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Abstract Background NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. Methods Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. Results Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1β (IL-1β), alongside decreased activation of NLRP3 inflammasome and IL-1β secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. Conclusion This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

Abstract Transport accessibility is crucial for defining urban clusters and evaluating a region's centrality and connectivity. To foster equitable growth in urban conglomerates, it is crucial to understand the relationship between transport accessibility and regional development. This study introduces the concept of 'regional efficiency'—the effectiveness of converting regional inputs into outputs—determined via the super-efficiency Data Envelopment Analysis methodology, to assess the progression of regional development. Employing a combination of bivariate spatial autocorrelation and spatial regression analysis, this research elucidates the spatial dynamics between transport accessibility and regional efficiency, both at macro and micro levels. A binary Logit model identifies the factors affecting the Moran's I correlation between regional efficiency and transport accessibility. Based on the diverse urban characteristics within a single conglomerate, tailored development strategies are suggested. Focusing on the Yangtze River Delta Urban Agglomeration in China as a case study, four distinct spatial clusters—High–High (HH), Low–Low (LL), High–Low (HL), and Low–High (LH)—are identified, based on the local correlation between regional efficiency and transport accessibility. The findings reveal that regions with a High–High Moran's I correlation between road accessibility and regional efficiency predominantly located in the eastern sectors of the Yangtze River Delta, exhibiting effective regional efficiency. These regions are characterized by superior road accessibility, aligning well with their regional efficiency metrics. For air accessibility, cities classified under the HH category, including Shanghai and its neighboring cities, demonstrate a significant spatial correlation with regional efficiency. Population density and urban tier are key predictors of the significance of the Moran's I correlation between road accessibility and regional efficiency. In contrast, for air accessibility, these factors assume an inverse role. The identified cluster types (HH, LL, LH, and HL) are proposed as predictive indicators for the significance of the Moran's I relationship between air accessibility and regional efficiency.

Abstract Green purchase behavior can significantly contribute to environmental protection, which should be further encouraged. In promoting green purchase behavior, individual green knowledge may play a vital role. This study aims to explore how and when green knowledge influences individual green purchase behavior. Based on trait activation theory, this study proposes that individuals with more green knowledge can better know the impact of their daily behaviors on the environment, including their consumption behaviors. Specifically, individuals with more green knowledge will have more environmental concerns and thus show higher preferences for green consumption. Further, by integrating the environment individuals live in, this study proposes that resource inadequacy will strengthen the effects of green knowledge. Survey data collected from 606 Chinese university students at three-time points supported our hypotheses. This study also discussed the theoretical and practical implications.

Artesunate (ART) is a classic antimalarial drug with high efficiency, low toxicity and tolerance. It has been shown to be safe and has good anti-tumor effect. Existing clinical studies have shown that the anti-tumor mechanisms of ART mainly include inducing apoptosis and autophagy of tumor cells, affecting tumor microenvironment, regulating immune response, overcoming drug resistance, as well as inhibiting tumor cell proliferation, migration, invasion, and angiogenesis. ART has been proven to fight against lung cancer, hepatocarcinoma, lymphoma, multiple myeloma, leukemia, colorectal cancer, ovarian cancer, cervical cancer, malignant melanoma, oral squamous cell carcinoma, bladder cancer, prostate cancer and other neoplasms. In this review, we highlight the effects of ART on various tumors with an emphasis on its anti-tumor mechanism, which is helpful to propose the potential research directions of ART and expand its clinical application.

In 2018, China implemented the Veterinary Antimicrobial Use Reduction Action to curb the rapid development of antibiotic resistance (AR). However, the AR-related pollutions in animal farms after the reduction policy has been poorly investigated. Here, we performed a comprehensive investigation combining UPLC-MS/MS, metagenomic, and bacterial genomic analyses in eight representative large-scale chicken farms in Guangdong, China. Our results showed that antibiotics and ARGs contaminations were more severe in broiler farms than in layer farms. Notably, diverse tet(X) variants were prevalent in the chicken farms. These tet(X)s was carried by diverse E. coli lineages and obviously correlated with ISCR2 and IS1B transposases. The resistomes in chicken farms was significantly correlated with microbial community, and multiple factor analyses indicated that the joint effect of antibiotics-microbial community-MGEs was the most dominant driver of ARGs. Host tracking identified a variety of ARG bacterial hosts and the co-occurrence of ARGs-MRGs-MGEs. Source tracking indicated that the inherent component represented the main feature of resistomes in different hosts, while ARG transfer between the chicken gut and farm environments were frequent. A multiperspective evaluation of AR risk revealed that the early effect of antibiotic reduction was exhibited by the mitigation of maximum level of risky ARGs, prevalence of environmental AR pathogens, and HGT potential of ARGs mediated by phage structures. Overall, our findings provide insights into the antibiotic and ARG profiles in large-scale chicken farms with different rearing strategies and demonstrate a preliminary view of the performance of antibiotic reduction actions in China.

ABSTRACT: Colistin (CST) is considered as “agent of last resort” against gram-negative bacteria as feed additive. Its clinical effectiveness has reduced since the emergence of mcr-1 gene in ducks. Isopropoxy benzene guanidine (IBG), a new guanidine derivative, showed positive effects on improving animal weights and alleviating intestinal pathogens, therefore, the objective of this study was to evaluate the effect of this compound supplement with CST in ducks and explore the possibilities in feed additive. A total of fifteen duck-origin Escherichia coli carrying the mcr-1 gene were included in this study. A checkerboard microdilution assay was used to evaluate the in vitro antibacterial activity of IBG combined with CST against mcr-1-positive E. coli. A 3-by-2 time–kill array of IBG (16, 32, and 64 μg/mL) and CST (1/2 MIC and 1/4 MIC) over 24 hours was utilized to characterize the activity of the agents alone and in combination against E. coli strain 1 in vitro. The intestinal colonization model was used to evaluate the in vivo effect of IBG combined with CST. These results indicated that the combination of IBG plus CST showed a synergistic effect against all clinical isolates (FICI < 0.5). The bacterial burden was reduced by more than 2 log10 CFU/mL when E. coli strain 1 was tested with 1/2 MIC CST plus 64 μg/mL IBG for 24 h. Further experiments in vivo demonstrated that the CST combined with IBG was able to increase duck weights, reduced intestinal pathogenic E. coli and showed a synergistic antibacterial effect. Combination of CST (4 mg/kg b.w.) plus IBG (32 or 64 mg/kg b.w.) achieved 1.84 to 3.29 log10 CFU/g killing after 7 d of therapy, which was significantly different from that in the challenge control group (p

