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Abstract Background Real-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited. Methods This cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights. Pairwise comparisons were made between DTG-based regimen and each of the other 3-drug regimens, stratified by ART experience. Results Among 15,702 PWH (across treatment groups, median age 58–62 years; 94–98% male; 5–11% Hispanic; 44–60% Black; 29–42% White), 5,800 received DTG-based regimens, 2,081 BIC-based regimens, 4,159 EVG-based regimens, 1,607 RAL-based regimens, and 2,055 received DRV-based regimens. Among ART-naïve PWH, there were no statistical differences in the odds of virologic suppression, and 6- and 12-month discontinuations were higher in those on DRV. Among ART-experienced PWH, compared to DTG, those on RAL and DRV were less likely to be suppressed at 6 months (RAL vs DTG: aOR 0.64, 95% CI 0.51–0.81; DRV vs DTG: aOR 0.63, 95% CI 0.51–0.76) and those on EVG and DRV were less likely suppressed at 12 months (EVG vs DTG: aOR 0.82, 95% CI 0.68–0.99; DRV vs DTG: aOR 0.64, 95% CI 0.52–0.80). Those on DRV were more likely to have virologic failure within 12 months (aOR 1.96, 95% CI 1.30–2.97). Six- and 12-month discontinuations were higher in those on RAL and DRV, but less likely for BIC-based regimens. Conclusions DTG-based regimens demonstrated higher levels of effectiveness and durability compared to DRV- or RAL-based regimens and had similar treatment responses as BIC- and EVG-based regimens among ART-experienced older PWH.

Abstract Cyclin-dependent kinase 9 (CDK9) is a crucial component of transcription and potential target for anti-cancer therapies, particularly for hematological malignancies. However, the precise mechanisms underlying the therapeutic effects of CDK9 inhibitors remain not fully understood. Here, we found that inhibiting CDK9 either pharmacologically or through gene downregulation, significantly reduced the levels of α-tubulin protein in a time- and dose-dependent manner. We further discovered that CDK9 inhibition led to increased susceptibility of α-tubulin to proteasomal degradation due to reduced acetylation at lysine 40 (K40), an important modification for microtubule stability. An acetylation-mimicking mutant of α-tubulin mitigated the anti-tumor effects of CDK9 inhibition. Mechanically, we identified that CDK9 inhibition downregulated the expression of ATAT1, the acetyltransferase responsible for α-tubulin acetylation, further compromising microtubule stability. We also conducted in vivo studies in a leukemic xenograft model, where AZD4573 treatment led to significant tumor regression, decreased ATAT1 expression, and α-tubulin degradation. Our study unravels a novel molecular mechanism by which CDK9 inhibition disrupts α-tubulin stability and provides valuable insights for exploring effective treatment regimens involving CDK9 inhibitors.

Abstract Background Couples undergoing artificial insemination by donor semen(AID) represent a unique group of infertility patients, the relationship between fertility pressure and attachment styles remains unclear. To investigate the fertility pressure and attachment dimensions in artificial insemination by donor semen(AID) couples, and develop an Actor-Partner Interdependence Model (APIM) for patient care. Methods This study is a cross-sectional study. From June to September 2021, couples who were about to receive AID treatment in our hospital were assessed using the Fertility Problem Inventory, and the Experiences in Close Relationships(ECR). Dyadic analysis applying the APIM was used. Results A total of 448 valid questionnaires were recovered, the effective response rate was 94.9%. The average score of men’s fertility pressure was higher than that of women’s(P = 0.021). The score of male attachment anxiety was higher than that of females(P = 0.038). Attachment avoidance(β = 0.46) and attachment anxiety(β = 0.33) in wives significantly impacted their fertility pressure. Attachment avoidance(β = 0.17) and attachment anxiety(β = 0.52) in husbands significantly impacted their fertility pressure. The attachment avoidance of wives’ had a significant impact on the husbands’ fertility pressure(β = 0.11). Conclusion Overall, the study revealed that in the couples who use donor sperm to expect pregnancy, the male has higher fertility pressure. Insecure attachment can cause more severe fertility pressure, fertility pressure is also affected by one’s partner.

Abstract Direct current optimal power flow (DC‐OPF) problems need to be solved more frequently to maintain safety and economic power system operation. Traditional solvers take too much time to get optimal results. To overcome it, a new self‐supervised augmented Lagrangian neural network (ALNN) is proposed to solve DC‐OPF problem. The proposed ALNN consists of two neural networks: the control net and the penalty net. The control net predicts active power of generators; the penalty net updates the Lagrangian multipliers. The equality constraints are embedded into the control net to guarantee no equality violations. The generalized reduced gradient method is used to reduce theviolations of inequality constraint. The effectiveness of the proposed model is demonstrated on IEEE 118‐bus. The results show that with the help of equality embedding, the equality constraints are always satisfied, which in turn improves the feasibility of ALNN. Compared to the state‐of‐art models, the proposed model has higher feasibility and less constraint violations without comprising optimality. What is more, most of the inactive constraints can be found during the training process and then they are used to speed up the post‐processing part.

Abstract Oxytocin has various effects ranging from promoting labor in pregnant women to alleviating stress. Recently, we reported the hair growth-promoting effects of oxytocin in hair follicle organoids. However, its clinical application faces challenges such as rapid degradation in vivo and poor permeability due to its large molecular weight. Therefore, in this study, we investigated the effects of the oxytocin receptor (OXTR) agonists WAY267464 and LIT001 as alternatives to oxytocin on hair growth. Human dermal papilla (DP) cells were cultured in WAY267464 or LIT001-supplemented medium. The addition of WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. We tested the hair growth-promoting effects of WAY267464 and LIT001 using hair follicle organoids in vitro and found that they significantly promoted hair follicle sprouting. Thus, our findings indicate that WAY267464 and LIT001 are potential hair growth agents and may encourage further research on the development of novel hair growth agents targeting OXTR in patients with alopecia.

