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Abstract Among the many adverse geological disasters, the surge water disaster in karst areas causes the greatest loss to underground engineering construction, so it is necessary to carry out relevant research on the management of surge water disaster in karst pipelines. This study presents the creation of an oily epoxy resin magnetic convergence grouting material (OEMS) specifically developed to prevent water infiltration in pipelines. A self-designed visual karst pipeline grouting simulation system was used to conduct an experimental study on the diffusion and plugging behavior of magnetic slurry grouting. A model was constructed to simulate the migration of a magnetic slurry in water inrush circumstances. The model is based on the theory of slurry diffusion and the concept of magnetic adsorption. The results suggest that:(i) The best performance in grouting sealing is achieved when the ratio of new OEMS epoxy resin A liquid to B liquid is 2:1, and the blending ratio of flyash and Fe3O4 powder falls between 25 and 55%. (ii) The primary and secondary correlations among the parameters that affect the rate of change in flow rate, plugging pressure, and slurry retention rate are as follows: Hydrodynamic velocity has the greatest correlation, followed by plugging length, Fe3O4 power ratio, and flyash mixture ratio. (iii) The validity of the model is verified by comparing empirical observations with calculated theoretical values.

Abstract This paper seeks to draw a research agenda for unveiling the underlying bottlenecks and possibilities for improving the agricultural total factor productivity in the European Union (EU). To this aim, the paper first surveys the key challenges for the modern agricultural economy. Then, the case of the EU is discussed by looking at the convergence in the partial productivity indicators (including the GHG emission) and growth efficiency that relate to the gap in the total factor productivity growth. The results suggest that the EU member states exhibited growth inefficiency (i.e., a gap in the total factor productivity growth) of 5–9% on average during 2004–2021. The paper also discusses the possibilities to utilize the production theory for assessing the pathways towards improvements in the productivity and sustainability of the EU agriculture.

Abstract Pulsed electromagnetic field (PEMF) therapy has been extensively investigated in clinical studies for the treatment of angiogenesis-related diseases. However, there is a lack of research on the impact of PEMFs on energy metabolism and mitochondrial dynamics during angiogenesis. The present study included tube formation and CCK-8 assays. A Seahorse assay was conducted to analyze energy metabolism, and mitochondrial membrane potential assays, mitochondrial imaging, and reactive oxygen species assays were used to measure changes in mitochondrial structure and function in human umbilical vein endothelial cells (HUVECs) exposed to PEMFs. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of antioxidants, glycolytic pathway-related genes, and genes associated with mitochondrial fission and fusion. The tube formation assay demonstrated a significantly greater tube network in the PEMF group compared to the control group. The glycolysis and mitochondrial stress tests revealed that PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis. Mitochondrial imaging revealed a wire-like mitochondrial morphology in the control group, and treatment with PEMFs led to shorter and more granular mitochondria. Our major findings indicate that exposure to PEMFs accelerates angiogenesis in HUVECs, likely by inducing energy metabolism reprogramming and mitochondrial fission.

Building use identification is crucial in urban planning and management. Current identification methods often rely on a single data source and neglect spatial proximity. In this paper, we propose a stepwise urban building use identification framework that integrates remote sensing and social sensing data with spatial constraints based on the association of buildings with Point of Interest (POI), Area of Interest (AOI) and remote sensing data. First, the study data are preprocessed using geometric correction and POI and AOI reclassification. Then, we identify buildings with the quantitative-density index of the POIs as well as the spatial relationships between the AOIs and the buildings. Next, we generate Traffic Analysis Zones (TAZs) from road network data and utilize the similarity in physical features of buildings from remote sensing data to identify building use within spatial constraints. Finally, POI kernel density estimation is used to determine the semantic features of the buildings, and the similarity of the features between the buildings is utilized to identify the remaining buildings. The specificity of our proposed framework lies not only in the combination of multiple source data at the building-level but also in the introduction of the spatial relationships of AOIs and spatial constraints. Shenyang is selected as an example. The proposed framework identifies buildings as commercial, residential, industrial, public service and scenic spots. The accuracy assessment indicates that the proposed framework performs well, with an Overall Accuracy (OA) of 87.1% and a kappa coefficient (kappa) of 73.4%. The results of the comparison experiments show that the consideration of spatial constraints and the integration of multiple data sources help to improve the accuracy of building use identification. The proposed framework provides a new tool for better identification of urban building use, and the generated data are suitable for in-depth analyses such as building-level urban heat islands.

Abstract Silicon nitride (Si3N4) is a bioceramic material with potential applications. Customization and high reliability are the foundation for the widespread application of Si3N4 bioceramics. This study constructed a new microwave heating structure and successfully prepared 3D printed dense Si3N4 materials, overcoming the adverse effects of a large amount of 3D printed organic forming agents on degreasing and sintering processes, further improving the comprehensive performance of Si3N4 materials. Compared with control materials, the 3D printed Si3N4 materials by microwave sintering have the best mechanical performance: bending strength is 928 MPa, fracture toughness is 9.61 MPa·m1/2. Meanwhile, it has the best biocompatibility and antibacterial properties, and cells exhibit the best activity on the material surface. Research has shown that the excellent mechanical performance and biological activity of materials are mainly related to the high-quality degreasing, high cleanliness sintering environment, and high-quality liquid-phase sintering of materials in microwave environments.