Abstract Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Objective To explore changes in prevalence characteristics and pathogen spectrum of severe hand, foot and mouth disease (HFMD) in Henan province before and after launching vaccination of enterovirus 71 (EV71) vaccine for developing strategies on HFMD prevention and control. MethodsThe data on all HFMD cases registered in Henan province from 2014 through 2020 were extracted from the Infectious Disease Report Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive statistics was performed on the data to assess changes in constituent ratio of and distribution of pathogens detected in the severe HFMD cases before and after of the launch of EV71 vaccination from 2017 in the province. ResultsDuring 2014 to 2020, totally 13 535 severe HFMD cases were reported in the province, with a male-to-female ratio of 1.58:1 and the most (97.34%, 13 175) of the cases were children under the age of 5 years. A unimodal pattern throughout the year was observed in the incidence of severe HFMD, with the peak season mainly occurring from April to July and 75.53% (10 223) of the registered severe cases occurred during the season. The ratio of severe cases decreased significantly from 3.19% (10 948/343 585) for the period of 2014 – 2016 to 0.93% (2 587/278 075) for the period of 2017 – 2020 with the launch of EV71 vaccination (χ2 = 3672.874, P < 0.001). For the severe HFMD cases reported during 2017 – 2020, the proportion of the cases of one- and two-year-old decreased significantly from 47.23% to 42.83% (χ2 = 16.311, P1 < 0.001) and from 25.57% to 22.84% (χ2 = 8.255, P2 = 0.004); but the proportion of the cases occurred in preschool care facilities increased significantly from 9.13% to 16.24% (χ2 = 112.359, P < 0.001). Following the promotion of EV71 vaccination among the public, the detection rate of EV71 among the severe HFMD cases decreased from 65.14% to 29.63%, while that of other enteroviruses increased from 27.49% to 56.13%, indicating that other enteroviruses became dominant serotypes for pathogens of HFMD epidemic. ConclusionThe ratio of severe cases among registered HFMD cases had significantly decreased after the launch of the EV71 vaccination in Henan province and the dominant pathogen of HFMD changed from EV71 to other enteroviruses. The results suggest that EV71 vaccination ought to be promoted among key populations and in peak season to prevent severe HFMD epidemic.

Abstract To improve the multiscale dynamic dispatching and distribution capacity of regional integrated energy, a multiscale dynamic time‐domain dispatching model of regional integrated energy with seasonal load difference is proposed. The master–slave game coordination planning model of regional comprehensive energy multiscale dispatching is constructed, and the difference fusion model of regional comprehensive energy multiscale dynamic dispatching is established by using the active and reactive power coordination control method according to the influence factors of voltage deviation and line overload absorption. Maximize the weight factors of the positive contribution of distributed photovoltaic (PV) power to the active distribution network. On the basis of the quantitative regulation analysis method of demand response power based on the equivalent slope of the load curve, establish an energy absorption capacity analysis model of seasonal load differentiation. On the basis of the dynamic interaction between different systems, a multiscale dynamic time‐domain analysis and dynamic simulation model of regional integrated energy is constructed by using the method of PV absorptive capacity assessment on both sides of demand uncertainty, to achieve multiscale dynamic time‐domain feature extraction of integrated energy and integrated scheduling of seasonal load differences. The simulation results show that the multiscale dynamic time‐domain allocation of regional comprehensive energy using this method improves the energy dispatching and balanced allocation capability, and the time‐domain dynamic allocation capability is good. Considering the terminal load demand and the electricity price demand formulated by the distribution network investment operators, the seasonal load response and comprehensive dispatching capability are improved.

There are about two billion people suffered malnourished because of the failing global food system, historical emphasis on crop yield, notably lacking in Fe and Zn. Breeding biofortified staple crops is a sustainable strategy to tackle this issue, but it poses challenges, primarily due to limited genetic resources in modern breeding populations. Simultaneously, global climate change, marked by rising temperatures and increased atmospheric CO2, threatens the stability of micronutrient concentrations in harvest organs, such as gain, fruit, root, tubers etc. The rich biodiversity of crop wild relatives, including wild species, landraces, and natives, offers a promising genetic response to climate change. Advanced breeding technologies, like marker-assisted selection breeding, genomic selection, gene editing provide opportunities to enhance Fe and Zn concentrations in staple crops, such as rice, maize, wheat, cassava, etc. Genome-wide association studies and population genetics research will help found qualitative genes and major-effect homeostasis genes for Fe and Zn, which purpose is to uncover the molecular mechanisms governing Fe and Zn regulation in staple crops. Despite these strides, enhancing Fe and Zn bioavailability for human, requires considering absorption enhancers and inhibitors, rather than solely increasing concentrations. Absorption testing systems like the Caco-2 cell line, elucidating the meta-process of Fe and Zn absorption in the human body should be considered when breeding Fe and Zn biofortified crops through traditional and molecular breeding.

Modifying surface characteristics and geometric structure to regulate heat transfer and flow fields is a classical issue. The study of wake dynamics and heat transfer efficiency in tandem grooved cylinders hold fundamental importance. This research proposes a configuration of tandem cylinders with triangle-grooved surfaces and numerical simulates the vorticity, fluid forces, Strouhal numbers, and convective heat transfer in tandem grooved cylinders. The parameters investigated include orientation angles θ = 0°, 30°, 45°, 60°, 90° and Reynolds numbers Re = 75, 100, 125, 150, 175, 200. This study focuses on how the triangle-grooved angle (θ) and Re affect wake dynamics and thermal performance. Numerical results are validated against available data in the literature for tandem smooth and tandem grooved cylinders. The results indicate that, compared to tandem smooth cylinders, the positive vorticity intensity of tandem grooved cylinders is 35.7 % higher, while the negative vorticity intensity is 23.5 % lower. Further observations show that at θ = 45°, the pressure variation on the upstream cylinder is most significant, approximately twice that at θ = 0° and θ = 90°. Notably, the variation values of the downstream cylinder (β = 0°) at θ = 0° and θ = 45° are triple and double that of the upstream cylinder in TF mode, respectively. Additionally, at θ = 0°, the root mean square lift coefficient of the downstream cylinder reaches the maximum value (Re = 75–100), approximately 1.34. When Re = 125, CL(rms),1 decreases by 15.7 % to 1.13. Particularly, when Re = 100–150, the time-averaged drag coefficient of the downstream cylinder shows a peak value of approximately 1.02. Interestingly, at Re = 200, a tadpole-shaped thermal distribution forms in the wake region of the upstream cylinder. Furthermore, the time-averaged Nusselt number ratio (θ = 0°) exhibits a trend opposite to other cases over a broader range (125 ≤ Re ≤ 200) and peaks at Re = 200, approximately 1.24.

Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.

