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Abstract Background Sterigmatocystin (STE) is a mycotoxin widely found in contaminated food and foodstuffs, and excessive long-term exposure to STE is associated with several health issues, including infertility. However, there is little information available regarding the effects of STE toxin on the female reproductive system, particularly concerning oocyte maturation. Methods In the present study, we investigated the toxic effects of STE on mouse oocyte maturation. We also used Western blot, immunofluorescence, and image quantification analyses to assess the impact of STE exposure on the oocyte maturation progression, mitochondrial distribution, oxidative stress, DNA damages, oocyte ferroptosis and asymmetric division defects. Results Our results revealed that STE exposure disrupted mouse oocyte maturation progression. When we examined the cellular changes following 100 µM STE treatment, we found that STE adversely affected polar body extrusion and induced asymmetric division defects in oocytes. RNA-sequencing data showed that STE exposure affects the expression of several pathway-correlated genes during oocyte meiosis in mice, suggesting its toxicity to oocytes. Based on the RNA-seq data, we showed that STE exposure induced oxidative stress and caused DNA damage in oocytes. Besides, ferroptosis and α-tubulin acetylation were also found in STE-exposed oocytes. Moreover, we determined that STE exposure resulted in reduced RAF1 protein expression in mouse oocytes, and inhibition of RAF1 activity also causes defects in asymmetric division of mouse oocytes. Conclusions Collectively, our research provides novel insights into the molecular mechanisms whereby STE contributes to abnormal meiosis.

Ground volume loss is an important parameter for settlement control and prediction in shield tunneling. This parameter is usually determined empirically, while its variation along the tunnel is not predictable. In this study, an analytical formula for ground volume loss is obtained based on physical derivation. The ground volume loss is divided into two components. Key operational parameters, i.e. face pressure, grouting pressure and grouting volume, are used to calculate the two components. The proposed formula is then validated against the field data collected from Changzhou Metro in thick silty clay layer. The validation shows that the new formula gives reasonable prediction of ground volume loss. Furthermore, the three model coefficients derived from physical calculation are very close to the regression coefficients based on statistical method. For EPB tunnels excavated in silty clay layer, the ground volume loss along a specific tunnel can be predicted by the new formula. The analysis also indicates that the surface settlement of EPB tunnel should be controlled by a balanced combination of varied operational parameters.

To investigate the impact of Jolkinolide B (JB) on renal cell carcinoma (RCC), we treated RCC cell lines with various concentrations of JB (0, 5, 25, 50 and 100 μM) for 24 hours and assessed cell viability using the cell counting kit-8 (CCK-8) analysis. Then, we examined JB’s effects on proliferation, migration, apoptosis, reactive oxygen species (ROS) accumulation, and endoplasmic reticulum (ER) stress through 5-ethynyl-2′-deoxyuridine (EdU) incorporation, transwell migration assays, flow cytometry, ROS level determination, and western blot assays. Furthermore, we investigated the potential mechanism using western blot. Our results showed that JB dose-dependently reduced cell viability in both 786-O and Caki1 cells. Additionally, JB at concentrations of 5, 25 and 50 μM decreased the number of EdU-positive and migrating cells in both cell lines. Additionally, these concentrations of JB increased apoptosis rates, relative protein expressions of cleaved caspase-3 and cleaved caspase-9, ROS levels, and relative protein expressions of C/EBP-homologous protein (CHOP) and activated transcription factor 4 (ATF4) in both 786-O and Caki1 cells. Mechanistically, treatment with all three concentrations of JB significantly downregulated phosphorylated p38 (p-p38)/p38, phosphorylated protein kinase B (p-AKT)/AKT and phosphorylated phosphatidylinositol-3-kinase (p-PI3K)/PI3K in a dose-dependent manner. In summary, JB inhibited proliferation and migration while promoting apoptosis, ROS accumulation, and ER stress in RCC cells, potentially through the inactivation of mitogen-activated protein kinase (MAPK) and AKT signaling pathways.

