CAR-NK92 cells targeting GPC3 were first developed, and their cytotoxic and migration activities towards HCC cells were evaluated. Next, the effects of irradiation on the anti-tumor activity of CAR-NK92 cells were assessed in vitro and in HCC-bearing NCG mice. Lastly, to demonstrate the potential mechanism mediating the sensitized effect of irradiation on CAR-NK cells, the differential gene expression profiles induced by irradiation were analyzed and the expression of some important ligands for the NK-cell activating receptors were further determined by qRT-PCR and flow cytometry. Results In this study, we developed CXCR2-armed GPC3-targeting CAR-NK92 cells that exhibited specific and potent killing activity against HCC cells and the enhanced migration towards HCC cells. Pretreating HCC cells with irradiation enhanced in vitro anti-HCC effect and migration activity of CXCR2-armed CAR-NK92 cells. We further found that only high-dose (8 Gy) but not low-dose (2 Gy) irradiation in one fraction could significantly enhanced in vivo anti-HCC activity of CXCR2-armed CAR-NK92 cells. Irradiation with 8 Gy significantly up-regulated the expression of NK cell-activating ligands on HCC cells. Conclusions Our results indicate the evidence that irradiation could efficiently enhance the anti-tumor effect of CAR-NK cells in solid tumor model. The combination with radiotherapy would be an attractive strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.

Abstract Xiaozhou mustard (Brassica napiformis) root tuber, a traditional fermented vegetable, has a long history in Rongan County, Guangxi Province. However, the frequent occurrence of root tuber sour rot by Geotrichum candidum (G. candidum) has seriously reduced Xiaozhou mustard production and quality in recent years. The objective of the present study is to investigate the antifungal efficacy of 2-chloro-5-trifluoromethoxybenzeneboronic acid (Cl-F-BBA) against G. candidum and its possible mechanisms. The results revealed that a concentration of 0.25 mg/mL Cl-F-BBA completely halted mycelial growth and spore germination. Furthermore, a slightly lower concentration of 0.20 mg/mL was sufficient to compromise the integrity of the plasma membrane in mycelia and mitochondria, leading to a reduction in respiratory rate, activities of malate dehydrogenase (MDH), and succinate dehydrogenase (SDH), ATP content, and energy charge. This concentration also significantly disordered antioxidant metabolism, resulting in the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), and caused intracellular leakage in mycelia. In vivo experiments further demonstrated that Xiaozhou mustard root tubers treated with Cl-F-BBA exhibited markedly lower decay rates and lesion diameters compared to the control group. In summary, Cl-F-BBA presents a promising solution for controlling root tuber sour rot in Xiaozhou mustard caused by G. candidum.

Abstract Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Abstract The liver plays a crucial role in the immune response during endotoxemia and is one of the critical targets for sepsis-related injuries. As a secretory factor involved in inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, the relationship between PTX3 and cell crosstalk between immune cells and hepatocytes in the liver remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3 −/− mice with lipopolysaccharide (LPS)-induced endotoxemia exhibited alleviated liver damage, with reduced serum alanine transaminase and aspartate transaminase levels and an improved survival rate. Mechanistically, RNA-Seq and western blot results revealed that Ptx3 knockdown in hepatocytes increased the expression of Tfrc and Ccl20; consequently, Ptx3 deficiency regulated LPS-induced hepatocyte ferroptosis via increased mitochondrial reactive oxygen species and Fe2+ and recruited more macrophages by CCL20/CCR6 axis to be involved in inflammation and the clearance of harmful substances. Moreover, western blot and immunofluorescence staining confirmed that the NF-κB signaling pathway was upregulated upon LPS treatment in Ptx3-knockdown macrophages, promoting phagocytosis and polarization toward M1 macrophages. Collectively, our findings show that the absence of Ptx3 can ameliorate sepsis-induced liver injury by regulating hepatocyte ferroptosis and promote the recruitment and polarization of M1 macrophages. These findings offer a key basis for the development of effective treatments for acute infections.

