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Abstract Overexpression of mitotic arrest deficiency 2 (MAD2/MAD2L1), a pivotal component of the spindle assembly checkpoint (SAC), resulted in many types of cancer. Here we show that the depletion of tumor susceptibility gene 101 (TSG101), causes synthetic dosage lethality (SDL) in MAD2-overexpressing cells, and we term this cell death MAD2-overexpressing interphase cell death (MOID). The induction of MOID depends on PML and DAXX mediating mitochondrial AIFM1-release. MAD2, TSG101, and AIF-PML-DAXX axis regulate mitochondria, PML nuclear bodies (NBs), and autophagy with close inter-dependent protein stability in survival cells. Loss of C-terminal phosphorylation(s) of TSG101 and closed (C-)MAD2-overexpression contribute to induce MOID. In survival cells, both MAD2 and TSG101 localize at PML NBs in interphase, and TSG101 Y390 phosphorylation is required for localization of TSG101 to PML NBs. PML release from PML NBs through PML deSUMOylation contributes to induce MOID. The post-transcriptional/translational cell death machinery and the non-canonical transcriptional regulation are intricately linked to MOID, and ER-MAM, may serve as a crucial intersection for MOID signaling.

Abstract Background Recreational drug use has been identified as a significant risk factor for the transmission of human immunodeficiency virus (HIV). This behavior is particularly prevalent among young men who have sex with men (YMSM). However, limited research has been conducted to investigate the correlation between recreational drug use and HIV incidence within this population. Objective To examine HIV incidence and explore the association between recreational drug use and HIV incidence among YMSM. Methods A retrospective cohort study was conducted by a local non-governmental organization (NGO) among MSM aged 18–24 years from October 2017 to December 2023 in Tianjin, China. Participants were included if they had at least two HIV test records during this period. HIV incidence density and its 95% confidence interval (CI) were calculated using person-years (PYs) with a Poisson distribution. Risk factors for HIV incidence were identified using univariable and multivariable Cox proportional hazards regression models. Results A total of 56 HIV seroconversions were reported with 2901.9 PYs, resulting in an overall incidence density of 1.9/100 PYs (95% CI: 1.4–2.4). Among YMSM who do not use recreational drugs (YMSM-URD), the incidence density was 1.1/100 PYs (95% CI: 0.5–1.6), while it was 2.8/100 PYs (95% CI: 1.9–3.7) among those who do use recreational drugs (YMSM-RD). Adjusted for confounders, factors associated with HIV infection included recreational drug use (adjusted hazard ratio = 2.6, 95% CI = 1.4–4.7) and unprotected anal intercourse in the past six months (adjusted hazard ratio = 2.3, 95% CI = 1.2–4.4). Conclusions Recreational drug use and unprotected anal intercourse significantly increase the risk of HIV infection. To effectively mitigate the spread of HIV, interventions should focus on these risk factors by employing HIV counseling and testing clinics, collaborating with NGOs focused on MSM, and establishing peer education programs aimed at YMSM.

Abstract According to WHO, plague, caused by Yersinia pestis, has resurged since 2000. Inner Mongolia, harboring a quarter of China’s plague foci, has accounted for 80% of national plague cases in the past five years. Despite its pivotal role in Chinese plague epidemiology, the genetic diversity and transmission dynamics of Y. pestis in this region remain under-investigated. Our analysis of 585 Y. pestis strains from Inner Mongolia (1948–2021) revealed three primary lineages, with 2.MED3 being predominant. We further delineated seven sub-phylogroups in 2.MED3, with 2.MED3.1.2 and 2.MED3.1.4 showing recent dominance. These two subgroups reveal dual transmission patterns: localized short-distance spread and long-distance dispersals over 300 km. Xilingol League is highlighted as a key source and reservoir for Y. pestis, predominantly spreading from central-eastern to southwestern Inner Mongolia, including occasional reverse transmissions. These findings enhance understanding of Y. pestis diversity and transmission in Inner Mongolia, aiding in enhanced surveillance and control measures.