After the resumption of work and production following the COVID-19 pandemic, many cities entered a “transition phase”, characterized by the gradual recovery of emission levels from various sources. Although the overall PM2.5 emission trends have recovered, the specific changes in different sources of PM2.5 remain unclear. Here, we investigated the changes in source contributions and the evolution pattern of pollution episodes (PE) in Wuhan during the “transition period” and compared them with the same period during the COVID-19 lockdown. We found that vehicle emissions, industrial processes, and road dust exhibited significant recoveries during the transition period, increasing by 5.4%, 4.8%, and 3.9%, respectively, during the PE. As primary emissions increased, secondary formation slightly declined, but it still played a predominant role (accounting for 39.1∼ 43.0% of secondary nitrate). The reduction in industrial activities was partially offset by residential burning. The evolution characteristics of PE exhibited significant differences between the two periods, with PM2.5 concentration persisting at a high level during the transition period. The differences in the evolution patterns of the two periods were also reflected in their change rates at each stage, which mostly depend on the pre-PE concentration level. The transition period shows a significantly higher value (8.4 μg m–3 h–1) compared with the lockdown period, almost double the amount. In addition to local emissions, regional transport should be a key consideration in pollution mitigation strategies, especially in areas adjacent to Wuhan. Our study quantifies the variations in sources between the two periods, providing valuable insights for optimizing environmental planning to achieve established goals.

Aviation emissions are continuously increasing along with the rapid development of air transportation, and results in the deterioration in regional air quality and the global climate. Accurate emission estimation is of great importance for relevant policies promotion and the sustainable development of the environment. Previous studies focused on the total emissions of a flight and lacked high precision in both spatial and temporal resolutions, especially aviation activities near ground. In this research, we propose an open-sourced emission calculation framework based on actual flight trajectories (TrajEmission), which calculates both the ground and airborne emissions simultaneously according to the configuration parameters, trajectory characteristics, and ambient conditions. We compare the emission results with five emission inventory methods. The results indicate that pollutant (nitrogen oxides, carbon monoxide, and unburned hydrocarbons) emissions in the landing and takeoff (LTO) cycle might usually be underestimated due to a lack of trajectory-based methods. In addition, in the overall results, the method based on the great circle route leads to an overestimation of 56.8% of pollutant emissions compared to the method based on actual routes. We also investigate the extent to which other factors could influence the emission results. To summarize, the TrajEmission framework can build inventories for the whole process of flight movements with high spatial–temporal resolutions and provide solid data support for environmental science and other related fields.

Accurately detecting and locating the fault point of the DC line is significant for eliminating the fault and restoring the power supply of the flexible DC distribution network as soon as possible. Firstly, a direction pilot protection scheme for a complex DC distribution network is proposed based on the integral of the current superposition to identify the fault direction. Then, an online time-domain fault location method based on the least square (LS) method to solve the overdetermined equations is proposed by analyzing the fault loop circuit after the DC line fault. The proposed location scheme utilizes fault data at both ends of the line to eliminate the theoretical impact of fault resistance, and the calculation of the current difference method is discussed to reduce the location error of whether the fault current-limiting reactor (CLR) exists. Finally, various simulations by PSCAD/EMTDC V4.5 demonstrate that the proposed scheme has high protection reliability and location results after different fault positions and resistances. The proposed scheme has low requirements for the sampling rate, fault data length, and implementation costs, which can meet practical application requirements.

Infrared small target detection is a key technology with a wide range of applications, and the complex background and low signal-to-noise ratio characteristics of infrared images can greatly increase the difficulty and error rate of small target detection. In this paper, an uncertainty measurement method based on local component consistency is proposed to suppress the complex background and highlight the detection target. The method analyzes the local signal consistency of the image. It then constructs a confidence assignment function and uses the mutation entropy operator to measure local uncertainty. Then, the target energy information is introduced through an energy-weighting function to further enhance the signal. Finally, the target is extracted using an adaptive threshold segmentation algorithm. The experimental results show that the algorithm can effectively detect small infrared targets in complex backgrounds. And, the algorithm is at the leading edge in terms of performance; the processing frame rate can reach 3051 FPS (frame per second), 96 FPS, and 54 FPS for image data with a resolution of 256 × 256, 1920 × 1080, and 2560 × 1440, respectively.

Drug combinations and repurposing have recently provided promising alternatives to cope with the increasingly severe issue of antibiotic resistance and depletion of natural drug molecular repertoires that undermine traditional antibacterial strategies. Closantel, an effective adjuvant, reverses antibiotic resistance in gram-negative bacteria. Herein, the combined antibacterial enantioselectivity of closantel is presented through separate enantiomer studies. Despite yielding unexpected differences, two closantel enantiomers (R, S) increased colistin activity against gram-negative bacteria both in vitro and in vivo. The fractional inhibitory concentration indices of R-closantel and S-closantel combined with colistin against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli ranged from 0.0087 to 0.5004 and from 0.0117 to 0.5312, respectively. This difference was further demonstrated using growth inhibition assays and time-killing curves. Mechanistically, a higher intracellular concentration of R-CLO is more effective in enhancing the antimicrobial activity of combination. A mouse cutaneous infection model confirmed the synergistic stereoselectivity of closantel. This discovery provides novel insights for developing precision medication and containment of increasing antibiotic resistance.

This paper investigates the effects of freeze-thaw cycles on the performance of asphalt mixtures containing 60% rejuvenated asphalt pavement (RAP). Two rejuvenation processes, traditional and bio-graded recycling, are compared regarding high-temperature performance, low-temperature performance, dynamic stability, flexural tensile strength, split tensile strength, water stability, and fatigue performance after various freeze-thaw cycles. The results indicate that bio-graded rejuvenation, compared to traditional rejuvenation, effectively enhances the high-temperature performance, low-temperature performance, water stability, and fatigue performance after freeze-thaw cycles. Both rejuvenations initially meet the dynamic stability requirements but show a decreasing trend with increasing freeze-thaw cycles, with traditional rejuvenation exhibiting more severe degradation. The flexural tensile strength initially exceeds that of conventional asphalt mixtures but decreases significantly with freeze-thaw cycles, especially in traditional rejuvenation. Additionally, freeze-thaw action increases the internal void ratio, affecting water stability and anti-freezing ability, particularly in traditional rejuvenated mixtures. These findings underscore the impact of freeze-thaw cycles on rejuvenated asphalt mixtures and emphasize the importance of innovative rejuvenation techniques for sustainable pavement.