Under the conditions of deep high stress, weak surrounding rock, and strong mining influence, the surrounding rock of deep-buried roadway frequently experiences large deformations, the controllability of large deformation support for this type of surrounding rock is generally poor, and the conventional anchor bolts often break or fail to anchor due to their low elongation rate, which cannot adapt to the large deformation of the roadway, resulting in the risk of roof caving in the roadway. The constant resistance device by using composite expansion pipe (CRD-cep) used in conjunction with cable bolt has been invented. The main structures include a stop end cover, an expansion pipe, an integrated tray and a conical lock. The conical lock overcomes the approximately constant composite resistance generated by the “expansion grinding” of the expanding pipe, thus, the constant resistance of the cable bolt during the large deformation process of the surrounding rock is achieved. The mechanical characteristics and working stability of the resistance stabilizer are improved by theoretical analysis, numerical simulation and static tensile testing and other comprehensive research methods, and the influence of the expansion increment and lock cone angle of the composite expansion tube constant resistance device on the deformation of the expansion pipe and the composite resistance of the CRD-cep has been understood. The test results indicate that the composite resistance of the CRD-cep is mainly divided into two processes: the fast rising resistance stage and the near constant resistance stage, and the nearly constant resistance section as the main stage reaches 85% to 90% of the entire test process. The lock cone angle and expansion increment directly affect the deformation of the expansion pipe and the mechanical characteristics of the CRD-cep. When the lock cone angle is less than 20°, the deformation of the expanding pipe is uniform and the composite resistance of the CRD-cep is stable. The expanding increment determines the size of the CRD-cep. The required constant resistance of the cable bolt can be obtained by adjusting the expanding increment. When the diameter of the anchor rope used is 17.8 mm, the lock cone angle is 15° and the expansion increment is 5 mm, the constant resistance of the CRD-cep is about 265.92 kN, when the diameter of the anchor rope used is 21.8 mm, the lock cone angle is 15° and the expansion increment is 8 mm, the constant resistance of the CRD-cep is about 424.15 kN, and the working state is stable and reliable, which can better meet the constant resistance support requirements of large deformation roadway. The CRD-cep has the characteristics of strong working stability, adjustable constant resistance stroke and resistance, simple structure, and convenient installation, which is an effective supplement to the control technology of surrounding rock in large deformation roadway.

Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8+ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8+ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8+ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8+ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8+ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2+ and HLA-A24+ donors, providing a novel method for SARS-CoV-2 infected case tracing.

Abstract Prediction of glioma is crucial to provide a precise treatment plan to optimize the prognosis of children with glioma. However, studies on the grading of pediatric gliomas using radiomics are limited. Meanwhile, existing methods are mainly based on only radiomics features, ignoring intuitive information about tumor morphology on traditional imaging features. This study aims to utilize multiparametric magnetic resonance imaging (MRI) to identify high-grade and low-grade gliomas in children and establish a classification model based on radiomics features and clinical features. A total of 85 children with gliomas underwent tumor resection, and part of the tumor tissue was examined pathologically. Patients were categorized into high-grade and low-grade groups according to World Health Organization guidelines. Preoperative multiparametric MRI data, including contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted images, and apparent diffusion coefficient sequences, were obtained and labeled by two radiologists. The images were preprocessed, and radiomics features were extracted for each MRI sequence. Feature selection methods were used to select radiomics features, and statistically significant clinical features were identified using t-tests. The selected radiomics features and conventional MRI features were used to train the AutoGluon models. The improved model, based on radiomics features and conventional MRI features, achieved a balanced classification accuracy of 66.59%. The cross-validated areas under the receiver operating characteristic curve for the classifier of AutoGluon frame were 0.8071 on the test dataset. The results indicate that the performance of AutoGluon models can be improved by incorporating conventional MRI features, highlighting the importance of the experience of radiologists in accurately grading pediatric gliomas. This method can help predict the grade of pediatric glioma before pathological examination and assist in determining the appropriate treatment plan, including radiotherapy, chemotherapy, drugs, and gene surgery.

Objective Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis‐derived BMSCs (OP‐BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6‐methyladenosine RNA binding protein 3) on the osteogenic traits of OP‐BMSCs and identify potential therapeutic targets to boost their bone formation ability. Methods We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single‐cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. Results Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single‐cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP‐BMSCs substantially impedes their proliferation and differentiation. Conclusion YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP‐BMSCs.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Abstract The long non-coding RNA X-inactive specific transcript (lncRNA XIST) and MUC1 gene are dysregulated in chronic inflammation and cancer; however, there is no known interaction of their functions. The present studies demonstrate that MUC1-C regulates XIST lncRNA levels by suppressing the RBM15/B, WTAP and METTL3/14 components of the m6A methylation complex that associate with XIST A repeats. MUC1-C also suppresses the YTHDF2-CNOT1 deadenylase complex that recognizes m6A sites and contributes to XIST decay with increases in XIST stability and expression. In support of an auto-regulatory pathway, we show that XIST regulates MUC1-C expression by promoting NF-κB-mediated activation of the MUC1 gene. Of significance, MUC1-C and XIST regulate common genes associated with inflammation and stemness, including (i) miR-21 which is upregulated across pan-cancers, and (ii) TDP-43 which associates with the XIST E repeats. Our results further demonstrate that the MUC1-C/XIST pathway (i) is regulated by TDP-43, (ii) drives stemness-associated genes, and (iii) is necessary for self-renewal capacity. These findings indicate that the MUC1-C/XIST auto-regulatory axis is of importance in cancer progression.

To accurately predict the dynamic characteristics of MR mounting, the nonlinear electromagnetic coupling law between MR liquid and soft magnetic material and the solid-liquid interaction, the electromagnetic coupling and fluid-structure coupling mathematical models and numerical simulation models of MR mounting are established. Through the magnetorheological mounting test, the simulation results are compared with the experimental results, and the validity of the numerical simulation model is verified. On this basis, the distribution effect of electromagnetic coupling in a magnetic circuit is analyzed. According to the Bingham model, the variation rule of magnetorheological fluid damping force was deduced. The magnetic field simulation results are introduced into the fluid model and the fluid-solid model, and the fluid-solid coupling effect of the numerical model of magnetorheological mounting is calculated. The dynamic and static characteristics of magnetorheological mounting under different current excitation conditions are simulated. It provides the basis for designing and simulating multi-physical field simulation of MR mounting.

