Search

Abstract Background The results of observational studies indicate a potential link between Helicobacter pylori infection and Sjogren’s syndrome (SS), but the causal relationship between them remains unknown. This study applied Mendelian randomization (MR) to evaluate this relationship. Method Genome-wide association study (GWAS) summary statistics on H. pylori infection [sample size=8735 (EBI, https://gwas.mrcieu.ac.uk/ )] and SS [sample size=368,028 (cases=2495, controls=365533) (FinnGen, https://r9.finngen.fi/ )] were analyzed. We used bidirectional MR to evaluate the association between H. pylori infection and SS and identify causation. The major MR analysis method was inverse-variance weighted (IVW) MR, supplemented by MR‒Egger and weighted median approaches. In addition, the stability and reliability of the results were tested using the retention method, heterogeneity test, and horizontal gene pleiotropy test. Results Evidence of the impact of H. pylori infection on SS risk was found in the IVW results [odds ratio (OR)=1.6705; 95% confidence interval (CI)=1.0966 to 2.5446; P=0.0168]. Evidence of the impact of SS on H. pylori infection risk was also found (OR=1.0158; 95% CI=1.0033 to 1.0285; P=0.0128). Conclusion The results of MR analysis support a causal association between H. pylori infection and SS and indicate that SS can lead to a greater risk of H. pylori infection. Our research will support the development of novel approaches for continued H. pylori and SS-related research and therapy that consider the genetic relationship between H. pylori infection and SS.

Abstract The utilization of low-energy photons in light-driven reactions is an effective strategy for improving the efficiency of solar energy conversion. In nature, photosynthetic organisms use chlorophylls to harvest the red portion of sunlight, which ultimately drives the reduction of CO2. However, a molecular system that mimics such function is extremely rare in non-noble-metal catalysis. Here we report a series of synthetic fluorinated chlorins as biomimetic chromophores for CO2 reduction, which catalytically produces CO under both 630 nm and 730 nm light irradiation, with turnover numbers of 1790 and 510, respectively. Under appropriate conditions, the system lasts over 240 h and stays active under 1% concentration of CO2. Mechanistic studies reveal that chlorin and chlorinphlorin are two key intermediates in red-light-driven CO2 reduction, while corresponding porphyrin and bacteriochlorin are much less active forms of chromophores.

Abstract Background This multicenter, double-blinded, randomized controlled trial (RCT) aims to assess the impact of an artificial intelligence (AI)-based model on the efficacy of intracranial aneurysm detection in CT angiography (CTA) and its influence on patients’ short-term and long-term outcomes. Methods Study design: Prospective, multicenter, double-blinded RCT. Settings: The model was designed for the automatic detection of intracranial aneurysms from original CTA images. Participants: Adult inpatients and outpatients who are scheduled for head CTA scanning. Randomization groups: (1) Experimental Group: Head CTA interpreted by radiologists with the assistance of the True-AI-integrated intracranial aneurysm diagnosis strategy (True-AI arm). (2) Control Group: Head CTA interpreted by radiologists with the assistance of the Sham-AI-integrated intracranial aneurysm diagnosis strategy (Sham-AI arm). Randomization: Block randomization, stratified by center, gender, and age group. Primary outcomes: Coprimary outcomes of superiority in patient-level sensitivity and noninferiority in specificity for the True-AI arm to the Sham-AI arm in intracranial aneurysms. Secondary outcomes: Diagnostic performance for other intracranial lesions, detection rates, workload of CTA interpretation, resource utilization, treatment-related clinical events, aneurysm-related events, quality of life, and cost-effectiveness analysis. Blinding: Study participants and participating radiologists will be blinded to the intervention. Sample size: Based on our pilot study, the patient-level sensitivity is assumed to be 0.65 for the Sham-AI arm and 0.75 for the True-AI arm, with specificities of 0.90 and 0.88, respectively. The prevalence of intracranial aneurysms for patients undergoing head CTA in the hospital is approximately 12%. To establish superiority in sensitivity and noninferiority in specificity with a margin of 5% using a one-sided α = 0.025 to ensure that the power of coprimary endpoint testing reached 0.80 and a 5% attrition rate, the sample size was determined to be 6450 in a 1:1 allocation to True-AI or Sham-AI arm. Discussion The study will determine the precise impact of the AI system on the detection performance for intracranial aneurysms in a double-blinded design and following the real-world effects on patients’ short-term and long-term outcomes. Trial registration This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT06118840 . Registered 11 November 2023.

Abstract Background Non-small cell lung cancer (NSCLC) is one of the predominant malignancies globally. Percutaneous thermal ablation (PTA) has gained widespread use among NSCLC patients, with the potential to elicit immune responses but limited therapeutic efficacies for advanced-stage disease. T-helper type 9 (Th9) cells are a subset of CD4+ effector T cells with robust and persistent anti-tumor effects. This study proposes to develop PTA-Th9 cell integrated therapy as a potential strategy for NSCLC treatment. Methods The therapeutic efficacies were measured in mice models with subcutaneously transplanted, recurrence, or lung metastatic tumors. The tumor microenvironments (TMEs) were evaluated by flow cytometry. The cytokine levels were assessed by ELISA. The signaling molecules were determined by quantitative PCR and Western blotting. The translational potential was tested in the humanized NSCLC patient-derived xenograft (PDX) model. Results We find that PTA combined with adoptive Th9 cell transfer therapy substantially suppresses tumor growth, recurrence, and lung metastasis, ultimately extending the survival of mice with NSCLC grafts, outperforming both PTA and Th9 cell transfer monotherapy. Analysis of TMEs indicates that combinatorial therapy significantly augments tumor-infiltrating Th9 cells, boosts anti-tumor effects of CD8+ T cells, and remodels tumor immunosuppressive microenvironments. Moreover, combinatorial therapy significantly strengthens the regional and circulation immune response of CD8+ T cells in mice with tumor lung metastasis and induces peripheral CD8+ T effector memory cells in mice with tumor recurrence. Mechanically, PTA reinforces the anti-tumor ability of Th9 cells primarily through upregulating interleukin (IL)-1β and subsequently activating the downstream STAT1/IRF1 pathway, which could be effectively blocked by intercepting IL-1β signaling. Finally, the enhanced therapeutic effect of combinatorial therapy is validated in humanized NSCLC PDX models. Conclusions Collectively, this study demonstrates that combinatorial therapy displays robust and durable anti-tumor efficacy and excellent translational potential, offering excellent prospects for translation and emerging as a promising approach for NSCLC treatment.

