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Abstract Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.

Abstract. Background:. Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. Methods:. We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. Results:. Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9–34.5%) and 43.8% (95% CI, 28.3–59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. Conclusion:. The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. Trial Registration:. ClinicalTrials.gov, NCT02879526.

Abstract Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.

Abstract Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.

Abstract Drug resistance remains a significant challenge in the treatment of pancreatic cancer. The development of drug-resistant cell lines is crucial to understanding the underlying mechanisms of resistance and developing novel drugs to improve clinical outcomes. Here, a novel pancreatic cancer cell line, PDAC-X1, derived from Chinese patients has been established. PDAC-X1 was characterized by the immune phenotype, biology, genetics, molecular characteristics, and tumorigenicity. In vitro analysis revealed that PDAC-X1 cells exhibited epithelial morphology and cell markers (CK7 and CK19), expressed cancer-associated markers (E-cadherin, Vimentin, Ki-67, CEA, CA19-9), and produced pancreatic cancer-like organs in suspension culture. In vivo analysis showed that PDAC-X1 cells maintained tumorigenicity with a 100% tumor formation rate. This cell line exhibited a complex karyotype, dominated by subtriploid karyotypes. In addition, PDAC-X1 cells exhibited intrinsic multidrug resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil, and oxaliplatin. In conclusion, the PDAC-X1 cell line has been established and characterized, representing a useful and valuable preclinical model to study the underlying mechanisms of drug resistance and develop novel drug therapeutics to improve patient outcomes.

Abstract Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson’s (STAB1, KCNA10), Alzheimer’s (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson’s. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.

Abstract Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy with complex heterogeneity within epithelial cells, which plays a crucial role in tumor progression and immune regulation. Yet, the clinical importance of the malignant epithelial cell-related genes (MECRGs) in ccRCC remains insufficiently understood. This research aims to undertake a comprehensive investigation into the functions and clinical relevance of malignant epithelial cell-related genes in ccRCC, providing valuable understanding of the molecular mechanisms and offering potential targets for treatment strategies. Using data from single-cell sequencing, we successfully identified 219 MECRGs and established a prognostic model MECRGS (MECRGs’ signature) by synergistically analyzing 101 machine-learning models using 10 different algorithms. Remarkably, the MECRGS demonstrated superior predictive performance compared to traditional clinical features and 92 previously published signatures across six cohorts, showcasing its independence and accuracy. Upon stratifying patients into high- and low-MECRGS subgroups using the specified cut-off threshold, we noted that patients with elevated MECRGS scores displayed characteristics of an immune suppressive tumor microenvironment (TME) and showed worse outcomes after immunotherapy. Additionally, we discovered a distinct ccRCC tumor cell subtype characterized by the high expressions of PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) and SAA1 (Serum Amyloid A1), which we further validated in the Renji tissue microarray (TMA) cohort. Lastly, ‘Cellchat’ revealed potential crosstalk patterns between these cells and other cell types, indicating their potential role in recruiting CD163 + macrophages and regulatory T cells (Tregs), thereby establishing an immunosuppressive TME. PLOD2 + SAA1 + cancer cells with intricate crosstalk patterns indeed show promise for potential therapeutic interventions.

Abstract Background Granular flows are common on the Qinghai–Tibet Plateau and the Hengduan Mountains in China, and their dynamic process processes have obvious erosional and entrainment effects. On the one hand, the volume of the granular flow increases by a factor of several or ten, which significantly increases its ability to cause a catastrophe; on the other hand, the eroded loose material affects the granular flow dynamics process and changes its state of motion. Methods In this paper, the dynamic mechanism of granular flow erosion and entrainment is investigated by DEM simulation. Purpose The effects of different substrate materials and substrate boundary conditions on granular flow erosion and entrainment are analyzed, and the effects of material mixing caused by erosion and entrainment on the state of motion of granular flow are discussed. It was verified that the kinetic mechanisms of granular flow erosion and entrainment includes impact erosion, ploughing, and shear abrasion. Results And discovered that small matrix particle size, small matrix boundary friction, and small matrix thickness lead to stronger ploughing and shear abrasion; Large matrix fractal dimensions result in stronger ploughing and weaker shear abrasion, and the granular flow does not entrain large amounts of material to the accumulation zone. Meanwhile, the dynamics of erosion and entrainment of granular flow were investigated, and the results showed that: 1. The greater the erosion rate, the greater the velocity and kinetic energy of the granular flow, the greater the distance traveled, and the smaller the apparent friction angle (i.e., the greater the mobility). 2. The amount of small granules in a granular flow changes its fluidity, the more small granules there are, the more fluid it is. 3. The fit reveals that the substrate fractal dimension has the strongest effect on the velocity and kinetic energy of granular flow, followed by substrate thickness and substrate boundary friction.

Abstract Purpose To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey. Methods In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings. Results After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values

Complex formation structures lead to significant differences in the failure mechanisms of hobs. WC-reinforced medium entropy composite coatings exhibit excellent comprehensive properties. However, the wear mechanism of coatings in different formation structures is still unclear. In this study, FeNiCr-WCx (x = 0, 40, 50, 60 wt%) composite coatings were prepared on the surface of H13 steel using laser cladding technology. The friction and wear mechanism of FeNiCr-WC composite coatings under different friction pair conditions was discussed. The results show that FeNiCr-WC composite coatings mainly consist of reinforced phase, lamellar eutectic structure and solid solution phase. As the WC content increases, the content of M6C and carbide phases in these coatings increases. The average microhardness of 40WC, 50WC and 60WC coatings is 3.28 times, 3.61 times and 4.20 times that of H13 steel, respectively. The wear rates of 40WC, 50WC and 60WC coatings are respectively about 0.25, 0.10 and 0.06 times that of FeNiCr coating under Al2O3 friction pair conditions. Three-body wear and oxidation wear mainly occurred on the surface of FeNiCr-WC composite coatings. The wear rates of 40WC, 50WC and 60WC coatings are respectively about 0.34, 0.35 and 0.16 times that of FeNiCr coating under Si3N4 friction pair conditions. Glaze layers with high Si content were formed on the surface of 50WC and 60WC coatings. The glaze layer is prone to cracking and peeling, resulting in increased wear rates for both coatings. As the hardness of the coating increases, the GCr15 friction pair undergoes severe abrasive wear.