Abstract In 2020, 123 PM2.5 samples were collected across different seasons in Huaxi District, Guiyang. The primary chemical components of PM2.5, including water-soluble ions (WSIIs), metallic elements, organic carbon (OC), and elemental carbon (EC), were analyzed. During the sampling period, the average PM2.5 concentration was 39.7 ± 22.3 µg/m2. Chemical mass closure (CMC) was used to reconstruct PM2.5 mass, yielding a reconstructed concentration of 29.1 ± 16.5 µg/m2. The major components were organic matter (OM), sulfate + nitrate + ammonium (SNA), and mineral dust (MD), with mean concentrations of 12.2 ± 6.3 µg/m2, 8.2 ± 4.0 µg/m2, and 6.3 ± 4.6 µg/m2, respectively. From clean days (CD) to lightly-moderately polluted days (LMPD), nitrate oxidation ratio (NOR) increased from 0.09 to 0.16, while sulfate oxidation ratio (SOR) and OC/EC ratio rose by 21.7% and 13.5%, indicating stronger secondary reactions on polluted days. The study also examined changes in chemical components under different atmospheric oxidizing and humidity conditions, revealing that sulfate and nitrate concentrations increased with relative humidity (RH) between 60 and 80%, while other components, especially MD, showed a declining trend due to hygroscopic growth and subsequent gravitational settling and precipitation. The average NO3 −/SO4 2− ratio was 0.67, indicating that fixed sources such as industrial and coal emissions were the main contributors to PM2.5. This study provides insights into the chemical composition, pollution processes, and formation mechanisms of PM2.5, which are crucial for developing effective air pollution control strategies. Furthermore, source apportionment was conducted with the positive matrix factorization (PMF) model. The Coal combustion, secondary, traffic, Industrial and dust source contributions to the PM2.5 mass were approximately 30.5%, 20.0%, 18.3%,16.7% and 14.5%, respectively.

Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical significance of patients with β-thalassemia. Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022. The expression level of miR-124-3p was detected. Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR. The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was evaluated. Results Compared with healthy control individuals, the expression of miR-124-3p was significantly up-regulated in patients with β-thalassemia (P＜0.001). The genotype of miR-124-3p high expression group was 84.2% β0 (16/19),the genotype of low expression group was 55.6% β+ (10/18). ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia (AUC:0.842). Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p. Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia, and ERF is negatively regulated by miR-124-3p. miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.

Piezo1 is a mechanosensitive ion channel protein widely expressed in mammalian cells with the function of sensing mechanical stimuli and of mediating signaling, and is embedded in the membranes of erythrocytes, the major cellular component of blood.Piezo1 regulates the morphology and function of erythrocytes by mediating the influx of Ca2+ into the cell in crosstalk with the Gardos channel (KCa3.1), constituting the “Piezo1-Ca2+-Gardos channel axis”. However, when Piezo1 is abnormally expressed or over-activated by its specific agonist (Yoda1), it can also lead to abnormal erythrocyte morphology and dysfunction, and even cause the development of related hereditary diseases.

Abstract This study aims to examine the impact of parent-child relationship on smartphone dependence among middle school students and explore the mediating role of self-respect and self-control. A cross-sectional survey was conducted using the Parent-Child Relationship Scale, Smartphone Dependence Scale, Self-Respect Scale, and Self-Control Scale with a sample of 2,311 middle school students. Correlation analysis revealed positive correlations among parent-child relationship, self-respect, and self-control. Specifically, the parent-child relationship was positively correlated with self-respect (r = 0.454) and self-control (r = 0.423), and negatively correlated with smartphone dependence (r=-0.380). Smartphone dependence was negatively correlated with self-respect (r=-0.409) and self-control (r=-0.629). Self-respect was positively correlated with self-control (r = 0.519). Structural equation modeling indicated that self-respect and self-control partially mediated the relationship between parent-child relationship and smartphone dependence. The mediation effect of self-respect was − 0.0843 (effect size = 8.99%, 95% CI=-0.1303 to -0.0379), and the mediation effect of self-control was − 0.3149 (effect size = 33.59%, 95% CI=-0.3802 to -0.2500). The total chain mediation effect of self-respect and self-control was − 0.2499 (effect size = 26.66%, 95% CI=-0.2915 to -0.2119). Self-respect and self-control serve as a chain-mediated pathway between parent-child relationship and smartphone dependence among middle school students.

Abstract Serum magnesium cannot accurately assess magnesium deficiency. The association between magnesium deficiency and metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Selecting 3,377 participants in the United States, we assessed the degree of magnesium deficiency in the population using magnesium depletion score (MDS). Multinomial logistic regression assessed the association between magnesium deficiency and MAFLD. Subgroup analyses assessed the association between dietary magnesium intake and MAFLD under different magnesium deficiency statuses. Structural equation modeling (SEM) revealed mediation effects. Magnesium deficiency was associated with MAFLD (ORseverevs.none: 1.69, 95%CI: 1.16–2.46; p for trend

