Search

Background: Sepsis-associated acute kidney injury (SA-AKI) is a severe complication associated with poorer prognosis and increased mortality, particularly in elderly patients. Currently, there is a lack of accurate mortality risk prediction models for these patients in clinic. Objectives: This study aimed to develop and validate machine learning models for predicting in-hospital mortality risk in elderly patients with SA-AKI. Methods: Machine learning models were developed and validated using the public, high-quality Medical Information Mart for Intensive Care (MIMIC)-IV critically ill database. The recursive feature elimination (RFE) algorithm was employed for key feature selection. Eleven predictive models were compared, with the best one selected for further validation. Shapley Additive Explanations (SHAP) values were used for visualization and interpretation, making the machine learning models clinically interpretable. Results: There were 16,154 patients with SA-AKI in the MIMIC-IV database, and 8426 SA-AKI patients were included in this study (median age: 77.0 years; female: 45%). 7728 patients excluded based on these criteria. They were randomly divided into a training cohort (5,934, 70%) and a validation cohort (2,492, 30%). Nine key features were selected by the RFE algorithm. The CatBoost model achieved the best performance, with an AUC of 0.844 in the training cohort and 0.804 in the validation cohort. SHAP values revealed that AKI stage, PaO2, and lactate were the top three most important features contributing to the CatBoost model. Conclusion: We developed a model capable of predicting the risk of in-hospital mortality in elderly patients with SA-AKI.

BackgroundNotwithstanding the acknowledged interplay between atrial fibrillation (AF) and the emergence of digestive system neoplasms, the intricacies of this relationship remain ambiguous. By capitalizing univariable Mendelian Randomization (MR) complemented by a mediated MR tactic, our pursuit was to elucidate the causative roles of AF in precipitating digestive system malignancies and potential intermediary pathways.MethodThis research endeavor seeks to scrutinize the causal clinical implications of whether genetic predispositions to AF correlate with an increased risk of digestive system malignancies, employing MR analytical techniques. Utilizing a dataset amalgamated from six studies related to AF, encompassing over 1,000,000 subjects, we performed univariable MR assessments, employing the random-effects inverse-variance weighted (IVW) methodology as our principal analytical paradigm. Subsequently, a mediated MR framework was employed to probe the potential mediating influence of AF on the nexus between hypertension (HT), heart failure (HF), ischemic stroke (IS), coronary artery disease (CAD), and digestive system neoplasms.ResultThe univariable MR evaluation unveiled a notable causal nexus between the genetic inclination toward AF and the genetic susceptibility to colon, esophageal, and small intestine malignancies. The mediated MR scrutiny ascertained that the genetic inclination for AF amplifies the risk profile for colon cancer via IS pathways and partially explains the susceptibility to esophageal and small intestine tumors through the HF pathway.ConclusionOur investigative endeavor has highlighted a definitive causative association between genetic inclination to AF and specific digestive system neoplasms, spotlighting IS and HF as instrumental mediators. Such revelations furnish pivotal perspectives on the complex genetic interconnections between cardiovascular anomalies and certain digestive tract tumors, emphasizing prospective therapeutic and diagnostic worthy of pursuit.

BackgroundOsteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis. We conducted a two-sample Mendelian randomization (MR) study to estimate the causal effects of two common occupational factors—job involves heavy manual or physical work and job involves mainly walking or standing—on OA and RA in individuals of European ancestry.MethodsInstruments were chosen from genome-wide association studies (GWASs) that identified independent single nucleotide polymorphisms (SNPs) robustly linked to job involves heavy manual or physical work (N = 263,615) as well as job involves mainly walking or standing (N = 263,556). Summary statistics for OA and RA were taken from the Integrative Epidemiology Unit (IEU) GWAS database; both discovery and replication GWAS datasets were considered. The primary analysis utilized the inverse variance weighted (IVW) MR method supplemented by various sensitivity MR analyses.ResultsIn the IVW model, we found that genetically predicted job involves heavy manual or physical work was significantly associated with OA in both the discovery [odds ratio (OR) = 1.034, 95% confidence interval (CI): 1.016–1.053, P = 2.257 × 10−4] and replication (OR = 1.857, 95% CI: 1.223–2.822, P = 0.004) analyses. The causal associations were supported in diverse sensitivity analyses. MR analyses suggested no causal effect of genetically predicted job involves heavy manual or physical work on RA. Similarly, our data provided no evidence that genetically predicted job involves mainly walking or standing was related to OA and RA.ConclusionsOur MR study suggests that job involves heavy manual or physical work is a risk factor for OA. It is of utmost importance to create preventive strategies aimed at reducing its impact on OA at such work sites.

Drug-resistant N. gonorrhoeae is an urgent threat to global public health, and vaccine development is the best long-term strategy for controlling gonorrhea. We have previously shown that adhesion and penetration protein (App) play a role in the adhesion, invasion, and reproductive tract colonization of N. gonorrhoeae. Here, we describe the immune response induced by intranasal immunization with passenger and translocator fragments of App. The recombinant App passenger and translocator fragments induced high titers of IgG and IgA antibodies in serum and vaginal washes. Antibodies produced by App passenger and the combination of passenger and translocator mediated the killing of N. gonorrhoeae via serum bactericidal activity and opsonophagocytic activity, whereas antisera from translocator-immunized groups had lower bactericidal activity and opsonophagocytic activity. The antisera of the App passenger and translocator, alone and in combination, inhibited the adhesion of N. gonorrhoeae to cervical epithelial cells in a concentration-dependent manner. Nasal immunization with App passenger and translocator fragments alone or in combination induced high levels of IgG1, IgG2a, and IgG2b antibodies and stimulated mouse splenocytes to secrete cytokines IFN-γ and IL-17A, suggesting that Th1 and Th17 cellular immune responses were activated. In vivo experiments have shown that immune App passenger and transporter fragments can accelerate the clearance of N. gonorrhoeae in the vagina of mice. These data suggest that the App protein is a promising N. gonorrhoeae vaccine antigen.

Summary: Background: Tumour-promoting inflammation is a “hallmark” of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. Findings: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10–1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20–1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53–0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88–0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48–4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. Interpretation: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated. Funding: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).

Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease, with limited understanding of the disease pathology. Exosomes are important mediators of intercellular communication that modulates various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies have indicated that a new long noncoding RNA (lncRNA), PICALM-AU1, is mainly expressed in cholangiocytes, and is dramatically induced in the liver during HPS. However, the mechanism by which cholangiocyte-derived PICALM-AU1 regulates Endothelial-mesenchymal transition (EndMT) in HPS remains unclear. Here, we observed that PICALM-AU1 was synthesized in the cholangiocytes of the liver and then, secreted as exosomes into the serum; serum exosomal PICALM-AU1 levels were positively correlated with the severity of HPS in a rat model and in human patients. PICALM-AU1 carrying serum exosomes induced the EndMT of pulmonary microvascular endothelial cells (PMVECs) and promoted lung injury in vivo and in vitro. Furthermore, PICALM-AU1 acted as a molecular sponge for microRNA 144-3p (miR144-3p), resulting in the up-regulation of Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a known target of EndMT and enhancement of EndMT, proliferation and migration of PMVECs. Taken together, our findings indicate that the cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT in HPS lungs. Thus, it represents a potential therapeutic target for the treatment of HPS.

In this paper, a partial differential equation approach based on the underlying stock price path decomposition is developed to price an American-style resettable convertible bond. The American-style resettable convertible bond is viewed as a mixture of three simple securities, which can be used to replicate the feature of payoffs of the resettable convertible bond completely. The partial differential equations under the Black–Scholes framework are established to price these simple securities. An implicit Euler method is used to discretize the first-order time derivative while a central finite difference method on a piecewise uniform mesh is used to discretize the spatial derivatives. The error estimates are developed by using the maximum principle in two mesh sets both for the time semi-discretization scheme and the spatial discretization scheme, respectively. It is proved that the scheme is first-order convergent for the time variable and second-order convergent for the spatial variable. Numerical experiments support these theoretical results.

In this article, the SIR model is used to fit the spread of influenza A in Ningbo, ranging from January 1, 2023 to June 30, 2023. The data that can be collected is the daily newly confirmed cases, but the daily number of infected individuals and recovered individuals is unknown. The initial number of susceptible individuals with exposure risk is also unknown. Based on the incompleteness of the data, the parameter estimation problem of the SIR model is transformed into an optimization problem. The Particle Swarm Optimization algorithm is used to solve the optimization problem. The goodness of fit (R2) of the daily cumulative number of confirmed cases is 0.998. The model can reflect the cycle, peak, and trend of the entire spread of influenza A and is consistent with reality during the post-COVID-19 period.

BackgroundFriedman's standards, developed almost 50 years ago, may no longer align with the needs of today's obstetric population and current pregnancy management practices. This study aims to analyze contemporary labor patterns and estimate labor duration in China, focusing on first-stage labor data from Chinese parturients with a spontaneous onset of labor.MethodsThis retrospective observational study utilized data from electronic medical records of a tertiary hospital in Changsha, Hunan. Out of a total of 2,689 parturients, exclusions were made for multiple gestations, preterm, post-term, or stillbirth, cesarean delivery, non-vertex presentation, and neonatal intensive care unit admission. Average labor curves were constructed by parity using repeated-measure analysis, and labor duration was estimated through interval-censored regression, stratified by cervical dilation at admission. We performed an analysis to assess the impact of oxytocin augmentation and amniotomy on labor progression and conducted a sensitivity analysis using women with complicated outcomes.ResultsNulliparous women take over 180 minutes for cervical dilation from 3 to 4 cm, and the duration from 5 to 6 cm exceeds 145 minutes. Multiparous women experience shorter labor durations than nulliparous. Labor acceleration is observed after 5 cm in nulliparous, but no distinct inflection point is evident in the average labor curve. In the second stage of labor, the 95th percentile for nulliparous, with and without epidural analgesia, is 142 minutes and 127 minutes, respectively.ConclusionsThese findings provide valuable insights for the reassessment of labor and delivery processes in contemporary obstetric populations, including current Chinese obstetric practice.

Throughout the Quaternary period, climate change has significantly influenced plant distribution, particularly affecting species within the genus Tsuga (Endl.) Carrière. This climatic impact ultimately led to the extinction of all Tsuga species in Europe. Today, there are ten recognized species of Tsuga worldwide, one of listed as a vulnerable species and four as near-threatened species. The genus Tsuga exhibits a disjunctive distribution in East Asia (EA), eastern North America (ENA), and western North America (WNA). It is crucial to comprehend the mechanisms underlying these distributional changes and to identify key climate variables to develop effective conservation strategies for Tsuga under future climate scenarios. In this study, we applied the maximum entropy (MaxEnt) model by combining distribution data for Tsuga with abundant pollen fossil data. Our objective was to investigate the climate factors that shape the distribution of Tsuga, identify climate thresholds, and elucidate distribution dynamics in the context of significant climate changes over the past 1070 thousand years (ka). Our findings highlight the pivotal role of precipitation as the key climate factor affecting the distribution of Tsuga. Specifically, in EA, summer precipitation was the key driver, while in North America (NA), winter precipitation exerted greater importance. Moreover, we observed similarities in climatic requirements between Tsuga species in Europe and EA, and declines in summer precipitation and winter temperature were major factors contributing to the extinction of Tsuga species in Europe. Quaternary glacial and interglacial fluctuations exerted substantial impacts on Tsuga distribution dynamics. The disappearance of Tsuga species in the Korean Peninsula may have occurred during the LGM (Last Glacial Maximum). The potential suitable area for Tsuga species in EA expanded during the cold periods, while in NA, it contracted. In the future, climate change may result Tsuga distribution area contraction in both the EA and NA. Our study has identified distinct response patterns of Tsuga in various geographic regions to Quaternary climate change and offers corresponding suggestions for Tsuga conservation. In the future, it will be imperative to prioritize the conservation of natural Tsuga distributions in EA and NA, with a focus on the impacts of precipitation fluctuation on the dynamic distribution of this genus.

Transient receptor potential (TRP) channels are a large and diverse family of transmembrane ion channels that are widely expressed, have important physiological roles, and are associated with many human diseases. These proteins are actively pursued as promising drug targets, benefitting greatly from advances in structural and mechanistic studies of TRP channels. At the same time, the complex, polymodal activation and regulation of TRP channels have presented formidable challenges. In this short review, we summarize recent progresses toward understanding the structural basis of TRP channel function, as well as potential ligand binding sites that could be targeted for therapeutics. A particular focus is on the current understanding of the molecular mechanisms of TRP channel activation and regulation, where many fundamental questions remain unanswered. We believe that a deeper understanding of the functional mechanisms of TRP channels will be critical and likely transformative toward developing successful therapeutic strategies targeting these exciting proteins. This endeavor will require concerted efforts from computation, structural biology, medicinal chemistry, electrophysiology, pharmacology, drug safety and clinical studies.