The preparation of amorphous alloys typically involves rapid solidification from a molten state. Since 1980, when Yermo and Koch first achieved the amorphization of alloys by mechanical alloying (MA), researchers worldwide have developed a strong interest in this technique, which allows for the amorphization of alloy components in a non-equilibrium state at room temperature without the need for a liquid phase. MA has been widely applied in the fabrication of both equilibrium and non-equilibrium materials over the past few decades, and it remains a crucial technique for the production of amorphous alloys. This review selectively summarizes research on MA-produced amorphous alloys reported over the past two decades. It explores key issues of MA amorphization from the perspectives of both the mechanism of amorphization and the design of amorphous compositions through MA. The first section primarily elucidates commonly used methods for designing amorphous compositions at present, while the second section expounds on the transformation mechanism of MA amorphization. The third section summarizes the influence of alloy element additions on its properties, and the fourth section mainly illustrates the contribution of computational advancements to the exploration of amorphous mechanisms and the design of amorphous compositions. Finally, prospects for the development trend of preparing amorphous alloys through MA are discussed.

Abstract Background Controversy surrounding Family Presence during Resuscitation (FPDR) continues internationally. The attitudes of medical professionals toward FPDR are particularly important for its clinical implementation. Currently, there is a lack of validated tools to evaluate medical professionals’ perceptions of FPDR in China. The study aimed to: (1) Cross-culturally adapt and validate the Family Presence Risk-Benefit Scale (FPR-BS) and the Self-Confidence Scale (FPS-CS) for use in China; and (2) investigate the nurses’ perceptions of FPDR and explore the relationships between the nurses’ perceptual variables and demographic variables. Methods The English version of the FPR-BS and FPS-CS underwent a rigorous process of translation, back-translation, proofreading, and cultural adaptation to create the Chinese versions. In the first stage, a sample of 200 nurses were recruited to evaluate the reliability and validity of the scales. In the second stage, a larger cohort 519 nurses were invited to assess their perceptions of FPDR and the relationships between these perceptual variables and demographic variables. Results Exploratory factorial analysis identified a single dimension for both the FPR-BS and FPS-CS, explaining 43.84% and 48.43% of the variance, respectively. The Scale-level content validity index (S-CVI) of the FPR-BS and the FPS-CS was 0.98 and 0.97, respectively. Reliability assessments yielded Cronbach’s alpha coefficients of 0.933 for the FPR-BS and 0.930 for the FPS-CS. The split-half reliability coefficients were 0.832 for the FPR-BS and 0.835 for the FPS-CS, while the retest reliability coefficients were 0.742 and 0.927, respectively. The average scores obtained were 2.76 (SD = 0.52) for the FPR-BS and 3.43 (SD = 0.58) for the FPS-CS. Statistical analyses revealed that factors such as patient type, family members’ prior experience with resuscitation, and the number of times nurses invited family members during resuscitation significantly influenced perceptions of the benefits and risks associated with FPDR (P

Abstract Accurate runoff forecasting is of great significance for water resource allocation flood control and disaster reduction. However, due to the inherent strong randomness of runoff sequences, this task faces significant challenges. To address this challenge, this study proposes a new SMGformer runoff forecast model. The model integrates Seasonal and Trend decomposition using Loess (STL), Informer’s Encoder layer, Bidirectional Gated Recurrent Unit (BiGRU), and Multi-head self-attention (MHSA). Firstly, in response to the nonlinear and non-stationary characteristics of the runoff sequence, the STL decomposition is used to extract the runoff sequence’s trend, period, and residual terms, and a multi-feature set based on ‘sequence-sequence’ is constructed as the input of the model, providing a foundation for subsequent models to capture the evolution of runoff. The key features of the input set are then captured using the Informer’s Encoder layer. Next, the BiGRU layer is used to learn the temporal information of these features. To further optimize the output of the BiGRU layer, the MHSA mechanism is introduced to emphasize the impact of important information. Finally, accurate runoff forecasting is achieved by transforming the output of the MHSA layer through the Fully connected layer. To verify the effectiveness of the proposed model, monthly runoff data from two hydrological stations in China are selected, and eight models are constructed to compare the performance of the proposed model. The results show that compared with the Informer model, the 1th step MAE of the SMGformer model decreases by 42.2% and 36.6%, respectively; RMSE decreases by 37.9% and 43.6% respectively; NSE increases from 0.936 to 0.975 and from 0.487 to 0.837, respectively. In addition, the KGE of the SMGformer model at the 3th step are 0.960 and 0.805, both of which can maintain above 0.8. Therefore, the model can accurately capture key information in the monthly runoff sequence and extend the effective forecast period of the model.