SLC45A1 encodes a glucose transporter protein highly expressed in the brain. Mutations in SLC45A1 may lead to neurological diseases and developmental disorders, but its exact role is poorly understood. DNA G-quadruplexes (DNA G4s) are stable structures formed by four guanine bases and play a role in gene regulation and genomic stability. Changes in DNA G4s may affect brain development and function. The mechanism linking alterations in DNA G-quadruplex structures to SLC45A1 pathogenicity remains unknown. In this study, we identify a functional DNA G-quadruplex and its key binding site on SLC45A1 (NM_001080397.3: exon 2: c.449 G>A: p.R150K). This variant results in the upregulation of mRNA and protein expression, which may lead to intellectual developmental disorder with neuropsychiatric features. Mechanistically, the mutation is found to disrupt DNA G-quadruplex structures on SLC45A1, leading to transcriptional enhancement and a gain-of-function mutation, which further causes increased expression and function of the SLC45A1 protein. The identification of the functional DNA G-quadruplex and its effects on DNA G4s may provide new insights into the genetic basis of SLC45A1 pathogenicity and highlight the importance of DNA G4s of SLC45A1 in regulating gene expression and brain development.

Abstract In response to abundant freshwater input from rainfall and river discharge, the northern Bay of Bengal (BoB) is featured by low sea surface salinity (SSS) and strong intraseasonal variability (ISV). This study investigates the characteristic and dynamic mechanisms of SSS ISV in the northern BoB based on satellite observations and the output of Simple Ocean Data Assimilation (SODA). The strong SSS ISV is mainly concentrated near the mouth of the Ganges–Brahmaputra River and along the east coast of India, where the horizontal salinity gradient varies greatly. SSS ISV in the northern BoB is notably in phase with freshwater transport, which peaks from July to November. The contribution of riverine freshwater is significant both geographically and temporally. The SSS budget analysis indicates that the horizontal advection plays a dominant role in SSS ISV. Once currents cross the salinity field, large horizontal advection anomalies become important and favor SSS ISV. Altered SSS patterns can impact water density, potentially influencing the strength and direction of currents. This, in turn, may have cascading effects on local and regional climate patterns.

Abstract Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.

Abstract Introduction Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti‐neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro‐PET/CT. Methods Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post‐surgery). In addition, fecal samples collection and micro‐PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. Results The RIF‐ and/or LAC‐treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN‐γ and IL‐10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p

Abstract Landslide in reservoirs imposes challenges to reservoir operation and dam safety management practices. The understanding of the landside mechanism during reservoir operation is crucial to landslide‐related risk migration. During the reservoir operation from 2018 to 2021, a massive landslide occurred with over 107 m3 in total volume on the bank of the NE reservoir. The surface movement characteristics before and after the occurrence of landslides in the NE reservoir in the region scale were detected and interpreted by Sentinel‐2 time series images. Experimental studies were conducted to investigate the geotechnical properties of the fine‐grained soil. The slope stability was evaluated for a typical slope profile considering the rising water level using the extended Bishop's simplified method, which was implemented in the code STAB‐UNSAT. It can be found that the landslide in the fine‐grained soil occurred simultaneously when the water level rose. The cumulative area of soil slope failure on the left bank of the NE reservoir increased continuously during the reservoir operation from 2018 to 2020, especially had a remarkable increment from August to October in 2019. The extended Bishop's simplified method provides a more rational method to evaluate the soil slope stability. The slope failure mechanism of the studied soil, that is, collapse–erosion–slide upon the rising reservoir water has been proposed.

Abstract Coronary chronic total occlusion (CTO) often occurs in patients with obstructive coronary artery disease, which remains one of the greatest challenges for interventional cardiologists. Coronary computed tomography angiography (CCTA) with its emerging post-processing techniques can provide a detailed assessment of CTO lesions before percutaneous coronary intervention (PCI), playing an important role in the clinical management of CTO PCI, from early diagnosis, pre-procedural outcome prediction, the crossing algorithm planning, intraprocedural guidance, and finally post-procedural assessment and follow-up. In addition, the feasibility of CT perfusion (CTP) in patients with CTO has been validated. Combined CCTA and CTP have the great potential to be the one-stop-shop imaging modality for assessing both anatomy and function of CTO lesions. This review aims to make radiologists understand the role of CCTA in the diagnosis and assessment of CTO lesions, thus assisting interventionalists in optimizing CTO PCI crossing strategies with the expertise of radiologists. Critical relevance statement The anatomical features of CTO on CCTA can reveal the complexity of CTO lesions and are associated with CTO PCI outcome, thus helping interventionalists optimize CTO PCI crossing strategies. Key points • CTO is the common lesion in invasive coronary angiography, and CTO PCI is technically difficult and its success rate is relatively low. • Length, collaterals, and attenuation-related signs can help distinguish CTO from subtotal occlusion. • The anatomical features of CTO lesions can help grade the difficulty of CTO PCI and predict procedural outcomes and long-term outcomes of CTO PCI. • The real-time fusion of CCTA with fluoroscopic angiography can be applied in highly complicated CTO lesions. • After CTO PCI, CCTA can help guide a second CTO PCI re-entry or follow up stent patency. Graphical Abstract

High‐throughput drug screening enables the discovery of new anticancer drugs. Although monolayer cell cultures are commonly used for screening, their limited complexity and translational efficiency require alternative models. Three‐dimensional cell cultures, such as multicellular tumor spheroids (MCTS), mimic tumor architecture and offer promising opportunities for drug discovery. In this study, we developed a neuroblastoma MCTS model for high‐content drug screening. We also aimed to decipher the mechanisms underlying synergistic drug combinations in this disease model. Several agents from different therapeutic categories and with different mechanisms of action were tested alone or in combination with selective inhibition of prostaglandin E2 by pharmacological inhibition of microsomal prostaglandin E synthase‐1 (mPGES‐1). After a systematic investigation of the sensitivity of individual agents and the effects of pairwise combinations, GFP‐transfected MCTS were used in a confirmatory screen to validate the hits. Finally, inhibitory effects on multidrug resistance proteins were examined. In summary, we demonstrate how MCTS‐based high‐throughput drug screening has the potential to uncover effective drug combinations and provide insights into the mechanism of synergy between an mPGES‐1 inhibitor and chemotherapeutic agents.