Controlling repeated thermal cycling is one of the key mechanisms to design microstructures in the interlayer regions for narrow gap laser wire filling welding (NGLWFW) of austenite stainless steels. Herein, the optimization of process parameters for individual layers is tailored to customize the molten pool morphology during the NGLWFW process, facilitating precise control over the microstructure and, consequently, enhancing both mechanical properties and corrosion resistance of the joint. The results showed that the molten pool morphology acquired by simulation are obviously diverse from the bottom zone (BZ), middle zone (MZ) to upper zone (UZ) of the welded joint ascribed to the high heat accumulation effect, leading to the variation of microstructure. At BZ, the combination of smaller grain size and reduced dendrite spacing reduce the number of corrosion sites and promote the formation of a denser and more uniform corrosion product layer. Additionally, the diverse grain orientation, characterized by lower texture strength, facilitated a more uniform distribution of elements. Furthermore, the significantly higher content of δ-ferrite showing smallish shape disrupted the directional growth of austenite columnar grains, contributing to the excellent corrosion resistance observed at the BZ.

In the case of electrical contact, copper alloys are often unable to withstand arc ablation and premature failure. To solve this issue, Ni-8wt.%Al (Ni–8Al) coatings were successfully prepared on copper substrates utilizing the high-speed laser cladding. In addition, the microstructure evolution, microhardness, electric conductivity and arc ablation resistance of the prepared coatings were investigated in detail. As a result, the achieved Ni–8Al coatings were structurally dense with good metallurgical bonding to the substrate, of which the microstructure showed a bottom-up evolution of fine sub-grain structure. Notably, the microhardness of the coating was 191.7 HV0.2, representing an increase of 82.57% compared to the substrate, and the electrical conductivity was 18.03 %IACS, approaching that of pure nickel. Additionally, the increase in ablation currents led to changes in the ablation behaviors and failure mechanisms of both the substrate and coating. At high currents, a huge arc ablation crater appeared in the center of the substrate due to the reaction force of the anode flame and the difference in surface tension between the liquid metal at the center and the edge of the molten pool. Nevertheless, the coatings showed better arc ablation resistance due to the improvement of molten pool stability during arc ablation by the in situ formed Al2O3 layer on the coating surface.

Abstract Wind power prediction for newly built wind farms is usually faced with the problem of no sufficient historical data. To efficiently extract the useful features from related wind farms, a novel transfer learning method based on temporal convolutional network (TCN)‐Bi‐long short‐term memory (LSTM) with dynamic loss weights is proposed. Firstly, a novel multi‐task TCN‐Bi‐LSTM model is designed to extract common features. The separate TCNs, and common Bi‐LSTM layers of the proposed model are designed to extract the temporal features from related wind farms. Secondly, in the pre‐training stage, to optimize the training process of the neural networks, a dynamic loss‐weighting strategy is proposed for multi‐task learning (MTL) to select the most related features, which increase the prediction accuracy by providing a suitable optimization object. Thirdly, the multi‐task TCN‐Bi‐LSTM model is re‐trained based on the samples from the target wind farm. Finally, a dataset of seven wind farms was employed to evaluate the efficiency of the proposed MTL structure and the dynamic loss‐weighting strategy. The result shows that the root mean squared error of the 12‐h short‐term prediction can be decreased by 4.19% compared with the traditional single‐task learning model, which verifies the validity of the proposed multi‐task transfer learning method.

Poverty threatens human development especially for developing countries, so ending poverty has become one of the most important United Nations Sustainable Development Goals (SDGs). This study aims to explore China’s progress in poverty reduction from 2016 to 2019 through time-series multi-source geospatial data and a deep learning model. The poverty reduction efficiency (PRE) is measured by the difference in the out-of-poverty rates (which measures the probability of being not poor) of 2016 and 2019. The study shows that the probability of poverty in all regions of China has shown an overall decreasing trend (PRE = 0.264), which indicates that the progress in poverty reduction during this period is significant. The Hu Huanyong Line (Hu Line) shows an uneven geographical pattern of out-of-poverty rate between Southeast and Northwest China. From 2016 to 2019, the centroid of China’s out-of-poverty rate moved 105.786 km to the northeast while the standard deviation ellipse of the out-of-poverty rate moved 3 degrees away from the Hu Line, indicating that the regions with high out-of-poverty rates are more concentrated on the east side of the Hu Line from 2016 to 2019. The results imply that the government’s future poverty reduction policies should pay attention to the infrastructure construction in poor areas and appropriately increase the population density in poor areas. This study fills the gap in the research on poverty reduction under multiple scales and provides useful implications for the government’s poverty reduction policy.

Abstract Cardiac‐cerebral vascular diseases (CCVDs) are acknowledged as a major threat to public health, leading to more than one‐third of all deaths worldwide. The complex anatomical structure and immune features of blood vessels significantly affect the development of CCVDs, and magnetic resonance angiography (MRA) is one of the main diagnostic approaches for the accurate diagnosis and prognosis of CCVDs. However, MRA suffers from intrinsic problems derived from its blood flow‐dependency, and the clinical Gd‐chelating contrast agents are limited by their rapid vascular extravasation. Over the past decade, spurred on by nanoscience and nanotechnology, numerous contrast agents based on magnetic nanomaterials have been developed to enhance the contrast of MRA, with these including iron oxide nanoparticles, rare earth‐doped nanoparticles, and metal‐organic coordination polymers. The molecular MR imaging of vasculopathy using specific nanoprobes has been explored to obtain a better understanding of the molecular aspects of CCVDs. In this review, the state of the art in MRA nanoprobes is introduced, and recent achievements in the diagnosis of CCVDs using MR imaging are summarized. Additionally, the future prospects and limitations of MRA based on nanoprobes are discussed. The current review provides methodological designs and ideas for subsequent MRA nanoprobes.