Abstract The coordinated development of urban e-commerce and green total factor productivity (GTFP) plays a crucial role in achieving high-quality development. This paper selects relevant data from the eight major urban agglomerations in China for research. A model that described the coupling coordination between the regions’ GTFP and urban e-commerce was presented. Then, unfold the spatiotemporal evolution characteristics of their coupling coordination from the “dynamic and static”, “overall and regional” dimensions. The results indicate: (1) The coupling coordination degree between two systems within China’s eight urban agglomerations exhibits an upward trend with fluctuations, transitioning from a state of near dysfunction to good coordination. (2) The spatial heterogeneity in the coupling coordination degree between the two systems in China’s eight major urban agglomerations is evident, with an overall downward trend and exhibiting a “V-shaped” pattern of “decline-rise”.(3) The coupling coordination degree between two systems across China’s eight urban agglomerations exhibits a trend toward centralization, with an amelioration of bipolar differentiation, and a progressive attenuation of spatial heterogeneity.

Abstract Background Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. Methods To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (n max = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with n max = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. Results MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10−6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, −0.041 to −0.015; P = 1.31 × 10−5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. Conclusion Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

Abstract Objective This study investigated the correlation between thyroid function and urinary iodine/creatinine ratio (UI/Cr) in pregnant women during different trimesters and explored potential influencing factors. Methods In this cross-sectional study, serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and UI/Cr were measured in 450 pregnant women. Correlations were analyzed using Pearson’s correlation coefficient and multiple linear regression. Subgroup analyses were performed based on age, body mass index (BMI), parity, gestational age, education, occupation, and family history of thyroid disorders. Results UI/Cr was positively correlated with FT4 levels in the first and second trimesters, particularly in women with older age, higher BMI, multiparity, higher education, and employment. No significant correlations were found between UI/Cr and TSH or FT3 levels. Conclusion UI/Cr is positively correlated with FT4 levels in early pregnancy, especially in women with certain risk factors. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health.

Abstract Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

Abstract Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3β pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3β pathway.

Abstract Background Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. Methods Age-specific mortality data for cervical and breast cancers among Chinese women aged 20–84 years were obtained from China’s National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban–rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. Results From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35–64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5–7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: − 0.7%, 95% CI − 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI − 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: − 2.7%, 95% CI − 4.6 to − 0.7%, P = 0.007) in urban areas. Urban–rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35–54 age group across urban and rural areas, periods, and regions in China. Conclusions Special attention should be given to women aged 35–54 years due to mortality trends and rural–urban disparities. Focusing on vulnerable age groups and addressing rural–urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

Abstract Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

The clinical success of implanted biomaterials such as dental implants is largely determined by the molecular signaling that occurs at the tissue-implant interface. The modification of surface topography is a widely-employed strategy for optimizing tissue integration with dental implants. However, little is known regarding the direct, cellular-level effects of substratum topography on platelet signaling and adhesion, despite these cells being the first to encounter the implant surface during surgical placement. Here we compared platelet adhesion and secretion on four (4) different titanium surfaces, notably, the modifications applied to commercially available dental implants: smooth (S) titanium; acid-etched (AE), sandblasted (SB) and a combined acid-etching/sandblasting procedure (SLA). Platelets were isolated from human blood, washed, and seeded on to the 4 test surfaces; platelet adhesion was quantified by microscopy. In addition, the secretion of critical molecules stored in platelet granules (platelet factor 4, PF4; soluble P-selectin, sCD62P; transforming growth factor-beta1, TGF-β1; platelet-derived growth factor-AB, PDGF-AB) was measured by enzyme-linked immunosorbent assay (ELISA) analysis of the supernatants. There was greater platelet adhesion to the rougher AE and SB surfaces, however, the concentration of the secreted growth factors was comparable on all surfaces. We conclude that while surface topography can be engineered to modulate initial platelet adhesion, granule secretion is likely regulated as a separate and independent process.