Abstract Gastric cancer (GC) is globally recognized as the fifth most common cancer and the third leading cause of cancer-related mortality. Early metastasis in GC significantly contributes to its high mortality and unfavorable prognosis. However, the underlying mechanisms of this phenomenon remain largely unexplored. Among the various factors involved, AKR1C3 has emerged as a crucial component in the pathways of tumorigenesis and metastasis across multiple cancer types. Yet, the precise significance of AKR1C3 in GC patients’ prognosis and its role in GC progression remain elusive. This study illuminated the significant downregulation of AKR1C3 in GC tissues, linking it to an aggressive phenotype and poor prognosis. Interestingly, while AKR1C3 overexpression did not affect the proliferation of GC cells, it significantly inhibited their ability to invade and metastasize. The underlying mechanism appears to involve AKR1C3’s inhibition of the p-JNK pathway, which leads to reduced phosphorylation of IKKα/β and IKBα, lowering p-NF-κB levels and hindering its movement into the nucleus, thereby stifling the epithelial-mesenchymal transition (EMT) process in GC cells. These insights reveal AKR1C3’s tumor-suppressive effects in GC and suggest its potential as a diagnostic and prognostic biomarker, offering new avenues for targeted therapies in gastric cancer management.

Abstract To improve the safety of ship navigation in complex sea areas and reduce planning time while achieving optimal path planning. The paper proposes an improved A* algorithm that incorporates ship collision risk assessment. The paper utilizes multi-scale raster maps to divide the sea chart in the context of complex sea areas, and combines the Line-of-sight (LOS) algorithm to solve the zigzag paths that may appear in this planning context. Moreover, in order to improve the efficiency of optimal path planning in the context of complex sea areas while ensuring path safety, the paper proposes a collision risk function to optimize the determination of the cost of A* algorithm nodes, thereby enhancing the heuristic function of the A* algorithm. The improved A* algorithm can consider both path length and collision risk to plan the optimal path and to enhance the overall quality of the planning results. To verify the advantages of the improved algorithm proposed in the paper, the Zhoushan Islands sea area with complex environment is selected as the planning background for simulation study. The results show that the improved algorithm with the introduction of the collision risk function reduces the path planning time, the number of expanded nodes, and the path length by 30%, 11%, and 5.8%, respectively, compared with the original algorithm, which can effectively reduce the computational burden of the algorithm. This study provides a relatively complete and scientific route planning strategy for the study of the safe navigation of smart ships in complex sea areas.

Abstract In random uncertain motor parameter identification field, there is low identification efficiency and ill-conditioned data coming from the second iteration involved in the uncertainty propagation and surrogate model between the motor parameters and the performance response. In this paper, the fourth-order moment method and trust region model management technology are combined to reduce the dependence of the surrogate model accuracy and improve the computational efficiency. In the framework, the inner layer calculates the cumulative probability under different motor performance response thresholds based on the fourth-order moment method, and obtain the probability density function of the calculated motor performance response. The outer layer transforms the random uncertain motor parameters identification into a deterministic optimization problem by minimizing the probability distribution between the calculated and the measured motor performance response. In the outer layer optimization, the trust region model management technology is used to divide the search interval of the entire parameter to be identified into a series of trust regions, construct a surrogate model on the trust region to calculate the motor performance response, and continuously update the trust region by comparing the response residuals between the calculated and measured motor performance response, so that the motor parameters to be identified continue to approach the interval where true values are located. At the same time, the genetic intelligent technology is introduced to further reduce the calculation cost. Finally, the probability distribution of random uncertain motor parameters is obtained according to the identified mean, standard deviation, skewness and kurtosis coefficients. The numerical results in the example verify that the random uncertain motor parameter identification can be effectively achieved by the proposed method.

Abstract As the core component of a swivel bridge, the spherical hinge structure exhibits complex mechanical behavior under high pressure, making it challenging to describe accurately through theoretical analysis or on-site monitoring. In this context, this paper systematically examined the mechanical characteristics and key design parameters of a simplified spherical hinge structure using numerical simulations and formula derivation. Additionally, an indoor scaled test was conducted based on a representative spherical hinge structure to further investigate its mechanical properties. The findings indicated that contact pressure along the spherical hinge interface increased radially outward and followed a cubic distribution pattern. The support radius was identified as the most critical factor influencing the maximum stress value within the spherical hinge structure. In the aperture ratio range of 0.042 to 0.083, the upper and lower spherical hinges are unable to achieve coordinated deformation under high pressure, resulting in negative pressure at the edge of the pin hole. Furthermore, for spherical hinge structures with sliders, the presence of the slider introduced additional complexity to the stress state, leading to a coexistence of tension and compression on the surface of the lower spherical hinge. The highest stress occurred between the inner ring slider and the pin hole, an area that requires careful monitoring. The research provides valuable insights for the design of spherical hinges in swivel bridges and can guide the development of spherical hinge structures tailored to different bridge types in the future.