Abstract Transition metal chalcogenides have been identified as low-cost and efficient electrocatalysts to promote the hydrogen evolution reaction in alkaline media. However, the identification of active sites and the underlying catalytic mechanism remain elusive. In this work, we employ operando X-ray absorption spectroscopy and near-ambient pressure X-ray photoelectron spectroscopy to elucidate that NiS undergoes an in-situ phase transition to an intimately mixed phase of Ni3S2 and NiO, generating highly active synergistic dual sites at the Ni3S2/NiO interface. The interfacial Ni is the active site for water dissociation and OH* adsorption while the interfacial S acts as the active site for H* adsorption and H2 evolution. Accordingly, the in-situ formation of Ni3S2/NiO interfaces enables NiS electrocatalysts to achieve an overpotential of only 95 ± 8 mV at a current density of 10 mA cm−2. Our work highlighted that the chemistry of transition metal chalcogenides is highly dynamic, and a careful control of the working conditions may lead to the in-situ formation of catalytic species that boost their catalytic performance.

Abstract How to effectively utilize renewable energy and improve the economic efficiency of microgrid system and its ability to consume renewable energy has become one of the main problems facing China at present. In response to this challenge, this paper establishes a multiobjective capacity optimization model with the minimum levelized cost of energy, the maximum proportion of renewable energy consumption, and the minimum comprehensive system cost. Based on this model, a new improved beluga whale optimization algorithm is proposed to solve the multiobjective optimization problem in the capacity allocation process of wind–solar–storage microgrid system with the goal of ensuring that the microgrid can meet the maximum load demand at different moments throughout the year. In this paper, opposition‐based learning, artificial bee colony, dynamic opposite, and beluga whale optimization are combined to improve the population diversity and convergence accuracy, thereby enhancing the optimization performance of the algorithm. Finally, after finding the optimal Pareto front solution, the Technique for Order Preference by Similarity to an Ideal Solution is used to help decision‐makers select the optimal solution. Using real load data and meteorological data, the results of this paper show that the multiobjective capacity allocation optimization method of grid‐connected scenic storage microgrid system based on the improved beluga whale optimization algorithm can improve the economics of the wind–solar–storage microgrid system and promote the photovoltaic consumption simultaneously, providing a solution for the realization of low‐carbon power and regional economic development. The best‐found levelized cost of energy for the wind–solar–storage microgrid system is 0.192 yuan/kWh.

Abstract Acrossocheilus fasciatus is a stream-dwelling fish species of the Barbinae subfamily. It is valued for its colorfully striped appearance and delicious meat. This species is also characterized by apparent sexual dimorphism and toxic ovum. Biology and aquaculture researches of A. fasciatus are hindered by the lack of a high-quality reference genome. Here, we report chromosome-level genome assemblies of the male and female A. fasciatus. The HiFi-only genome assemblies for both female and male individuals were 899.13 Mb (N50 length of 32.58 Mb) and 885.68 Mb (N50 length of 33.06 Mb), respectively. Notably, a substantial proportion of the assembled sequences, accounting for 96.15% and 98.35% for female and male genomes, respectively, were successfully anchored onto 25 chromosomes utilizing Hi-C data. We annotated the female assembly as a reference genome and identified a total of 400.62 Mb (44.56%) repetitive sequences, 27,392 protein-coding genes, and 35,869 ncRNAs. The high-quality male and female reference genomes will provide genomic resources for developing sex-specific molecular markers, inform single-sex breeding, and elucidate genetic mechanisms of sexual dimorphism.

Abstract This study analyzed two glass eye beads discovered in an ancient tomb complex at Dongxin Furniture Square in Datong, Shanxi Province in China. The tomb complex was dated to the Northern Wei Dynasty (398–494 AD), when Datong was known as Pingcheng. We used scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) as well as a 3D microscope system with ultra-depth of field to conduct non-destructive tests on the beads. We examined the beads’ manufacturing techniques, including matrices, eye patterns, and bead holes. The composition analysis revealed that both beads belonged to the mix of v-Na-Ca and m-Na-Al glass system, which is a key indicator of local production in Java. The bases were colored using Co2+, whereas the white, red, and yellow colors of the eye patterns were achieved using SnO2, Cu2O, or Cu0, and PbSnO3, respectively. These findings indicated that both objects were Jatim beads originating in the Kingdom of Java in Southeast Asia. This study provides valuable insights into ancient trade routes between different regions and offers reliable scientific evidence of the glass trade and technical exchanges in ancient times.

Abstract Background Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. Methods The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. Results The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. Conclusion COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

In the context of repositories for nuclear waste, understanding the behavior of gas migration through clayey rocks with inherent anisotropy is crucial for assessing the safety of geological disposal facilities. The primary mechanism for gas breakthrough is the opening of micro-fractures due to high gas pressure. This occurs at gas pressures lower than the combined strength of the rock and its minimum principal stress under external loading conditions. To investigate the mechanism of microscale mode-I ruptures, it is essential to incorporate a multiscale approach that includes subcritical microcracks in the modeling framework. In this contribution, we derive the model from microstructures that contain periodically distributed microcracks within a porous material. The damage evolution law is coupled with the macroscopic poroelastic system by employing the asymptotic homogenization method and considering the inherent hydro-mechanical (HM) anisotropy at the microscale. The resulting permeability change induced by fracture opening is implicitly integrated into the gas flow equation. Verification examples are presented to validate the developed model step by step. An analysis of local macroscopic response is undertaken to underscore the influence of factors such as strain rate, initial damage, and applied stress, on the gas migration process. Numerical examples of direct tension tests are used to demonstrate the model's efficacy in describing localized failure characteristics. Finally, the simulation results for preferential gas flow reveal the robustness of the two-scale model in explicitly depicting gas-induced fracturing in anisotropic clayey rocks. The model successfully captures the common behaviors observed in laboratory experiments, such as a sudden drop in gas injection pressure, rapid build-up of downstream gas pressure, and steady-state gas flow following gas breakthrough.

Abstract The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T‐ALL, ALAL, AML, and B‐ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low‐dose Ara‐C, granulocyte colony‐stimulating factor (G‐CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long‐term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.