ObjectiveTo understand the prevalence level and trend of hepatitis C virus (HCV) among 11 specific populations in Yunnan province, and to provide evidence for formulating and evaluating the effectiveness of prevention and control measures. MethodsThe annual report data from 2013 to 2022 on comprehensive prevention and control of hepatitis C were collected from all medical institutions in 16 prefectures/municipalities in Yunnan province and were analyzed using R software and the Cochran-Armitage trend test was used to assess the changing trends in HCV antibody (anti-HCV) positivity rates among different population groups and for different regions. ResultsOf a total of 64 879 772 person-times of anti-HCV detection performed in medical institutions during the period, 392 971 (0.61%) were anti-HCV positive, and the annual anti-HCV positive rates ranged from 0.49% (45 069/9 286 175) to 0.83% (20 819/2 494 869) during the period, with a decreasing trend (Z = – 100.05, P < 0.05). The top three population groups with the highest anti-HCV positive rate were drug users (27.46%, 52 508/191 184), detainees (3.31%, 3 183/96 038), and female sex workers (0.92%, 1 152/125 832). The anti-HCV positive rate showed a decreasing trend in all population groups, including preoperative patients, blood transfusion recipients, other medical clients, pregnant women, blood donors, drug users, female sex workers, detainees, and others (all P < 0.05), except for premarital checkups and men who have sex with men, whose anti-HCV positive rates showed an increasing trend (Z = 2.9252, P < 0.05; Z = 7.0807, P < 0.05). The top three regions with the highest anti-HCV positive rate were Dehong prefecture, Baoshan municipality, Honghe prefecture and Kunming municipality. The anti-HCV positive rate showed a decreasing trend in all prefectures/municipalities of the province during the period (all P < 0.05), except for in Diqing and Nujiang prefectures and Zhaotong municipality, whose anti-HCV positive rate showed an increasing trend (Z = 3.518, P < 0.05; Z = 7.2602, P < 0.05; Z = 4.5373, P < 0.05). ConclusionThe prevalence of anti-HCV positive in Yunnan province from 2013 to 2022 was mainly among key populations such as drug users, detainees, and female sex workers, with regions with higher positive rate including Dehong and Honghe prefectures, and Baoshan and Kunming municipalities, where the prevalence of former drug abuse was also higher.

Abstract Infertility affects approximately one-sixth of couples globally, with the incidence of male infertility steadily increasing. However, our understanding of the impact of viral infections on fertility remains limited. This review consolidates findings from previous studies, outlining 40 viruses identified in human semen and summarizing their key characteristics, modes of transmission, and their effects on both the reproductive and endocrine systems. Furthermore, it elucidates potential pathogenic mechanisms and treatment prospects of viruses strongly associated with male infertility. This synthesis will enhance our comprehension of how viral infections influence male reproductive health, offering valuable insights for future research as well as the diagnosis and treatment of infectious infertility. Graphical Abstract Abbreviated summary: Semen viral infections can damage the male reproductive system, further affecting semen quality and causing infertility, as well as sexually transmitted infections to partners and vertical transmission resulting in poor pregnancy outcomes.

Abstract The beveling process is an important process in the manufacturing of resonators, which has a significant impact on the frequency stability of resonators. Without understanding the frequency characteristics of the resonator after beveling, it is impossible to accurately design the beveled resonators. Thus, in order to investigate the vibration characteristics of AT-cut beveled resonators, we investigated the high-frequency vibration in this work by using the subregional geometric fitting method (SGFM) based on Mindlin’s plate theory. Quartz crystal plates with nonuniform thicknesses are partitioned into three regions and each region is fitted by using the polynomial functions based on the measured geometric morphology data. The governing equations are obtained based on Mindlin’s two-dimensional theory and the coupled vibrations are further solved using the partial differential equation module of COMSOL. In the numerical calculation, we compare the results obtained by the SGFM with those obtained by the global fitting method and the measured data. The accuracy and effectiveness of the SGFM are also verified. It is found that the frequencies obtained by the SGFM are slightly higher than the frequencies obtained by the global fitting method, and the results of SGFM are closer to the measured results. Meanwhile, as the beveling time increases, the frequency increases and the energy trapping effect becomes more significant. The proposed method can significantly improve the computational efficiency of thickness-shear vibration while ensuring accuracy. It is expected to provide a new geometric fitting method for the analysis of beveled crystal resonators.