Abstract In a natural light-field imaging scene, lighting is usually performed using a mixed light field of multiple wavelengths. To better meet the requirements of human vision, this study proposes a correlation reconstruction method based on dual-wavelength imaging and a neural network (compression sensing correlation fusion-reconstruction by dual-wavelength imaging and auto-encoder neural network, CSCFR-DWI-AENN). Two different wavelengths of light are mixed through an optical multiplexer unit (OMU) to form a dual-wavelength illumination light field, and the light intensity value reflected by the object is received by the detector. The object information was reconstructed using the compressed sensing ghost imaging algorithm, and the distribution of the illumination field was taken as prior information. Two single-wavelength illumination information and the detection value are used for compressed sensing reconstruction, and the high-quality reconstructed image of the target to be measured is obtained by combining the noise reduction advantage of the autoencoder neural network. Then the target information is fused by the New Sum of Modified Laplacian (NSML) algorithm. Two single-wavelength reconstruction, dual-wavelength direct reconstruction and the proposed reconstruction were compared respectively, and non-reference image quality evaluation functions such as EN, MI, EAV and SF were used to process and analyze the reconstruction effect. It is proved that this algorithm can reconstruct the object image comprehensively, reproduce the complete detail information, and achieve a more accurate, more comprehensive and more reliable description of the same object. It provides a theoretical basis for multi-wavelength imaging technology and has a good application prospect.

Abstract Chronic high-altitude hypoxia (CHH) induces irreversible abnormalities in various organisms. Emerging evidence indicates that CHH markedly suppresses bone mass and bone strength. Targeting senescent cells and the consequent senescence-associated secretory phenotype (SASP) with senolytics is a recently developed novel therapy for multiple age-related diseases. The combination of dasatinib and quercetin (DQ) has been proven to selectively target senescent cells and attenuate SASP in multiple tissues. In this study, experimental mice were subjected to an environment simulating 5,000 m above sea level for 8 weeks to induce CHH conditions. Our results indicated that DQ supplementation was well-tolerated with negligible toxicity. In vivo, DQ prevented reductions in BMD and BMC and improved bone microarchitecture against CHH-induced changes. Biomechanical testing demonstrated that DQ significantly improved the mechanical properties of femoral bones in CHH-exposed mice. Furthermore, DQ mitigated senescence in LepR + BMSCs and decreased the population of senescent cells, as evidenced by reduced senescence markers and SA-β-Gal staining. An analysis of serum and bone marrow aspirates showed that DQ treatment preserved angiogenic and osteogenic coupling in the bone marrow microenvironment by maintaining type H vessels and angiogenic growth factors. The results suggest that DQ has significant anti-senescence effects on BMSCs and a positive impact on the bone marrow microenvironment, supporting its clinical investigation as a therapeutic agent for CHH-related osteoporosis.

Abstract This study aims to investigate the association between the platelet-to-high-density lipoprotein cholesterol ratio (PHR) and diabetes/prediabetes in US adults. Data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. The PHR was calculated by dividing platelet count by HDL-C concentration. Diabetes and prediabetes were classified according to established clinical criteria. Multivariate logistic regression analyses were employed to estimate odds ratios (ORs) and 95% CIs. We used a two-stage logistic regression model with restricted cubic splines (RCS) to evaluate potential non-linear relationships and to identify inflection points. The discriminative ability of the model was evaluated using receiver operating characteristic (ROC) curves, with the area under the curve (AUC) used to measure model performance. Sensitivity and specificity at the optimal threshold were also reported. Furthermore, subgroup and interaction analyses were conducted to determine variations across different population groups. The study included 20,229 eligible participants, with a mean age of 47.84 years, and 51.80% being female. Among the participants, 14.29% were diagnosed with diabetes, and 44.36% with prediabetes. A positive association was observed between PHR and diabetes/prediabetes. After adjusting for model 3, the OR for the combined outcome of diabetes and prediabetes associated with a per-unit increase in PHR was 1.17 (95% CI: 1.05–1.30). Participants in the highest PHR quartile had an OR of 2.55 (95% CI: 1.52–4.28) compared to those in the lowest quartile. Two-stage regression analysis identified a breakpoint at PHR = 4.55, with a positive association observed when PHR was below this value (OR = 1.33, 95% CI: 1.03–1.70). ROC analysis demonstrated good discriminatory ability of the model, with an AUC of 0.824 (95% CI: 0.803–0.845), sensitivity of 83.2%, and specificity of 66.5%. Stratified analyses revealed significant associations between PHR and diabetes/prediabetes across most demographic groups, with interactions observed for sex, alcohol consumption, and BMI, suggesting these factors may modify the association. This study suggests that an elevated PHR may be associated with a higher likelihood of diabetes and prediabetes. Consequently, PHR could serve as a valuable marker for estimating the association of diabetes and prediabetes development.