Abstract Objectives Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods We employed an RNA‐sequencing cohort (n = 50) from Sun Yat‐Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA‐BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results In our study, chitinase 3‐like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P

NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are rare soft tissue tumor molecularly characterized by NTRK gene rearrangement, which occurs mostly in children and young adults, and rarely in adults. The abnormal tumor located in superficial or deep soft tissues of human extremities and trunk mostly, and rarely also involves abdominal organs. In this case, we report a malignant NTRK-RSCN that occurred in the pelvic region of an adult. The patient was found to have a large tumor in the pelvic region with a pathological diagnosis of infiltrative growth of short spindle-shaped tumor cells with marked heterogeneity. Immunohistochemistry of this patient showed positive vimentin, pan-TRK and Ki67 (approximately 60%) indicators with negative S100, Desmin and DOG1. Molecular diagnosis revealed c-KIT and PDGFRα wild type with TPM3-NTRK1 fusion, unfortunately this patient had a rapidly progressive disease and passed away. This case highlights the gene mutation in the molecular characteristics of NTRK-RSCNs, and the significance of accurate molecular typing for the diagnosis of difficult cases.

For people with lower limb muscle weakness, effective and timely rehabilitation intervention is essential for assisting in daily walking and facilitating recovery. Numerous studies have been conducted on rehabilitation robots; however, some critical issues in the field of human-following remain unaddressed. These include potential challenges related to the loss of sensory signals for intention recognition and the complexities associated with maintaining the relative pose of robots during the following process. A human-following surveillance robot is introduced as the basis of the research. To address potential interruptions in motion signals, such as data transmission blockages or body occlusion, we propose a human walking intention estimation algorithm based on set-membership filtering with incomplete observation. To ensure uninterrupted user walking and maintain an effective aid and detection range, we propose a human-following control algorithm based on prescribed performance. The experiment verifies the effectiveness of the proposed methods. The proposed intention estimation algorithm achieves continuous and accurate intention recognition under incomplete observation. The control algorithm presented in this paper achieves constrained robot following with respect to the relative pose.

With the increasing applications of high-power lasers in fields such as laser fabrication, laser measurement, laser therapy and scientific research, there is an increasing demand for high-performance nonlinear optical limiters (NOLs) to protect human eyes and optical sensitive elements. Here we propose a brand-new approach to design a reflective NOL with an ultra-wide stop band based on coupled Tamm plasmon polaritons (TPPs) and optical Kerr effect. The NOL permits the transmission of weak signal light at the desired wavelength while effectively blocking potentially harmful or accidentally intense lasers at the same wavelength to avoid damage to sensitive optical elements or human eyes. The design can be optimized for the desired operating wavelength and threshold intensity by using different dielectric layers. In a proof-of-concept design, taking the 1064 nm laser as an example, we design a NOL capable of dynamically adjusting its transmission in response to laser intensity. The NOL has a high transmission of 85.21 % at weak light (intensity less than 0.20 MW/cm2), and the transmission can be rapidly reduced to 1.39 % when the incident light intensity increases to 60.37 MW/cm2. Furthermore, the broad stop band effectively safeguards the limiter from potential damage caused by intense light at different wavelengths. Our proposed limiter exhibits an exceptionally wide stop band range spanning from 0.5 ∼ 20 µm, nearly 30 times broader than conventional reflective NOLs. The proposed NOL design scheme provides a new promising method to design an excellent reflective NOL at the desired wavelength.

Copper-doped Zinc Tellurium (ZnTe:Cu) films were deposited on borosilicate glass using magnetron co-sputtering technique. The influence of the substrate temperature on the structural, morphological, optical and electrical properties of ZnTe:Cu films was investigated by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), UV–Vis spectrophotometer and Hall effect measurement system. The results indicate that substrate temperature significantly affects the properties of the ZnTe:Cu films. When the substrate temperature increases from room temperature to 600 °C, the (111)-preferred orientation of ZnTe:Cu films is gradually replaced by the (220)-preferred orientation. At high substrate temperatures (≥500 °C), the CuxTe phase appears in the ZnTe:Cu films, resulting in higher carrier concentration (>1019 cm−3) and lower resistivity (

Summary: Background: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. Methods: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis was performed to identified independent risk factors and establish a nomogram to predict the post-ET MF free survival. Both bias-corrected area under the curve (AUC), calibration curves and concordance index (C-index) were employed to assess the predictive accuracy of the nomogram. Findings: Multivariate Cox regression demonstrated that elevated red blood cell distribution width (RDW), elevated levels of lactate dehydrogenase (LDH) and the level of haemoglobin (Hb), a history of smoking and the presence of splenomegaly were independent risk factors for post-ET MF. The C-index displayed of the training and validation cohorts were 0.877 and 0.853. The 5 years, 10 years AUC values in training and external validation cohorts were 0.948, 0.769 and 0.978, 0.804 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction. Interpretation: We developed a nomogram capable of predicting the post-ET MF free survival probability at 5 years and 10 years in ET patients. This tool helps doctors identify patients who need close monitoring and appropriate counselling. Funding: This research was funded by the Key R&D Program of Zhejiang (No. 2022C03137); the Public Technology Application Research Program of Zhejiang, China (No. LGF21H080003); and the Zhejiang Medical Association Clinical Medical Research special fund project (No. 2022ZYC-D09).

Abstract Small extracellular vesicles (sEVs) are essential mediators of intercellular communication within the tumor microenvironment (TME). Although the biological features of sEVs have been characterized based on in vitro culture models, recent evidence indicates significant differences between sEVs derived from tissue and those derived from in vitro models in terms of both content and biological function. However, comprehensive comparisons and functional analyses are still limited. Here, we collected sEVs from breast cancer tissues (T‐sEVs), paired normal tissues (N‐sEVs), corresponding plasma (B‐sEVs), and tumor organoids (O‐sEVs) to characterize their transcriptomic and proteomic profiles. We identified the actual cancer‐specific sEV signatures characterized by enriched cell adhesion and immunomodulatory molecules. Furthermore, we revealed the significant contribution of cancer‐associated fibroblasts in the sEV network within the TME. In vitro model‐derived sEVs did not entirely inherit the extracellular matrix‐ and immunity regulation‐related features of T‐sEVs. Also, we demonstrated the greater immunostimulatory ability of T‐sEVs on macrophages and CD8+ T cells compared to O‐sEVs. Moreover, certain sEV biomarkers derived from noncancer cells in the circulation exhibited promising diagnostic potential. This study provides valuable insights into the functional characteristics of tumor tissue‐derived sEVs, highlighting their potential as diagnostic markers and therapeutic agents for breast cancer.