Reducing the formation of large carbon clusters during the combustion of energetic materials (EMs) and improving their comprehensive performance hold great significance. With fluororubber (F2604) as a binder, this study prepared HNS/n-Al microspheres with different n-Al contents (5%, 10%, and 15%) using droplet microfluidic technology. Then, it characterized and tested the morphology, particle size distribution, dispersibility, crystal structure, thermal properties, mechanical sensitivity, and combustion behavior of the microspheres. The results show that the prepared microspheres had regular shapes, uniform particle sizes, and excellent dispersibility and contained more homogeneous components than physically mixed samples. Furthermore, the microspheres retained the crystal structures of the raw materials, enjoying high safety performance. The thermal analysis shows that HNS/n-Al microspheres had high heat resistance (thermal decomposition temperature: over 354 °C) and that a higher n-Al content was associated with more thorough thermal decomposition reactions of HNS (HNS: 83%, HNS/n-Al: 84%, 86%, and 93%). The ignition experiments show that the HNS/n-Al microspheres possessed excellent and stable combustion performance, as evidenced by more complete combustion reactions and significantly elevated energy release efficiency. Therefore, it is expected to achieve high-energy and high-speed responses of carbon-rich EMs and promote their practical applications.

Abstract Background The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture. Methods A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death. Results Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days. Conclusions Patients over 80 years old with haemoglobin

Abstract The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.

Abstract This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA (n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

Abstract The human brain has been implicated in the pathogenesis of several complex diseases. Taking advantage of single-cell techniques, genome-wide association studies (GWAS) have taken it a step further and revealed brain cell-type-specific functions for disease loci. However, genetic causal associations inferred by Mendelian randomization (MR) studies usually include all instrumental variables from GWAS, which hampers the understanding of cell-specific causality. Here, we developed an analytical framework, Cell-Stratified MR (csMR), to investigate cell-stratified causality through colocalizing GWAS signals with single-cell eQTL from different brain cells. By applying to obesity-related traits, our results demonstrate the cell-type-specific effects of GWAS variants on gene expression, and indicate the benefits of csMR to identify cell-type-specific causal effect that is often hidden from bulk analyses. We also found csMR valuable to reveal distinct causal pathways between different obesity indicators. These findings suggest the value of our approach to prioritize target cells for extending genetic causation studies.

ABSTRACT Objectives This study aimed to investigate the prognostic value of miRNAs and ferroptosis‐related genes in cervical squamous cell carcinoma. Methods We mined data from public databases for differentially expressed miRNAs, ferroptosis‐related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses. We combined the clinicopathological features to construct a nomogram and evaluated its efficacy using calibration and clinical decision curves. The correlation between miRNA characteristics, risk score, and the tumor microenvironment was also studied. Next, consensus and key genes were screened, and their biological functions were analyzed using KEGG, GO, GSEA, and drug sensitivity analysis. Finally, the expression of miRNAs and key genes was detected using qRT‐PCR and western blotting to verify the prediction results. Results Seven miRNA signatures (miR‐100‐3p, miR‐301a‐5p, miR‐331‐3p, miR‐425‐5p, miR‐502‐3p, miR‐505‐5p, and miR‐629‐3p) were generated, and prognostic risk and nomogram models were successfully constructed. These models exhibited good accuracy. miRNA signatures correlated with the tumor microenvironment. Twelve consensus genes and three key genes (SLC2A1, ANO6, and TXNIP) were screened and their biofunctional diversity was identified using various analytical methods. qRT‐PCR and western blotting were used to verify the expression of miR‐301a‐5p, miR‐505‐5p, SLC2A1, and TXNIP in cervical squamous carcinoma. The results were consistent with those of bioinformatics analyses. Conclusions Seven miRNAs may serve as prognostic biomarkers of cervical squamous cell carcinoma. SLC2A1, ANO6, and TXNIP are associated with cervical squamous cell carcinoma and may serve as ferroptosis‐related markers of the disease.

IntroductionRare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood–brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd2O3) during pregnancy, and its involved mechanism of BGA injury.MethodsWe used rat model to investigated the mechanisms of the offspring’s neural damage that Nd2O3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators.ResultsMaternal Nd2O3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring’s neural development and weakening their spatial learning ability. Nd2O3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd2O3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability.ConclusionMaternal exposure to Nd2O3 affects the offspring’s BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children’s gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd2O3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd2O3, such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention.