Osteoporosis (OS) is characterized by low bone mass and altered bone microarchitecture. Patients with OS are at significantly increased risk for fragility fractures, which ultimately suffer fractures. Biochemical indicators of bone metabolism are important for assessing the risk of fracture occurrence. In this study, we aimed to investigate the risk factors for osteoporotic fracture in the elderly based on bone metabolism biochemical indexes and to analyze their predictive efficacy through relevant bone metabolism biochemical indexes. Methods: A total of 254 elderly OS patients diagnosed and treated in our hospital during May 2019 to April 2022 was randomly picked, of which 100 patients were finally enrolled. Patients were divided into OS fracture group and non-fracture group according to whether they had OS fracture. The contents of bone mineral density (BMD) and bone metabolism biochemical indexes, including Dickkopf1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (BGP) and 25 hydroxyvitamin D (25 (OH) D) were detected in lumbar L2č4 and left femoral greater trochanter. The correlation between bone metabolism and BMD was evaluated using Pearson analysis. The risk factors of OS fracture were analyzed using Multivariate logistic regression analysis. The predictive value of biochemical indexes of bone metabolism on the risk of OS fracture was analyzed using ROC curve. Results: The OS fracture group had a higher proportion of patients with age and lack of sunlight compared to the non-fracture group (P < 0.05). Patients in the OS fracture group exhibited lower BMD in lumbar L2č4 and left femoral greater trochanter compared to the non-fracture group (P < 0.05). At 14 weeks and 16 weeks after surgery, levels of DKK-1, SOST and OPN were higher in the OS fracture group than these in the non-fracture group, while levels of OPG, BGP and 25 (OH) D were lower (P < 0.05). BMD in lumbar L2č4, BMD in femoral greater trochanter, OPG, BGP and 25 (OH) D were the protective factors (P < 0.05), and the age, lack of sunlight, DKK-1, SOST and OPN were the risk factors for OS fractures (P < 0.05). BMD in lumbar L2č4 was negatively correlated with DKK1, SOST and OPN (P < 0.05), and positively correlated with BGP and 25 (OH) D (P < 0.05). 25 (OH) D was positively correlated with femoral greater trochanter BMD (P < 0.05). OPG, OPN, BGP and 25 (OH) D had predictive value for OS fracture occurrence, with respective areas under the curve (AUC) of 0.709, 0.761, 0.720 and 0.730. When all indicators were combined, the AUC increased to 0.940 (P < 0.05), signifying high predictive value for OS fractures. Conclusion: Biochemical bone metabolism indicators were closely correlated with the risk of OS fracture and had a high predictive value as influencing factors for OS fracture occurrence. Therefore, an accurate combination of biochemical indices may help reduce the risk of fracture in the elderly, enabling the development of targeted treatment plans for elderly fracture patients.

Abstract Background Moyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology. Methods Data for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted. Results A cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6–37.8) mg/dL vs. 14.9 (7.8–30.5) mg/dL, P

Summary: Immunotherapy has revolutionized cancer treatment but its efficacy depends on a robust immune response in the tumor. Silencing of the tumor suppressor p53 is common in tumors and can affect the recruitment and activation of different immune cells, leading to immune evasion and poor therapy response. We found that the p53 activating stapled peptide MDM2/MDMX inhibitor Sulanemadlin (ALRN-6924) inhibited p53 wild-type cancer cell growth in vitro and in vivo. In mice carrying p53 wild-type CT26.WT tumors, monotherapy with the PD-1 inhibitor DX400 or Sulanemadlin delayed tumor doubling time by 50% and 37%, respectively, while combination therapy decreased tumor doubling time by 93% leading to an increased median survival time. Sulanemadlin treatment led to increased immunogenicity and combination treatment with PD-1 inhibition resulted in an increased tumor infiltration of lymphocytes. This combination treatment strategy could potentially turn partial responders into responders of immunotherapy, expanding the patient target group for PD-1-targeting immunotherapy.

Accurate analysis of regional ecological quality and its drivers is crucial for the sustainable development of human society. The remote sensing eco-index (RSEI) has been widely used to monitor changes in ecological quality in many countries or regions, but it ignores the problem of declining air quality caused by economic development and population growth. Consequently, an improved remotely sensed ecological index (ARSEI) was developed to evaluate China's ecological environment quality by incorporating aerosol optical depth (AOD) into the index system. Additionally, a random forest regression model was used to rank the importance of ecological indexes in the ARSEI. Furthermore, a geographical detector was utilized to assess the impact of natural and socioeconomic factors on the spatial heterogeneity of the ARSEI in six geographic regions of China, identifying their primary drivers. The research findings revealed the following: (1) There are similarities and differences in the order of importance of ecological indicators in the ARSEI across the six geographic regions. (2) ARSEI values significantly increased in 24.70% of China's areas, primarily in the Northeast Plain, Loess Plateau, and Tarim Basin, while they significantly decreased in 5.35% of the areas, mainly in the Qinghai-Tibetan Plateau, the northern part of the Tianshan Mountains, eastern coastal cities, and central urban agglomerations. (3) Rainfall and vegetation conditions are the main factors affecting environmental quality in the Three-North region (XB, HB and DB). In the southern (XN, ZN and HD) regions, vegetation cover and land use change, population density and PM2.5 concentrations were greater than the influence of climate factors. The interaction of socioeconomic factors, including PM2.5, land use change, and population density had a greater impact on the spatial heterogeneity of the ARSEI in the southern regions. The results of this study can provide data support for the coordinated development of regional ecosystems and socioeconomics.

The present study demonstrated the digestion behavior and fermentation characteristics of a sulfated polysaccharide from Sargassum fusiforme (SFSP) in the simulated digestion tract environment. The results showed that the molecular weight of two components in SFSP could not be changed by simulated digestion, and no free monosaccharide was produced. This indicates that most of SFSP can reach the colon as prototypes. During the fermentation with human intestinal flora in vitro, the higher-molecular-weight component of SFSP was utilized, the total sugar content decreased by 16%, the reducing sugar content increased, and the galactose content in monosaccharide composition decreased relatively. This indicates that SFSP can be selectively utilized by human intestinal flora. At the same time, SFSP also changed the structure of intestinal flora. Compared with the blank group, SFSP significantly increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes. At the genus level, the abundances of Bacteroides and Megamonas increased, while the abundances of Shigella, Klebsiella, and Collinsella decreased. Moreover, the concentrations of total short-chain fatty acids (SCFAs), acetic, propionic and n-butyric acids significantly increased compared to the blank group. SFSP could down-regulate the contents of trimethylamine, piperidone and secondary bile acid in fermentation broth. The contents of nicotinic acid, pantothenic acid and other organic acids were increased. Therefore, SFSP shows significant potential to regulate gut microbiota and promote human health.

Amid the backdrop of carbon neutrality, traditional energy production is transitioning towards integrated energy systems (IES), where model-based scheduling is key in scenarios with multiple uncertainties on both supply and demand sides. The development of artificial intelligence algorithms, has resolved issues related to model accuracy. However, under conditions of high proportion renewable energy integration, component load adjustments require increased flexibility, so the mathematical model of the component must adapt to constantly changing operating conditions. Therefore, the identification of operating condition changes and rapid model updating are pressing issues. This study proposes a modeling and updating method for IES components based on knowledge distillation. The core of this modeling method is the light weighting of the model, which is achieved through a knowledge distillation method, using a teacher-student mode to compress complex neural network models. The triggering of model updates is achieved through principal component analysis. The study also analyzes the impact of model errors caused by delayed model updates on the overall scheduling of IES. Case studies are conducted on critical components in IES, including coal-fired boilers and turbines. The results show that the time consumption for model updating is reduced by 76.67 % using the proposed method. Under changing conditions, compared with two traditional models, the average deviation of this method is reduced by 12.61 % and 3.49 %, respectively, thereby improving the model's adaptability. The necessity of updating the component model is further analyzed, as a 1.00 % mean squared error in the component model may lead to a power deviation of 0.075 MW. This method provides real-time, adaptable support for IES data modeling and updates.