Abstract The rupture of vulnerable plaque (VP) are significant pathogenic factors leading to cardiovascular and cerebrovascular diseases. This study aims to construct a vulnerable plaque prediction model (VPPM) by combining multimodal vascular ultrasound parameters and clinical risk factors, and to validate it. A total of 196 atherosclerotic patients who underwent carotid endarterectomy (CEA) from January 2017 to December 2023 were collected and divided into a modeling group (n = 137) and a validation group (n = 59). Clinical information including: hypertension, diabetes, smoking history, and body mass index (BMI) was included in the analysis. All patients underwent carotid ultrasound and contrast-enhanced ultrasound (CEUS) examination after admission, with main ultrasound parameters including thickness, echogenicity types, stenosis degree, and CEUS neovascularization grading of plaques. Independent risk factors for VP in CEA patients were screened through binary Logistic regression analysis, and a prediction model was established along with a nomogram. The calibration curve, receiver-operating characteristic curve (ROC), and decision curve analysis (DCA) were employed to assess the calibration, diagnostic efficacy, and clinical utility of the VPPM model. There were no significant statistical differences in multimodal vascular ultrasound parameters and clinical risk factors between the modeling and validation groups (P > 0.05). Binary Logistic regression analysis identified plaque thickness, echo type, CEUS neovascularization grading, BMI, and smoking history as 5 variables entering the prediction model. The VPPM model showed good diagnostic efficacy, with an area under the ROC curve of 0.959 (95% CI 0.915–0.999). Using the nomogram with a VPPM risk assessment score of 135.42 as the diagnostic cutoff value in the modeling group, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Youden index were 88.1%, 94.1%, 14.98, 0.126, and 82.2%, respectively. In the DCA curve, the VPPM model curve was significantly better than two extreme lines, indicating good clinical utility. The VPPM model constructed by integrating multimodal ultrasound parameters and clinical key risk factors has high diagnostic efficacy and is expected to be an auxiliary tool for clinical diagnosis of vulnerable plaques.

Abstract Papillary thyroid carcinoma (PTC) involves complex genetic mechanisms, notably involving CLDN1 and EGFR. This study investigates the expression and variations of these genes and their effects on tumor behavior and patient outcomes. Meta-analysis of CLDN1 and EGFR expression in TCGA–PTC patients and GEO datasets was conducted. cBioPortal was used for clinical analysis. GSEA, GO, KEGG, Hallmark pathways, and cibersort analysis were applied. Cell proliferation, migration, invasion, and apoptosis were assessed in vitro. Co-culturing with CD8+ T cells, MTT assay, ELISA, subcutaneous tumor models, and immunohistochemistry were performed. TGF-β pathway-related proteins were analyzed via Western blot. CLDN1 and EGFR were overexpressed in PTC tumors, correlating with higher-risk patients and reduced CD8+ T cell infiltration. Silencing these genes inhibited tumor cell functions and enhanced CD8+ T cell activity, both in vitro and in vivo. CLDN1 and EGFR are crucial in PTC, linked to tumor invasiveness, EMT, and immune suppression, presenting them as potential therapeutic targets.

In the construction of the Shenzhen–Zhongshan Link, a temporary anchorage system, distributed uniformly along the pipe wall, has been employed. To assess the safety and reliability of this system, a combined method utilizing numerical analysis and model experiments was applied to study the safety of the temporary anchorage system and the reliability of the tension rods. Firstly, an overall model of the caisson segment based on GINA rebound force was established to analyze the stress state of the entire system. Secondly, a comprehensive numerical analysis and model experiment verification were conducted for the single tensioning system, revealing its failure mode and safety margin. The results indicate that the tension rod systems are uniformly stressed at an average of 444 kN during underwater jointing, with a safety factor of 1.94. At this point, the maximum von Mises stresses appearing at the front plate corners and the lower edge of the U-groove, with stress values of 181.8 MPa and 172.4 MPa, and safety factors of 1.54 and 1.71, respectively. When the tension rod force reaches 940 kN, the tensioning system reaches its bearing limit, with initial yielding occurring at the front plate corners. Model experiments were conducted to verify the theoretical analysis results, under a test load of 444 kN, the stresses at the front plate corners and the lower edge of the U-groove were 159.6 and 195.9 MPa, respectively. As the test load increased to 940 kN, these stresses reached 390 and 389 MPa, exhibiting good agreement with the numerical analysis. Considering the uncertainty of loads and materials, a reliability analysis of the tension rods was conducted, yielding a reliability index of 4.34, meeting the secondary safety standard. Based on the comprehensive analysis, it can be concluded that the temporary anchorage system in the caisson segments of the Shenzhen–Zhongshan Link exhibits excellent safety margins.