BackgroundAlthough large language models (LLMs) have demonstrated powerful capabilities in general domains, they may output information in the medical field that could be incorrect, incomplete, or fabricated. They are also unable to answer personalized questions related to departments or individual patient health. Retrieval-augmented generation technology (RAG) can introduce external knowledge bases and utilize the retrieved information to generate answers or text, thereby enhancing prediction accuracy.MethodWe introduced internal departmental data and 17 commonly used gastroenterology guidelines as a knowledge base. Based on RAG, we developed the Endo-chat medical chat application, which can answer patient questions related to gastrointestinal endoscopy. We then included 200 patients undergoing gastrointestinal endoscopy, randomly divided into two groups of 100 each, for a questionnaire survey. A comparative evaluation was conducted between the traditional manual methods and Endo-chat.ResultsCompared to ChatGPT, Endo-chat can accurately and professionally answer relevant questions after matching the knowledge base. In terms of response efficiency, completeness, and patient satisfaction, Endo-chat outperformed manual methods significantly. There was no statistical difference in response accuracy between the two. Patients showed a preference for AI services and expressed support for the introduction of AI. All participating nurses in the survey believed that introducing AI could reduce nursing workload.ConclusionIn clinical practice, Endo-chat can be used as a highly effective auxiliary tool for digestive endoscopic care.

Abstract Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast‐specific knock‐in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK‐49F cells suppresses the pro‐fibrotic response induced by transforming growth factor‐β1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer‐aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.

Soil visible-near-infrared (vis–NIR) spectroscopy offers a rapid, uncontaminated, and cost-efficient method for estimating physicochemical properties such as soil organic carbon (SOC). The development of soil spectral libraries (SSLs) and localized modeling methods has significantly improved the selection of appropriate modeling sets from SSLs for soil analysis. Nevertheless, most studies assume that the SSLs sufficiently cover the target samples for prediction. This study challenges this assumption by investigating the feasibility of using an SSL to predict SOC accurately in a local area when the dataset to be predicted (156,800 samples) vastly exceeds the SSL capacity (3755 samples). We utilized 1-meter-deep whole-soil profile and employed spectral similarity and continuum-removal (SS-CR) calculation to construct a Local dataset from the SSL, with a Global subset serving as a baseline for comparison. The effectiveness of partial least-squares regression (PLSR) and random forest (RF) algorithms in establishing quantitative relationships between spectra and SOC content was evaluated. Our results demonstrated that the Local model, with significantly fewer samples (1116), achieved higher predictive accuracy than the Global model. Both Global (R2 = 0.80, RMSE = 0.74 %) and Local (R2 = 0.83, RMSE = 0.75 %) models, developed using the RF algorithm, not only exhibited excellent accuracy but also enabled detailed and cost-effective characterization of the spatial distribution of SOC. Thus, leveraging SSLs enhances the cost-efficiency and predictive capacity of vis–NIR spectral analysis, particularly in handling large datasets at a local scale, underscoring the value of localized approaches in soil spectroscopy.

BackgroundRecurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL.MethodsImmune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored.ResultsIn the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis.ConclusionThe study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL.

Background: Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have improved the survival rates of lung cancer patients with ALK fusion mutations, their effectiveness varies significantly across different subtypes. We report a case of small intestine metastasis in a lung adenocarcinoma patient with co-occurring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 3 (V3) and tumor protein 53 (TP53) mutations after distinct responses to ALK-TKIs. Case presentation: A 45-year-old woman was diagnosed with stage IV lung adenocarcinoma with brain metastasis. Next-generation sequencing revealed EML4-ALK V3 and TP53 co-mutations. After the initial treatment with ensartinib, the patient experienced intracranial disease progression. Radiation therapy (RT) was then administered. Despite good response to RT for the intracranial disease, the primary tumor enlarged. Thus, the patient was treated with oral ensartinib concurrent with chemotherapy, with a partial response in both the primary tumor and intracranial metastases. However, after three cycles of treatment, the patient discontinued chemotherapy because of acute kidney injury. Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib. The patient developed symptoms of intestinal obstruction 14 months after the initial diagnosis. Surgical intervention revealed a poorly differentiated metastatic lung adenocarcinoma of the upper jejunum. Genetic testing confirmed EML4-ALK V3 and TP53 co-mutations and high expression of programmed cell death-ligand 1. Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away. Conclusion: We reported a rare case of small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3/TP53 mutations after distinct responses to ALK-TKIs in different lesions. Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.