Laser powder bed fusion (L-PBF) of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts. Layer thickness (LT) is of great significance to the L-PBF process but has not been studied for Mg alloys. In this study, WE43 Mg alloy bulk cubes, porous scaffolds, and thin walls with layer thicknesses of 10, 20, 30, and 40 µm were fabricated. The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds. Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input. For thin wall parts, a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used, and the porosity disappeared by reducing the layer thickness or laser energy input. A deeper keyhole penetration was found in all occasions with porosity, explaining the influence of layer thickness, geometrical structure, and laser energy input on the porosity. All the samples achieved a high fusion quality with a relative density of over 99.5% using the optimized laser energy input. The increased layer thickness resulted to more precipitation phases, finer grain sizes and decreased grain texture. With the similar high fusion quality, the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41% with the 10 µm layer to 287 MPa and 15.12% with the 40 µm layer, in accordance with the microstructural change. The effect of layer thickness on the compressive properties of porous scaffolds was limited. However, the corrosion rate of bulk samples accelerated with increasing the layer thickness, mainly attributed to the increased number of precipitation phases.

Abstract Aims Cardiovascular disease is the leading cause of death worldwide. Anxiety disorders are common psychiatric conditions associated with cardiovascular outcomes. This two‐sample Mendelian randomization (MR) study investigated the causal relationship between anxiety disorders and coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Methods Single nucleotide polymorphisms (SNPs) associated with anxiety disorders (16 730 cases; 101 021 controls) were obtained from the UK Biobank genome‐wide association study (GWAS). Cardiovascular outcome data were derived from the FinnGen study (CHD: 21 012 cases and 197 780 controls; MI: 12 801 cases and 187 840 controls; HF: 23 397 cases and 194 811 controls; and AF: 22 068 cases and 116 926 controls). Inverse variance weighted (IVW), MR–Egger, weighted median, simple mode, and weighted mode analyses examined causality. Results IVW analysis demonstrated significant causal relationships between anxiety disorders and increased risk of CHD [odds ratio (OR): 4.496; 95% confidence interval (CI): 1.777–11.378; P = 0.002], MI (OR: 5.042; 95% CI: 1.451–17.518; P = 0.011), and HF (OR: 3.255; 95% CI: 1.461–7.252; P = 0.004). No relationship was observed with AF (OR: 1.775; 95% CI: 0.612–5.146; P = 0.29). Other methods showed non‐significant associations. Two‐way analysis indicated no reverse causality. Conclusions Anxiety disorders were causally associated with greater risk of CHD, MI, and HF but not AF among individuals of European descent. Further research on mediating mechanisms and in diverse populations is warranted.

Laser powder bed fusion (L-PBF) has been employed to additively manufacture WE43 magnesium (Mg) alloy biodegradable implants, but WE43 L-PBF samples exhibit excessively rapid corrosion. In this work, dense WE43 L-PBF samples were built with the relativity density reaching 99.9%. High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding durations. The oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface, a transition layer in the middle and the matrix. The oxide layer consisted of rare earth (RE) oxides, and became dense and thick with increasing the holding duration. The matrix was composed of α-Mg, RE oxides and Mg24RE5 precipitates. The precipitates almost disappeared in the transition layer. Enhanced passivation effect was observed in the samples treated by a suitable high temperature oxidation. The original L-PBF samples lost 40% weight after 3-day immersion in Hank's solution, and broke into fragments after 7-day immersion. The casted and solution treated samples lost roughly half of the weight after 28-day immersion. The high temperature oxidation samples, which were heated at 525 °C for 8 h, kept the structural integrity, and lost only 6.88% weight after 28-day immersion. The substantially improved corrosion resistance was contributed to the gradient structure at the surface. On one hand, the outmost dense layer of RE oxides isolated the corrosive medium; on the other hand, the transition layer considerably inhibited the corrosion owing to the lack of precipitates. Overall, high temperature oxidation provides an efficient, economic and safe approach to inhibit the corrosion of WE43 L-PBF samples, and has promising prospects for future clinical applications.

Abstract Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.

Microglia are resident immune cells in the central nervous system (CNS) that play vital roles in CNS development, homeostasis and disease pathogenesis. Genetic defects in microglia lead to microglial dysfunction, which in turn leads to neurological disorders. The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects. Traditional genetic defect correction approaches are dependent on viral vector-based genetic defect corrections. However, the viruses used in these approaches, including adeno-associated viruses, lentiviruses and retroviruses, do not primarily target microglia; therefore, viral vector-based genetic defect corrections are ineffective in microglia. Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia. In this paper, we systematically review the history, rationale and therapeutic perspectives of microglia replacement, which would be a novel strategy for treating CNS disorders.

Abstract Suicidal behavior and non-suicidal self-injury (NSSI) are common in adolescent patients with major depressive disorder (MDD). Thus, delineating the unique characteristics of suicide attempters having adolescent MDD with NSSI is important for suicide prediction in the clinical setting. Here, we performed psychological and biochemical assessments of 130 youths having MDD with NSSI. Participants were divided into two groups according to the presence/absence of suicide attempts (SAs). Our results demonstrated that the age of suicide attempters is lower than that of non-attempters in participants having adolescent MDD with NSSI; suicide attempters had higher Barratt Impulsiveness Scale (BIS-11) impulsivity scores and lower serum CRP and cortisol levels than those having MDD with NSSI alone, suggesting levels of cortisol and CRP were inversely correlated with SAs in patients with adolescent MDD with NSSI. Furthermore, multivariate regression analysis revealed that NSSI frequency in the last month and CRP levels were suicidal ideation predictors in adolescent MDD with NSSI, which may indicate that the increased frequency of NSSI behavior is a potential risk factor for suicide. Additionally, we explored the correlation between psychological and blood biochemical indicators to distinguish suicide attempters among participants having adolescent MDD with NSSI and identified a unique correlation network that could serve as a marker for suicide attempters. Our research data further suggested a complex correlation between the psychological and behavioral indicators of impulsivity and anger. Therefore, our study findings may provide clues to identify good clinical warning signs for SA in patients with adolescent MDD with NSSI.