Abstract To investigate the role of the geometry of the left atrial lateral ridge (LLR) in the atrial fibrillation (AF) recurrence after radiofrequency ablation (RFA). A total of 225 patients with AF who underwent RFA for the first time were retrospectively enrolled and divided into the recurrence (n = 53) and non-recurrence (n = 172) groups. The clinical data and the volume of left atrium (LAV) and the LLR geometry were analyzed. The LAV in the recurrence group was greater than that in the non-recurrence group (P

Abstract The impact of volatile organic compounds (VOCs) on type 2 diabetes (T2D) among older adults is unknown. The multiple linear regression model and the multiple binary logistic regression were used to evaluate the relationships between mVOCs and glucose homeostasis/T2D, respectively. Among the 19 mVOCs, the higher levels of urinary N-acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA, compound CID:44146439) and N-acetyl-S-(2-hydroxypropyl)-L-cysteine (HPMMA, compound CID:107774684) were significantly associated with higher odds of T2D (OR = 1.16, 95% confidence interval [CI]:1.01–1.34 for 2HPMA; and OR = 1.27, 95% CI:1.04–1.54 for HPMMA). In addition, higher concentrations of multiple mVOCs in urine were significantly correlated with glucose homeostasis biomarkers, including 2HPMA and 2-thioxothiazolidine-4-carboxylic acid (TTCA, compound CID:3034757) with fasting glucose, HPMMA and mandelic acid (MA, compound CID:1292) with HbA1c, phenylglyoxylic acid (PGA, compound CID:11915) with serum insulin, HbA1c and HOMA-IR. Our findings suggested that exposure to VOCs were associated with increased odds of T2D in older adults, which might be mediated by impaired glucose homeostasis. Mitigating VOCs should be a necessary component of public health strategies aimed at reducing the burden of type 2 diabetes.

Abstract To address geotechnical engineering issues such as pile driving, lateral pressure tests, and static cone penetration tests on increasing number of infrastructure projects being constructed on landfills, an elasto-plastic theoretical solution for the undrained cylindrical cavity expansion in refuse soil is proposed in this paper based on an elasto-plastic constitutive model for refuse soil considering the reinforcement effect of fibers, along with a large deformation theory. The correctness of the results is validated through comparison with existing solutions based on the modified Cam-clay model. The results indicate that the response of columnar pore expansion in refuse soil is significantly different from that in ordinary soil. Near the pore, refuse soil does not enter a critical state, only the slurry-like components do. Subsequently, the reinforcement effect of the fiber material begins to manifest. Refuse soils with different fiber contents undergo both elastic and plastic stages before reaching the critical state line of the slurry-like components in the soil. They then move a certain distance along this line to reach a maximum. Given the rarity of engineering construction on similar sites in the past, the unique response of refuse soil during cylindrical cavity expansion should be given special attention.

Abstract Compared with the traditional frame structures, the novel composite frame with replaceable steel links can realize the rapid recovery of building occupancy after seismic actions to provide the capacity of reducing structural damage and ensure the reuse of a structure. In this system, plastic deformation and damage mainly concentrated in the steel links serving as the structural fuses and other structural members still remained elastic or minor plastic, and then the damaged steel links can be easy for replace. In order to study the seismic performance of the replaceable steel links, a total of four test specimens with different short length ratios were designed. A low-cycle reversed loading test was carried out in terms of failure characteristic, hysteretic response and shear strength. The results indicated that all tested specimens presented a stable and full hysteretic response while the steel links especially exhibited a large inelastic deformation capacity and fully developed shear strength as the structural fuses. Besides, failure modes of steel links included two types of shear failure and bending-shear failure, followed by two types of damage features, including web-to-stiffener weld tear, web buckling, flange-to-end plate weld tear and flange buckling, respectively. Finally, nonlinear finite element models (FEMs) of test specimens were implemented by the Abaqus software. The numerical results were in good agreement with the experimental results in terms of load-deformation curves, initial stiffness, the development of Von Mises stress and cumulative plastic equivalent strain (PEEQ) indexes to facilitate design practice.