Abstract In eukaryotes, the nuclear membrane that encapsulates genomic DNA is composed of an inner nuclear membrane (INM), an outer nuclear membrane (ONM), and a perinuclear space. SUN proteins located in the INM and KASH proteins in the ONM form the SUN-KASH NM-bridge, which functions as the junction of the nucleocytoplasmic complex junction. Proteins containing the SUN domain showed the highest correlation with differentially accumulated proteins (DAPs) in the wheat response to fungal stress. To understand the characteristics of SUN and its associated proteins in wheat responding to pathogen stress, here we investigated and comprehensive analyzed SUN- and KASH-related proteins among the DAPs under fungi infection based on their conserved motifs. In total, four SUN proteins, one WPP domain-interacting protein (WIP), four WPP domain-interacting tail-anchored proteins (WIT), two WPP proteins and one Ran GTPase activating protein (RanGAP) were identified. Following transient expression of Nicotiana benthamiana, TaSUN2, TaRanGAP2, TaWIT1 and TaWIP1 were identified as nuclear membrane proteins, while TaWPP1 and TaWPP2 were expressed in both the nucleus and cell membrane. RT-qPCR analysis demonstrated that the transcription of TaSUN2, TaRanGAP2 and TaWPP1 were strongly upregulated in response to fungal infection. Furthermore, using the bimolecular fluorescence complementation, the luciferase complementation and a nuclear and split-ubiquitin-based membrane yeast two-hybrid systems, we substantiated the interaction between TaSUN2 and TaWIP1, as well as TaWIP1/WIT1 and TaWPP1/WPP2. Silencing of TaSUN2, TaRanGAP2 and TaWPP1 in wheat leaves promoted powdery mildew infection and hyphal growth, and reduced the expression of TaBRI1, TaBAK1 and Ta14-3–3, indicating that these NM proteins play a positive role in resistance to fungal stress. Our study reveals the characteristics of NM proteins and propose the preliminary construction of SUN-WIP-WPP-RanGAP complex in wheat, which represents a foundation for detail elucidating their functions in wheat in future.

Abstract Loess areas, such as the Loess Plateau, are characterized by a fragile ecological environment, high soil erosion, and frequent geological disasters due to the unique hydrological properties of loess (e.g., collapsibility and permeability). Therefore, the loess must be stabilized for use in engineering construction. Traditional stabilizers (lime, cement, and fly ash) cause environmental problems, such as soil salinization and greenhouse gas emissions. Therefore, this study investigated the effect of nanosilica on the hydrological properties of loess and the microscopic mechanism. Different nanosilica contents (0.2%, 0.4%, 0.8%, 1%, and 3%) were added to loess sample, and the particle size distribution, Atterberg limits, collapsibility, and soil water characteristics were analyzed. The results revealed the following. The addition of nanosilica changed the particle size distribution, liquid limit, plastic limit, and plasticity index of loess. After the addition of nanosilica with different contents, the loess collapsibility coefficient curve shifted downward, the soil water retention curve shifted upward, and the unsaturated permeability coefficient curve shifted downward. The pores between particles were filled, and the number of large and medium pores and the pore connectivity were lower after the nanosilica addition. The surface of the coarse particles adsorbed more fine particles, and a large number of micro-aggregates or clay aggregates were present in the pores between particles. In conclusion, the environmentally friendly material nanosilica can be used to improve the hydrological properties of loess, which is applicable to alleviating soil erosion and preventing geological disasters on the Loess Plateau.

Abstract Background The prognosis of advanced ovarian cancer is often poor. Although there are several treatment options for stage IV epithelial ovarian cancer, it is not clear which treatment will benefit the patient’s prognosis.We conducted an analysis using the SEER database to compare the impact of different treatment modalities on the prognosis of advanced ovarian cancer. Methods The present study conducts a retrospective analysis of relevant data from the SEER database pertaining to patients diagnosed with stage IV epithelial ovarian cancer between 2011 and 2020 (n = 5345). Statistical methods including Kaplan-Meier curves, log-rank tests, and Cox regression analysis are employed to ascertain the impact of different treatment regimens on the prognosis of patients with stage IV epithelial ovarian cancer. Results Among patients with stage IV epithelial ovarian cancer, age ≥ 60 and the presence of lung metastases or multiple metastases were identified as poor prognostic factors. Conversely, being Asian or Pacific Islander, married, and testing negative for CA125 were associated with favorable prognoses. In terms of the choice of treatment for patients, surgery plus chemotherapy was the best treatment modality, and timely surgery could significantly improve the prognosis of patients, but there was no difference between chemoradiotherapy alone and the surgery group among patients with lung metastases. Conclusion The prognosis of patients with stage IV epithelial ovarian cancer is influenced by many factors. In terms of the choice of treatment, patients with surgery plus chemotherapy have the best prognosis. In cases where lung metastases are inoperable, a combination of radiotherapy and chemotherapy can be used. In other cases, radiotherapy does not improve outcomes in patients with stage IV epithelial ovarian cancer. This study provides a basis for the choice of treatment for patients with stage IV epithelial ovarian cancer.

Abstract Raphidioptera (snakeflies) are a holometabolan order with the least species diversity but play a pivotal role in understanding the origin of complete metamorphosis. Here, we provide an annotated, chromosome-level reference genome assembly for an Asian endemic snakefly Mongoloraphidia duomilia (Yang, 1998) of the family Raphidiidae, assembled using PacBio HiFi and Hi-C data from female specimens. The resulting assembly is 653.56 Mb, of which 97.90% is anchored into 13 chromosomes. The scaffold N50 is 53.50 Mb, and BUSCO completeness is 97.80%. Repetitive elements comprise 64.31% of the genome (366.04 Mb). We identified 599 noncoding RNAs and predicted 11,141 protein-coding genes in the genome (97.70% BUSCO completeness). The new snakefly genome will facilitate comparison of genome architecture across Neuropterida and Holometabola and shed light on the ecological and evolutionary transitions between Neuropterida and Coleopterida.