Abstract Gallstone disease (GSD) is thought to be associated with the risk of coronary heart disease (CHD) or acute myocardial infarction (AMI), which may be due to abnormal cholesterol metabolism. We used multiple Mendelian randomization (MR) methods based on publicly available genome-wide association study data to assess whether this association is genetically causal and to search for loci driving causality. Pooled data for GSD were obtained from FinnGen Biobank and Biobank Japan, while CHD and AMI were obtained as pooled data from the CARDIoGRAMplusC4D consortium. In this MR study, we found a significant negative causal effect of genetic susceptibility to GSD on AMI in the Finnish population, but no causal effect was found on CHD. This causal effect was not confounded by reverse causality and the same findings were obtained in the Japanese population. Furthermore, the negative causal effect of GSD on AMI risk may be driven by the rs4245791-regulated ABCG5/8 protein. In conclusion, the results of this MR study support a negative causal effect of GSD on AMI and suggest that rs4245791 is the causal driver locus of this effect, which provides new ideas and evidence for the prevention and etiologic study of AMI in patients with GSD.

Abstract Background Reliable pre-surgical prediction of spreading through air spaces (STAS) in primary lung cancer is essential for precision treatment and surgical decision-making. We aimed to develop and validate a dual-delta deep-learning and radiomics model based on pretreatment computed tomography (CT) image series to predict the STAS in patients with lung cancer. Method Six hundred seventy-four patients with pre-surgery CT follow-up scans (with a minimum interval of two weeks) and primary lung cancer diagnosed by surgery were retrospectively recruited from three Chinese hospitals. The training cohort and internal validation cohort, comprising 509 and 76 patients respectively, were selected from Shanghai Chest Hospital; the external validation cohorts comprised 36 and 53 patients from two other centers, respectively. Four imaging signatures (classic radiomics features and deep learning [DL] features, delta-radiomics and delta-DL features) reflecting the STAS status were constructed from the pretreatment CT images by comprehensive methods including handcrafting, 3D views extraction, image registration and subtraction. A stepwise optimized three-step procedure, including feature extraction (by DL and time-base radiomics slope), feature selection (by reproducibility check and 45 selection algorithms), and classification (32 classifiers considered), was applied for signature building and methodology optimization. The interpretability of the proposed model was further assessed with Grad-CAM for DL-features and feature ranking for radiomics features. Results The dual-delta model showed satisfactory discrimination between STAS and non-STAS and yielded the areas under the receiver operating curve (AUCs) of 0.94 (95% CI, 0.92–0.96), 0.84 (95% CI, 0.82–0.86), and 0.84 (95% CI, 0.83–0.85) in the internal and two external validation cohorts, respectively, with interpretable core feature sets and feature maps. Conclusion The coupling of delta-DL model with delta-radiomics features enriches information such as anisotropy of tumor growth and heterogeneous changes within the tumor during the radiological follow-up, which could provide valuable information for STAS prediction in primary lung cancer.

[Introduction] With the emphasis and promotion of the electricity market system construction by the government, the electricity market is constantly growing towards a deeper and more unified direction. In order to promote the electricity market construction, the influence factors of the electricity market risk and its evaluation remain to be studied further. [Method] Based on the consideration of the whole cycle of electricity market trading, this paper took pre-trade risk, during-trade risk, and post-trade riskas the entry points, integrated the existing risks in each stage of electricity market, and established the risk evaluation index system for electricity market. Based on the thought of subjective and objective weighting, analytic hierarchy process (AHP) and entropy weight method were used to assign weights to the index system respectively, and fuzzy comprehensive evaluation (FCE) was adopted to evaluate the comprehensive risk level of the electricity market. [Result] The rationality, comprehensiveness and validity of the proposed model are verified through the analysis of the calculation examples of different electricity markets. [Conclusion] The model eatablished in this paper can conduct a comprehensive risk evaluation for the electricity market, and provide a theoretical reference for the construction of the risk system of the electricity market and its future development direction.

Phosphorus (P) deficiency significantly affects crop productivity, especially legume crops. Therefore, it is important to understand the P-acquisition strategies of different leguminous crops. In this study, we undertook a pot experiment with 11 legume crops (soybean, faba bean, pea, cowpea, common bean, lentil, adzuki bean, chickpea, grass pea, red kidney bean and common vetch) to investigate P-acquisition strategies related to root morphology, organic acid and acid phosphatase exudations, and arbuscular mycorrhizal fungi (AMF) colonisation under low (4.4 mg/kg) and optimal (40 mg/kg) P conditions. The results revealed that P deficiency significantly decreased biomass and P accumulation, root length (10.5%), and root surface area (7.9%), increased organic acid exudation (80.2%) and acid phosphatase activity (16.8%), and did not affect root diameter or root AMF colonisation rate. Principal component analysis revealed a positive correlation between organic acid exudation and acid phosphatase activity, while root length and root surface area negatively correlated with organic acid exudation, acid phosphatase activity and root AMF colonisation rate. P accumulation positively correlated with root length, surface area, and diameter but negatively correlated with organic acid exudation, acid phosphatase activity, and AMF colonisation rate. These findings confirmed the following: (1) legume crops use a P-mobilisation strategy related to organic acid exudation and acid phosphatase activity to acquire P under low soil P conditions; (2) organic acid exudation coincided with acid phosphatase activity to mobilise soil inorganic and organic P, improving P accumulation; (3) a trade-off exists between the P-scavenging strategy related to root morphology traits and mobilisation strategy.

Abstract Adsorption‐based carbon capture has been recognized as an attractive method for mitigating global warming. Metal–organic frameworks (MOFs) are promising candidate adsorbents for this purpose due to their high adsorption uptake and selectivity for carbon dioxide. However, in real‐world applications, such as direct air capture, the presence of moisture in the feed gas may pose a grand challenge for CO2 adsorption in MOFs. This paper aims to address the issue of water–CO2 co‐adsorption in MOFs and present screening criteria for selecting MOFs that preferentially adsorb CO2 under humid conditions. First, we uncover a comprehensive overview of CO2–water co‐adsorption characteristics of various MOFs. Then, the high‐throughput screening methods are summarized. Both computational and experimental efforts have been dedicated to identify the promising MOFs for humid CO2 capture. According to the screening results and adsorption mechanism, the optimal preparation strategies are proposed to modulate the effect of water on CO2 uptake in MOFs. Finally, current MOF‐based CO2 capture prototypes are presented to evaluate their practical feasibility and performance. This work could offer valuable guidance for the development and application of MOFs for CO2 capture in the presence of water and inspire further research in this field.