The Fe3O4 nanoparticle synthesized by Acidithiobacillus ferrooxidans have a broad practical value, while the low yield limits their commercial application. Herein, we employed a 12C6+ heavy-ion beam to induce mutagenesis of A. ferrooxidans BYM and successfully screened a mutant BYMT-200 with a 1.36 mg/L Fe3O4 nanoparticle yield, which could stably inherit over many generations based on assessing cell magnetism and Fe3O4 nanoparticle synthesis. Comparative genome analysis detected 14 mutation sites, causing six synonymous mutations, one missense mutation, and one nonsense mutation. We further annotated the genes involved in the mutation, such as hcp, hsdM, yghU, K7B00_11365, and K7B00_11355, which are responsible for the substantial changes in the Fe3O4 nanoparticle yield of A. ferrooxidans. Additionally, we performed a pan-genome analysis to understand how these genes regulate Fe3O4 nanoparticle synthesis. The core genome of 2376 orthologous clusters was identified and visualized by progressive Mauve alignment and OrthoVenn. A total of 109 regulatory genes related to iron metabolism were identified, mainly involved in electron transport, iron acquisition, iron storage, and oxidative stress. The mutant genes are closely related to iron-sulfur clusters and oxidative stress. Accordingly, we proposed a hypothetical mechanism for increasing Fe3O4 nanoparticle production in A. ferrooxidans BYMT-200 to withstand high oxidative stress caused by heavy ion radiation. Our study offers significant theoretical guidance for further acquiring the high-yield Fe3O4 nanoparticle-producing bacteria and studying the mechanism of its synthesis.

The construction of accurate and interpretable predictive model for high abundance fishing ground is conducive to better sustainable fisheries production and carbon reduction. This article used refined statistical maps to visualize the spatial and temporal patterns of catch changes based on the 2014-2021 fishery statistics of the Japanese sardine Sardinops melanostictus fishery in the Northwest Pacific Ocean. Three models (XGBoost, LightGBM, and CatBoost) and two variable importance visualization methods (model built-in (split) and SHAP methods) were used for comparative analysis to determine the optimal modeling and visualization strategies. Results: 1) From 2014 to 2021, the annual catch showed an overall increasing trend and peaked at 220,009.063 tons in 2021; the total monthly catch increased and then decreased, with a peak of 76, 033.4944 tons (July), and the catch was mainly concentrated in the regions of 39.5°-43°N and 146.75°-155.75°E; 2) Catboost model predicted better than LightGBM and XGBoost models, with the highest values of accuracy and F1-score, 73.8% and 75.31%, respectively; 3) the overall importance ranking of the model’s built-in method differed significantly from that in the SHAP method, and the overall importance ranking of the spatial variables in the SHAP method increased. Compared to the built-in method, the SHAP method informs the magnitude and direction of the influence of each variable at the global and local levels. The results of the research help us to select the optimal model and the optimal visualization method to construct a prediction model for the Japanese sardine fishing grounds in the Northwest Pacific Ocean, which will provide a scientific basis for the Japanese sardine fishery to achieve environmental and economically sustainable fishery development.

Background: Cholangiocarcinoma (CHOL) is a malignant epithelial carcinoma of the digestive system with poor prognosis and high mortality. WNK lysine deficient protein kinase 1 (WNK1) is known to be associated with tumorigenesis in various cancers. However, the relationship between WNK1 and CHOL development, as well as the potential mechanisms involved, remains poorly understood. Methods: Microarray datasets of CHOL (GSE22633 and GSE32879) were retrieved from the Gene Expression Omnibus (GEO) database. Functional enrichment and immunoinfiltration analyses were performed for genes co-expressed with WNK1. GraphPad Prism 9 was utilized for statistical data analysis and the construction of receiver operating characteristic (ROC) curves. The impact of WNK1 on the CHOL tumor microenvironment was analyzed using Tumor Immune Estimation Resource (TIMER), Venn diagrams, STRING, and TISIDB database for information on WNK1-related chemokines and chemokine receptors. Protein-protein interaction (PPI) networks were used to predict transcription factors and microRNAs interacting with WNK1 and the associated hub genes. Results: Differential expression of WNK1 was observed between CHOL and normal samples, suggesting its diagnostic value. Functional analysis showed that WNK1 and its associated genes were primarily enriched in pathways such as leukocyte transendothelial migration and chemokine signaling. Neutrophils were the only type of infiltrating immune cells associated with WNK1 in the CHOL tumor microenvironment (TME). VEGFA and ALB were identified as hub genes, and X-C motif chemokine receptor 1 (XCR1) and C-X-C motif chemokine ligand 5 (CXCL5) were identified as core chemokines and chemokine receptors related to WNK1 and neutrophil infiltration in CHOL. Conclusions: Based on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.

Background Sepsis-associated acute kidney injury (S-AKI) is a critical illness and is often associated with high morbidity and mortality rates. The soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator and is involved in kidney injury. However, its diagnostic value in S-AKI patients remains unclear. Therefore, we assessed the early predictive value of suPAR for S-AKI patients.Methods We prospectively enrolled adult patients, immediately after fulfilling the sepsis-3 criteria. Plasma suPAR levels at 0-, 12-, 24-, and 48-h post-sepsis diagnosis were measured. S-AKI development was the primary outcome. S-AKI risk factors were analyzed using logistic regression, and the value of plasma suPAR for early S-AKI diagnosis was assessed using receiver operating characteristic (ROC) curves.Results Of 179 sepsis patients, 63 (35.2%) developed AKI during hospitalization. At 12-, 24-, and 48-h post-sepsis diagnosis, plasma suPAR levels were significantly higher in patients with S-AKI than in patients without S-AKI (p

3D packaging mainly uses TSVs (Through Silicon via) to vertically interconnect multiple chips, achieving the purpose of signal transmission and electrical connection. As a popular advanced packaging method, its research is of great significance. Although stacked chips can achieve stronger performance in smaller spaces, they can also cause a series of reliability issues, among which thermal stress and warping due to differences in the thermal expansion coefficients of materials can even lead to chip failure. Therefore, it is highly valuable to simulate and analyze the entire 3D packaging model.In this study, the thermal stress and deformation of the whole three-dimensional package model were simulated by finite element analysis. The results showed that there were significant stress and deformation effects at the joint of the TSV structure at normal temperature, and the stress and deformation reached 209.99 MPa and 0.0018519 mm, respectively. After that, the temperature of the double-sided package system containing 3D package under electrothermal coupling conditions was optimized by heat dissipation design, which verified the ‘quantity first’ scheme of heat dissipation fins and reduced the temperature by 40 %.