Abstract Background Multicenter non-small cell lung cancer (NSCLC) patient data is information-rich. However, its direct integration becomes exceptionally challenging due to constraints involving different healthcare organizations and regulations. Traditional centralized machine learning methods require centralizing these sensitive medical data for training, posing risks of patient privacy leakage and data security issues. In this context, federated learning (FL) has attracted much attention as a distributed machine learning framework. It effectively addresses this contradiction by preserving data locally, conducting local model training, and aggregating model parameters. This approach enables the utilization of multicenter data with maximum benefit while ensuring privacy safeguards. Based on pre-radiotherapy planning target volume images of NSCLC patients, a multicenter treatment response prediction model is designed by FL for predicting the probability of remission of NSCLC patients. This approach ensures medical data privacy, high prediction accuracy and computing efficiency, offering valuable insights for clinical decision-making. Methods We retrospectively collected CT images from 245 NSCLC patients undergoing chemotherapy and radiotherapy (CRT) in four Chinese hospitals. In a simulation environment, we compared the performance of the centralized deep learning (DL) model with that of the FL model using data from two sites. Additionally, due to the unavailability of data from one hospital, we established a real-world FL model using data from three sites. Assessments were conducted using measures such as accuracy, receiver operating characteristic curve, and confusion matrices. Results The model’s prediction performance obtained using FL methods outperforms that of traditional centralized learning methods. In the comparative experiment, the DL model achieves an AUC of 0.718/0.695, while the FL model demonstrates an AUC of 0.725/0.689, with real-world FL model achieving an AUC of 0.698/0.672. Conclusions We demonstrate that the performance of a FL predictive model, developed by combining convolutional neural networks (CNNs) with data from multiple medical centers, is comparable to that of a traditional DL model obtained through centralized training. It can efficiently predict CRT treatment response in NSCLC patients while preserving privacy.

Abstract Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Abstract Background ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear. Results Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment. Conclusions ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.

Meroplius fukuharai is an important sanitary and ecological resource insect. We sequenced and annotated the mitogenome of Meroplius fukuharai which is the first representative of the genus Meroplius with nearly complete mitochondrial data. This mitogenome is 14,803 bp long, which consists of 22 transfer RNA genes, 13 protein-coding genes (PCGs), and two ribosomal RNA genes. All genes have a conservational arrangement with other published species of Sepsidae. Our results also supported the monophyly of Sepsidae, and the genus Meroplius is more closely related to genus Sepsis, Microsepsis, and Archisepsis.

Abstract In recent years, contrastive language‐image pre‐training (CLIP) has gained popularity for processing 2D data. However, the application of cross‐modal transferable learning to 3D data remains a relatively unexplored area. In addition, high‐quality, labelled point cloud data for Mechanical, Electrical, and Plumbing (MEP) scenarios are in short supply. To address this issue, the authors introduce a novel object detection system that employs 3D point clouds and 2D camera images, as well as text descriptions as input, using image‐text matching knowledge to guide dense detection models for 3D point clouds in MEP environments. Specifically, the authors put forth the proposition of a language‐guided point cloud modelling (PCM) module, which leverages the shared image weights inherent in the CLIP backbone. This is done with the aim of generating pertinent category information for the target, thereby augmenting the efficacy of 3D point cloud target detection. After sufficient experiments, the proposed point cloud detection system with the PCM module is proven to have a comparable performance with current state‐of‐the‐art networks. The approach has 5.64% and 2.9% improvement in KITTI and SUN‐RGBD, respectively. In addition, the same good detection results are obtained in their proposed MEP scene dataset.

Abstract Miniaturized passive fliers based on smart materials face challenges in precise control of shape-morphing for aerodynamics and contactless modulation of diverse gliding modes. Here, we present the optical control of gliding performances in azobenzene-crosslinked liquid crystal networks films through photochemical actuation, enabling reversible and bistable shape-morphing. First, an actuator film is integrated with additive constructs to form a rotating glider, inspired by the natural maple samara, surpassing natural counterparts in reversibly optical tuning of terminal velocity, rotational rate, and circling position. We demonstrate optical modulation dispersion of landing points for the photo-responsive microfliers indoors and outdoors. Secondly, we show the scalability of polymer film geometry for miniature gliders with similar light tunability. Thirdly, we extend the material platform to other three gliding modes: Javan cucumber seed-like glider, parachute and artificial dandelion seed. The findings pave the way for distributed microflier with contactless flight dynamics control.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π–π interaction to prepare g–C3N4–loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt–N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g–C3N4–loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage in vitro and an OA joint model in vivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

Introduction Lung cancer continues to be a common form of cancer worldwide and a primary contributor to cancer-related fatalities. Non-small cell lung cancer (NSCLC) is the most prevalent form, making up 80% to 85% of newly identified malignant lung tumours, and remains a major concern for worldwide health. Surgical resection is the preferred treatment for localised NSCLC, but more than one-third of patients present with locally advanced, unresectable tumours. Concurrent radiation therapy and chemotherapy are believed to offer the potential for prolonged disease-free and overall survival to those patients. However, the results are inconsistent, and systematic meta-analysis is lacking to evaluate its treatment effect comprehensively. Therefore, we will conduct a meta-analysis to evaluate the efficacy and safety of 3D-CRT concurrent chemotherapy in unresectable stage III NSCLC to provide evidence-based medical support for clinical treatment.Methods and analysis This systematic review and meta-analysis will adhere to the guidelines outlined in the PRISMA statement. Based on the predetermined criteria for inclusion, we will conduct a comprehensive search for randomised controlled trials (RCTs) examining the efficacy and safety of three-dimensional conformal radiation therapy (3D-CRT) concurrent chemotherapy in unresectable stage III NSCLC. The search will be performed across multiple databases including PubMed, Embase, Cochrane, Scopus and Web of Science from inception to 1 November 2024 using terms including NSCLC, 3D-CRT concurrent chemotherapy, radiation therapy, RCT and controlled clinical trial. Furthermore, relevant literature citations will be gathered, and relevant journals will be manually searched. The primary outcomes in the study were overall survival; progression-free survival; 1-, 3- and 5-year survival rates; event-free survival; and median survival time. Secondary outcomes included treatment effectiveness, all adverse events (AEs), all treatment-related adverse events (TRAEs), AEs (grade ≥3) and TRAEs (grade ≥3). Two separate reviewers will be responsible for screening, extracting data and evaluating quality. Our reviewers will perform subgroup analysis, sensitivity analysis and publication bias analysis to evaluate the heterogeneity and robustness. Review Manager 5.4 will be used for the analysis and synthesis process. The risk of bias will be assessed using the Cochrane Risk of Bias tool (RoB 2), and the Grading of Recommendations Assessment, Development and Evaluation will be employed to evaluate the study’s overall evidence quality.Ethics and dissemination This study is based on a secondary analysis of the literature, so ethical review approval is not required. The final report will be published in a peer-reviewed journal.Trial registration The protocol of the systematic review has been registered on Open Science Framework, with a registration DOI https://doi.org/10.17605/OSF.IO/R7WCG.