Abstract Background The RNA‐binding motif single‐stranded interacting protein 3 (RBMS3) is a constituent of the RNA‐binding motif (RBM) protein family, which assumes a pivotal role in governing cellular biogenesis processes such as the cell cycle and apoptosis. Despite an abundance of studies elucidating RBMS3's divergent roles in the genesis and advancement of various tumors, its involvement in colon cancer remains enigmatic. Methods The present investigation employed data analysis from TCGA and GTEx to unveil that RBMS3 expression demonstrated a diminished presence in colon cancer tissues when juxtaposed with normal colon tissues. The effect of RBMS3 and LIM zinc finger domain 1 (LIMS1) on colon cancer was substantiated via animal models and cellular experiments. The connection between RBMS3 and LIM zinc finger domain 1 (LIMS1) was verified by molecular biology methods. Results The study conclusively ascertained that augmenting RBMS3 expression quells the proliferation, migration, and invasion of colon cancer cells. Furthermore, the inquiry unveiled a plausible mechanism through which RBMS3 impacts the expression of LIMS1 by modulating its mRNA stability. The investigation ascertained that RBMS3 inhibits the progression of colon cancer by regulating LIMS1. The inhibitory function of LIMS1 and RBMS3 is closely intertwined in colon cancer, with knocking down LIMS1 being able to rescue the inhibitory effect of RBMS3 overexpression on the functionality of colon cancer cell Conclusions The discernments delineate RBMS3 as a novel suppressor of cancer via LIMS1, thereby bestowing fresh therapeutic possibilities and illuminating the intricacies of colon cancer.

Pseudocapacitive polymers have garnered significant attention in the realm of supercapacitors due to their versatile molecular design capabilities, cost‐effectiveness, and impressive electrical conductivity. However, limited by the low capacity and short cycle life, the investigation on conducting polymers for potential electrode materials is still insufficient. Herein, a series of pyrenetetraone‐derived polymers with pyrazine units are designed and synthesized. Furthermore, UV–vis spectroscopy demonstrates the different interaction behavior between the polymers and reduced graphene oxide (rGO), which can further indicate the performance difference of the composite electrodes. As a result, the pseudocapacitive polymer/rGO composite electrode (2/1 PPYT/rGO) exhibits a high specific capacitance of 591 F g−1 at 1 A g−1 in a 1 m sulfuric acid electrolyte. The asymmetric supercapacitor (ASC) assembled by the 2/1 PPYT/rGO cathode and the annealed Ti3C2Tx anode (2/1 PPYT/rGO//A‐Ti3C2Tx) delivers an excellent energy density of 38.1 Wh kg−1 at a power density of 950 W kg−1. Additionally, both devices demonstrate outstanding stability, retaining over 90% of their capacity after 15 000 charge/discharge cycles. As a result, these carefully engineered organic polymers, with their well‐thought‐out structural designs, showcase exceptional electrochemical performance, positioning them as highly promising candidates for the next generation of high‐performance energy storage materials.

Abstract Bladder cancer (BCa) is heterogeneous in the tumour microenvironment (TME). However, the role of the TME in BCa in modulating the response to immunotherapy has not been fully explored. We therefore analysed fractions of immune cells using CIBERSORTx and clustered BCa into subtypes. We also analyzed weighted correlation networks to generate immunotherapy-related hub genes that we used to construct a prediction model using multivariate Cox and LASSO regression analyses. We found that BCa comprised three subtypes (C1‒C3). The prognosis of the patients was the most favourable and the response rate to anti-programmed death ligand 1 (PD-L1) was the highest in C1 among the three subtypes. Immune cells, including CD8+, CD4+ memory activated, and follicular helper T cells, activated NK cells, and M1 macrophages infiltrated the C1 subtype. The C2 subtype was enriched in M0 macrophages and activated mast cells, and the C3 subtype was enriched in B and resting immune cells. Mechanistically, the enhanced immunogenicity of subtypes C1 and C2 correlated positively with a higher response rate, whereas the dysregulated ECM-related pathways in the C2 subtype and glycolytic and fatty acid metabolic pathways in the C3 subtype impaired the responses of patients to anti-PD-L1 therapy. We also constructed a TME-related signature based on 18 genes that performed well in terms of overall survival. In conclusion, we determined prognoses and anti-PD-L1 responses by analysing TME heterogeneity in BCa.

Abstract Accurate control of front wheel angle is essential in intelligent vehicle electric‐hydraulic power steering (EHPS) system, because it has a significant impact on the safety, comfort, and reliability of vehicle steering. However, the accurate control of front wheel angle is a challenging problem due to the non‐linearity of hydraulic power in steering system and the uncertainty of steering resistance. In this paper, a model predictive control (MPC) method for front wheel angle based on steering resistance estimation is proposed. Firstly, through theoretical analysis and practical experiment of EHPS system model, the relationship between front wheel angle and steering wheel angle and the non‐linear characteristics of hydraulic power are obtained. Secondly, a sliding mode observer is established to estimate the front axle lateral tyre force and steering resistance, which is verified by MATLAB/TruckSim co‐simulation. Then a controller based on the MPC theory is designed and applied to the accurate control unit of front wheel angle in the EHPS system for real‐time control. Finally, the simulation and test platform results show that the control algorithm proposed in this paper can precisely control the vehicle's front wheel turning angle within a certain frequency range.

ObjectiveTo examine the prevalence of underlying diseases potentially associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection among residents in Henan province for developing targeted strategies on the containment of coronavirus disease 2019 (COVID-19) epidemic. MethodsWe carried out a face-to-face survey during March 2023 among 5 200 permanent residents (elder than one year) recruited with multistage random cluster sampling in 10 counties/districts across Henan province. The prevalence of eight uderlying diseases (hypertension, diabetes mellitus, heart disease, cerebral apoplexy, allergic asthma, chronic obstructive pulmonary disease [COPD], neoplasm, and chronic kidney disease [CKD]) potentially associated with SARS-CoV-2 reinfection among the participants were analyzed based on the information collected using a questionnaire having been used by Chinese Center for Disease Control and Prevention. ResultsAmong the 5188 participants with valid responses, 1 253 (24.2%) reported suffering from one or more of the eight underlying diseases and the number (proportion) of the participants suffering from one of the eight diseases were 883 (17.0%) for hypertension, 302 (5.8%) for diabetes mellitus, 254 (4.9%) for cardiac disease, 106 (2.0%) for stroke, 20 (0.4%) for allergic asthma, 17 (0.3%) for COPD, 17 (0.3%) for neoplasm, and 12 (0.2%) for CKD, respectively. There were 283 (5.5%) of the participants reported suffering from two or more of the eight underlying diseases; of the participants having comorbidities, 82.7%, 15.5%, and 1.8% suffered from 2, 3, and 4 of the eight underlying diseases, with the top four multimorbidity patterns of diabetes plus hypertension (reported by 95 [33.6%] of the participants), hypertension plus heart disease (83, 29.3%), hypertension plus stroke (28, 9.9%), and diabetes mellitus plus hypertension and heart disease (24, 8.5%). ConclusionThe prevalence of underlying diseases potentially associated with SARS-CoV-2 reinfection was higher and hypertension was a predominant underlying disease among the residents in Henan province. The results suggest that the risk of SARS-CoV-2 reinfection for persons with underlying diseases needs to be assessed.