Introduction: MDM2 is known as the primary negative regulator of p53, MDM2 promotes lung cancer fibrosis and lung injury through p53-dependent and p53-independent pathways. However, the mechanism by which MDM2 influences the pathogenesis of asthma is unknown. In this study, we investigated the function of MDM2 in lung epithelial cells in type 2 lung inflammation. Methods: We used type II alveolar epithelial cell-specific heterozygous knockout of Mdm2 mice to validate its function. Then papain-induced asthma model was established, and changes in inflammation were observed by measuring immunohistochemistry and flow cytometry analysis. Results: In this study, we knockdown the mouse Mdm2 gene in type 2 alveolar epithelial cells. We demonstrated that heterozygous Mdm2 gene-deleted mice were highly susceptible to protease allergen papain-induced pulmonary inflammation characterized by increased ILC2 numbers, IL-5 and IL-13 cytokine levels, and lung pathology. A mechanistic study showed that following the decreased expression of Mdm2 in lung epithelial cells and A549 cell line, p53 was overactivated, and the expression of its downstream genes p21, Puma, and Noxa was elevated, which resulted in apoptosis. After Mdm2 knockdown, the mRNA expression of inflammation-related gene IL-25, HMGB1 and TNF-α were increased, which further amplified the downstream ILC2 response and lung inflammation. Conclusion: These results indicate that Mdm2 maintains the homeostasis of lung epithelial cells by targeting P53, and regulate the function of lung epithelial cells under type 2 lung inflammation.

IntroductionMesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.MethodsIn this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).ResultsThe median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.DiscussionThese finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

Abstract Compared with the traditional two‐step localization methods, the direct position determination (DPD) method is more robust at low signal‐to‐noise ratio. However, to guarantee the optimal location result, the computational complexity of DPD with grid search is too high, especially for moving targets. Therefore, a new DPD method is proposed for moving targets with low computational complexity. First, using a proposed cost function, the position information is obtained from the received array signals directly, which enhances the accuracy of localization. Second, utilizing the method of successional difference the velocity is extracted, which avoid the multi‐dimensional grid search and reduces the computational complexity. Simulation results demonstrate that the proposed method reduces the computational complexity greatly and outperforms the conventional methods.

Abstract Background Lysine methyltransferase 2D (KMT2D) mediates mono‐methylation of histone H3 lysine 4 (H3K4me1) in mammals. H3K4me1 mark is involved in establishing an active chromatin structure to promote gene transcription. However, the precise molecular mechanism underlying the KMT2D‐mediated H3K4me1 mark modulates gene expression in triple‐negative breast cancer (TNBC) progression is unresolved. Methods and Results We recognized Y‐box‐binding protein 1 (YBX1) as a “reader” of the H3K4me1 mark, and a point mutation of YBX1 (E121A) disrupted this interaction. We found that KMT2D and YBX1 cooperatively promoted cell growth and metastasis of TNBC cells in vitro and in vivo. The expression levels of KMT2D and YBX1 were both upregulated in tumour tissues and correlated with poor prognosis for breast cancer patients. Combined analyses of ChIP‐seq and RNA‐seq data indicated that YBX1 was co‐localized with KMT2D‐mediated H3K4me1 in the promoter regions of c‐Myc and SENP1, thereby activating their expressions in TNBC cells. Moreover, we demonstrated that YBX1 activated the expressions of c‐Myc and SENP1 in a KMT2D‐dependent manner. Conclusion Our results suggest that KMT2D‐mediated H3K4me1 recruits YBX1 to facilitate TNBC progression through epigenetic activation of c‐Myc and SENP1. These results together unveil a crucial interplay between histone mark and gene regulation in TNBC progression, thus providing novel insights into targeting the KMT2D‐H3K4me1‐YBX1 axis for TNBC treatment. Highlights YBX1 is a KMT2D‐mediated H3K4me1‐binding effector protein and mutation of YBX1 (E121A) disrupts its binding to H3K4me1. KMT2D and YBX1 cooperatively promote TNBC proliferation and metastasis by activating c‐Myc and SENP1 expression in vitro and in vivo. YBX1 is colocalized with H3K4me1 in the c‐Myc and SENP1 promoter regions in TNBC cells and increased YBX1 expression predicts a poor prognosis in breast cancer patients.

Abstract As a potential solution to improve wireless security, specific emitter identification is a lightweight access authentication technology. However, the existed deep learning‐based specific emitter identification methods are highly dependent on the training sample size, leading to serious overfitting problem when the training samples are inadequate, which obstructs their practical applications. To address this issue, an innovative data augmentation method to effectively expand the sample size is proposed. In this design, after data preprocessing, a random integration based data augmentation is applied to integrate several initial samples and generate new samples. Furthermore, compared with the existed methods, chaotic sequences are utilized to randomly set the integration weight of each initial sample, and thus enhancing the diversity of augmented samples. The superiority of the proposed chaotic integration‐based data augmentation method in accuracy, generalization ability and robustness is validated by the hardware implementation on digital mobile radio portable radios.

Due to the fluctuating and intermittent nature of wind energy, its prediction is uncertain. Hence, this paper suggests a method for predicting wind power in the short term and analyzing uncertainty using the VDM-TCN approach. This method first uses Variational Mode Decomposition (VDM) to process the data, and then utilizes the temporal characteristics of Temporal Convolutional Neural Network (TCN) to learn and predict the dataset after VDM processing. Through comparative experiments, we found that VDM-TCN performs the best in short-term wind power prediction. In wind power prediction for 4-h and 24-h horizons, the RMSE errors were 1.499% and 4.4518% respectively, demonstrating the superiority of VDM-TCN. Meanwhile, the Gaussian Mixture Model (GMM) can effectively quantify the uncertainty of wind power generation at different time scales.