Abstract There are no studies discussing the significance of neutrophil-to-lymphocyte ratio (NLR), neutrophil-percentage-to-albumin ratio (NPAR), and systemic immune-inflammation index (SII) in predicting poor prognosis in patients with metabolic dysfunction associated steatotic liver disease (MASLD); this study aimed to investigate the relationship between these three inflammatory markers and all-cause mortality and cardiovascular disease (CVD) mortality in patients with MASLD. Survival data for 3970 participants were obtained from National Death Index (NDI) records associated with the National Health and Nutrition Examination Survey (NHANES) dataset, the associations of NPAR, NLR, and SII with all-cause and CVD mortality were analyzed using multivariate COX regression modeling, restricted cubic spline (RCS) was used to explore nonlinear relationships and to determine the inflection point, regrouping was done according to the nonlinear inflection point, using multivariate COX regression modeling, subgroup analysis, and the Kaplan-Meier survival curves to evaluate differences in risk of death between the two groups. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive efficacy of NPAR, NLR, and SII on survival outcomes. Multivariate COX regression and RCS analyses revealed a positive linear correlation between NLR and all-cause and CVD mortality, whereas a nonlinear relationship was found between NPAR and SII and all-cause and CVD mortality. Further reclassified into two groups according to the inflection point, multivariate COX regression analyses showed a significant difference in the risk of death between the two NPAR groups (HR 1.37, 95% CI = (1.01, 1.86) for all-cause mortality and HR 2.03, 95% CI = (1.24, 3.32) for CVD mortality ) and no difference in the risk of death between the two SII groups (HR 1.11, 95% CI = (0.87, 1.42) for all-cause mortality and HR 1.35, 95% CI = (0.86, 2.12) for CVD mortality), and Kaplan-Meier survival curves showed that both all-cause and CVD mortality rates were higher in patients with MASLD above the NPAR inflection point (log-rank P 0.05). Also, COPD subgroups had a significant effect on the correlation between high levels of NPAR and CVD mortality (P interaction < 0.05). Time-dependent ROC show the predictive value of NPAR, NLR, and SII for all-cause and CVD mortality in MASLD patients. The correlation between NPAR and mortality was nonlinear, and NLR was linearly and positively correlated with mortality, Measuring NPAR and NLR may be useful in assessing risk and predicting prognosis in populations of patients with MASLD.

Abstract Background Status epilepticus (SE) is a common severe neurological emergency. Cerebral edema caused by SE is unavoidable and may exacerbate epilepsy. Recent studies have identified cerebrospinal fluid (CSF) as a crucial fluid source of initial cerebral edema following ischemic stroke and cardiac arrest. Moreover, synchronized neuronal firings drive CSF influx into interstitial fluid (ISF). Parenchymal border macrophages (PBMs) have been found to play a role in regulating CSF flow dynamics. However, the involvement of CSF and PBMs in cerebral edema during SE remains unclear. Here, we investigated the fluid source of cerebral edema in the initial phase of SE with the role of PBMs involved. Methods Lithium chloride-pilocarpine was used to induce SE in C57BL/6 J mice. Electroencephalogram (EEG) was acquired to assess changes in relative EEG power pre- and post-seizure onset. Apparent diffusion coefficient (ADC) maps reconstructed from diffusion-weighted imaging (DWI) were utilized to evaluate cytotoxic edema. Blood–brain barrier (BBB) permeability was examined using sodium fluorescein (NaFl). CSF tracer influx into the brain was assessed by transcranial imaging and brain slices. PBMs were depleted using clodronate liposomes. Immunohistochemistry was used to evaluate PBM depletion, severity of vasogenic edema, inflammation, and neuronal damage. Results During the initial stage of SE, relative EEG power sharply increased and ADC values significantly decreased. Concurrently, CSF tracer influx into the cortex significantly elevated, though NaFl leakage from blood to brain parenchyma did not evidently alter. Following depletion of PBM, CSF influx declined but AQP4 expression and polarization remained unaffected. Post-PBM depletion, there was no significant alteration in relative EEG power, yet CSF influx decreased substantially during the initial stage of SE. The degree of ADC decline lessened, IgG extravasation after SE decreased, activated microglia and proliferating astrocytes count fell, and neuronal damage post-SE alleviated. Conclusions CSF appeared to contribute to cerebral edema in SE. Depletion of PBM alleviated cytotoxic edema in the initial phase of SE, and subsequent vasogenic edema, inflammatory response and neurological damage were reduced. These findings may provide potential novel strategies for treating cerebral edema following SE.