Abstract The complement system, comprising over 30 proteins, is integral to the immune system, and the coagulation system is critical for vascular homeostasis. The activation of the complement and coagulation systems involves an organized proteolytic cascade, and the overactivation of these systems is a central pathogenic mechanism in several diseases. This review describes the role of complement and coagulation system activation in critical illness, particularly sepsis. The complexities of sepsis reveal significant knowledge gaps that can be compared to a profound abyss, highlighting the urgent need for further investigation and exploration. It is well recognized that the inflammatory network, coagulation, and complement systems are integral mechanisms through which multiple factors contribute to increased susceptibility to infection and may result in a disordered immune response during septic events in patients. Given the overlapping pathogenic mechanisms in sepsis, immunomodulatory therapies currently under development may be particularly beneficial for patients with sepsis who have concurrent infections. Herein, we present recent findings regarding the molecular relationships between the coagulation and complement pathways in the advancement of sepsis, and propose potential intervention targets related to the crosstalk between coagulation and complement, aiming to provide more valuable treatment of sepsis.

Abstract Aims/Introduction Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti‐oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes‐related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. Materials and Methods To induce insulin resistance, mice were fed a high‐fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose‐regulated protein 78, phosphodiesterase type 5, protein kinase R‐like endoplasmic reticulum (ER) kinase, and phospho‐protein kinase R‐like endoplasmic reticulum kinase in heart tissue. Results The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate‐specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high‐fat diet‐induced cardiac dysfunction and decreased ER stress. Conclusions PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Abstract The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

Abstract The worldwide occurrence of wind droughts challenges the balance of power systems between energy production and consumption. Expanding inter‐day energy storage serves as a strategic solution, yet optimizing its capacity depends on accurately modeling future renewable energy uncertainties to avoid over‐ or under‐investment. Existing approaches that use the historical extreme scenario set (HESS) to represent future conditions are contentious due to potential inadequacies in forecasting future extreme scenarios (ESs), including those on a decadal or centennial scale. This study addresses the issue by proposing an advanced energy storage expansion framework that leverages Extreme Value Theory (EVT) and a novel Deep Generative Model, namely the Diffusion Model. To model the extremes in a principled way, this work leverages EVT to establish a severity‐probability mapping for wind droughts, guiding the training process of the Diffusion Model. This model excels in generating ESs that accurately reflect the distribution of real‐world extremes, thereby significantly enhancing the predictive capacity of HESS. Case studies on a real‐world power system confirm the method's capacity to generate high‐quality ESs, encompassing the most severe historical wind droughts not included in the training dataset, thereby facilitating resilient energy storage expansion against unforeseen extremes.

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Abstract CD8+ T-cell exhaustion is a promising prognostic indicator of sepsis-induced acute respiratory distress syndrome (ARDS). Patients with sepsis-related ARDS had reduced levels of HSP90AA1. However, whether the changes in CD8+ T cells were related to HSP90α, encoded by the HSP90AA1 gene, was unclear. This study aimed to examine the regulatory mechanism of HSP90α and its impact on CD8+ T-cell exhaustion in lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, by conducting a mouse model of ALI, we found that one week after LPS-induced ALI, CD8+ T cells showed exhaustion characteristics. At this time, proliferation and cytokine release in CD8+ T cells were reduced. The inhibitory costimulatory factors PD-1 and Tim-3, on the other hand, were enhanced. Meanwhile, the expression of HSP90α and STAT1 decreased significantly. The in vitro studies showed that HSP90α stimulation or inhibition affected the CD8+ T-cell exhaustion phenotype. Interference with STAT1 reduced the expression of HSP90α and impaired its regulation of CD8+ T cells. The Co-Immunoprecipitation results indicated that HSP90α can directly or indirectly bind to TOX to regulate TOX expression and downstream signal transduction. In summary, by inhibiting TOX-mediated exhaustion signaling pathways, HSP90α inhibited CD8+ T-cell exhaustion in ALI. The participation of STAT1 in the regulation of HSP90α was required.

Abstract Background Wheat is one of the important grain crops in the world. The formation of lesion spots related to cell death is involved in disease resistance, whereas the regulatory pathway of lesion spot production and resistance mechanism to pathogens in wheat is largely unknown. Results In this study, a pair of NILs (NIL-Lm5 W and NIL-Lm5 M) was constructed from the BC1F4 population by the wheat lesion mimic mutant MC21 and its wild genotype Chuannong 16. The formation of lesion spots in NIL-Lm5 M significantly increased its resistance to stripe rust, and NIL-Lm5 M showed superiour agronomic traits than NIL-Lm5 W under stripe rust infection.Whereafter, the NILs were subjected to transcriptomic (stage N: no spots; stage S, only a few spots; and stage M, numerous spots), metabolomic (stage N and S), and hormone analysis (stage S), with samples taken from normal plants in the field. Transcriptomic analysis showed that the differentially expressed genes were enriched in plant-pathogen interaction, and defense-related genes were significantly upregulated following the formation of lesion spots. Metabolomic analysis showed that the differentially accumulated metabolites were enriched in energy metabolism, including amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Correlation network diagrams of transcriptomic and metabolomic showed that they were both enriched in energy metabolism. Additionally, the contents of gibberellin A7, cis-Zeatin, and abscisic acid were decreased in leaves upon lesion spot formation, whereas the lesion spots in NIL-Lm5 M leaves were restrained by spaying GA and cytokinin (CTK, trans-zeatin) in the field. Conclusion The formation of lesion spots can result in cell death and enhance strip rust resistance by protein degradation pathway and defense-related genes overexpression in wheat. Besides, the formation of lesion spots was significantly affected by GA and CTK. Altogether, these results may contribute to the understanding of lesion spot formation in wheat and laid a foundation for regulating the resistance mechanism to stripe rust.