A soil removal device for the root-soil complex of Gentian imitating the percussion function of a woodpecker was designed to improve the soil removal efficiency of harvesting devices for rhizome-type traditional Chinese herbal medicines. Based on the physical parameters of roots and the root-soil complex of Gentian, the structure parameters of the striking arm and the actual profile of the cam are determined according to the physical parameters when the woodpecker knocks on the tree. The key parameters that affect the working performance of the soil removal device and their suitable value ranges have been identified through the impact test and analysis of the root-soil complex of Gentian. The mass of the striking hammer, the swing angle of the striking arm, and the rotation speed of the cam were taken as the experimental factors and the soil removal rate and the energy consumption per hammer percussion were taken as the experimental indicators. The ternary quadratic orthogonal regression combination experiment was carried out using Design-Expert. The regression model of the influence factors and evaluation indicators was established through the analysis of variance. The interaction effects of the influence factors on the indicators were analyzed using the response surface method. Using multiobjective optimization method, the optimal parameter combination was obtained as that of the mass of the striking hammer of 0.9 kg, the swing angle of the striking arm of 47°, and the rotation speed of the cam of 100 r/min, then the soil removal rate was the maximum and the energy consumption of single-hammer knocking was the minimum, with the values of 89.12% and 31.21 J, respectively. This study can provide a reference for the design and optimization of soil removal devices for rhizome-type traditional Chinese herbal medicines.

Poor CO2 capture stability and serious elutriation are the issues commonly occur when limestone circulating in the fluidized bed-based Calcium Looping (CaL) system. Hence, three types of coal fly ash-bound (CFA-bound) limestone-derived sorbents were synthesized via mixing the limestone, calcined lime and hydrated lime with coal fly ash, respectively. The generated ternary Ca-Al-O and Ca-Si-O phases offer structural stability for CFA-bound limestone-derived sorbents and improve their cyclic CO2 capture performance. Moreover, extrusion-spheronization method was adopted to produce CFA-bound limestone and hydrated lime sorbent pellets to synergistically enhance cyclic CO2 capture capability and mechanical properties. It is found that hydrated lime is superior to limestone as the calcium precursor to prepare CaO-based sorbent pellets due to its desirable pore structure and high binding force. Therefore, the CFA-bound hydrated lime pellets containing 15 wt % of fly ash (HL/CFA15-P) exhibits a high carbonation conversion of 40 % after 17 cycles, which is nearly 1.4 times that of limestone pellets. The discrepancy on carbonation conversion between the two sorbent pellets is enlarged to ∼1.6 times after 100 cycles, which is calculated using a semi-empirical equation. Moreover, HL/CFA15-P exhibits outstanding mechanical property, whose compressive strength reaches 6±1.7 MPa, which is comparable to the cement-bound CaO-based sorbent pellets.

BackgroundExtramammary Paget’s disease (EMPD) is a rare cutaneous malignancy, commonly affecting the external genitalia and perianal area of the elderly with unclear pathogenesis. Metabolomics provides a novel perspective for uncovering the metabolic mechanisms of a verity of cancers.Materials and methodsHere, we explored the metabolome of EMPD using an untargeted strategy. In order to further investigate the potential relationship between metabolites and gene expression, we re-analyzed the gene expression microarray data (GSE117285) using differential expression analysis and functional enrichment analyses.ResultsResults showed that a total of 896 metabolites were identified and 87 metabolites including 37 upregulated and 50 downregulated significantly in EMPD were sought out. In the following feature selection analyses, four metabolites, namely, cyclopentyl fentanyl-d5, LPI 17:0, guanosine-3’,5’-cyclic monophosphate, kynurenine (KYN, high in EMPD) were identified by both random forest and support vector machine analyses. We then identified 1,079 dysfunctional genes: 646 upregulated and 433 downregulated in EMPD. Specifically, the tryptophan-degrading enzyme including indoleamine-2,3-dioxygenase-1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) were also increased. Generally, cancers exhibit a high expression of IDO1 and TDO2 to catabolize tryptophan, generating abundant KYN. Moreover, we also noticed the abnormal activation of sustaining proliferative signaling in EMPD.ConclusionIn conclusion, this study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD.

Abstract Lung cancer and liver cancer are the leading and third causes of cancer death, respectively. Both lung and liver cancer are with clear major risk factors. A thorough understanding of their burdens in the context of globalization, especially the convergences and variations among WHO regions, is useful in precision cancer prevention worldwide and understanding the changing epidemiological trends with the expanding globalization. The Global Burden of Disease (GBD) and WHO Global Health Observatory (GHO) database were analyzed to evaluate the burden metrics and risk factors of trachea, bronchus, and lung (TBL) cancer and liver cancer. Western Pacific Region (WPR) had the highest age-standardized incidence rate (ASIR) for both liver cancer (11.02 [9.62–12.61] per 100,000 population) and TBL cancer (38.82 [33.63–44.04] per 100,000 population) in 2019. Disability-adjusted life years (DALYs) for liver and TBL cancer elevated with the increasing sociodemographic index (SDI) level, except for liver cancer in WPR and TBL cancer in European Region (EUR). Region of the Americas (AMR) showed the biggest upward trends of liver cancer age-standardized rates (ASRs), as well as the biggest downward trends of TBL cancer ASRs, followed by Eastern Mediterranean Region (EMR). Alcohol use and smoking were the leading cause of liver and TBL cancer death in most WHO regions. Variances of ASRs for liver and TBL cancer among WHO memberships have been decreasing during the past decade. The homogenization and convergence of cancer burdens were also demonstrated in different agegroups and sexes and in the evolution of associated risk factors and etiology. In conclusion, our study reflects the variations and convergences in the liver and lung cancer burdens among the WHO regions with the developing globalization, which suggests that we need to be acutely aware of the global homogeneity of the disease burden that accompanies increasing globalization, including the global convergences in various populations, risk factors, and burden metrics. Graphical Abstract

Direct air capture (DAC) is one of the most potential technologies to mitigate CO2 emission. Adsorption technology is recognized as a promising CO2 capture method in view of its desirable characteristics including reusability of adsorbents and low capital investment. To further improve thermal performance, evaporation/condensation heat of vapor compression refrigeration (VCR) cycle in air condition system of buildings is adopted for adsorption/desorption process of DAC. Thermal performance of a 4-step temperature swing adsorption process (TSA) is analyzed at various adsorption/desorption temperatures by using different adsorbents. Analysis on Coefficient of Performance (COP) of VCR cycle is also conducted in search for a balance between adsorbent and refrigerant. Taking both real working capacity and COP into consideration, Mg-MOF-74&R134a is the best choice for more amounts of CO2. Real working capacity of Mg-MOF-74 is up to 0.38 mol•kg−1 at 70 °C, which is twice as much as that of zeolite 13X. While zeolite 13X&R134a shows the best performance of two cycles in view of exergy efficiency and COP, which could reach 81.9% and 7.21, respectively, at 35 °C. These matches will provide some guidelines for the practical application of the combination of DAC with heating, ventilation and air conditioning (HVAC).