ObjectiveTo examine time-dependent variations in serum antibodies of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) among confirmed coronavirus disease 2019 (COVID-19) cases at different stages and inactivated COVID-19 vaccine recipients after inoculation. MethodsThe study was conducted in a city of Henan province. Totally 86 serum samples were collected from 43 confirmed COVID-19 cases at acute stage (1th – 23rd day of onset) and recovery state (25th – 58th day of onset) during January 2020 – October 2021; other 184 serum samples from 46 healthy recipients of inactivated COVID-19 vaccine at 4/8/12/31 weeks after inoculations and 50 serum samples from 50 residents without confirmed SARS-CoV-2 infections were also collected during March – October 2021. Anti-SARS-CoV-2 immunoglobulin A/G/M (IgA/G/M) were detected with magnetic particle chemiluminescence method and enzyme-linked immunosorbent assay for all the serum samples. The levels of the serum antibodies among the three groups′ participants were analyzed statistically. ResultsAmong the confirmed COVID-19 cases, the positivity rates of anti-SARS-CoV-2 IgA, IgM and IgG of the serum samples collected at recovery stage were significantly higher than those at acute stage (all P < 0.05) ; while, the concentrations of anti-SARS-CoV-2 IgM and IgG of the serum samples collected at recovery stage were significantly higher than those at acute stage (both P < 0.05). Among the healthy COVID-19 vaccine recipients 31 weeks after the inoculations, the positivity rate was 63.04% (29/46) for anti-SARS-CoV-2 IgG and 36.96% (17/46) for anti-SARS-CoV-2 IgA, but all samples were negative for anti-SARS-CoV-2 IgM. No significant differences were observed in the absorbance ratios anti-SARS-CoV-2 IgA among the samples collected 4, 8, 12, and 31weeks after the inoculation (F = 2.365, P = 0.073), but there were significant differences in the concentrations of anti-SARS-CoV-2 IgM and IgG (both P < 0.05) among the samples. Both the positivity rate of anti-SARS-CoV-2 IgA and IgM and the concentrations of anti-SARS-CoV-2 IgG and IgM were significantly higher among the confirmed COVID-19 cases than those among the inactivated COVID-19 vaccine recipients during a comparable period of time (P < 0.05 for all). ConclusionThe positivity rate of serum anti-SARS-CoV-2 IgG is the highest during early stage and recovery stage among COVID-19 cases. The positivity of serum anti-SARS-CoV-2 IgA and IgG occur earlier than that of IgM and could maintain till 31 weeks after the inoculation among inactivated COVID-19 vaccine recipients. The concentration of serum anti-SARS-CoV-2 IgG and IgM are higher among COVID-19 cases than those among inactivated COVID-19 vaccine recipients during a comparable period of time.

With the rapid development of the civil aviation industry, the number of flights has increased rapidly. However, the availability of flight slot resources remains limited, and how to allocate flight slot resources effectively has been a hot research topic in recent years. A comprehensive flight slot optimization method can significantly enhance the rationality of the allocation results. The effective allocation of flight slot is the key to improving the operational efficiency of the multi-airport system. We will optimize the flight schedule of the entire multi-airport system considering the fairness of each airport in it. The optimization results will provide an important reference for the reasonable allocation of flight slot within the multi-airport system. Based on the operation characteristics of the multi-airport system, we have established a multi-objective flight slot allocation optimization model. In this model, we set the airport capacity limit, shared waypoint capacity limit and aircraft turnaround time limit as the constraints. The optimization goal of the model is to minimize total flight schedule displacement and the maximum deviation of fairness from the absolute fairness. Gurobi solver is used to solve the model. We have innovatively incorporated the rolling capacity constraint method into our model to ensure more accurate flight slot allocation results. The Beijing-Tianjin-Hebei regional multi-airport system is selected as an example to verify the above model, and the flight slot optimization results have successfully met the fairness goal. The comparative analysis has demonstrated that the rolling capacity constraint method significantly improves the accuracy of solution results, leading to more stable flight slot allocation. The results also prove that the flight slot allocation method of multi-airport system based on absolute fairness of peak demand can improve the fairness of the allocation results. To achieve a higher level of fairness, we have found that the peak-demand based fairness method requires a smaller slot displacement compared to the non-peak demand-based method. Through the optimization of flight slot of the multi-airport system, the coordination between airports can be significantly improved. It can provide a new solution for the efficient operation of the multi-airport system.

Recent years have seen increasing interest in uranyl(VI) photocatalysis. In this study, uranyl complexes were successfully synthesized from ligands L1–L6 and UO2(NO3)2·6H2O under reflux conditions, yielding products 1–6 with yields ranging from 30% to 50%. The complexes were thoroughly characterized using NMR spectroscopy, single-crystal X-ray diffraction, and elemental analysis. The results indicate that complexes 1–5 possess a pentagonal bipyramidal geometry, whereas complex 6 exhibits an octahedral structure. The photocatalytic properties of these novel complexes for sp3 C-H bond functionalization were explored. The results demonstrate that complex 4 functions as an efficient photocatalyst for converting C-H bonds to C-C bonds via hydrogen atom transfer under blue light irradiation.

Abstract The prognosis of lung cancer is poor with few effective therapies. Targeting ferroptosis is a new promising strategy for cancer therapy. LINC00641 has been involved in several cancers, however, its specific roles in lung cancer treatment remain largely unknown. Here, we reported that LINC00641 was down-regulated in tumor tissues and its downregulation was associated with poor outcomes in lung adenocarcinoma. LINC00641 was localized primarily in the nucleus and was modified by m6A. The nuclear m6A reader YTHDC1 regulated LINC00641 expression by affecting its stability. We demonstrated that LINC00641 suppressed lung cancer by inhibiting migration and invasion in vitro and metastasis in vivo. Knockdown of LINC00641 upregulated HuR protein level (especially in the cytoplasm), which subsequently increased N-cadherin levels by stabilizing its mRNA, then ultimately promoted EMT. Interestingly, LINC00641 knockdown in lung cancer cells increased the arachidonic acid metabolism and promoted ferroptosis sensitivity. Our findings identified LINC00641 as a tumor suppressor through inhibiting EMT. In another aspect, low expression of LINC00641 caused a ferroptotic vulnerability in lung cancer cells, which may serve as a potential ferroptosis-related therapeutic target for lung cancer.