Abstract In this paper, an ultra-wideband stealth antenna with high gain on the basis of asymmetric transmission metasurface (ATMS) is proposed. ATMS can convert an incident y-polarised sphere wave into an x-polarised plane wave at the front side and controls the scattering of the incident y-polarised wave to the back side. Excitation of ATMS via a horn antenna, a low radar cross-section (RCS) and wideband antenna system is designed. Furthermore, through design of the meta-atoms and optimization of the macrosequencing, broadband RCS reduction is achieved. The experimental data indicated the reduction of the RCS of the antenna system by up to 10 dB and more than 20 dB in the frequency range of 10.1 GHz to 18 GHz (relative bandwidth is 56.2%) and 13.9 GHz to 18 GHz (relative bandwidth is 25.7%), respectively. In addition, a 3 dB gain relative bandwidth of 57.4% is achieved between 10 and 18 GHz, with a peak gain of 28.2 dB. It is noteworthy that the high gain and low scattering performance of the antenna are achieved in the same spectral range (10–18 GHz), and there is no interference between the scattering performance and radiation performance of the antenna, which could be controlled separately.

Tendinopathy leads to low-grade tissue inflammation and chronic damage, which progresses due to pathological imbalance in angiogenesis. Reducing early pathological vascularization may be a new approach in helping to regenerate tendon tissue. Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy. In this study, tissue engineered stem cells (TSCs) generated using human umbilical cord mesenchymal stem cells (hUC-MSCs) were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy. By preventing VEGF receptor activation through their paracrine function, TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells. TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics. Furthermore, local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization. Mechanistically, transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue, attributed to Rap1-mediated vascular inhibition. TSCs may serve as a novel and practical approach for suppressing tendon vascularization, and provide a promising therapeutic agent for early-stage clinical tendinopathy.

Abstract Triple-negative breast cancer (TNBC) has high heterogeneity, poor prognosis, and limited treatment success. Recently, an immunohistochemistry-based surrogate classification for the “Fudan University Shanghai Cancer Center (FUSCC) subtyping” has been developed and is considered more suitable for clinical application. Seventy-one paraffin-embedded sections of surgically resected TNBC were classified into four molecular subtypes using the IHC-based surrogate classification. Genomic analysis was performed by targeted next-generation sequencing and the specificity of the subtypes was explored by bioinformatics, including survival analysis, multivariate Cox regression, pathway enrichment, Pyclone analysis, mutational signature analysis and PHIAL analysis. AKT1 and BRCA1 mutations were identified as independent prognostic factors in TNBC. TNBC molecular subtypes encompass distinct genomic landscapes that show specific heterogeneities. The luminal androgen receptor (LAR) subtype was associated with mutations in PIK3CA and PI3K pathways, which are potentially sensitive to PI3K pathway inhibitors. The basal-like immune-suppressed (BLIS) subtype was characterized by high genomic instability and the specific possession of signature 19 while patients in the immunomodulatory (IM) subtype belonged to the PD-L1 ≥ 1% subgroup with enrichment in Notch signaling, suggesting a possible benefit of immune checkpoint inhibitors and Notch inhibitors. Moreover, mesenchymal-like (MES) tumors displayed enrichment in the receptor tyrosine kinase (RTK)-RAS pathway and potential sensitivity to RTK pathway inhibitors. The findings suggest potential treatment targets and prognostic factors, indicating the possibility of TNBC stratified therapy in the future.

Abstract Recycling strategies for mixed plastics and textile blends currently aim for recycling only one of the components. Here, we demonstrate a water coupling strategy to co-hydrolyze polyester/cotton textile blends into polymer monomers and platform chemicals in gamma-valerolactone. The blends display a proclivity for achieving an augmented 5-hydroxymethylfurfural yield relative to the degradation of cotton alone. Controlled experiments and preliminary mechanistic studies underscore that the primary driver behind this heightened conversion rate lies in the internal water circulation. The swelling and dissolving effect of gamma-valerolactone on polyester enables a fast hydrolysis of polyester at much lower concentration of acid than the one in the traditional hydrolysis methods, effectively mitigating the excessive degradation of cotton-derived product and undesirable product formation. In addition, the system is also applicable to different kinds of blends and PET mixed plastics. This strategy develops an attractive path for managing end-of-life textiles in a sustainable and efficient way.

Abstract The time difference of arrival is a common method to find the leakage point of water pipeline. The leakage point localization is achieved by calculating the time delay between the signals reaching different sensors. Mainstream time delay estimation algorithms based on signal correlation analysis are susceptible to the introduction of noise signals, low sampling rates, and signal clipping, resulting in inaccurate localization results. The article analyzed the impact of different interference factors and proposed a new time delay estimation algorithm based on signal cross-zero information modulation (CZIM) to address these problems. By normalizing the amplitude of the two signals at the detection points on both sides of the pipeline leakage position, two sets of sparse signal sequences with only two eigenvalues of 0 and 1 are obtained. The error coefficient function is calculated by a similar traversal method to finally index the time delay. In this paper, the principle and characteristics of the algorithm are analyzed and compared with the most commonly used GCC method. In both numerical simulations and actual pipe leakage localization experiments, the CZIM algorithm has shown its wide applicability, low impact by low sampling rate, and adaptability to low signal-to-noise ratios, etc. At the same time, the algorithm is simple in design and has a small amount of calculation and can meet the demand for real-time data processing, providing a new idea for the development of acoustic localization technology.