Cytoplasmic 6-phosphogluconate dehydrogenase (G6PGH) is a key enzyme in the pentose phosphate pathway that is involved in regulating various biological processes such as material metabolism, and growth and development in plants. However, it was unclear if OsG6PGH1 affected rice grain quality traits. We perform yeast one-hybrid experiments and reveal that OsG6PGH1 may interact with OsAAP6. Subsequently, yeast in vivo point-to-point experiments and local surface plasmon resonance experiments verified that OsG6PGH1 can bind to OsAAP6. OsG6PGH1 in rice is a constitutive expressed gene that may be localized in the cytoplasm. OsAAP6 and protein-synthesis metabolism-related genes are significantly upregulated in OsG6PGH1 overexpressing transgenic positive endosperm, corresponding to a significant increase in the number of protein bodies II, promoting accumulation of related storage proteins, a significant increase in grain protein content (GPC), and improved rice nutritional quality. OsG6PGH1 positively regulates amylose content, negatively regulates chalkiness rate and taste value, significantly affects grain quality traits such as appearance, cooking, and eating qualities of rice, and is involved in regulating the expression of salt stress related genes, thereby enhancing the salt-stress tolerance of rice. Therefore, OsG6PGH1 represents an important genetic resource to assist in the design of high-quality and multi-resistant rice varieties.

BackgroundElevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation.MethodsIn our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells.ResultsIn lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions.ConclusionThe involvement of PPP4C in LUAD is deeply intertwined with the tumor’s immune microenvironment. PPP4C’s over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.

Diagenetic physical simulation is a reliable means to study patterns of pore evolution and variations of physical properties, however, the current compaction model is mostly based on sandstone, and there is a lack of quantitative compaction and porosity reduction studies for more complex rock fabrics. In order to simulate the continuous change of intergranular porosity in the reservoir under compaction during the diagenesis of buried sedimentary strata, a self-designed diagenesis simulation experimental system was adopted. Using different modern sediment samples, the simulation experiment of mechanical compaction of glutenite was carried out. The experiment shows that during the process of mechanical compaction of glutenite, the change of porosity with depth is segmented, and there is a good logarithmic relationship between depth and porosity in the process of diagenetic compaction. The larger the grain size in the reservoir rock, the better the pore preservation capacity; When the sand particles fill the pores among gravel, stable secondary support structure formed by gravel and sand grades can effectively take over the bearing pressure, and when the sand-grade particle content is about 30%, the pressure-bearing capacity is the strongest; Intergranular heterobase filling is greater in samples with high heterobase content, high heterobasic content is not favourable to the preservation of primary pores. This study provides favorable experimental support for the preservation mechanism of deep clastic reservoir pores, and has important theoretical and practical significance for oil and gas exploration in the study area. The use of simulation experiment provides a useful idea for the evaluation and prediction of reservoirs and the search for favorable reservoir development zones in the future.

Moraxella catarrhalis (M. catarrhalis) was an underestimated respiratory infection pathogen that has been largely overlooked. The limited availability of rapid and sensitive detection methodologies has hindered M. catarrhalis diagnostic in clinical settings and contributed to its underestimation. To address this issue, we devised two recombinase polymerase amplification (RPA)-based assays for rapid, sensitive and reliable detection of M. catarrhalis, termed M. catarrhalis-RPA-Flu and M. catarrhalis-RPA-LFB, which utilized fluorescence and nanoparticle-based lateral flow biosensor (LFB) for reporting the detection results, respectively. In both assays, the specific copB gene of M. catarrhalis was amplified at 37°C for only a period of 20 minutes. In M. catarrhalis-RPA-Flu system, the detection results were analyzed by either using a real-time fluorescent detector or by direct observation using the naked eye under blue light, while, in M. catarrhalis-RPA-LFB system, biosensors were used for interpreting the results without any specialized instruments. Both methods were able to finalize the entire detection process within a duration of 40 minutes, detect down to 35 fg genomic DNA per test, and correctly differentiate M. catarrhalis from non-M. catarrhalis strains. The feasibility of both techniques was validated by analyzing 96 BALF (Broncho alveolar lavage fluid) samples in clinical settings. Collectively, the newly developed two RPA-based assays exhibit great potential for rapid and accurate identification of M. catarrhalis in standard microbiology laboratories as well as diagnosis of M. catarrhalis infection in clinical settings.

To achieve the safe and stable structural condition of the roof along the goaf under the roof cutting by dense drilling method, the stress distribution and fracture process of the roof strata between normal and dense drilling conditions were studied. Based on rock fracture theory and elastic theory, the stress distribution of the surrounding rock between dense drilling and the fracture process were analyzed before and after mining, clarifying the cutting mechanism of dense drilling and the interaction mechanism of concentrated stress between adjacent drilling. The calculation formula for the tensile-shear stress of the surrounding rock between dense drilling in the arc-shaped triangular panel structure at the end of the working face was derived. Based on this, the influence of different parameters on the tensile-shear stress of the surrounding rock between drilling was analyzed, and a determination method for the key parameters of roof cutting by dense drilling holes along the goaf was proposed. Research has shown that the dense drilling mainly increases the concentration of the surrounding rock's tensile and shear stress by changing the stress conditions around the densely drilled holes before and after mining, causing the expansion and connection of fractures between drilling and forming key rock layers for cutting. Before mining, the drill holes are mainly affected by horizontal compression stress, and after mining, the stress gradually changes to the tensile and shear stress caused by the rotation and subsidence of the goaf roof, and the state of the surrounding rock between the holes transitions from the weakening stage to the formation of crack stage, and then to the fracture stage. The magnitude of the tensile and shear stress of the surrounding rock between the densely drilled holes mainly depends on the thickness of the key rock layer and the ratio of the hole diameter to the hole spacing, and is negatively correlated with the hole height and spacing, and positively correlated with the angle and diameter of the drill holes. Based on this, a method for determining the key parameters of intensive drilling and cutting is proposed, and a plan for intensive drilling and cutting in the goaf with hard roof conditions on the 3124 N working face of Longtan Mine is designed, with a hole length of 8.3 m, an angle of 15°, a hole diameter of 48 mm, and a spacing of 500 mm. The deformation of the goaf roof after cutting is controllable and the overall stability is good, which proves that the arrangement parameters of intensive drilling and cutting are reasonable, and the determination method for the key parameters of roof cutting by dense drilling holes is effective and feasible.