To quantitatively represent the deterioration law of the mechanical properties of siltstone after exposure to supercritical CO2(SC-CO2), experiments were conducted to test the mechanical parameters of rocks under the coupling effect of CO2–water–rock interactions. The purpose of this study is to determine the evolution law and damage characteristics of each siltstone mechanical parameter under the action of SC-CO2. In combination with numerical simulation results, this study revealed the damage evolution characteristics of rocks in a CO2 geological storage reservoir. The research findings indicate that SC-CO2 exhibits a certain time effect and causes non-uniform damage to siltstone. Both the deterioration law of the mechanical parameters and soaking time exhibited an exponential relationship. With increasing soaking time, both the uniaxial compressive strength and elastic modulus showed a decreasing tendency, whereas the Poisson's ratio showed a varying degree of increase. The total degree of deterioration gradually increased as the soaking time increased and approached a stable value. After exposure to SC-CO2, the damage deformation and failure mode transitioned from brittle to plastic in the siltstone samples. In addition, there was a shift from a single axial crack failure pattern to a complex failure mode with multiple cracks. This study also derived a uniaxial compressive strength prediction model for siltstone based on soaking time, constructed an elastic modulus damage model, and established a fluid–solid coupling model considering damage in the CO2 geological storage process. The experimental and numerical simulation results revealed that microstructural alterations occurred in the siltstone after exposure to SC-CO2. Furthermore, it was discovered that damage accumulation from the micro- to macroscale ultimately led to a gradual deterioration in mechanical properties. The research results provide a theoretical basis for mechanical stability evaluation in CO2 geological storage.

Summary: Genomics studies have detected numerous genetic alterations in esophageal squamous cell carcinoma (ESCC). However, the functions of these mutations largely remain elusive, partially due to a lack of feasible animal models. Here, we report a convenient platform with CRISPR-Cas9-mediated introduction of genetic alterations and orthotopic transplantation to generate a series of primary ESCC models in mice. With this platform, we validate multiple frequently mutated genes, including EP300, FAT1/2/4, KMT2D, NOTCH2, and TGFBR2, as tumor-suppressor genes in ESCC. Among them, TGFBR2 loss dramatically promotes tumorigenesis and multi-organ metastasis. Paradoxically, TGFBR2 deficiency leads to Smad3 activation, and disruption of Smad3 partially restrains the progression of Tgfbr2-mutated tumors. Drug screening with tumor organoids identifies that pinaverium bromide represses Smad3 activity and restrains Tgfbr2-deficient ESCC. Our studies provide a highly efficient platform to investigate the in vivo functions of ESCC-associated mutations and develop potential treatments for this miserable malignancy.

Linezolid-resistant enterococci have increased in recent years due to the worldwide spread of acquired resistance genes (cfr, optrA, and poxtA) in clinical, animal, and environmental settings. This study investigated the carriage of optrA-positive enterococci among patients in the anorectal surgery ward in Hangzhou, China, and characterized the genetic context of optrA. A total of 173 wound secretion samples were obtained to screen optrA-positive enterococci. Of the 173 samples, 15 (8.67%) were positive for optrA, including 12 Enterococcus faecalis, two E. faecium, and one E. hirae. Multilocus sequence type analysis revealed that 12 optrA-positive E. faecalis isolates belonged to eight different sequence types (STs), of which ST16 was the main type. Eight optrA variants were identified, whose optrA flanking regions with a fexA gene downstream were bounded by different mobile genetic elements. Furthermore, the optrA gene in 8 out of 15 optrA-positive enterococci could be successfully transferred through conjugation. The findings revealed a high carriage rate of optrA in enterococci from one anorectal surgery ward in China. The dissemination of optrA-positive enterococci isolates in clinical settings should be continually monitored.

Summary: Constructing electric vehicle charging piles (EVCPs) is crucial for promoting electric vehicle (EV) sales. Yet, empirical evidence on the bidirectional relationship between EV sales and public EVCPs is limited, with most related works relying on simulations. We empirically investigate this relationship using panel vector autoregression (PVAR) across 95 Chinese cities from 2018 to 2022. Results show EVCPs significantly boost EV sales, especially in colder regions. Higher air pollution and purchase subsidies inhibit the promoting impact of EV sales on EVCPs. The propelling effect of EVCPs on EV sales is impaired in higher housing prices regions. A significant and positive bidirectional relationship exists between EVCPs and battery electric vehicles (BEVs) sales exists, but not with plug-in hybrid electric vehicles (PHEVs) present. Our findings have implications for stakeholders, such as the construction of fast charging infrastructure under lower temperatures, and differentiated charging demands of EVs with different powertrains need to be addressed.

Metallic foam composite phase change materials (MF-PCMs) have a high thermal energy storage capacity. However, obtaining a high heat transfer coefficient and a consistent temperature distribution remains challenging. Here, we present a novel double-gradient void metallic foam construction. Furthermore, we build a three-dimensional numerical model to study how pore size, porosity, and diameters affect heat transport and thermal storage performance. The results show that the homogeneity of the cooled wall temperature distribution is well improved by the enhancement of thermal conductivity produced by this double-gradient design. With a graded gradient, the maximum deviation between the individual temperature and the average temperature of the cooled wall is within 15 K, as the total thermal storage capacity is close to 75.5 % of the pure PCMs. Meanwhile, for pure PCMs, this deviation can reach 67 K. These characteristics hold promise for lithium-ion battery thermal management because the spaces between neighboring individual cell units must absorb and retain the heat emitted. Our novel composite structure offers a significant method for designing battery temperature control.