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. Methods Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. Results Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. Conclusions Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Abstract Microbial contamination of plastic surfaces is a significant source of hospital‐acquired infections. To produce antimicrobial surfaces, chlorhexidine was attached to nitrided acrylonitrile butadiene styrene (ABS). The uniformity of chlorhexidine distribution on the plastic surfaces was revealed by time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) imaging. Its antimicrobial efficacy was established against model pathogenic Gram‐positive and Gram‐negative bacteria, fungi, and viruses. The stability of the bonded chlorhexidine was evaluated via a leaching test. The surfaces rapidly killed microbes: no viable colonies of Escherichia coli, Staphylococcus aureus, or Candida albicans were recoverable after 45 minutes. It was effective against SARS‐COV‐2, with no viable virions found after 30 minutes. Additionally, the surfaces were as effective in killing chlorhexidine‐resistant strains of bacteria as they were in killing naïve strains. The surface was stable; after 2 weeks of leaching, no detectable chlorhexidine was found in the leachate. We believe that the technology is widely applicable to prevent the spread of fomite infection.

Abstract Background The application of video‐assisted thoracoscopic surgery (VATS) for complex carina surgeries in treating non–small cell lung cancer (NSCLC) patients with involved carina is controversial. This study compared short‐ and medium‐term outcomes of VATS versus thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC, aiming to assess the potential benefit of VATS over thoracotomy for these patients. Methods A total of 37 consecutive NSCLC cases receiving VATS (n = 14) or thoracotomy (n = 23) for carinal lung resection with carina reconstruction from 2016 to 2021 were retrospectively identified. Baseline clinicopathological characteristics, perioperative outcomes, and survival profiles were investigated. Results Patients in the VATS and thoracotomy groups had comparable baseline clinicopathological characteristics (all p > 0.050). VATS decreased postoperative drainage volume compared with thoracotomy (1280 [1170–1510] vs. 1795 [1510–1905] mL, p = 0.012). Regarding surgical‐related pains, VATS reduced numeric rating scale scores on the postoperative day 1 (4 [3, 4] vs. 5 [4, 5], p = 0.021) and day 2 (3 [3, 4] vs. 5 [3–5], p = 0.023) than thoracotomy. No difference was found between the VATS and thoracotomy groups in other perioperative outcomes, postoperative complications, and assessment of lymph nodes (LNs) and LN stations (all p > 0.050). Moreover, patients in the two groups had comparable 3‐year disease‐free survival (DFS), overall survival (OS), and recurrence and mortality patterns. Further subgroup and Cox hazards regression analyses also observed no difference in DFS or OS between the two groups. Conclusions VATS reduced postoperative drainage volume and ameliorated surgical‐related pain, and achieved comparable medium‐term survival compared to thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC.

Major pathologic remission (MPR, residual tumor

Abstract Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53. Here, we evaluated whether hypoxia could render cancer cells insensitive to two MDM2 inhibitors with different potencies, nutlin-3a and navtemadlin. Inhibitor efficacy and potency were evaluated under short-term hypoxic conditions in human and mouse cancer cells expressing different p53 genotypes (wild-type, mutant, or null). Treatment of wild-type p53 cancer cells with MDM2 inhibitors reduced cell growth by > 75% in hypoxia through activation of the p53–p21 signaling pathway; no inhibitor-induced growth reduction was observed in hypoxic mutant or null p53 cells except at very high concentrations. The concentration of inhibitors needed to induce the maximal p53 response was not significantly different in hypoxia compared to normoxia. However, inhibitor efficacy varied by species and by cell line, with stronger effects at lower concentrations observed in human cell lines than in mouse cell lines grown as 2D and 3D cultures. Together, these results indicate that MDM2 inhibitors retain efficacy in hypoxia, suggesting they could be useful for targeting acutely hypoxic cancer cells.

Small-molecule ionic liquids (ILs) are frequently employed as efficient bulk phase modifiers for perovskite materials. However, their inherent characteristics, such as high volatility and ion migration properties, pose challenges in addressing the stability issues associated with perovskite solar cells (PSCs). In this study, we design a poly(IL) with multiple active sites, named poly[4-styrenesulfonyl(trifluoromethylsulfonyl)imide]pyridine (P[STFSI][PPyri]), as an efficient additive of perovskite materials. The S=O in the sulfonyl group chelates with uncoordinated Pb2+ and forms hydrogen bonds with the organic cations in the perovskite, suppressing the volatilization of the organic cations. The N+ in pyridine can fix halide ions through electrostatic interaction with I− and Br− ions to prevent halide ion migration. P[STFSI][PPyri] demonstrates the ability to passivate defects and suppress nonradiative recombination in PSCs. Additionally, it facilitates the fixation of organic and halide ions, thereby enhancing the device’s stability and photoelectric performance. Consequently, the introduction of P[STFSI][PPyri] as a dopant in the devices resulted in an excellent efficiency of 24.62%, demonstrating outstanding long-term operational stability, with the encapsulated device maintaining 87.6% of its initial efficiency even after 1500 h of continuous maximum power point tracking. This strategy highlights the promising potential of poly(IL) as an effective additive for PSCs, providing a combination of high performance and stability.

Coatings with different boron content were prepared by magnetic field-assisted Co-based laser metal deposition on 300 M ultra-high strength steel. The effects of boron content on the magnetic properties, mechanical properties, friction and wear properties, and corrosion resistance of the coating were investigated. The research results indicate that adding 6 wt% of boron to cobalt alloy in a 35 mT alternating magnetic field is beneficial for refining the microstructure, which can improve the mechanical properties of the coating. This research also discusses the effect of boron content on the wear and corrosion resistance of the coating. The results show that adding boron content enhances the magnetostrictive effect, and reduces the elastic modulus of the laser metal deposition coating while ensuring its hardness, thereby improving the wear and corrosion resistance of the laser metal deposition layer. The hardness of the coating can reach 1215 HV. The friction coefficient and corrosion current density of the coating are reduced by 26.9% and 60.2% respectively compared with the substrate. This work can help promote the application of laser metal deposition technology, reduce costs, and ensure performance.