BackgroundThere is a lack of precision in the immunotherapy strategy tailored for patients exhibiting diverse clinical characteristics. This study aims to employ a rigorous network meta-analysis (NMA) approach to systematically evaluate the effectiveness of immune-combination therapies among patients with advanced hepatocellular carcinoma, taking into account their varying clinico-characteristics.MethodsStudies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science databases. The included first-line phase III studies were categorized into three types: immunotherapy combined with anti-angiogenetic agents, immunotherapy combined with tyrosine kinase inhibitors, and dual immunotherapy, with sorafenib serving as the control group. The primary endpoint used to assess efficacy was overall survival (OS), facilitating a comparative analysis among the three treatment modalities. Furthermore, subgroup analyses were conducted to evaluate the varying effectiveness for patients with diverse clinico-characteristics. Secondary outcome measures included progression-free survival, objective response rate, and toxicity assessment.ResultsA total of 6 studies were included in the NMA, encompassing a cohort of 3840 patients. The results revealed that immunotherapy combined with anti-angiogenetic agents exhibited a significantly enhanced therapeutic effect in terms of improving OS compared to sorafenib (HR = 0.61, 95% CrI, 0.42-0.90). Furthermore, based on various clinicopathological features, this combination therapy demonstrated superior OS responses in specific patient subgroups: BCLC C (HR = 0.63, 95% CrI, 0.42-0.93), ECOG 1 (HR = 0.57, 95% CrI, 0.36-0.91), with extrahepatic spread (EHS) (HR = 0.59, 95% CrI, 0.37-0.92), alpha fetoprotein (AFP)ConclusionsImmunotherapy combined with anti-angiogenetic agents could represent the most effective first-line intervention for achieving improved OS, particularly in patients with viral hepatitis positivity.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

Metal–insulator transition has long been one of the key subjects in condensed matter systems. Herein, the emergence of a large energy gap (Eg, 0.8–1.0 eV) in Bi(110) two‐atomic‐layer nanoribbons grown on a SnSe(001) substrate is reported, which normally has an intrinsic semimetal‐like characteristic. The existence of this abnormally large Eg in Bi(110) is, however, determined by Bi coverage. When coverage is above ≈64 ± 2%, Eg vanishes, and instead, a Bi(110) semimetal‐like phase appears through a singular insulator–metal transition. Measurements using qPlus atomic force microscopy demonstrate that either insulating or semimetal‐like Bi(110) possesses a distorted black phosphorous structure with noticeable atomic buckling. Density function theory fully reproduces the semimetal‐like Bi(110) on SnSe(001). However, none of the insulating phases with this large Eg could be traced. Although the underlying mechanism of the large Eg and the insulator‐metal transition requires further exploration, experiments demonstrate that similar results can be achieved for Bi grown on SnS, the structural analog of SnSe, exhibiting an even larger Eg of ≈2.3 eV. The experimental strategy may be generalized to utilization of group‐IV monochalcogenides to create Bi(110) nanostructures with properties unachievable on other surfaces, providing an intriguing platform for exploring the interesting quantum electronic phases.

Drought causes a decrease in tobacco yield and quality as well as a reduction in net photosynthetic rate. Salicylic acid (SA) is involved in the regulation of many physiological processes and has been widely used to improve plant drought tolerance. The hydroponic experiment was carried out on flue-cured tobacco variety K326. SA solutions (0.3 mM) were sprayed on the leaves every day for three days, after which 15% PEG-6000 was used to simulate moderate drought. The results showed that drought stress reduced the photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr), while it enhanced the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), malondialdehyde (MDA), proline and protein content. Compared with PEG drought stress, SA improved the Pn, Gs and Tr by 45.74%, 26.82%, and 52.22% respectively. Besides, the activities of SOD, POD, CAT, protein and proline content increased by 44.27%, 50.18%, 25%, 34.69% and 24.88%, respectively, while the MDA content decreased by 23.89%. Furthermore, SA spraying increased the drought tolerance of tobacco by modulating the expression level of the genes associated with photosynthesis, carbon metabolism, and photosynthesis-antenna proteins. Hence, SA spraying reduced the inhibition of drought on photosynthesis and stimulated the antioxidant system, thus improving the drought resistance in tobacco.

Objective: This study was designed to explore the effect of camel milk on glucose and lipid metabolism metabolism in mice with nonalcoholic fatty liver disease induced by high fat, high sugar and high cholesterol diet. Methods: 50 C57BL6/J male mice were randomly divided into control group (NC), model group (Mod), control camel milk group (NCM, 3g·kg−1 bw), camel milk group (CaM, 3 g·kg−1 bw) and silymarin group (PC, 200 mg·kg−1 bw). The model of nonalcoholic fatty liver was established for 12 weeks. The mice in the camel milk group and the silymarin group were gavaged with the corresponding doses of camel milk and silymarin at a fixed time every day, respectively. Body weight, fasting blood glucose, serum biochemical, insulin resistance and insulin sensitivity, oral glucose tolerance and insulin tolerance were measured to investigate the effect of camel milk on glucolipid metabolism in mice with non-alcoholic fatty liver disease induced by high fat, high sugar, and high cholesterol diet. Results: Camel milk significantly inhibited the increase of body weight and blood sugar of NAFLD mice and notably reduced the levels of total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), tumor necrosis factor (TNF-α), leptin (LEP) and insulin (INS) (P

In this paper, a novel electric-hydraulic power steering (EHPS) system and a vehicle stability coordination control algorithm are proposed which can not only ensure the accuracy of the trajectory tracking but also solve the coordination control problem between the stability of the lateral control and the stability of the roll in the extreme condition. Firstly, the EHPS system is designed to provide accurate control input of front wheel angle for vehicle lateral dynamics control. Secondly, on the basis of optimal preview theory, a new trajectory tracking fusion controller combined with sliding mode control is proposed to improve the accuracy and stability of the system in the process of vehicle lateral trajectory tracking control. Then, the stability domain boundary function of the phase plane is determined according to the phase plane of the sideslip angle-yaw rate, and the stability margin of the phase plane is calculated during the steering process. Finally, considering the tracking accuracy, lateral stability and roll stability performance in the process of trajectory tracking, the linear weighted algorithm is used to coordinate above three objectives, and the HIL bench test and real vehicle experiment verify that the proposed algorithm has good reliability and effectiveness.

Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections.

Abstract Electrocatalytic urea synthesis via coupling of nitrate with CO2 is considered as a promising alternative to the industrial urea synthetic process. However, the requirement of sub‐reaction (NO3RR and CO2RR) activities for efficient urea synthesis is not clear and the related reaction mechanisms remain obscure. Here, the construction, breaking, and rebuilding of the sub‐reaction activity balance would be accompanied by the corresponding regulation in urea synthesis, and the balance of sub‐reaction activities was proven to play a vital role in efficient urea synthesis. With rational design, a urea yield rate of 610.6 mg h−1 gcat.−1 was realized on the N‐doped carbon electrocatalyst, superior to that of noble‐metal electrocatalysts. Based on the operando SR‐FTIR measurements, we proposed that urea synthesis arises from the coupling of *NO and *CO to generate the key intermediate of *OCNO. This work provides new insights and guidelines into urea synthesis from the aspect of activity balance.

Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.

Abstract Background Acute myeloid leukemia (AML) patients with normal karyotype (NK-AML) have significant variabilities in outcomes. The European Leukemia Net stratification system and some prognostic models have been used to evaluate risk stratification. However, these common standards still have some limitations. The biological functions and mechanisms of Small Integral Membrane Protein 3 (SMIM3) have seldomly been investigated. To this date, the prognostic value of SMIM3 in AML has not been reported. This study aimed to explore the clinical significance, biological effects and molecular mechanisms of SMIM3 in AML. Methods RT-qPCR was applied to detect the expression level of SMIM3 in bone marrow specimens from 236 newly diagnosed adult AML patients and 23 healthy volunteers. AML cell lines, Kasumi-1 and THP-1, were used for lentiviral transfection. CCK8 and colony formation assays were used to detect cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to explore relevant signaling pathways. The biological functions of SMIM3 in vivo were validated by xenograft tumor mouse model. Survival rate was evaluated by Log-Rank test and Kaplan–Meier. Cox regression model was used to analyze multivariate analysis. The correlations between SMIM3 and drug resistance were also explored. Results Through multiple datasets and our clinical group, SMIM3 was shown to be significantly upregulated in adult AML compared to healthy subjects. SMIM3 overexpression conferred a worse prognosis and was identified as an independent prognostic factor in 95 adult NK-AML patients. Knockdown of SMIM3 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. The reduced SMIM3 expression significantly suppressed tumor growth in the xenograft mouse model. Western blot analysis showed downregulation of p-PI3K and p-AKT in SMIM3-knockdown AML cell lines. SMIM3 may also be associated with some PI3K-AKT and first-line targeted drugs. Conclusions SMIM3 was highly expressed in adult AML, and such high-level expression of SMIM3 was associated with a poor prognosis in adult AML. Knockdown of SMIM3 inhibited the proliferation of AML through regulation of the PI3K-AKT signaling pathway. SMIM3 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

The direct electrocatalytic synthesis of urea via C–N coupling is of great significance. The authors report a diatomic catalyst with bonded Fe–Ni pairs to improve the efficiency of electrochemical urea synthesis from nitrate and CO2.

Poor tenderness of camel meat has seriously hampered the development of the camel meat industry. This study investigated the effects of muscle fiber composition and ageing time on meat quality, glycolytic potential, and glycolysis-related enzyme activities. Muscle samples of the longissimus thoracis (LT), psoas major (PM), and semitendinosus (ST) were collected from eight 8–10 year old Sonid Bactrian camels (females). Muscle fiber composition was examined by ATPase staining and immunohistochemistry. Meat quality indexes, glycolytic potential, and activities of major glycolytic enzymes were examined at 4 °C aging for 1, 6, 24, 72, and 120 h. The results showed that LT was mainly composed of type IIb muscle fibers, whereas PM and ST were mainly composed of type I muscle fibers. The PCR results of the myosin heavy chain (MyHC) were consistent with the ATPase staining results. During aging, the shear force of LT muscle was always greater than that of PM and ST, and its glycolysis was the strongest; type IIa, IIb, and IIx muscle fibers were positively correlated with muscle shear force and glycolysis rate, and type I muscle fibers were significantly and negatively correlated with the activities of the key enzymes of glycolysis within 6 h. The results showed that the muscle fibers of LT muscle had the greatest glycolysis capacity. These results suggest that an excessive type IIb muscle fiber number percentage and area in camel meat accelerated the glycolysis process, but seriously affected the sensory profile of the camel meat. The results of this study provide directions for the camel industry when addressing the poor tenderness of camel meat.

In recent years, photobiomodulation (PBM) has attracted widespread attention for the treatment of various causes of pain and inflammation. Primary dysmenorrhea (PD) is a common gynecological condition characterized by severe menstrual pain, and the limited effectiveness and side effects of conventional treatments have highlighted the urgent need to develop and identify new adjunct therapeutic strategies. The present study from the perspective of light morphology aimed to bypass the heat risk limitation and evaluate the efficacy and safety of pulsed 630 nm PBM therapy for reducing pain associated with PD. The pulse light parameters were designed according to the transmittance of red light. In this randomized, cross-over design, sham-controlled study, 46 women with PD were included and randomly assigned to either pulsed 630 nm light therapy or white light sham control therapy. The intervention lasted for 20 min per day and was administered for 7 consecutive days before and during menstruation. The results showed that the pulsed 630 nm PBM treatment demonstrated a significant reduction in pain levels compared to the placebo treatment (p < 0.001), with 55.00% of active treatment participants experiencing a pain intensity differential concentration exceeding 50.00%. Moreover, participants reported an improved quality of life during the active treatment phase and generally preferred it as a more effective method for relieving PD. No adverse events or side effects were reported throughout the trial. Based on the results, pulsed 630 nm LED therapy showed significant relief of menstrual pain compared to white light placebo treatment and improved quality of life under certain circumstances. Therefore, this study proposes that pulsed red light PBM therapy may be a promising approach for future clinical treatment of PD.

Supply Chain Finance (SCF) refers to the financial service in which banks rely on core enterprises to manage the capital flow and logistics of upstream and downstream enterprises. SCF adopts a self-testing and closed-loop credit model to control funds and risks. The key factor in a successful SCF service is the deployment of SCF business-oriented information systems that allow businesses to form partnerships efficiently and expedite cash flows throughout the supply chain. Blockchain Technology (BCT), featuring decentralization, tamper-proofing, traceability, which is usually paired with the Internet of Things (IoT) in real-world contexts, has been widely adopted in the field of finance and is perfectly positioned to facilitate innovative collaborations among participants in supply chain networks. In this paper, we propose a BCT and IoT-based information management framework (named BC4Regu), which works as the regulatory to improve the information transparency in the business process of SCF. With BC4Regu, the operation cost of the whole supply chain can be significantly reduced through the coordination and integration of capital flow, information flow, logistics and trade flow in the supply chain. The contributions in this paper include: (1) proposing a novel information management framework which leverages Blockchain and IoT to solve the problem of information asymmetry in the trade of SCF; (2) proposing the technical design of BC4Regu, including the Blockchain infrastructure, distributed ledger-based integrated data flow service, and reshaped SCF process; and (3) applying BC4Regu to a group of scenarios and conducting theoretical analysis by introducing the principal-agent model to validate the BC4Regu.