Abstract Erythropoiesis is a crucial process in hematopoiesis, yet it remains highly susceptible to disruption by various diseases, which significantly contribute to the global challenges of anemia and blood shortages. Current treatments like erythropoietin (EPO) or glucocorticoids often fall short, especially for hereditary anemias such as Diamond-Blackfan anemia (DBA). To uncover new erythropoiesis-stimulating agents, we devised a screening system using primary human hematopoietic stem and progenitor cells (HSPCs). We discovered that BRAF inhibitors (BRAFi), commonly used to treat BRAFV600E melanoma, can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation. Notably, these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA. Mechanistically, although these BRAFi inhibit the MAPK cascade in BRAFV600E mutant cells, they paradoxically act as amplifiers in wild-type BRAF cells, potently enhancing the cascade. Furthermore, we found that while the oncogenic BRAFV600E mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation, BRAFi minimally impact HSPC self-renewal and differentiation. In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model, as well as other relevant anemia models. This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias, including DBA.

Abstract Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.

Abstract Although third-generation Epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKI) is standard of care for patients with EGFR-mutant Non-small cell lung cancer (NSCLC), little is known about the predictors of response or resistance. Here, we integrated single-cell RNA (scRNA) sequencing, bulk RNA sequencing, multiplexed immunofluorescence and flow cytometry data from pretreatment and post-resistant tumor samples of EGFR-mutant NSCLC patients received third-generation EGFR-TKIs. We show that resistant samples had a markedly enriched CXCR1+ neutrophils infiltration (P

Objective To investigate the effect of different effect compartment concentrations of propofol on the ste-reotactic electroencephalography (SEEG) of the left cerebral neocortex and limbic system in adult patients with epilepsy. Methods Fourteen patients undergoing elective electrode removal following robot-guided stereotactic implantation of left intracerebral electrodes in the Department of Epilepsy Surgery at our hospital from January 2021 to December 2022 were selected. Patients were divided into neocortex group and limbic system group according to the location of electrodes in the brain. The power range and percentage of δ, θ, α, β, and γ waves on SEEG at the intraoperative effect compartment concentrations of propofol of 0, 2, 3, 4, and 5 mg/L (concentrations of D1-D5) as well as the modulation index (MI) of phase-amplitude coupling (PAC) in the wave bands of δ-γ, θ-γ, α-γ, and β-γ were recorded and compared between the two groups. Results The power ranges of γ wave on SEEG of the left limbic system and cerebral neocortex were significantly lower at the concentrations of D2-D5 than at the concentration of D1 (F=15.13,20.33,t=4.33-8.72,P

Test anxiety disorder is a group of symptoms related to stress caused by tests, exams, evaluations, and others. It is among the severe psychological problems in exams. Long-term test anxiety is likely to cause tension, fear, irritability, depression, and other negative emotions, and it disturbs working memory, attention, and other cognitive abilities and even leads to suicidal ideation. In order to standardize the clinical diagnosis and treatment of test anxiety disorder, under the organization of the Test Anxiety Disorder Collaboration of the Chinese Society of Psychosomatic Medicine, this expert consensus was formulated by 13 experts in the field of psychiatry and psychology. We collaborate and announce the expert consensus based on current research and clinical experience. We hope the consensus can provide clinicians with scientific and comprehensive guidance on test anxiety disorder, including epidemiology, etiology, clinical manifestations, evaluation, and treatment.

Background In the context of "comprehensively promoting the construction of a healthy China" and "actively responding to the national strategy of aging population", scientific evaluation of the performance of community embedded integrated medical and nursing care with characteristics of TCM is the key to improving the quality of integrated medical and nursing care. Objective Evaluate the performance of community embedded integrated medical and nursing care with characteristics of TCM and analyze main obstacles, providing practical basis for government departments to formulate relevant policies and carry out performance evaluation of it. Methods In November 2022, the performance evaluation index system for community embedded integrated medical and nursing care with characteristics of TCM was transformed into three questionnaires: basic information of the institution, satisfaction of staff and the elderly. From November 2022 to January 2023, a questionnaire survey method was used to collect basic data from 10 sample institutions, as well as satisfaction data from staff and the elderly. From February to March 2023, the TOPSIS method was used to evaluate the performance of community embedded integrated medical and nursing care with characteristics of TCM, and the obstacle degree model was used to analyze the main obstacle factors of service performance. Results The overall embeddedness, structural embeddedness, relationship embeddedness, and embedded performance Cn of the 10 institutions are ranked consistently, 7 institutions have the same ranking of cognitive embedding and embedding performance Cn, and the ranking is consistent with the service performance Cn of each institution. The main obstacles to the performance of community embedded integrated medical and nursing care with characteristics of TCM are C33 (number of TCM health care guidance services), C44 (elderly satisfaction), C8 (institutions and partners adhere to win-win cooperation), C37 (the proportion of TCM non pharmacological therapy rehabilitation nursing personnel), C39 (number of elderly people served) . Conclusion The embeddedness, structural embeddedness, and relational embeddedness of community embedded integrated medical and nursing care with characteristics of TCM have a positive impact on its embedding performance. Cognitive embedding has a basic positive impact on embedding performance. Government departments should clarify their functional positioning, strengthen policy support, improve the evaluation system, pay attention to dynamic evaluation, and guide and promote the high-quality development of community embedded integrated medical and nursing care with characteristics of TCM. Institutions with characteristics of TCM should strengthen their structural embedding, relationship embedding, and cognitive embedding with partners, in order to continuously improve their service performance, to meet the diversified and multi-level health care service needs of the elderly in home communities. At the same time, should grasp the degree of embedding, so as not to produce the negative effect of embedding.