Given their potential to demonstrate near-term quantum advantage, variational quantum algorithms (VQAs) have been extensively studied. Although numerous techniques have been developed for VQA parameter optimization, it remains a significant challenge. A practical issue is that quantum noise is highly unstable and thus it is likely to shift in real time. This presents a critical problem as an optimized VQA ansatz may not perform effectively under a different noise environment. For the first time, we explore how to optimize VQA parameters to be robust against unknown shifted noise. We model the noise level as a random variable with an unknown probability density function (PDF), and we assume that the PDF may shift within an uncertainty set. This assumption guides us to formulate a distributionally robust optimization problem, with the goal of finding parameters that maintain effectiveness under shifted noise. We utilize a distributionally robust Bayesian optimization solver for our proposed formulation. This provides numerical evidence in both the quantum approximate optimization algorithm and the variational quantum eigensolver with hardware-efficient ansatz, indicating that we can identify parameters that perform more robustly under shifted noise. We regard this work as the first step toward improving the reliability of VQAs influenced by shifted noise from the parameter optimization perspective.

Wind power poses a challenge to the stability of the power grid due to its unpredictability and intermittency. This study aims to analyze the forecasting law and uncertainties of short-term wind farm power forecasting (WFPF) at various time scales, in order to support the stability of energy generation. To achieve this, we propose a framework for short-term WFPF and uncertainty analysis, utilizing the whale optimization algorithm (WOA), convolutional neural network-bidirectional long short-term memory network (CNN-BiLSTM), cloud model (CM), and non-parametric kernel density estimation (NPKDE). The data is trained using a hybrid model of CNN-BiLSTM with multiple convolution and pooling methods, while the parameters are optimized using the WOA algorithm. The uncertainty of WFPF is described qualitatively by the expectation, entropy, and hyper-entropy of the cloud model, and quantified through the confidence interval based on non-parametric kernel density estimation. Test results show that the proposed WOA-CNN-BiLSTM model achieves RMSE forecasting errors of 3.79%, 4.52%, and 5.12% at 4 hours, 24 hours, and 72 hours, respectively. The maximum peak errors are less than 10.5758MW, 21.128MW, and 20.0292MW, and are better than other models. Additionally, the WOA optimization performance is superior, consistent with the results described by the cloud model. Furthermore, the RMSE forecasting value of WFPF increases with the time scale, while the growth rate of RMSE decreases with the increase of time scale. This study provides valuable insights into the uncertainties of short-term WFPF and offers a robust framework for improving the stability of energy generation.

Accurate prognostic prediction in patients with disorders of consciousness (DOC) is a core clinical concern and a formidable challenge in neuroscience. Resting-state EEG has shown promise in identifying electrophysiological prognostic markers and may be easily deployed at the bedside. However, the lack of brain dynamic modeling and the spatial mixture of signals in scalp EEG have constrained our exploration of biomarkers and comprehension of the mechanisms underlying consciousness recovery. Here, we introduce EEG source space analysis and brain dynamics to investigate the brain networks of patients with DOC (n = 178) with different outcomes (six-month follow-up), followed by graph theory and high-order topological analysis to explore the relationship between network structure and prognosis, and finally assess the importance of features. We show that a positive prognosis is associated with large-scale lower levels of low-frequency hypersynchrony. Moreover, we provide evidence that this pattern is driven not by all brain states but only by specific states. Analyses reveal that the positive prognosis is attributed to the network retaining lower segregation, higher integration, and stronger stability compared to the negative prognosis. Furthermore, our results highlight the importance of brain networks derived from brain dynamics in prognosis. The prognosis models based on clinical and neural features can achieve acceptable and even excellent performance under different outcome definitions (AUC = 0.714–0.893). Overall, our study offers new perspectives for the identification of prognostic biomarkers and provides avenues for profound insights into the mechanisms underlying consciousness improvement or recovery.

Abstract High temperature vulcanised silicone rubber (SR) has excellent hydrophobicity and thus is widely applied both in indoor and outdoor insulation. According to the analysis of different experimental ageing tests and field investigation of SR, temperature and humidity are considered to be the fundamental factors during degradation. Hygrothermal ageing was proposed in this study to simulate the chalking state of the SR, finally leading to the irreversible degradation far below the thermal decomposition temperature. The variation of morphology, hardness and polydimethylsiloxane (PDMS) content was quantified during the yearlong hygrothermal ageing test. It is implied that the gradual process of whitening and hardening are accompanied by the decline of the PDMS content. Finally, ageing delamination in SR and its degradation mechanism were proposed.