BackgroundThe burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. ObjectiveTo preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. MethodsA mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. ResultsThe mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P0.05), but the renal histopathological injury scores were significantly increased (P0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P

Abstract Currently, many real-time semantic segmentation networks aim for heightened accuracy, inevitably leading to increased computational complexity and reduced inference speed. Therefore, striking a balance between accuracy and speed has emerged as a crucial concern in this domain. To address these challenges, this study proposes a dual-branch fusion network with multiscale atrous pyramid pooling aggregate contextual features for real-time semantic segmentation (MAFNet). The first key component, the semantics guide spatial-details module (SGSDM) not only facilitates precise boundary extraction and fine-grained classification, but also provides semantic-based feature representation, thereby enhancing support for spatial analysis and decision boundaries. The second component, the multiscale atrous pyramid pooling module (MSAPPM), is designed by combining dilation convolution with feature pyramid pooling operations at various dilation rates. This design not only expands the receptive field, but also aggregates rich contextual information more effectively. To further improve the fusion of feature information generated by the dual-branch, a bilateral fusion module (BFM) is introduced. This module employs cross-fusion by calculating weights generated by the dual-branch to balance the weight relationship between the dual branches, thereby achieving effective feature information fusion. To validate the effectiveness of the proposed network, experiments are conducted on a single A100 GPU. MAFNet achieves a mean intersection over union (mIoU) of 77.4% at 70.9 FPS on the Cityscapes test dataset and 77.6% mIoU at 192.5 FPS on the CamVid test dataset. The experimental results conclusively demonstrated that MAFNet effectively strikes a balance between accuracy and speed.

Abstract Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g−1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

IntroductionIn recent years, coxsackievirus (CV) A10 has been associated with increasing sporadic hand, foot, and mouth disease (HFMD) cases and outbreaks globally. In addition to mild symptoms such as pharyngitis and herpangina, CVA10-related complications or even fatality can occur. Currently, systematic phylogenetic studies of CVA10 are limited.MethodsIn this study, we first explored the epidemiological and genetic characteristics of CVA10 in Nanchang, an inland southeastern city of China, based on the HFMD surveillance network from 2015-2023.ResultsAmong 3429 enterovirus-positive cases, 110 (3.04%) were associated with CVA10, with a male-to-female ratio of 1.62. The median age of the CVA10 patients was 2.3 years (interquartile range, IQR 1.0-4.0), with 94.55% (104/110) of the patients aged less than 5 years. Phylogenetic analyses using the full-length VP1, 5’UTR, P1, P2, P3 sequences and near full-length genomes indicated that CVA10 strains (n = 57) isolated in Nanchang belonged to genogroup C; two strains identified in 2017 belonged to C1 subtypes clustered with strains from Vietnam, Madagascar, France and Spain; and the others belonged to C2 subtypes interdigitating with CVA10 isolates from mainland China, the United States and Australia. Through extensive analysis, we identified a rare F168Y mutation in epitope 4 of VP1 in a Madagascar strain of genogroup F and a Chinese strain of genogroup C. Based on Bayesian evolutionary analyses, the average nucleotide substitution rate for the VP1 gene of CV10 strains was 3.07×10–3 substitutions/site/year. The most recent common ancestor (tMRCA) of genogroup C was dated 1990.84, and the tMRCA of CVA10 strains from Nanchang was dated approximately 2003.16, similar to strains circulating in other regions of China, suggesting that the viruses were likely introduced and cryptically circulated in China before the establishment of the HFMD surveillance network. Recombination analysis indicated intertypic recombination of the Nanchang strain with the genogroup G strain in the 3D region.DiscussionGiven the shifting dominance of viral genotypes and frequent recombination events, the existing surveillance system needs to be regulated to enhance genomic surveillance efforts on a more diverse spectrum of genotypes in the future.

Psoriasis is a chronic, relapsing, inflammatory skin disease and has been increasing year by year. It is linked to other serious illnesses, such as psoriatic arthritis, cardiometabolic syndrome, and depression, resulting in a notable decrease in the quality of life for patients. Existing therapies merely alleviate symptoms, rather than providing a cure. An in-depth under-standing of the pathogenesis of psoriasis is helpful to discover new therapeutic targets and develop effective novel therapeutic agents, so it has important clinical significance. This article reviews the new progress in the study of pathogenesis and natural products of psoriasis in recent years. These natural products were summarized, mainly classified as terpenoids, polyphenols and alkaloids. However, the translation of experimental results to the clinic takes a long way to go.