BackgroundBasal metabolic rate (BMR) is the minimum amount of energy needed by the body to carry out essential physiological functions. The goal of this study was to evaluate whether BMR causally influences venous thromboembolism (VTE) and its subtypes in European individuals.MethodsA two-sample Mendelian randomization (MR) was performed. Within a genome-wide association study (GWAS) involving 454,874 people, genetic variants were chosen as instrumental variables based on their significant associations (p

The rise of fentanyl has introduced significant new challenges to public health. To improve the examination and identification of biological samples in cases of fentanyl misuse and fatalities, this study utilized a zebrafish animal model to conduct a comparative investigation of the metabolites and biotransformation pathways of fentanyl in the zebrafish’s liver and brain. A total of 17 fentanyl metabolites were identified in the positive ion mode using ultra-high-pressure liquid chromatography Q Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometry (UHPLC-QE HF MS). Specifically, the zebrafish’s liver revealed 16 fentanyl metabolites, including 6 phase I metabolites and 10 phase II metabolites. Conversely, the zebrafish’s brain presented fewer metabolites, with only 8 detected, comprising 6 phase I metabolites and 2 phase II metabolites. Notably, M′4, a metabolite of dihydroxylation, was found exclusively in the brain, not in the liver. Through our research, we have identified two specific metabolites, M9-a (monohydroxylation followed by glucuronidation) and M3-c (monohydroxylation, precursor of M9-a), as potential markers of fentanyl toxicity within the liver. Furthermore, we propose that the metabolites M1 (normetabolite) and M3-b (monohydroxylation) may serve as indicators of fentanyl metabolism within the brain. These findings suggest potential strategies for extending the detection window and enhancing the efficiency of fentanyl detection, and provide valuable insights that can be referenced in metabolic studies of other new psychoactive substances.

Diabetes is a chronic metabolic disease, and its therapeutic goals focus on the effective management of blood glucose and various complications. Drug combination therapy has emerged as a comprehensive treatment approach for diabetes. An increasing number of studies have shown that, compared with monotherapy, combination therapy can bring significant clinical benefits while controlling blood glucose, weight, and blood pressure, as well as mitigating damage from certain complications and delaying their progression in diabetes, including both type 1 diabetes (T1D), type 2 diabetes (T2D) and related complications. This evidence provides strong support for the recommendation of combination therapy for diabetes and highlights the importance of combined treatment. In this review, we first provided a brief overview of the phenotype and pathogenesis of diabetes and discussed several conventional anti-diabetic medications currently used for the treatment of diabetes. We then reviewed several clinical trials and pre-clinical animal experiments on T1D, T2D, and their common complications to evaluate the efficacy and safety of different classes of drug combinations. In general, combination therapy plays a pivotal role in the management of diabetes. Integrating the effectiveness of multiple drugs enables more comprehensive and effective control of blood glucose without increasing the risk of hypoglycemia or other serious adverse events. However, specific treatment regimens should be tailored to individual patients and implemented under the guidance of healthcare professionals.

AbstractBackground Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

A novel virtual experimental testing methodology that utilizes virtual microstructures representative of genuine fiber distribution, is devised to micromechanically simulate and scrutinize the inter-fiber failure of unidirectional (UD) carbon fiber reinforced polymer (CFRP) composites. The experimentally identified nonlinear behavior of the matrix is incorporated by utilizing the Drucker-Prager plasticity model. The interaction behavior between fiber-matrix interfaces, including delamination and friction, is represented by means of a cohesive interaction approach. The results of virtual testing demonstrate that interfacial parameters and the epoxy properties exert considerable influences on the predicted macroscopic responses under individual loading cases. Additionally, the interface and epoxy material properties are inversely determined through virtual testing analysis assisted by experimental results. Furthermore, the validated virtual testing method is utilized to obtain the inter-fiber failure envelope of the composites. The predictions are then compared with those theoretically derived from classical failure criteria. The current comparative studies indicate that the existing classical failure criterion exhibits limited predictive ability with computational data.

Primary liver cancer is a common and lethal malignancy in China. Transcatheter arterial chemoembolization (TACE) is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular carcinoma (HCC), while transcatheter arterial infusion (TAI) is another effective interventional treatment for HCC. In recent years, hepatic arterial infusion chemotherapy (HAIC) has gained increasing attention as an application-regulated modality for TAI. Owing to the current debate in the medical community regarding the use of HAIC and TACE for the treatment of HCC, the application of both approaches should be considered at a higher level, with a broader perspective and a more normative aspect. Accordingly, we aimed to define the rational combination of liver cancer TAI/HAIC with TACE as infusion transcatheter chemoembolization (iTACE), which suggests that the two interventions are not superior but lead to a mutually beneficial situation. In this review, we sought to discuss the development, specification, application, challenge and innovation, debate, and union of TAI/HAIC and TACE, and the clinical application and latest research on iTACE. We aimed to introduce new concepts of iTACE and expect new breakthroughs in the treatment of liver cancer owing to the combined use of the two major interventional tools.

Alcoholic liver disease (ALD) is a global liver disease that manifests in a variety of forms, including alcoholic hepatitis, liver inflammation, fatty liver, and liver cirrhosis. One of the early stages of ALD is alcoholic fatty liver (AFL) disease, which is primarily characterized by the accumulation of lipids and inflammation in hepatocytes. Guanylate binding protein 5 (GBP5) has been investigated for its involvement in disease progression. The regulatory effects of GBP5 on the progression of AFL disease are still not well understood. This study aims to investigate the impact of GBP5 on AFL progression and its underlying mechanism of action. To achieve this, gene expression was evaluated using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods. Lipid accumulation was confirmed using the Oil Red O staining assay, while the levels of Triglyceride (TG), aspartate aminotransferases (AST), and alanine aminotransferases (ALT) were measured using commercial kits. The levels of inflammatory cytokines were assessed using enzyme-linked immuno sorbent assay (ELISA) assay. Finally, cell apoptosis was evaluated using flow cytometry. Cell apoptosis was evaluated through flow cytometry. Our work demonstrated that GBP5 expression was up-regulated in the Ethyl Alcohol (EtOH) group. Additionally, lipid accumulation was increased after EtOH inducement, but this change was attenuated by silencing GBP5. Silencing of GBP5 reduced EtOH-mediated inflammation and cell apoptosis. Finally, it was discovered that knockdown of GBP5 retarded the EtOH-stimulated nuclear factor kappa-B (NF-κB) pathway. Knockdown of GBP5 alleviated lipid accumulation and inflammation in AFL through inhibition of NF-κB pathway. This finding suggested that GBP5 may be a useful bio-target for AFL treatment.