Abstract Background This study aimed to investigate the feasibility, effectiveness, and safety of pancreatic duct stenting in managing acute biliary pancreatitis (ABP) necessitating endoscopic retrograde cholangiopancreatography (ERCP). It further aimed to provide valuable insights for subsequent clinical diagnosis and treatment. Methods This research employs an observational retrospective case–control study design, encompassing patients with ABP who underwent ERCP at the hepatobiliary surgery department of the General Hospital of Ningxia Medical University between August 1, 2018, and December 31, 2020. A total of 229 cases were screened based on inclusion and exclusion criteria. Regardless of ABP severity, patients were categorized into the stent group (141) and the non-stent group (88). Changes in blood amylase (Amy), lipase (LIP), leukocyte count (WBC), total bilirubin (TBIL), alanine aminotransferase (ALT), hematocrit (HCT), and creatinine (CR) were compared between the two groups. Moreover, variables such as recovery time for oral feeding, hospitalization duration, hospitalization costs, local complications, systemic complications, and new organ failure were recorded to assess the therapeutic effect of pancreatic duct stenting. Results No significant differences were observed in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ABP severity grade, organ failure (OF), cholangitis, or biliary obstruction between the pancreatic stent and non-stent groups (P > 0.05). There was no significant difference in the incidence of complications related to acute pancreatitis between the two groups (P > 0.05). The median fasting and hospitalization times of patients in the stent group were significantly shorter than those in the non-stent group (P 0.05). There were no significant variations in white blood cell (WBC) count, TBIL, ALT, and creatinine (Cr) at admission, 72 h, and in the differences between the two groups (P > 0.05). The levels of Amy at admission and 72 h in the stent group were significantly higher than those in the non-stent group (P 0.05), the mean 72-h HCT in the stent group was 38.39% (95% confidence interval [CI] 37.82%–38.96%) was lower than that in the non-stent group (39.44%, 95% CI 38.70–40.17%) (P

Abstract The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

Abstract Background Heat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress. Results Rice plants were pretreated with distilled water, 50 μM ABA and 10 μM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2 – and H2O2) by 15.0–25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4–16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress. Conclusion Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

This study explores the role of disulfidptosis in monocytes and its relation to postmenopausal osteoporosis (PMOP). Using single-cell RNA sequencing and microarray assays, we identified key genes: LONRF1, ACAP2, IPO9, and PGRMC2. Through differential analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning, these genes were linked to PMOP. Functional enrichment and ROC curve analysis demonstrated their effectiveness in distinguishing postmenopausal fracture patients from healthy individuals. Notably, PGRMC2 exhibited significant expression differences, highlighted by a notable Area Under the Curve (AUC) value of 0.665. Further investigation involved Western blotting and immunohistochemical assays, revealing decreased PGRMC2 expression in ovariectomized (OVX) mice. This decrease was consistent across both experimental methods, emphasizing PGRMC2's role in PMOP. Moreover, PGRMC2 was predominantly present in macrophages compared to monocytes within bone tissue and was significantly located in bone marrow mesenchymal stem cells (BM-MSCs) in PMOP patients. It was also abundantly found in osteoblasts and adipocytes. Additionally, a Mendelian randomization analysis using the TwoSampleMR R package, with data from decode and GWAS databases, was conducted. This analysis showed a significant impact of PGRMC2 on osteoporosis risk (p = 0.0048, OR = 0.6836), suggesting a potential protective effect against the disease. Our results suggest that PGRMC2 may facilitate the differentiation of monocytes into macrophages in bone tissue, influencing the behavior of BM-MSCs. This, in turn, could impact the progression and severity of PMOP. The study provides new insights into the molecular mechanisms underlying postmenopausal osteoporosis and highlights the potential of PGRMC2 as a therapeutic target or biomarker for this condition.

Objectives: To assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. Methods: In this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. Results: The group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the

Abstract Background In a multi‐institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy. Methods Between January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X‐tile software to obtain the optimum cut‐off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer‐specific survival (CSS) in patients with RCC by Kaplan–Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C‐index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time‐dependent ROC curves. Results The optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M‐stage (p = 0.008), T‐stage (p

Glioma is a common tumor originating in the brain that has a high mortality rate. Temozolomide (TMZ) is the first-line treatment for high-grade gliomas. However, a large proportion of gliomas are resistant to TMZ, posing a great challenge to their treatment. In the study, the specific functions and mechanism(s) by which cortistatin (CORT) regulates TMZ resistance and glioma progression were evaluated. The decreased expression of CORT was detected in glioma tissues, and highly expressed CORT was associated with a better survival rate in patients with glioma. CORT overexpression notably decreased the capacity of glioma cells to proliferate and migrate in vitro and to form tumors in vivo. CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT, p21, and Puma expression. Importantly, CORT overexpression reduced the resistance of gliomas to TMZ in vivo. CORT expression was negatively correlated with MGMT expression in both glioma tissues and cells, and it was found that CORT inhibited NF-κB pathway activation in glioma cells, thereby inhibiting MGMT expression. In conclusion, CORT regulates glioma cell growth, migration, apoptosis, and TMZ resistance by weakening the activity of NF-κB/p65 and thereby regulating MGMT expression. The CORT/NF-κB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ. Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells, independent of its effects on TMZ resistance, providing evidence of novel therapeutic targets for glioma that should be evaluated in further studies.

IntroductionAutism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in motor skills, communication, emotional expression, and social interaction. Accurate diagnosis of ASD remains challenging due to the reliance on subjective behavioral observations and assessment scales, lacking objective diagnostic indicators.MethodsIn this study, we introduced a novel approach for diagnosing ASD, leveraging T1-based gray matter and ASL-based cerebral blood flow network metrics. Thirty preschool-aged patients with ASD and twenty-two typically developing (TD) individuals were enrolled. Brain network features, including gray matter and cerebral blood flow metrics, were extracted from both T1-weighted magnetic resonance imaging (MRI) and ASL images. Feature selection was performed using statistical t-tests and Minimum Redundancy Maximum Relevance (mRMR). A machine learning model based on random vector functional link network was constructed for diagnosis.ResultsThe proposed approach demonstrated a classification accuracy of 84.91% in distinguishing ASD from TD. Key discriminating network features were identified in the inferior frontal gyrus and superior occipital gyrus, regions critical for social and executive functions in ASD patients.DiscussionOur study presents an objective and effective approach to the clinical diagnosis of ASD, overcoming the limitations of subjective behavioral observations. The identified brain network features provide insights into the neurobiological mechanisms underlying ASD, potentially leading to more targeted interventions.