Aristolochic acid (AA) exposure is a severe public health concern worldwide. AAs damage the kidney with an inevitable acute phase that is similar to acute kidney injury (AKI). Gasdermin E (GSDME) is abundant in the kidney; thus; it-mediated pyroptosis might be essential in connecting cell death and inflammation and promoting AAs-AKI. However, the role and exact mechanism of pyroptosis in AAs-AKI have not been investigated. In this study, aristolochic acid I (AAI) was used to establish AKI models. The expression and translocation results showed GSDME-mediated pyroptosis in AAI-AKI. Knocking down GSDME attenuated AAI-induced cell death and transcription of proinflammatory cytokines. Mechanistic research inhibiting caspase (casp) 3, casp 8, and casp 9 with specific chemical antagonists demonstrated that GSDME was activated by cleaved casp 3. Furthermore, the kinase activity of upstream receptor-interacting protein kinase 1 (RIPK1) was significantly elevated, and inhibiting RIPK1 with specific inhibitors markedly improved AAI-induced cell damage. In addition, the level of autophagy was obviously increased. Pretreatment with a specific autophagic inhibitor (3-methyladenine) or knockdown of autophagic genes (Atg5 or Atg7) evidently reduced the activity of RIPK1 and downstream apoptosis and pyroptosis, thus attenuating AA-induced cell injury, which suggested that RIPK1 was a novel link conferring autophagic promotion of pyroptosis. These findings reveal GSDME-mediated pyroptosis for the first time in AAI-induced AKI, propose its novel role in the transcription of cytokines, and demonstrate that autophagy promotes pyroptosis via the RIPK1-dependent apoptotic pathway. This study promotes the understanding of the toxic effects and exact mechanisms of AAs. This will contribute to evaluating the environmental risk of AA exposure and might provide potential therapeutic targets for AA-AKI.

The paper proposes a low-pass filter adaptive iterative learning control (LPF-AILC) strategy for unmatched, uncertain, time-varying, non-parameterized nonlinear systems (NPNL systems). To address the difficulty of nonlinear parameterization terms in system models, a new function approximator (FSE-RBFNN), which combines the radial basis function neural network (RBFNN) and Fourier series expansion (FSE), is introduced to model each time-varying nonlinear parameterized function. The adaptive backstepping method is used to design control laws and parameter adaptive laws. In the process of controller design, we may encounter the problem of too many derivatives, which can cause parameter explosions after derivatives. Therefore, we introduce a first-order low-pass filter to solve this problem and simplify the structure of the controller. As the number of iterations increases, the maximum tracking error gradually decreases until it converges to the nearby region, approaching zero within the entire given interval [0,T], according to the Lyapunov-like synthesis. To mitigate the impact of initial state errors, a dynamically changing boundary layer is introduced, along with a series to deal with the unknown error upper bounds. Finally, two simulation examples prove the correctness of the proposed control method.

Abstract CD74 is a type-II transmembrane glycoprotein that has been linked to tumorigenesis. However, this association was based only on phenotypic studies, and, to date, no in-depth mechanistic studies have been conducted. In this study, combined with a multi-omics study, CD74 levels were significantly upregulated in most cancers relative to normal tissues and were found to be predictive of prognosis. Elevated CD74 expression was associated with reduced levels of mismatch-repair genes and homologous repair gene signatures in over 10 tumor types. Multiple fluorescence staining and bulk, spatial, single-cell transcriptional analyses indicated its potential as a marker for M1 macrophage infiltration in pan-cancer. In addition, CD74 expression was higher in BRCA patients responsive to conventional chemotherapy and was able to predict the prognosis of these patients. Potential CD74-activating drugs (HNHA and BRD-K55186349) were identified through molecular docking to CD74. The findings indicate activation of CD74 may have potential in tumor immunotherapy.

Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Abstract Considerable global demand exists for the development of novel drugs for the treatment of alopecia. A recent report demonstrated that oxytocin promotes hair growth activity in human dermal papilla (DP) cells; however, its application in drugs or cosmetic products is challenging because rapid degradation and relatively large molecular weight prevent long-term topical administration on the scalp. Here, we examined cinnamic acid, a small molecule activator for oxytocin receptor (OXTR) expression. Treatment with cinnamic acid led to upregulation of OXTR and trichogenic gene expression in human DP cells. Furthermore, inhibition of OXTR with an antagonist, L-371,257, suppressed hair growth-related gene expression in DP cells. These findings suggest that cinnamic acid enhances the hair growth ability of DP cells via oxytocin signaling. Additionally, we tested the hair growth-promoting effects of cinnamic acid using hair follicle organoids in vitro and observed that cinnamic acid significantly promoted the growth of hair peg-like sprouting. These promising results may be useful for developing hair growth-promoting products targeting oxytocin.

Abstract NRAS mutations are most frequently observed in hematological malignancies and are also common in some solid tumors such as melanoma and colon cancer. Despite its pivotal role in oncogenesis, no effective therapies targeting NRAS has been developed. Targeting NRAS localization to the plasma membrane (PM) is a promising strategy for cancer therapy, as its signaling requires PM localization. However, the process governing NRAS translocation from the Golgi apparatus to the PM after lipid modification remains elusive. This study identifies GOLGA7 as a crucial factor controlling NRAS’ PM translocation, demonstrating that its depletion blocks NRAS, but not HRAS, KRAS4A and KRAS4B, translocating to PM. GOLGA7 is known to stabilize the palmitoyltransferase ZDHHC9 for NRAS and HRAS palmitoylation, but we found that GOLGA7 depletion does not affect NRAS’ palmitoylation level. Further studies show that loss of GOLGA7 disrupts NRAS anterograde trafficking, leading to its cis-Golgi accumulation. Remarkably, depleting GOLGA7 effectively inhibits cell proliferation in multiple NRAS-mutant cancer cell lines and attenuates NRASG12D-induced oncogenic transformation in vivo. These findings elucidate a specific intracellular trafficking route for NRAS under GOLGA7 regulation, highlighting GOLGA7 as a promising therapeutic target for NRAS-driven cancers.