Background Insomnia not only decreases the quality of life and working efficiency, but also relates to other deceases. Suitable exercises may be useful to improve sleep quality. However, comparative studies on the effects of different types of exercise on sleep outcomes are currently lacked. Objective To compare the effects of different exercise types on sleep in insomnia patients and to provide insights for developing exercise prescriptions to improve sleep in this population. Methods Randomized controlled trials (RCT) investigating the effects of different types of exercises on the sleep of people with insomnia were retrieved from the PubMed, Web of Science, EBSCO, Scopus, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform from database inception to December 2023. The quality of the literatures was assessed using the Jadad scale. A network meta-analysis was performed using the random-effects model of the frequency framework in Stata 17.0 software, and publication bias was observed using a funnel plot. Results A total of 36 articles representing 2 706 participants were included in this study. Exercise interventions were categorized into five types, including the aerobic exercise (AE), resistance training (RT), mind-body exercise (ME), prolonged time of exercise (PTE), and AE combined with RT (AE+RT). The results of the network meta-analysis showed that there was a significant difference in the total score of the subjective evaluation tools between AE group and blank control group (SMD=2.20, 95%CI=0.35-4.05, P0.05). The maximum SUCRA of SQ was detected in the AE group (84.2%), followed by AE+CT (75.5%), ME (24.9%) and CT groups (15.4%). Publication bias analysis of the total score of subjective evaluation tools, SL, SE, WASO, TST, and SQ revealed some asymmetry in all six outcome indicators, indicating a certain risk of publication bias. Conclusion Given the favorable effects of AE on multiple sleep parameters, we recommend insomnia patients engage in moderate-intensity AE, such as jogging or brisk walking, three times a week for approximately 30 minutes. Additionally, options include moderate-intensity RT or AE+RT four to five times a week. When engaging in the above exercises, attention should be paid to the choice of time period, and exercise within 3 hours before bedtime should be avoided as much as possible.

Background Pseudomonas aeruginosa (P. aeruginosa) is widely distributed in air, soil, and water, human respiratory tract, intestinal tract, and skin. It can induce bloodstream infection, urinary tract infection, gastrointestinal tract infection, respiratory tract infection, etc. Conventional bacterial isolation, culture, and identification are time-consuming, and many false negative results, which cannot meet the needs of precise clinical diagnosis，and proper treatment. This study aims to develop a rapid isothermal amplification assay of Pseudomonas aeruginosa.Methods Specific primers were designed according to the National Center for Biotechnology Information (NCBI) database based on the highly conserved sequence of Pseudomonas aeruginosa virulence factor gene lecA, and a recombinase polymerase amplification (RPA) detection method was established. The sensitivity and specificity were calculated, as well as the collection and processing of clinical samples.Results The thermostatic amplification technique for Pseudomonas aeruginosa established in this paper allows nucleic acid detection within 10 minutes without cross-amplification with other bacterial strains. 27 P. aeruginosa infections were accurately detected in 300 clinical samples.Conclusion The rapid detection system based on thermostatic amplification had shown high sensitivity and specificity in this study, indicated that this method can effectively assist clinical bacterial detection.

Donor haemovigilance (DHV) is one of the main contents of haemovigilance. In recent years, great progress has been made in improving DHV regulations and standards, establishing and developing DHV systems and promoting blood donor safety. Herein we review the contribution of WHO to promote the construction and development of the global haemovigilance system, the ethical principles of donor safety of the

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Skeletal maturity can reflect an individual's developmental status and predict their future growth potential, provide clinicians with valuable diagnostic information. In recent years, significant progress has been made in imaging techniques for assessing skeletal maturity. This article aims to review the application status and research progress of X-ray, MRI and ultrasound in assessing skeletal maturity in adolescents and children, with a view of providing clinical reference.

Abstract. Background:. Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis. Methods:. In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results:. Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions:. Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.