Acute myocardial infarction (AMI) remains a significant health challenge globally, highlighting the ongoing need for effective treatments. Shexiang-Tongxin dropping pill (STDP) is widely utilized as a therapeutic option for AMI in China and Southeast Asia. However, the intricate mechanisms of action of STDP against AMI remain largely unknown. The pharmacodynamic effects of STDP in treating AMI were evaluated both in vitro and in vivo using human umbilical vein endothelial cell oxygen-glucose deprivation, RAW264.7 cell inflammatory injury, and rat left anterior descending surgery models. The whole transcriptome sequencing was performed to analyze gene expression changes in experimental rat hearts after left anterior descending surgery. An integrative approach combining network pharmacology and sequencing data was used to determine the multi-target and multi-pathway mechanisms underlying the action of STDP against AMI. Molecular docking was conducted to identify the primary anti-AMI ingredients in STDP. STDP treatment significantly resisted AMI in vivo and protected against inflammatory and hypoxic injuries in vitro. It resulted in 63 % (901 of 1430) of genes showing restorative regulation in the AMI disease network, relating to the TGF-β, PI3K, apoptosis, and MAPK pathways. Validation experiments indicated that inhibiting apoptosis and ERK/MAPK pathways by reducing Bax and p-ERK1/2 expression levels in rat hearts may be a crucial mechanism of STDP against AMI. Molecular target prediction indicated that tanshinone IIA, salvianolic acid A, salvianolic acid B, and resibufogenin were the essential pharmacodynamic substances of STDP in AMI treatment. This study sheds light on novel mechanisms by which STDP rebalances the AMI disease network through its multi-target and multi-pathway effects. The findings offer data support for the more precise clinical application of STDP.

Supersonic and hypersonic flows have gained considerable attention in the aerospace industry in recent years. Flow control is crucial for refining the quality of these high-speed flows and improving the performance and safety of fast aircraft. This paper discusses the distinctive characteristics of supersonic flows compared to low-speed flows, including phenomena such as boundary layer transition, shock waves, and sonic boom. These traits give rise to significant challenges related to drag, noise, and heat. Therefore, a review of several active and passive control strategies is provided, highlighting their significant advancements in flow transitions, reducing drag, minimizing noise, and managing heat. Furthermore, we provide a comprehensive analysis of various research methodologies used in the application of flow control engineering, including wind tunnel testing, flight testing, and computational fluid dynamics (CFD). This work gives an overview of the present state of flow control research and offers insights into potential future advancements.

ObjectivePneumonia is a common clinical condition primarily treated with antibiotics and organ support. Exploring the pathogenesis to identify therapeutic targets may aid in the adjunct treatment of pneumonia and improve survival rates.MethodsTranscriptomic data from peripheral blood of 183 pneumonia patients were analyzed using Gene Set Variation Analysis (GSVA) and univariate Cox regression analysis to identify signaling pathways associated with pneumonia mortality. A pneumonia mouse model was established via airway injection of Klebsiella pneumoniae, and pathway-specific blockers were administered via tail vein infusion to assess whether the identified signaling pathways impact the mortality in pneumonia.ResultsThe combination of GSVA and Cox analysis revealed 17 signaling pathways significantly associated with 28-day mortality in pneumonia patients (P < 0.05). Notably, the RIG-I-like receptor signaling pathway exhibited the highest hazard ratio of 2.501 with a 95% confidence interval of [1.223–5.114]. Infusion of RIG012 via the tail vein effectively inhibited the RIG-I-like receptor signaling pathway, significantly ameliorated lung injury in pneumonia mice, reduced pulmonary inflammatory responses, and showed a trend toward improved survival rates.ConclusionRIG012 may represent a novel adjunctive therapeutic agent for pneumonia.

The partial removal of lignin from bamboo materials, a prevalent method to soften the material for plastic forming. It increases bending toughness and improves forming quality, albeit at the expense of load-bearing capacity. This study employs an innovative approach using deep eutectic solvent pretreatment on bamboo green strips (BGS) to establish a balance between strength and toughness, resulting in a significant enhancement of the elastic modulus. The mechanical properties of the DES-treated BGS displayed notable improvements compared to bamboo timber strips (BTS) and bamboo yellow strips (BYS), which either showed no enhancement or suffered degradation after extended treatment durations. Notably, BGS treated for one hour exhibited increases of 8.22 % in flexural toughness and 33.45 % in elastic modulus, while strength diminished by a mere 5.72 %. Concurrently, its porosity increased by 29.36 %, predominantly in the mesopore range. In addition, the crystallinity of the treated BGS increased, whereas the grain size decreased. Silicon-aluminum compounds form on the outer surface of BGS, along with an increase in silicon oxide content, contributed to the observed improvements in stiffness and toughness. These works suggest a novel method for balancing modulus and strength of bamboo structural units, with potential applications in architecture, furniture and transportation sectors.

In situ online observation of surface morphology during degradation processes is of paramount importance for exploring the stability of organic photovoltaic materials. In this study, we designed an in situ online characterization system based on hyperspectral and neural network technologies, and observed the degradation processes of P3HT:PCBM thin film materials. The system is capable of collecting hyperspectral image data from 101 channels within the 400–700 nm wavelength range for characterizing detailed surface features of materials. Additionally, to automate the processing of hyperspectral image data, we designed a spectral image segmentation algorithm based on neural networks and proposed a foreground attention mechanism to improve the segmentation accuracy of the algorithm. The experimental results indicate that the system can achieve high spectral characterization of P3HT:PCBM thin film materials and automate image data processing through artificial intelligence algorithms, with an image segmentation accuracy of 99.62 %. Furthermore, owing to the higher spectral resolution of this system and its computer-assisted analysis capabilities for material image data, not only are the in-situ variations in size, density, and formation rate of aggregates formed during the thermal degradation process of P3HT:PCBM thin film materials experimentally analyzed, but also the fluorescence changes at the edges of aggregates during the photodegradation process are revealed. The reliable code can be found at the following link: https://github.com/HyperSystemAndImageProc/IONFMDP-UHHNN.