The fallback disk model is widely accepted to explain long-period neutron stars (NSs) that cannot be simulated by magnetic dipole radiation. However, there was no confirmed detection of disks from the newly discovered long-period pulsars GLEAM-X 162759.5-523504.3 and GPM J1839-10 and the slowest known isolated NS 1E 161348-5055. This might be because the disks have either been in a noninteracting/inactive state where their emission is too weak to be detected or have been disrupted. In this work, we conduct simulations to examine the lifetime of supernova fallback disks around isolated NSs. We assume that the disks' mass varies in a self-similar way, and their interaction with the NS occurs only in an interacting/active state. Our results reveal that nearly all the interacting lifetimes for the disks are shorter than 10 ^5 yr, while the existence lifetimes are considerably longer.

PSR J1012+5307 is a millisecond pulsar with an extremely low-mass white dwarf (WD) companion in an orbit of 14.5 hr. Magnetic braking (MB) plays an important role in influencing the orbital evolution of binary systems with a low-mass (≲1–2 M _⊙ ) donor star. At present, there exist several different MB descriptions. In this paper, we investigate the formation of PSR J1012+5307 as a probe to test plausible MB models. Employing a detailed stellar evolution model with the MESA code, we find that the convection- and rotation-boosted MB and “Intermediate” MB models can reproduce the WD mass, WD radius, WD surface gravity, neutron star mass, and orbital period observed in PSR J1012+5307. However, our simulated WD has a higher effective temperature than the observations. Three other MB mechanisms, including the standard MB model, are too weak to account for the observed orbital period in the Hubble time. A long cooling timescale caused by H-shell flashes of the WD may alleviate the discrepancy between the simulated effective temperature and the observed value.

Coronary artery disease is a leading cause of death worldwide. Major adverse cardiac events are associated not only with coronary luminal stenosis but also with atherosclerotic plaque components. Coronary computed tomography angiography (CCTA) enables non-invasive evaluation of atherosclerotic plaque along the entire coronary tree. However, precise and efficient assessment of plaque features on CCTA is still a challenge for physicians in daily practice. Artificial intelligence (AI) refers to algorithms that can simulate intelligent human behavior to improve clinical work efficiency. Recently, cardiovascular imaging has seen remarkable advancements with the use of AI. AI-assisted CCTA has the potential to facilitate the clinical workflow, offer objective and repeatable quantitative results, accelerate the interpretation of reports, and guide subsequent treatment. Several AI algorithms have been developed to provide a comprehensive assessment of atherosclerotic plaques. This review serves to highlight the cutting-edge applications of AI-assisted CCTA in atherosclerosis plaque characterization, including detecting obstructive plaques, assessing plaque volumes and vulnerability, monitoring plaque progression, and providing risk assessment. Finally, this paper discusses the current problems and future directions for implementing AI in real-world clinical settings.

Benefitting from lightweight, high strength, long life, and green recyclability, continuous fiber reinforced thermoplastic composite (CFTPC) pipes have attracted extensive interest, especially in the on-orbit additive manufacturing of structural components. However, the preparation of CFTPC pipes remains challenging due to the on-orbit limited space and high processing temperature of thermoplastic resin. Here, we report an effective approach for high performance carbon fiber/polyether-ether-ketone (CF/PEEK) thin-walled pipes via bidirectional reinforcement using the pultrusion-winding technique. The continuous fabrication of thin-walled pipes can be achieved, but the limitation by the size of core mold is also broken. The compressive and shear performance of CF/PEEK pipes with different layer designs have been studied based on experiments and simulations. With the increase in axial prepreg tape layer, the resultant CF/PEEK pipes exhibit greatly improved axial compression strength. The finite element analysis indicates that the maximum axial stress is decreased due to the axial enhancement. The flexural strength is greatly proved with pultrusion–winding cycles. The simulation confirms that the circumferential strain is effectively reduced. The high performance of bidirectional reinforced CF/PEEK pipes and the facile controllability of this approach highlight their suitability for utilization in on-orbit manufacturing of large-scale structures.

Black hole (BH) ultracompact X-ray binaries (UCXBs) are potential Galactic low-frequency gravitational wave (GW) sources. As an alternative channel, BH UCXBs can evolve from BH+He star binaries. In this work, we perform a detailed stellar evolution model for the formation and evolution of BH UCXBs evolving from the He star channel to diagnose their detectability as low-frequency GW sources. Our calculations found that some nascent BH+He star binaries after the common-envelope (CE) phase could evolve into UCXB-LISA sources with a maximum GW frequency of ∼5 mHz, which can be detected in a distance of 10 kpc (or 100 kpc). Once BH+He star systems become UCXBs through mass transfer, they would emit X-ray luminosities of ∼10 ^38 erg s ^−1 , making them ideal multimessenger objects. If the initial He-star masses are ≥0.7 M _⊙ , those systems are likely to experience two Roche lobe overflows, and the X-ray luminosity can reach a maximum of 3.5 × 10 ^39 erg s ^−1 in the second mass-transfer stage. The initial He-star masses and initial orbital periods of progenitors of Galactic BH UCXB-LISA sources are in the range of 0.32–2.9 M _⊙ and 0.02–0.19 days, respectively. Nearly all BH+He star binaries in the above parameter space can evolve into GW sources whose chirp masses can be accurately measured. Employing a population synthesis simulation, we predict the birthrate and detection number of Galactic BH UCXB-LISA sources evolving from the He star channel are R = 2.2 × 10 ^−6 yr ^−1 and 33 for an optimistic CE parameter, respectively.

Familial hypercholesterolemia (FH) is a common hereditary cholesterol metabolic disease that usually leads to an increase in the level of low-density lipoprotein cholesterol in plasma and an increase in the risk of cardiovascular disease. The lack of disease screening and diagnosis often results in FH patients being unable to receive early intervention and treatment, which may mean early occurrence of cardiovascular disease. Thus, more requirements for FH identification and management have been proposed. Recently, machine learning (ML) has made great progress in the field of medicine, including many innovative applications in cardiovascular medicine. In this review, we discussed how ML can be used for FH screening, diagnosis and risk assessment based on different data sources, such as electronic health records, plasma lipid profiles and corneal radian images. In the future, research aimed at developing ML models with better performance and accuracy will continue to overcome the limitations of ML, provide better prediction, diagnosis and management tools for FH, and ultimately achieve the goal of early diagnosis and treatment of FH.

Key Clinical Message A 31‐year‐old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of alprazolam. Abstract Alprazolam is a widely used antidepressant and antianxiety drug. Mild to moderate side effect of alprazolam was commonly seen, including lethargy, dizziness, headache, dry mouth, nausea, fatigue, constipation, and blurred vision. In this case, we reported a patient developed black hairy tongue after alprazolam intake, and her symptom resolved after 10‐day discontinuation of alprazolam. This rare adverse event should be of concern to clinicians. This is the first paper to report an alprazolam‐induced BHT. This rare side effect of alprazolam should be concern of clinicians; we hope our report will promote the understand of BHT and acknowledge clinicians of this rare side effect of alprazolam.