Abstract Objective This study was conducted to examine the association between the A118G polymorphism of the OPRM1 gene and the risk of increased VAS scores in patients with colorectal cancer who underwent laparoscopic radical resection for which fentanyl was used. Methods The OPRM1 A118G genotype in subjects were detected. The relationship between the A118G polymorphism of the OPRM1 gene and increased Visual Analogue Scale (VAS) scores throughout the perioperative period was explored. A total of 101 patients receiving fentanyl anesthesia undergoing laparoscopic radical resection of colon tumors at Zhongshan Hospital, Fudan University between July 2018 and December 2020 were investigated in the present study. The relative risk between the A118G polymorphism of the OPRM1 gene and VAS ≥ 4 in the PACU was estimated using the adjusted effect relationship diagram, baseline characteristic analysis, and multiple logistic regression analysis. The relationship between the A118G polymorphism of the OPRM1 gene and VAS in the PACU, as well as perioperative fentanyl usage, was examined after confounders were adjusted. Results Subjects with OPRM1 A118G wild gene A were less sensitive to fentanyl, which was a risk factor for PACU VAS ≥ 4. Before the model was adjusted, the odds ratio (OR) was 14.73 (P = 0.001). After adjusting for age, sex, weight, height, and the duration of surgery, the OR increased to 16.55 (P = 0.001). When adjusting for age, sex, weight, height, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3gene polymorphism, the OR was 19.94 (P = 0.002). Moreover, OPRM1 A118G wild type gene A was found to be a risk factor for increased dosage of fentanyl in the PACU. Before the model was adjusted, the OR reached 16.90 (P = 0.0132). After adjusting for age, sex, body weight, intraoperative fentanyl dosage, surgery duration, and height, the OR was 13.81, (P = 0.0438). When adjusting for age, sex, weight, height, intraoperative fentanyl dosage, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3 gene polymorphism, the OR reached 15.23, (P = 0.0205). Conclusion The A118G polymorphism of the OPRM1 gene carrying wild gene A was a risk factor for VAS ≥ 4 in the PACU. Moreover, it is a risk factor for increased dosage of fentanyl in the PACU.

Abstract Background Remimazolam tosilate (RT) is a novel short-acting GABA (A) receptor agonist that has a rapid recovery from procedural sedation and can be fully reversed by flumazenil. To date, there have been relatively few articles comparing RT and propofol for general anesthesia. This study aimed to assess the efficacy and safety of RT with or without flumazenil compared with propofol in general anesthesia for day surgery. Methods 115 patients scheduled for day surgery were randomized into three groups: RT (n = 39), RT + flumazenil (n = 38) and propofol (n = 38). The primary endpoints were anesthesia induction time and time until fully alert. Anesthesia success rate, bispectral index (BIS) values, injection pain, opioid and vasopressor dosages, postoperative recovery profiles and perioperative inflammatory and cognitive changes were assessed. Any adverse events were recorded. Results Induction times were similar among the three groups (P = 0.437), but the median time until fully alert in patients treated with RT was longer than that of the propofol or RT + flumazenil groups (17.6 min vs. 12.3 min vs. 12.3 min, P 0.05). Smaller percentages of patients who received RT (26.3%) and RT + flumazenil (31.6%) developed hypotension during anesthesia maintenance compared with propofol (68.4%), and consequently less ephedrine (P

Abstract Introduction The effectiveness and safety of immune checkpoint inhibitor (ICI) monotherapy in advanced upper tract urothelial carcinoma (UTUC) is less reported. Methods In total, 106 consecutive advanced UTUC patients receiving ICI monotherapy were collected from nine high volume centers. Clinical outcomes were analyzed according to multiple parameters (e.g., treatment line, metastatic sites). Objective response rate (ORR), overall survival (OS) and progression‐free survival (PFS) were captured after ICI initiation. Results With a median follow‐up of 12.0 months, 25 patients in the first‐line group and 15 patients in the second‐line group died of UTUC. We reported a median OS of 18.0 months, a median PFS of 5.0 months, and an ORR of 38.6% for patients in the first‐line group; a median OS of 10.0 months, a median OS of 4.0 months, and an ORR of 27.8% for patients in the second‐line group. Complete response was observed in two patients in the first‐line group and one patient in the second‐line group with a total complete response rate of 2.8%. In the univariate and multivariate analysis, visceral metastasis with a hazard ratio of 2.4 was associate with poor OS. The most common treatment‐related adverse events included fatigue (11.3%), pruritus (10.4%), and diarrhea (6.6%). Conclusions This real‐world study suggests that ICI monotherapy is active and has acceptable toxic effects for unresectable or metastatic UTUC as first‐line therapy in cisplatin‐ineligible patients or second‐line therapy in platinum‐refractory patients.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28–75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30–9.11) and 3.72 (95% CI, 1.91–5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58–0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Abstract Background Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. Methods In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). Results From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1–5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6–52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8–8.2) months, and the median overall survival was 24.5 (95%CI: 10.2–38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. Conclusions Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. Clinical trial registration Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018)

Abstract As one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.

Abstract Background Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc. Methods The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level. Results Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc. Conclusion The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.

Abstract Substituting hydrazine oxidation reaction for oxygen evolution reaction can result in greatly reduced energy consumption for hydrogen production, however, the mechanism and the electrochemical utilization rate of hydrazine oxidation reaction remain ambiguous. Herein, a bimetallic and hetero-structured phosphide catalyst has been fabricated to catalyze both hydrazine oxidation and hydrogen evolution reactions, and a new reaction path of nitrogen-nitrogen single bond breakage has been proposed and confirmed in hydrazine oxidation reaction. The high electro-catalytic performance is attributed to the instantaneous recovery of metal phosphide active site by hydrazine and the lowered energy barrier, which enable the constructed electrolyzer using bimetallic phosphide catalyst at both sides to reach 500 mA cm−2 for hydrogen production at 0.498 V, and offer an enhanced hydrazine electrochemical utilization rate of 93%. Such an electrolyzer can be powered by a bimetallic phosphide anode-equipped direct hydrazine fuel cell, achieving self-powered hydrogen production at a rate of 19.6 mol h−1 m−2.