Introduction Physical inactivity is prevalent and associated with adverse outcomes among patients with chronic kidney disease (CKD). Most previous studies have relied on subjective questionnaires to assess levels of physical activity (PA) and mainly focused on patients undergoing dialysis. Therefore, the Physical Activity Elements and Adverse Outcomes in Patients with Chronic Kidney Disease in Guangdong study aims to investigate the levels and types of PA elements and their association with adverse outcomes in Chinese non-dialysis CKD (ND-CKD) patients.Methods and analysis In this prospective cohort study, 374 patients with ND-CKD will be recruited from Guangdong province, South of China. The primary exposure will be levels of PA assessed by ActiGraph GT3X+ accelerometer including the intensity, duration, frequency and type of PA. The traditional Chinese exercises such as tai chi and Baduanjin will also be assessed. The primary outcomes will be all-cause mortality. Other variables including demographics, comorbidities, medication and laboratory markers will be registered. All data will be updated annually for at least 5 years, or until the occurrence of death or initiation of renal replacement therapy. The Spearman correlation coefficient will be used to investigate the correlation between questionnaire-derived and accelerometry-derived PA. The Cox proportional hazards model will be used to investigate the association between level of PA and adverse outcomes. Non-linear associations between PA levels and outcomes, as well as the minimum desirable PA level, will be evaluated using restricted cubic splines.Ethics and dissemination The ethical permission for this study was obtained from the ethics committee of Guangdong Provincial Hospital of Chinese Medicine in Guangzhou, China (B2015-152-02). Written informed consent is obtained from all participants. The results will be disseminated by publication in a peer-reviewed journal and presented at relevant conferences.

Abstract The PEGylated ultrasmall iron oxide nanoparticles (PUSIONPs) exhibit longer blood residence time and better biodegradability than conventional gadolinium‐based contrast agents (GBCAs), enabling prolonged acquisitions in contrast‐enhanced magnetic resonance angiography (CE‐MRA) applications. The image quality of CE‐MRA is dependent on the contrast agent concentration and the parameters of the pulse sequences. Here, a closed‐form mathematical model is demonstrated and validated to automatically optimize the concentration, echo time (TE), repetition time (TR) and flip angle (FA). The pharmacokinetic studies are performed to estimate the dynamic intravascular concentrations within 12 h postinjection, and the adaptive concentration‐dependent sequence parameters are determined to achieve optimal signal enhancement during a prolonged measurement window. The presented model is tested on phantom and in vivo rat images acquired from a 3T scanner. Imaging results demonstrate excellent agreement between experimental measurements and theoretical predictions, and the adaptive sequence parameters obtain better signal enhancement than the fixed ones. The low‐dose PUSIONPs (0.03 mmol kg−1 and 0.05 mmol kg−1) give a comparable signal intensity to the high‐dose one (0.10 mmol kg−1) within 2 h postinjection. The presented mathematical model provides guidance for the optimization of the concentration and sequence parameters in PUSIONPs‐enhanced MRA, and has great potential for further clinical translation.

Abstract The early diagnosis of hepatocellular carcinomas (HCCs) remains challenging in the clinic. Primovist‐enhanced magnetic resonance imaging (MRI) aids HCC diagnosis but loses sensitivity for tumors

Abstract Arboviruses, transmitted by medical arthropods, pose a serious health threat worldwide. During viral infection, Post Translational Modifications (PTMs) are present on both host and viral proteins, regulating multiple processes of the viral lifecycle. In this study, a mammalian E3 ubiquitin ligase WWP2 (WW domain containing E3 ubiquitin ligase 2) is identified, which interacts with the NS1 protein of Zika virus (ZIKV) and mediates K63 and K48 ubiquitination of Lys 265 and Lys 284, respectively. WWP2‐mediated NS1 ubiquitination leads to NS1 degradation via the ubiquitin‐proteasome pathway, thereby inhibiting ZIKV infection in mammalian hosts. Simultaneously, it is found Su(dx), a protein highly homologous to host WWP2 in mosquitoes, is capable of ubiquitinating NS1 in mosquito cells. Unexpectedly, ubiquitination of NS1 in mosquitoes does not lead to NS1 degradation; instead, it promotes viral infection in mosquitoes. Correspondingly, the NS1 K265R mutant virus is less infectious to mosquitoes than the wild‐type (WT) virus. The above results suggest that the ubiquitination of the NS1 protein confers different adaptations of ZIKV to hosts and vectors, and more importantly, this explains why NS1 K265‐type strains have become predominantly endemic in nature. This study highlights the potential application in antiviral drug and vaccine development by targeting viral proteins' PTMs.

Abstract The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti‐inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti‐inflammation and anti‐infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory‐microenvironment‐responsive nanomedicine is designed by using poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non‐toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus‐induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET‐based nanoparticles by simultaneously controlling infections and inflammation may be promising nano‐therapeutics for treatment of severe infectious diseases.

Planktonic microorganisms have been recognized as important components in biogeochemical cycling in lakes. However, research into the impact of phyllosphere microorganisms, particularly those involved in carbon cycling, on CO2 fluxes in macrophyte-dominated lakes within the context of global environmental changes remains scarce. Here, by employing high-throughput sequencing techniques, we experimentally tested how nutrient enrichment, top-down effects of fish and increases in dissolved organic carbon (DOC) affect CO2 exchange flux at the water-air interface by altering the community structure and functioning of phyllosphere bacteria on macrophytes. We found that our mesocosm ecosystems exhibited a net absorption of CO2, but nutrient enrichment significantly decreased the absorption ability. Mantel tests and multiple regression modeling also showed that eutrophication-associated parameters (total nitrogen, total phosphorus and ammonium nitrogen), pH, and extinction coefficient were the key drivers influencing abundance of phyllosphere functional microorganisms. In addition, these experimental treatments significantly altered the composition, diversity and co-occurrence networks of carbon cycling-associated phyllosphere microorganisms, which impacted the CO2 flux. Structural equation models and linear regression further showed that the Shannon Index of phyllosphere functional microorganisms related to carbon cycling (rather than plant volume inhabited - PVI) had a significant positive impact on CO2 fixation. This means that environmental changes—especially eutrophication—may hinder carbon sequestration by decreasing the diversity of phyllosphere microorganisms rather than reducing the abundance of submerged macrophytes. This study increases our understanding of carbon cycling processes in aquatic environments from a management perspective by emphasizing the importance of protecting the diversity of phyllosphere microorganisms in macrophyte-dominated lakes.