Due to a dramatic increase in livestock, the impact of grazing on animal communities is a global conservation concern, especially in temperate forests. Recognizing the interaction between livestock and wildlife is essential for developing more effective and holistic strategies for wildlife conservation and sustainable livestock management. In this study, we conducted systematic camera trapping at 129 sites within the central portion of the Giant Panda National Park in China to assess the interspecific relationships between livestock and 21 sympatric wild species. Using the joint species distribution model, we fitted a null model and a constrained model to investigate the distinction between the spatial distribution relationship of species (as raw associations) and the interactions between livestock and wildlife (as residual associations). The results of raw associations showed that livestock exhibited a significant positive spatial co-occurrence with Temminck's tragopan, Himalayan porcupine, Chinese serow, Reeves's muntjac, and forest musk-deer (p 0.05), indicating no strong evidence of negative interactions between livestock and wildlife. Since livestock grazing is a source of income for residents, grazing management policies within the Giant Panda National Park should not prohibit all grazing practices.

The fermentation metabolites significantly influence the quality of jujube wine. However, the dynamics of these metabolites during fermentation are not well understood. In this study, a total of 107 volatile and 1758 non-volatile compounds were identified using a flavor-directed research strategy and non-targeted metabolomics. The increase in esters and alcohols during fermentation shifted the aroma from grassy, mushroomy, and earthy to a floral and fruity flavor in the jujube wine. Leucine and phenylalanine were notably enriched during fermentation, potentially benefiting human health and enriching the flavor of fruit wines. Moreover, pathway analysis identified four key metabolic pathways and two crucial metabolic substrates, pyruvate and l-aspartate. This study provides a theoretical reference for optimizing the fermentation process and enhancing the quality of jujube wine.

N6-methyladenosine (m6A) modification is a common RNA modification in the central nervous system and has been linked to various neurological disorders, including Alzheimer's disease (AD). However, the dynamic of mRNA m6A modification and m6A enzymes during the development of AD are not well understood. Therefore, this study examined the expression profiles of m6A and its enzymes in the development of AD. The results showed that changes in the expression levels of m6A regulatory factors occur in the early stages of AD, indicating a potential role for m6A modification in the onset of the disease. Additionally, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains. The genes with differential methylation were found to be enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negatively lryassociated with genes involved in microglia hemostasis, but positively associated with genes related to “disease-associated microglia” (DAM) associated genes. These findings suggest that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.

Background: Tactile sensors are utilized to measure multichannel pulse signals in pulse wave analysis (PWA). Owing to noise interferences, researchers have applied various denoising algorithms on multichannel pulse signals. To comprehensively assess these algorithms, numerous evaluation metrics have been proposed. However, these studies did not investigate the noise mechanisms in depth and lacked reference pulse signals, thus making the evaluations insufficiently objective. Materials and methods: An applicable denoising evaluation approach for multichannel pulse signal algorithms based on an arterial pulse acquisition system is established by superimposing real-world multichannel noise to the reference signals. The system, comprising a SphygmoCor and a uniaxial noise acquisition device, allows us to acquire single-reference pulse signals as well as real-world multichannel noise. Results: We assess eight popular denoising algorithms with three evaluation metrics, including amplitude relative error (ARE), mean square error (MSE) and increased percentage signal-noise ratio (SNR%). Our proposed approach provides accurate and objective evaluations of multichannel pulse signal denoising. Notably, classic algorithms for single-channel denoising are not recommended for multichannel denoising. Comparatively, RPCA-based algorithms can denoise pulse signals independently for each channel. Conclusion: This study sets the stage for the establishment of accurate and objective pulse signal denoising evaluations and provides insights for data-driven clinical diagnoses in cardiovascular medicine.

Objective: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients’ health outcomes, and set priorities in addressing research gaps in this area. Methods: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. Results: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). Conclusion: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Abstract In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic axons to the superior colliculus (SC). However, whether and how vLGN contributes to fundamental visual information processing remains largely unclear. Here, we report in mice that vLGN facilitates visually-guided approaching behavior mediated by the lateral SC and enhances the sensitivity of visual object detection. This can be attributed to the extremely broad spatial integration of vLGN neurons, as reflected in their much lower preferred spatial frequencies and broader spatial receptive fields than SC neurons. Through GABAergic thalamocollicular projections, vLGN specifically exerts prominent surround suppression of visuospatial processing in SC, leading to a fine tuning of SC preferences to higher spatial frequencies and smaller objects in a context-dependent manner. Thus, as an essential component of the central visual processing pathway, vLGN serves to refine and contextually modulate visuospatial processing in SC-mediated visuomotor behaviors via visually-driven long-range feedforward inhibition.

The current global energy crisis has prompted a significant rise in the use of low carbon units, making it a crucial research trend in the field of urban energy system, especially in terms of addressing the intermittency of renewable energy generation. This study proposes an integrated energy system planning model (UIES) for urban areas. In addition, to tackle the issue of carbon emissions, a reward and punishment ladder-type carbon transaction model is presented, which aims to control the level of carbon emissions within urban areas. To evaluate the performance of the UIES model, the authors develop an objective function that integrates the sum of equipment operation and maintenance costs, equipment daily acquisition costs, purchased energy costs, carbon trading costs, and integrated demand response (IDR) costs. The stochastic features of renewable energy sources are taken into account in the proposed approach, and an information gap decision theory (IGDT) based strategy is designed to quantify the uncertainty interval and intermittent fluctuations associated with renewable energy. This approach also aims to mitigate any negative effects and variations that may occur during the urban energy system's IDR process. Finally, the simulation tests to demonstrate that the average decrease in operating cost of both models based on IGDT strategy are 7.36 %, and the peak of electrical (EL), heating (HL) and cooling load (CL) are reduced by 20.45 %, 12.38 % and 5.02 % respectively. in conclusion, the energy service providers in urban areas can effectively manage renewable energy fluctuations by independently adjusting the operation sequence of equipment, and the economy and stability of the UIES can be effectively improved by the proposed dispatch strategy.