Abstract Deletion of ABL1 was detected in a cohort of hematologic malignancies carrying AML1-ETO and NUP98 fusion proteins. Abl1−/− murine hematopoietic cells transduced with AML1-ETO and NUP98-PMX1 gained proliferation advantage when compared to Abl1 + /+ counterparts. Conversely, overexpression and pharmacological stimulation of ABL1 kinase resulted in reduced proliferation. To pinpoint mechanisms facilitating the transformation of ABL1-deficient cells, Abl1 was knocked down in 32Dcl3-Abl1ko cells by CRISPR/Cas9 followed by the challenge of growth factor withdrawal. 32Dcl3-Abl1ko cells but not 32Dcl3-Abl1wt cells generated growth factor-independent clones. RNA-seq implicated PI3K signaling as one of the dominant mechanisms contributing to growth factor independence in 32Dcl3-Abl1ko cells. PI3K inhibitor buparlisib exerted selective activity against Lin-cKit+ NUP98-PMX1;Abl1−/− cells when compared to the Abl1 + /+ counterparts. Since the role of ABL1 in DNA damage response (DDR) is well established, we also tested the inhibitors of ATM (ATMi), ATR (ATRi) and DNA-PKcs (DNA-PKi). AML1-ETO;Abl1−/− and NUP98-PMX1;Abl1−/− cells were hypersensitive to DNA-PKi and ATRi, respectively, when compared to Abl1 + /+ counterparts. Moreover, ABL1 kinase inhibitor enhanced the sensitivity to PI3K, DNA-PKcs and ATR inhibitors. In conclusion, we showed that ABL1 kinase plays a tumor suppressor role in hematological malignancies induced by AML1-ETO and NUP98-PMX1 and modulates the response to PI3K and/or DDR inhibitors.

Abstract Background We performed Mendelian randomization (MR) to assess the causal effect of tea intake on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods Genetic instruments for tea intake were obtained from a large genome-wide association study (GWAS) dataset of the UK Biobank. Genetic association estimates for RA (6236 cases and 147,221 controls) and SLE (538 cases and 213,145 controls) were obtained from the FinnGen study through the IEU GWAS database. Results MR analyses using the inverse-variance weighted method showed that tea intake was not associated with risk of RA [odds ratio (OR) per standard deviation increment in genetically predicted tea intake = 0.997, 95% confidence interval (CI) 0.658–1.511] and SLE (OR per standard deviation increment in genetically predicted tea intake = 0.961, 95% CI 0.299–3.092). Weighted median, weighted mode, MR-Egger, leave-one-out and multivariable MR controlling for several confounding factors including current tobacco smoking, coffee intake, and alcoholic drinks per week yielded completely consistent results. No evidence of heterogeneity and pleiotropy was found. Conclusion Our MR study did not suggest a causal effect of genetically predicted tea intake on RA and SLE.

Five new wood-inhabiting fungi, Lyomyces albopulverulentus, L. yunnanensis, Xylodon daweishanensis, X. fissuratus, and X. puerensis spp. nov., are proposed based on a combination of morphological features and molecular evidence. Lyomyces albopulverulentus is characterized by brittle basidiomata, pruinose hymenophore with a white hymenial surface, a monomitic hyphal system with clamped generative hyphae, and ellipsoid basidiospores. Lyomyces yunnanensis is characterized by a grandinioid hymenial surface, the presence of capitate cystidia, and ellipsoid basidiospores. Xylodon daweishanensis is characterized by an odontioid hymenial surface, a monomitic hyphal system with clamped generative hyphae, and broad ellipsoid-to-subglobose basidiospores. Xylodon fissuratus is characterized by a cracking basidiomata with a grandinioid hymenial surface, and ellipsoid basidiospores. Xylodon puerensis is characterized by a poroid hymenophore with an angular or slightly daedaleoid configuration, and ellipsoid-to-broad-ellipsoid basidiospores. Sequences of ITS and nLSU rRNA markers of the studied samples were generated and phylogenetic analyses were performed with the maximum likelihood, maximum parsimony, and Bayesian inference methods. The phylogram based on the ITS+nLSU rDNA gene regions (Fig. 1) included six genera within the families Chaetoporellaceae, Hyphodontiaceae, Hymenochaetaceae, and Schizoporaceae (Hymenochaetales)—Fasciodontia, Hastodontia, Hyphodontia, Kneifiella, Lyomyces, and Xylodon—in which the five new species were grouped into genera Lyomyces and Xylodon. The phylogenetic tree inferred from the ITS sequences highlighted that Lyomyces albopulverulentus formed a monophyletic lineage and was then grouped closely with L. bambusinus, L. orientalis, and L. sambuci; additionally, L. yunnanensis was sister to L. niveus with strong supports. The topology, based on the ITS sequences, revealed that Xylodon daweishanensis was retrieved as a sister to X. hyphodontinus; X. fissuratus was grouped with the four taxa X. montanus, X. subclavatus, X. wenshanensis, and X. xinpingensis; and X. puerensis was clustered with X. flaviporus, X. ovisporus, X. subflaviporus, X. subtropicus, and X. taiwanianus.

Abstract Stimulated by the enhancing requirements for system safety as well as process reliability in complex industrial processes, this paper investigates a data‐driven fault detection and fault‐tolerant control scheme for large‐scale systems. To this end, a pair‐wise decomposition approach is first presented based on the inclusion principle, which expands the original large‐scale system into a set of disjointed pair‐wise subsystems. Then, for the pair‐wise subsystems, the observer‐based residual generators and observer‐based state feedback controllers for fault detection and fault‐tolerant control purpose are further developed in a decentralized way. On this basis, the fault‐tolerant controller for the original large‐scale system is obtained by the coordination and contraction of the decentralized observer‐based state feedback controllers. Finally, the feasibility and effectiveness of the proposed scheme are demonstrated through the case study on a multi‐area interconnected power system.

Background: Missed miscarriage patients with residual tissue in the uterine cavity after medical abortion can be treated by surgery and expectant therapy. Because surgery may cause damage to the endometrium, expectant treatment is preferred clinically. However, the individual probability of expulsion of residual tissue from the uterus remains unelucidated. The present study used logistic regression analysis and nomogram to create a scoring system for quantitatively evaluating the individual probability of residual tissue expulsion in patients with missed miscarriage. Methods: A cohort of 126 patients with missed miscarriage who had residual tissue after medical abortion were included in the trial after receiving their informed consent. Of these patients, 102 and 24 patients had successful and failed expectant treatment, respectively. Results: Logistic regression analysis showed that gravidity, residual tissue size, and residual tissue with blood supply significantly affected the probability of expulsion of residual tissue after medical abortion. A special nomogram was constructed for predicting the probability of successful expulsion. At the maximum Youden index of 0.696, the area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.849; this corresponded to a score of 77.78 and probability of residual tissue expulsion of 71%. Conclusion: A scoring system was established based on a nomogram. The success rate of residual tissue expulsion from the uterine cavity was significantly improved at the total score of 77.78 points after assigning influence weights to each influencing factor and an AUC of 0.849.