Summary: Background: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. Methods: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human–AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. Findings: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969–0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738–0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497–0·554) and 0·799 (0·778–0·822), respectively. In the human–AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383–0·633) and 0·800 (0·700–0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345–0·411) and top-3 accuracy by 13·0% (0·545–0·616). Interpretation: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Background and aimsFamilial hypercholesterolemia (FH) is becoming a global burden. However, it remains underdiagnosed and undertreated worldwide. This study aimed to observe the screening rate of FH patients and department distribution among hospitalized patients using different diagnostic criteria.MethodsA total of 45,410 inpatients with LDL-C ≥3.5 mmol/L between 2008 and 2019 were included from The Second Affiliated Hospital of Nanchang University. Inpatients are diagnosed and divided into groups by Dutch Lipid Clinic Network (DLCN) criteria, Chinese-modified DLCN criteria and Chinese expert consensus (CEC) criteria.ResultsThere were 172, 1,076 and 115 inpatients included in the DLCN group, Chinese-modified DLCN group and CEC group, respectively (screening rates: 0.38%, 2.37% and 0.25%). These FH patients had a very high risk of atherosclerotic cardiovascular disease (ASCVD) (55.7%–74.4%), especially in the DLCN group and CEC group (70.4%–74.4%). More than half of the patients were in the Department of Cardiology, and other high-risk departments included Neurology, Nephrology, Vascular Surgery, Otolaryngology & Head Neck Surgery and Traditional Chinese Medicine (24.35%–31.51%). Overall, hypertension, coronary heart disease, carotid arteriosclerosis, hepatic cyst, arrhythmia, and nonalcoholic fatty liver disease were common accompanying diseases with FH.ConclusionsIt is necessary to establish appropriate diagnostic criteria and more positive treatment strategies for the FH inpatient population. In addition, promoting awareness of FH among doctors from other departments is also necessary. Therefore, developing a comprehensive management strategy for FH disease is very important.

BackgroundNeoadjuvant immunochemotherapy has been increasingly applied to treat non-small cell lung cancer (NSCLC). However, the comparison between robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the feasibility and oncological efficacy following neoadjuvant immunochemotherapy is scarce. This study aims to assess the superiorities of RATS over (VATS) concerning short-term outcomes in treating NSCLC patients with neoadjuvant immunochemotherapy.MethodsNSCLC patients receiving RATS or VATS lobectomy following neoadjuvant immunochemotherapy at Shanghai Chest Hospital from 2019 to 2022 were retrospectively identified. Baseline clinical characteristics, perioperative outcomes, and survival profiles were analyzed.ResultsForty-six NSCLC patients with neoadjuvant immunochemotherapy were included and divided into the RATS (n=15) and VATS (n=31) groups. The baseline clinical characteristics and induction-related adverse events were comparable between the two groups (all p>0.050). The 30-day mortality in the RATS and VATS groups were 0% and 3.23%, respectively (p=1.000). Patients undergoing RATS were associated with reduced surgical-related intensive unit care (ICU) stay than those receiving VATS (0.0 [0.0-0.0] vs. 0.0 [0.0-1.0] days, p=0.026). Moreover, RATS assessed more N1 LNs (6.27 ± 1.94 vs 4.90 ± 1.92, p=0.042) and LN stations (3.07 ± 1.03 vs 2.52 ± 0.57, p=0.038) compared with VATS. By comparison, no difference was found in surgical outcomes, pathological results, and postoperative complications between the RATS and VATS groups (all p>0.050). Finally, RATS and VATS achieved comparable one-year recurrence-free survival (82.96% vs. 85.23%, p=0.821) and the timing of central nervous system, LN, and bone recurrences (all p>0.050).ConclusionRATS is safe and feasible for NSCLC patients with neoadjuvant immunochemotherapy, reducing surgical-related ICU stay, assessing increased N1 LNs and stations, and achieving similar survival profiles to VATS.

Abstract Silver (Ag)-containing agents or materials are widely used today in plant protection for their antimicrobial activity. In view of the superior inhibitory ability of biosynthesized (aldehyde-modified sodium alginate based) silver nanoparticles (AgNPs) against plant pathogenic fungi in our previous research, here we explored the antagonistic effect of biosynthesized AgNPs on plant pathogenic bacteria and the underlying mechanism. We selected Pseudomonas syringae pv. tabaci, the causal agent of tobacco wildfire disease, as the target and found that 1.2 μg/mL biosynthesized AgNPs completely inhibited the growth of P. syringae pv. tabaci in vitro and in vivo by partly destroying the cell membrane structure of the pathogen, resulting in cytoplasmic leakage. Moreover, Nicotiana benthamiana treated with 1.2 μg/mL biosynthesized AgNPs exhibited a significant upregulation of nonexpressor of pathogenesis-related genes 1 (NPR1) and pathogenesis-related gene 2 (PR2), the typical markers of the salicylic acid (SA)-mediated defense system, and an increase in peroxidase (POD) and polyphenol oxidase (PPO) activities as well as the production of reactive oxygen species (ROS). Furthermore, biosynthesized AgNPs treatment increased the chlorophyll content and dry weight of N. benthamiana. Overall, we demonstrated that biosynthesized AgNPs at a low concentration have high inhibitory effect on the pathogen causing tobacco wildfire disease by destroying bacterial cell membrane and inducing defense resistance in host plant. These results lay a theoretical foundation for further application of biosynthesized AgNPs in the control of plant bacterial diseases.

Abstract Background and aims The role of serum lipoprotein(a) [Lp(a)] levels in atrial fibrillation (AF) is still uncertain, especially in the Chinese population. Here, we aimed to elucidate the potential relationship between Lp(a) quantiles and AF. Methods All data were collected through inpatients with electronic health records from the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The propensity score matching (PSM) method was used to match control and case groups. Interactions between AF, Lp(a) quantiles, and other clinical indices were analyzed by logistic regression and stratified analysis. Statistical analyses were performed with IBM SPSS statistical software and R software. Results From 2017 to 2021, 4,511 patients with AF and 9,022 patients without AF were 1:2 matched by the propensity score matching method. A total of 46.9% of the study group was women, and the baseline mean age was 65 years. The AF group exhibited lower median Lp(a) than the non-AF group (15.95 vs. 16.90 mg/dL; P 32.42 mg/dL). The AF prevalence of each group decreased from 34.2% (Q1) to 30.9% (Q4) (P

Measurement(s) mRNA Expression Technology Type(s) spatial transcriptomics Sample Characteristic - Organism Homo sapiens