The occurrence and ecological risks of 16 polycyclic aromatic hydrocarbons (PAHs) in different types of urban road runoff in Beijing during two typical rainfall events were studied. The average concentration of PAHs in road runoff particulate was in the order of Guanyuanqiao Road (ring road, 15,175 ng/L) > Huayuanqiao Road (primary road, 4,792 ng/L) > Dongcheng Alley (alley, 4,774 ng/L) > Nansihuan Viaduct (viaduct, 770 ng/L), much higher than dissolved PAHs. The total concentration of ∑16PAHs decreased with runoff scouring. Rainfall conditions and the accumulation of PAHs in the early rainfall period show a significant impact on PAHs pollution. The event mean concentration range of PAHs is 674–21,596 ng/L, following in the order of ring road > primary road > alley > viaduct. The proportion of four-ring PAHs was the highest. The first flush effect of PAHs is found in both rainfall events, and the effect of different ring PAHs is relatively similar. The content of PAHs is positively correlated with the amount of total organic carbon and suspended substance in runoff (r2> 0.72). The ecological risk assessment indicated that PAHs in road runoff except viaduct road corresponded to high risk. HIGHLIGHTS Polycyclic aromatic hydrocarbon (PAH) concentration decreased with runoff scouring and particulate PAHs was much higher than dissolved PAHs.; The event mean concentration of PAHs in road runoff is 674–21,596 ng/L where four-ring PAHs is most.; The first flush of PAHs occurs and the effect of different ring PAHs is similar.; PAHs amount is positively correlated with total organic carbon and suspended substance in runoff (r2 > 0.72).; PAHs in road runoff except for viaduct road corresponded to high ecological risk.;

Microplastics (MPs) have emerged as a significant pollutant, threatening agricultural ecosystem sustainability and global food security. However, relatively few studies have investigated biochar remedial effects on plant growth and biochemical properties in soils contaminated with MPs. In polyethylene microplastic (PE-MP)-contaminated soil, we investigated corn stover biochar effects on soybean growth, soil nutrient content, enzyme activity, and microbial biomass and assessed its impact on soil microbial resource limitations. The addition of MPs inhibited soybean growth in various forms across four stages. Conversely, the addition of biochar to MPs improved soybean growth to some extent, where above-ground biomass increased by 5.82% after adding biochar to soils containing microplastics. In soil treated with MPs and biochar, nitrate nitrogen (N), available phosphorus (P), and available potassium (K) increased by 20.1, 27.4, and 57.2%, respectively, while available nitrogen significantly decreased to 128.3 mg kg−1 compared to the MP-only treatment. PE-MPs alone significantly reduced soil carbon (C), N, and P enzyme activities, as well as microbial biomass, with β-glucosidase, leucine aminopeptidase, and acid phosphatase activities decreasing by 29.9, 27.8, and 25.5%, respectively. Interestingly, biochar addition to MPs significantly alleviated these detrimental effects. Microbial biomass C, N, and P increased by up to 56.0, 22.5, and 96.6%, respectively, following biochar addition to soils containing MPs. Analysis of vector lengths, vector angles, and scatter plots indicated that the presence of MPs reduced soil N and P availability. Overall, while MPs inhibited soybean development, biochar addition alleviated this effect to some extent. Furthermore, partial least-squares path modeling revealed that MPs negatively affected soil chemical properties, microbial biomass, and enzyme activities, whereas biochar positively influenced soil enzyme activities.

Soil salinization is a major factor threatening global food security. Soil improvement strategies are therefore of great importance in mitigating the adverse effect of salt stress. Our study aimed to evaluate the effect of biochar (BC) and nitric acid-modified biochar (HBC) (1%, 2%, and 3%; m/m) on the properties of salinized soils and the morphological and physiological characteristics of pakchoi. Compared with BC, HBC exhibited a lower pH and released more alkaline elements, reflected in reduced contents of K+, Ca2+, and Mg2+, while its hydrophilicity and polarity increased. Additionally, the microporous structure of HBC was altered, showing a rougher surface, larger pore size, pore volume, specific surface area, and carboxyl and aliphatic carbon content, along with lower aromatic carbon content and crystallinity. Moreover, HBC application abated the pH of saline soil. Both BC and HBC treatments decreased the sodium absorption rate (SAR) of saline soil as their concentration increased. Conversely, both types of biochar enhanced the cation exchange capacity (CEC), organic matter, alkali-hydrolyzable nitrogen, and available phosphorus and potassium content in saline soils, with HBC demonstrating a more potent improvement effect. Furthermore, biochar application promoted the growth-related parameters in pakchoi, and reduced proline and Na+ content, whilst increasing leaf K+ content under salt stress. Biochar also enhanced the activity of key antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) in leaves, and reduced hydrogen peroxide (H2O2) and malondialdehyde (MDA) content. Collectively, modified biochar can enhance soil quality and promote plant growth in saline soils.