Unmanned aerial vehicles (UAVs) are commonly employed in pursuit and rescue missions, where the target’s trajectory is unknown. Traditional methods, such as evolutionary algorithms and ant colony optimization, can generate a search route in a given scenario. However, when the scene changes, the solution needs to be recalculated. In contrast, more advanced deep reinforcement learning methods can train an agent that can be directly applied to a similar task without recalculation. Nevertheless, there are several challenges when the agent learns how to search for unknown dynamic targets. In this search task, the rewards are random and sparse, which makes learning difficult. In addition, because of the need for the agent to adapt to various scenario settings, interactions required between the agent and the environment are more comparable to typical reinforcement learning tasks. These challenges increase the difficulty of training agents. To address these issues, we propose the OC-MAPPO method, which combines optimal control (OC) and Multi-Agent Proximal Policy Optimization (MAPPO) with GPU parallelization. The optimal control model provides the agent with continuous and stable rewards. Through parallelized models, the agent can interact with the environment and collect data more rapidly. Experimental results demonstrate that the proposed method can help the agent learn faster, and the algorithm demonstrated a 26.97% increase in the success rate compared to genetic algorithms.

Salient object detection (SOD) aims to accurately identify significant geographical objects in remote sensing images (RSI), providing reliable support and guidance for extensive geographical information analyses and decisions. However, SOD in RSI faces numerous challenges, including shadow interference, inter-class feature confusion, as well as unclear target edge contours. Therefore, we designed an effective Global Semantic-aware Aggregation Network (GSANet) to aggregate salient information in RSI. GSANet computes the information entropy of different regions, prioritizing areas with high information entropy as potential target regions, thereby achieving precise localization and semantic understanding of salient objects in remote sensing imagery. Specifically, we proposed a Semantic Detail Embedding Module (SDEM), which explores the potential connections among multi-level features, adaptively fusing shallow texture details with deep semantic features, efficiently aggregating the information entropy of salient regions, enhancing information content of salient targets. Additionally, we proposed a Semantic Perception Fusion Module (SPFM) to analyze map relationships between contextual information and local details, enhancing the perceptual capability for salient objects while suppressing irrelevant information entropy, thereby addressing the semantic dilution issue of salient objects during the up-sampling process. The experimental results on two publicly available datasets, ORSSD and EORSSD, demonstrated the outstanding performance of our method. The method achieved 93.91% Sα, 98.36% Eξ, and 89.37% Fβ on the EORSSD dataset.

Plasma-initiated polymerization (PIP) is generally attributed to a radical process due to its inhibiting property. However, its unique polymerization behaviors like long-lived radical and solvent effect do not comply well with the traditional radical mechanism. Herein, the PIP of methyl methacrylate (MMA) was conducted in a high-voltage DC electric field to investigate the charged nature of its radicals. Consequently, the polymerization presented a preferential distribution of polymers at the anode but not the cathode, revealing the negatively charged nature of the growing radicals. An acceleration phenomenon, accompanied by the growth in molecular weights and the reduction in molecular weight distributions (Ð), was observed at the voltages above 16 kV, suggesting the dissociation of ion pairs of growing radicals. The PIP yielded PMMA with analogous chemical and steric structures to those of PMMA from traditional radical initiation, whether in the presence or absence of the external electric field. This work offers new insights into the PIP of vinyl monomers, wherein a one-electron transfer reaction is inferred to be involved in the monomer activation.

Global positioning systems often fall short in dense forest environments, leading to increasing demand for innovative localization methods. Notably, existing methods suffer from the following limitations: (1) traditional localization frameworks necessitate several fixed anchors to estimate the locations of targets, which is difficult to satisfy in complex and uncertain forestry environments; (2) the uncertain environment severely decreases the quality of signal measurements and thus the localization accuracy. To cope with these limitations, this paper proposes a new method of trajectory localization for forestry environments with the assistance of UAVs. Based on the multi-agent DRL technique, the topology of UAVs is optimized in real-time to cater for high-accuracy target localization. Then, with the aid of RSS measurements from UAVs to the target, the least squares algorithm is used to estimate the location, which is more flexible and reliable than existing localization systems. Furthermore, a shared replay memory is incorporated into the proposed multi-agent DRL system, which can effectively enhance learning performance and efficiency. Simulation results show that the proposed method can obtain a flexible and high-accuracy localization system with the aid of UAVs, which exhibits better robustness against high-dimensional heterogeneous data and is suitable for forestry environments.

The production of manufactured sand and stone processing can cause dust pollution due to the generation of a significant amount of stone powder. This dust (mainly granite powder) was collected and incorporated as a cement replacement into mass-manufactured sand concrete in order to enhance the mechanical properties and microstructures. The heat of the hydration was measured by adding the granite powder into the cementitious material system. The mechanical properties, autogenous shrinkage, and pore structures of the concrete were tested. The results showed that the mechanical strength of the concrete increased first and then decreased with the increase in granite powder content. By replacing the 5% cement with the granite powder, the 28 d compressive and flexural strength increased by 17.6% and 20.9%, respectively. The autogenous shrinkage was mitigated by the incorporation of the 10% granite powder and decreased by 19.7%. The mechanism of the granite powder in the concrete was studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), and mercury intrusion porosimetry (MIP). The porosity decreased significantly within the 10% granite powder. A microstructure analysis did not reveal a change in the type of hydration products but rather that the granite powder played a role in the microcrystalline nucleation during the hydration process.

It has been strongly suggested that selenium deficiency and T-2 toxin contamination have a strong relationship with the occurrence and development of Kashin–Beck disease (KBD). In order to provide information for understanding the high prevalence of KBD in Tibet, this study collected the responses to a cubital venous blood and dietary questionnaire of 125 subjects including 75 KBD patients and 50 healthy controls in a KBD-prevalent county (Luolong County) in Tibet, China. A total of 10 household local families were randomly selected in this area, and local diet samples of brick tea, Zanba powder, milk residue, and hulless Barley were collected from these residents. Selenium content in blood was detected by inductively coupled plasma mass spectrometry (ICP-MS). The T-2 toxin contamination level in food sample was assayed using an ELISA kit. The selenium levels of patients and controls were 42.0 ± 19.8 and 56.06 ± 22.4 μg/L, respectively. The serum selenium level in controls was higher than that in patients, but there was no significant difference, and the serum selenium level both in patients and controls in Tibet was lower than the normal range. The results of the dietary survey showed that the number of respondents who consumed butter tea was large; 46.67% of patients indicated that they drank buttered tea every day, which was significantly higher than in controls. The contents of T-2 toxin in Zanba powder, milk residue, hulless barley and drinking water samples were below the detection limit (0.05 μg/kg); this result was labeled Tr. Unexpectedly, the contents of T-2 toxin in brick tea were higher, with average levels of 424 ± 56 μg/kg in Detong village and 396 ± 24 μg/kg in Langcuo village. For the first time, we report the presence of an extremely high concentration of T-2 toxin in brick tea of Tibet.