Abstract Flash floods can carry substantial sediment, posing significant sedimentation hazards in hilly cities. The sedimentation hazard map can reproduce the sediment thickness and extent of an extreme events scenario, playing an important role in sediment risk management. However, current research primarily focuses on modeling the inundation area and depth of floods, while studying sedimentation hazard caused by flash floods in urban areas remains insufficient. This paper aims to address this gap by utilizing a numerical model that simulates hyperconcentrated flow in hilly urban areas using the two‐dimensional hydro‐sediment‐morphological model to compile the cumulative sedimentation hazard map. The model, built upon the open‐source TELEMAC‐MASCARET framework, incorporates Zhang Hongwu's formula to simulate sediment‐carrying capacity, particularly suitable for hyper‐sediment concentration near the riverbed. This paper uses the data of extreme flash flood events in the Wuding River basin in 2017 to simulate and compile the cumulative sedimentation hazard map. The hazard map delineates the sedimentation hazard extent and level attributable to overbank floodplain sedimentation. Notably, the sediment thickness is highest in areas near the levees on both sides of the Dali River. Moreover, the map illustrates the extent of channel erosion resulting from hyperconcentrated floods, which could jeopardize bank stability.

ABSTRACT: Semen quality is an important indicator that can directly affect fertility. In mammals, miRNAs in seminal plasma extracellular vesicles (SPEVs) and sperms can regulate semen quality. However, relevant regulatory mechanism in duck sperms remains largely unclear. In this study, duck SPEVs were isolated and characterized by transmission electron microscopy (TEM), western blot (WB), and nanoparticle tracking analysis (NTA). To identify the important molecules affecting semen quality, we analysed the miRNA expression in sperms and SPEVs of male ducks in high semen quality group ((DHS, DHSE) and low semen quality group (DLS, DLSE). We identified 94 differentially expressed (DE) miRNAs in the comparison of DHS vs. DLS, and 21 DE miRNAs in DHSE vs. DLSE. Target genes of SPEVs DE miRNAs were enriched in ErbB signaling pathway, glycometabolism, and ECM-receptor interaction pathways (P < 0.05), while the target genes of sperm DE miRNAs were enriched in ribosome (P < 0.05). The miRNA-target-pathway interaction network analyses indicated that 5 DE miRNAs (miR-34c-5p, miR-34b-3p, miR-449a, miR-31-5p, and miR-128-1-5p) targeted the largest number of target genes enriched in MAPK, Wnt and calcium signaling pathways, of which FZD9 and ANAPC11 were involved in multiple biological processes related to sperm functions, indicating their regulatory effects on sperm quality. The comparison of DE miRNAs of SPEVs and sperms found that mir-31-5p and novel-273 could potentially serve as biomarkers for semen quality detection. Our findings enhance the insight into the crucial role of SPEV and sperm miRNAs in regulating semen quality and provide a new perspective for subsequent studies.

Estimating bioavailable heavy metals in seawater is closely related to the indication of ecological risk. This study combined a CadR-regulated vioABE expression module and a MerR-regulated VioC expression module to generate a novel dual-colored bacterial cell-based biosensor. After genetic optimization, the preferred biosensor could detect as low as 9.7 nM Cd(II), 24.4 nM Pb(II), and 0.5 nM Hg(II). Increased grey-green intensities were observed in Cd(II) (4.9 nM to 40 μM) and Pb(II) (24.4 nM to 200 μM) exposure groups. Interestingly, increased purple intensity was observed in the Hg(II) exposure group (3.7 to 468.8 nM) in a dose-dependent manner. A low-cost and mini-equipment biosensing process was established for detecting pollutant heavy metals in seawater, with the added advantage of providing information on the bioavailability and cytotoxicity of heavy metals. High salinity weakly interferes with the biosensing response to Hg(II). This study shows that novel colorimetric biosensors have the potential to simultaneously report various toxic metals in environmental water samples, contributing to protecting marine ecology.