Abstract. Background:. The CHA2DS2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA2DS2–VASc score in stroke and all-cause mortality. Methods:. Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA2DS2–VASc score model. Results:. Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA2DS2–VASc score significantly improved the discrimination and reclassification power of the CHA2DS2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA2DS2–VASc model for predicting all-cause mortality. Conclusions:. Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA2DS2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

Increasing frequencies of heatwaves combined with simultaneous drought stress in Europe threaten the ecosystem water and carbon budgets of alpine grasslands. Dew as an additional water source can promote ecosystem carbon assimilation. It is known that grassland ecosystems keep high evapotranspiration as long as soil water is available. However, it is rarely being investigated whether dew can mitigate the impact of such extreme climatic events on grassland ecosystem carbon and water exchange. Here we use stable isotopes in meteoric waters and leaf sugars, eddy covariance fluxes for H2O vapor and CO2, in combination with meteorological and plant physiological measurements, to investigate the combined effect of dew and heat-drought stress on plant water status and net ecosystem production (NEP) in an alpine grassland (2000 m elevation) during the June 2019 European heatwave. Before the heatwave, enhanced NEP in the early morning hours can be attributed to leaf wetting by dew. However, dew benefits on NEP were cancelled out by the heatwave, due to the minor contribution of dew in leaf water. Heat-induced reduction in NEP was intensified by the combined effect of drought stress. The recovery of NEP after the peak of the heatwave could be linked to the refilling of plant tissues during nighttime. Among-genera differences of plant water status affected by dew and heat-drought stress can be attributed to differences in their foliar dew water uptake, and their reliance on soil moisture or the impact of the atmospheric evaporative demand. Our results indicate that dew influence on alpine grassland ecosystems varies according to the environmental stress and plant physiology.

It is important yet challenging to improve the interface contact between commonly used carbon conductive layer and metal oxide catalysts. Here the authors propose BiCuSeO with alternant active [Bi2O2]2+ sublayers and conductive [Cu2Se2]2- sublayer within its superlattice as efficient catalyst for CO2 electroreduction to formate.

ABSTRACT: Objectives: The aim of this study was to explore the prevalence of blaCTX-M and elucidate the characteristics of transferable blaCTX-M-55 plasmids. Methods: Escherichia coli were isolated from 10 large-scale duck farms from nine counties and cities in Guizhou Province. They were identified, subjected to antimicrobial susceptibility testing and screened for antibiotic resistance genes. blaCTX-M-positive strains were subtyped, and blaCTX-M-55-containing strains were further analysed by multilocus sequence typing, conjugation experiments and polymerase chain reaction–based replicon typing. Three transferable plasmids were selected for whole genome sequencing sequencing and further analysis of genetic context. Results: In total, 128 E. coli strains were identified, and 23 were blaCTX-M-positive. Subtype analysis of blaCTX-M-positive strains revealed that 23 were blaCTX-M-55 and one of the strains contained both blaCTX-M-65 and blaCTX-M-55. They were divided into 12 multilocus sequence typing types, and 6 were undetermined. blaCTX-M-55-bearing plasmids in seven were transferred to E. coli C600 at frequencies between 10−6 and 10−9, and blaCTX-M-55 was found to be located on IncN, IncFⅡ and IncFII-N fusion type plasmids. Three plasmids (IncFⅡ plasmids pEC99_Plas3 and pS1_Plas2 and IncFII-N plasmid pD2_plas2) shared a homologous region of IS26-ARGs-IS26-blaTEM-orf477-blaCTX-M-55-ISEcp1△-IS26. Conclusion: Our study demonstrates the environmental presence of blaCTX-M-55 harbouring E. coli in Guizhou. Analysis of the genetic context of blaCTX-M-55 aids in understanding possible dissemination routes of ESBL genes and controlling widespread antibiotic resistance.

Abstract. Cardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.

China lacks design strategies to improve home-based care environments for its older adults. This study investigated the perception of indoor environmental quality in housing environments and analyzed its impact on health and satisfaction among home-living older adults. A cross-sectional survey in Northern China was conducted during the COVID-19 pandemic (October 2021–March 2022) to test the effects of five housing environmental factors on home-living older adults’ health and satisfaction, including noise, lighting and view, temperature and humidity, air quality, and maintenance and cleanliness. A total of 356 home-living adults aged 60 years and older participated in the survey. The 12-item Short Form Health Survey was used to measure health-related quality of life among respondents. Using multiple regression analyses, we found that overall satisfaction can be positively predicted by four housing environmental qualities: lighting and view, temperature and humidity, air quality, and maintenance and cleanliness. Air quality was found to be a predictor of respondents’ physical health. Only noise had a significant predictive effect on respondents’ mental health. Age, marital status, and health status (cardiovascular and chronic diseases) were significantly correlated with the physical health of the respondents, whereas educational status, monthly income, and alcohol consumption could predict their mental health.

Abstract Nitrate is an important precursor of tobacco-specific nitrosamines (TSNAs) and a remarkable difference in nitrate accumulation between lamina and midrib of flue-cured tobacco has long been observed. However, the physiological and molecular mechanisms underpinning this difference remain poorly understood. In this study, physiological and genetic factors impacting nitrate accumulation were identified in pot experiments using flue-cured tobacco K326 with contrasting nitrate content between lamina and midrib. The results showed that three times higher NO3-N content was observed in midrib than that in the lamina, along with lower pigment, NH4-N content, nitrate reductase activity (NRA), sucrose synthetase activity (SSA), and glutamine synthetase activity (GSA) in midrib. Transcriptome analysis revealed that expression of genes involved in porphyrin and chlorophyll metabolism, carotenoid biosynthesis, photosynthesis-antenna proteins, photosynthesis, carbon fixation in photosynthetic organisms, starch and sucrose metabolism, nitrogen metabolism, and biosynthesis of amino acids were significantly lower in midrib than in lamina. qRT-PCR results showed that the expression level of nitrate transporter genes LOC107782967, LOC107806749, LOC107775674, LOC107829632, LOC107799198, LOC107768465 decreased by 2.74, 1.81, 49.5, 3.5, 2.64 and 2.96-folds while LOC107789301 increased by 8.23-folds in midrib but not in lamina. Reduced chlorophyll content might result in low carbohydrate formation which is the source of energy and carbon skeleton supply, then the low capacity of nitrogen reduction, assimilation and transportation, and the poor ability of nitrate reallocation but the high capacity of accumulation might lead to nitrate accumulation in midrib. The results laid the foundation for reducing nitrate content and TSNA formation in tobacco midribs and their products.

Nitrogen deficiency can cause floral abortion during reproductive development of rice. Here the authors show that when nitrogen is limited, rice plants require the ETFβ protein, which is involved in branched chain amino acid catabolism, to promote nitrogen reutilization and support the initiation of meiosis.