Research on vehicle trajectory prediction based on road monitoring video data often utilizes a global map as an input, disregarding the fact that drivers rely on the road structures observable from their own positions for path planning. This oversight reduces the accuracy of prediction. To address this, we propose the CVAE-VGAE model, a novel trajectory prediction approach. Initially, our method transforms global perspective map data into vehicle-centric map data, representing it through a graph structure. Subsequently, Variational Graph Auto-Encoders (VGAEs), an unsupervised learning framework tailored for graph-structured data, are employed to extract road environment features specific to each vehicle’s location from the map data. Finally, a prediction network based on the Conditional Variational Autoencoder (CVAE) structure is designed, which first predicts the driving endpoint and then fits the complete future trajectory. The proposed CVAE-VGAE model integrates a self-attention mechanism into its encoding and decoding modules to infer endpoint intent and incorporate road environment features for precise trajectory prediction. Through a series of ablation experiments, we demonstrate the efficacy of our method in enhancing vehicle trajectory prediction metrics. Furthermore, we compare our model with traditional and frontier approaches, highlighting significant improvements in prediction accuracy.

Due to their significant environmental impact, there has been a gradual restriction of the production and utilization of legacy per- and polyfluoroalkyl substances (PFAS), leading to continuous development and adoption of novel alternatives. To effectively identify the potential environmental risks from crop consumption, the levels of 25 PFAS, including fourteen perfluoroalkyl acids (PFAAs), two precursor substances and nine novel alternatives, in agricultural soils and edible parts of various crops around a fluoride industrial park (FIP) in Changshu city, China, were measured. The concentration of ΣPFAS in the edible parts of all crops ranged from 11.64 to 299.5 ng/g, with perfluorobutanoic acid (PFBA) being the dominant compound, accounting for an average of 71% of ΣPFAS. The precursor substance, N-methylperfluoro-octanesulfonamidoacetic acid (N-MeFOSAA), was detected in all crop samples. Different types of crops showed distinguishing accumulation profiles for the PFAS. Solanaceae and leafy vegetables showed higher levels of PFAS contamination, with the highest ΣPFAS concentrations reaching 190.91 and 175.29 ng/g, respectively. The highest ΣAlternative was detected in leafy vegetables at 15.21 ng/g. The levels of human exposure to PFAS through crop consumption for various aged groups were also evaluated. The maximum exposure to PFOA for urban toddlers reached 109.8% of the standard value set by the European Food Safety Authority (EFSA). In addition, short-chained PFAAs and novel alternatives may pose potential risks to human health via crop consumption.

In this paper, we propose a three-layer distributed simulation network architecture, which consists of a distributed virtual simulation network, a perception and control subnetwork, and a cooperative communication service network. The simulation architecture runs on a distributed platform, which can provide unique virtual scenarios and multiple simulation services for the verification of basic perception, control, and planning algorithms of a single-robot system and can verify the distributed collaboration algorithms of heterogeneous multirobot systems. Further, we design simulation experimental scenarios for classic heterogeneous robotic systems such as unmanned aerial vehicles (UAVs) and unmanned ground vehicles (UGVs). Through the analysis of experimental measurement data, we draw several important conclusions: firstly, the replication time characteristics and update frequency characteristics of entity synchronization in our system indicate that the replication time of entity synchronization in our system is relatively short, and the update frequency can meet the needs of multirobot collaboration and ensure the real-time use and accuracy of the system; secondly, we analyze the bandwidth usage of data frames in the whole session and observe that the server side occupies almost half of the data throughput during the whole session, which indicates that the allocation and utilization of data transmission in our system is reasonable; and finally, we construct a bandwidth estimation surface model to estimate the bandwidth requirements of the current model when scaling the server-side scale and synchronization-state scale, which provides an important reference for better planning and optimizing of the resource allocation and performance of the system. Based on this distributed simulation framework, future research will improve the key technical details, including further refining the coupling object dynamic model update method to support the simulation theory of the coupling relationship between system objects, studying the impact of spatiotemporal consistency of distributed systems on multirobot control and decision making, and in-depth research on the impact of collaborative frameworks combined with multirobot systems for specific tasks.

Exoplanet imaging with high-contrast imaging adaptive optics systems, though challenging, is a promising path toward the characterization of terrestrial planets. We analyzed the fundamental limitations associated with the direct imaging of terrestrial exoplanets around low-mass stars with Extremely Large Telescopes using laser tomographic adaptive optics (LTAO) and derived the post-coronagraph image shape in the focal plane from LTAO systems. Additionally, the fundamental limitation of direct imaging was found to come from unseen spatial frequencies during tomographic reconstruction. Through the provision of optimization strategies for laser guide star (LGS) asterisms, based on the post-coronagraph image contrast, we aimed to assist in the design of LTAO systems for Extremely Large Telescopes, resulting in a six-fold improvement in the LTAO post-coronagraph image plane at 0.1 arcseconds.

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus’s pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine–cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity.

Chemical warfare agents (CWAs) refer to toxic chemical substances used in warfare. Recently, CWAs have been a critical threat for public safety due to their high toxicity. Metal–organic frameworks have exhibited great potential in protecting against CWAs due to their high crystallinity, stable structure, large specific surface area, high porosity, and adjustable structure. However, the metal clusters of most reported MOFs might be highly consumed when applied in CWA hydrolysis. Herein, we fabricated a two-dimensional piezoresponsive UiO-66-F4 and subjected it to CWA simulant dimethyl-4-nitrophenyl phosphate (DMNP) detoxification under sonic conditions. The results show that sonication can effectively enhance the removal performance under optimal conditions; the reaction rate constant k was upgraded 45% by sonication. Moreover, the first-principle calculation revealed that the band gap could be further widened with the application of mechanical stress, which was beneficial for the generation of 1O2, thus further upgrading the detoxification performance toward DMNP. This work demonstrated that mechanical vibration could be introduced to CWA protection, but promising applications are rarely reported.