Arbuscular mycorrhizal fungi (AMF) have been shown to play a major role in regulating the accumulation, transport, and toxicity of cadmium (Cd) in plant tissues. This review aims to highlight the current understanding of the mechanisms by which AMF alleviate Cd toxicity in plants. Cd accumulation in agricultural soils has become an increasing global concern due to industrial activities and the use of phosphatic fertilizers. Cd toxicity disrupts various physiological processes in plants, adversely affecting growth, photosynthesis, oxidative stress responses, and secondary metabolism. AMF alleviate Cd stress in plants through multiple mechanisms, including reduced Cd transport into plant roots, improved plant nutritional status, modulation of organic acid and protein exudation, enhanced antioxidant capacity, and maintenance of ion homeostasis. AMF colonization also influences Cd speciation, bioavailability, and compartmentalization within plant tissues. The expression of metal transporter genes, as well as the synthesis of phytochelatins and metallothioneins, are modulated by AMF during Cd stress. However, the efficacy of AMF in mitigating Cd toxicity depends on several factors, such as soil properties, plant species, AMF taxa, and experimental duration. Further knowledge of the intricate plant–AMF–Cd interactions is crucial for optimizing AMF-assisted phytoremediation strategies and developing Cd-tolerant and high-yielding crop varieties for cultivation in contaminated soils.

Soil salinization is an important factor that limits crop production. The effects of spraying salicylic acid (SA) during the grain-filling stage on the salt tolerance of progeny seeds in wheat (Triticum aestivum L.) were investigated in this study. The results showed that spraying SA during the grain-filling stage significantly increased the grain weight and yield of wheat plants. Meanwhile, the seeds from the SA-treated plants showed a higher germination rate, length and dry mass of the coleoptile and radicle, and a lower mean germination time compared to the seeds of water-treated plants under the salt germination condition, indicating that SA pretreatment during the grain-filling stage could effectively improve the salt tolerance of progeny seeds in wheat. SA pretreatment significantly increased the activities of amylases and the respiration rate, accompanied by a decrease in starch content, and a higher accumulation in the level of soluble sugars and adenosine triphosphate (ATP) in the germinated seedlings compared to the water pretreatment under salt stress. In addition, SA pretreatment obviously alleviated the increase in malondialdehyde (MDA) content and the reactive oxygen species (ROS) release rate in seedlings by activating antioxidant enzymes (superoxide dismutase (SOD) and peroxidase (POD)) under salt stress. Moreover, the seedlings of the SA-treated plants showed lower Na+ and higher K+ contents compared to the seeds of water-treated plants under salt stress. The results of this study indicate that spraying SA during the grain-filling stage improves the capacity of offspring seeds to maintain osmotic and ion balance and redox homeostasis under salt stress, thereby conferring salt tolerance to the wheat seeds.

Hybrid Aerial Underwater Vehicles (HAUVs), capable of operating effectively in both aerial and underwater environments, offer promising solutions for a wide range of applications. This paper presents the design and development of a novel foldable wing HAUV, detailing the overall structural framework and key design considerations. We employed fluid simulation software to perform comprehensive hydrodynamic and aerodynamic analyses, simulating the vehicle’s behavior during aerial flight, underwater navigation, water entry and exit, and surface gliding. The motion characteristics under different speed and angle conditions were analyzed. Additionally, a physical prototype was constructed, and experimental tests were conducted to evaluate its performance in both aerial and underwater environments. The experimental results confirmed the vehicle’s ability to seamlessly transition between air and water, demonstrating its viability for dual-environment operations.

BackgroundMalignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE.MethodsFrom July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram’s performance, including calibration, discrimination, and clinical applicability.ResultsSeven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients.ConclusionThis study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE.

BackgroundDespite previous literature exploring the factors influencing lower urinary tract symptoms (LUTS), few studies have examined the relationship between nutritional status and LUTS.ObjectivesThe objective of this research was to evaluate the relationship between LUTS and Geriatric Nutritional Risk Index (GNRI) in middle-aged and older men.MethodsWe included 2,607 men in the NHANES 2005–2006 and 2007–2008 cycles for cross-sectional analysis. We screened for LUTS based on four specific questions on the relevant questionnaire. We calculated GNRI according to the relevant calculation formula and included other covariates. Multivariate logistic analysis using GNRI as the principal independent variable and adjusting for other covariates were used to determine the association with LUTS, nocturia, and daytime LUTS.ResultsAccording to the responses to the questionnaire, out of 2,607 eligible participants, 471 had LUTS, 906 had nocturia, and 819 had daytime LUTS. In the unadjusted regression model, LUTS (OR = 0.93, 95% CI = 0.91–0.96, p

Abstract Background Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. Methods Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single‐cell RNA‐sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single‐cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. Results There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone‐lysine N‐methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto‐oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. Conclusions We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti‐inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. Highlights Single‐cell RNA‐sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A‐mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

BackgroundWith increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief.MethodsData were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18–24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire.ResultsThe main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs.ConclusionThis study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.

We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.

Abstract Disulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan–Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.

Abstract A large‐scale AC/DC hybrid power network has recently been constructed in China because of the fast development of high voltage direct current (HVDC) technology. The receiving AC system must have sufficient system strength to guarantee the safe operation of the DC side. The paradox is that raising the AC side system's strength will increase the short‐circuit current (SCC) level, endangering the safety of the system. In order to resolve the contradiction between the system strength of multi‐infeed DC receiving‐end power networks and SCC, this paper proposes an optimal transmission switching strategy. Firstly, the system strength is characterised by the multi‐infeed short‐circuit ratio (MISCR), followed by constructing a comprehensive constraint set that considers the MISCR and SCC simultaneously. Secondly, to optimize SCC with MISCR and N−1 safety constraints, a mixed integer linear programming model is developed. Finally, to enhance the computing performance for large power systems, a new connectivity constraint set and decision space reduction techniques are provided. The proposed method is tested for effectiveness using the IEEE 30‐bus and IEEE 118‐bus systems.

Abstract Objective There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results. Methods The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model. Results Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety. Conclusions The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.