A range of fire experiments were conducted to explore fire characteristics and smoke dynamics in a 1/6-scale stairwell adjacent to a room at different external wind velocities. The results indicated that the flame volume during the initial stage and the time taken for combustion to enter the steady stage both decrease with the increasing wind velocity. There are two opposite effects of the external wind on the fire combustion in a burning room adjacent to a stairwell. The inhibition effect plays an important role at lower wind velocities, leading to a decrease in the mass loss rate (MLR) of the pool fire. Conversely, the promotion effect dominates at higher wind velocities, resulting in an increase in the MLR. Stack effect and external wind demonstrate a synergistic relationship during experiments, and a correlation of the airflow velocity, wind velocity and heat release rate (HRR) is established. There are intersections in temperature curves at different wind velocities due to the smaller temperature decay rate in the stairwell and the lower smoke temperature near the pool fire at a higher velocity. Furthermore, a prediction model is also proposed for the smoke temperature distribution inside the stairwell, taking into account the wind velocity and HRR.

Abstract Background Neuroepithelial transforming gene 1 (NET1) is a RhoA subfamily guanine nucleotide exchange factor that governs a wide array of biological processes. However, its roles in meiotic oocyte remain unclear. We herein demonstrated that the NET1-HACE1-RAC1 pathway mediates meiotic defects in the progression of oocyte maturation. Methods NET1 was reduced using a specific small interfering RNA in mouse oocytes. Spindle assembly, chromosomal alignment, the actin cap, and chromosomal spreads were visualized by immunostaining and analyzed under confocal microscopy. We also applied mass spectroscopy, and western blot analysis for this investigation. Results Our results revealed that NET1 was localized to the nucleus at the GV stage, and that after GVBD, NET1 was localized to the cytoplasm and predominantly distributed around the chromosomes, commensurate with meiotic progression. NET1 resided in the cytoplasm and significantly accumulated on the spindle at the MI and MII stages. Mouse oocytes depleted of Net1 exhibited aberrant first polar body extrusion and asymmetric division defects. We also determined that Net1 depletion resulted in reduced RAC1 protein expression in mouse oocytes, and that NET1 protected RAC1 from degradation by HACE1, and it was essential for actin dynamics and meiotic spindle formation. Importantly, exogenous RAC1 expression in Net1-depleted oocytes significantly rescued these defects. Conclusions Our results suggest that NET1 exhibits multiple roles in spindle stability and actin dynamics during mouse oocyte meiosis.

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund’s adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide and has emerged as a serious public health threat, due in large part to its multiple virulence factors and remarkable resistance capabilities. Stk1, a eukaryotic-type Ser/Thr protein kinase, has been shown in our previous work to be involved in the regulation of several signalling pathways and biological processes. Here, we demonstrate that deletion of stk1 leads to alterations in several virulence- and resistance-related physiological functions, including reduced pyocyanin and pyoverdine production, attenuated twitching motility, and enhanced biofilm production, extracellular polysaccharide secretion, and antibiotic resistance. Moreover, we identified AlgR, an important transcriptional regulator, as a substrate for Stk1, with its phosphorylation at the Ser143 site catalysed by Stk1. Intriguingly, both the deletion of stk1 and the mutation of Ser143 of AlgR to Ala result in similar changes in the above-mentioned physiological functions. Furthermore, assays of algR expression in these strains suggest that changes in the phosphorylation state of AlgR, rather than its expression level, underlie changes in these physiological functions. These findings uncover Stk1-mediated phosphorylation of AlgR as an important mechanism for regulating virulence and resistance in P. aeruginosa.

Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. The availability of appropriate and well-characterized preclinical models for RMS is limited, posing a challenge for investigating the molecular mechanisms and evaluating new targeted compounds in preclinical settings. Here, we collected 51 RMS specimens (referred to as ZJUCH-RMS cohort) and established 9 patient-derived cells (PDCs) and validated the identity of these cells by the expression of RMS-specific markers. Whole-transcriptome analysis identified high-confidence mutations in ZJUCH-RMS cohort including RAS, TP53, ARID1A, MYOD1, and MYCN. Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.

Study Region: China. Study Focus: Water resources are one of the indispensable and irreplaceable natural resources in the operation of social and economic sustainable development. When economic measures are used to manage water resources, the market mechanism can be used to fully optimize resource allocation and boost water use efficiency (WUE). While existing research have begun to explore the impact of water rights trading (WRT) on WUE, most remain theoretical, with empirical studies often neglecting time differences in WRT implementation across provinces, leading to unresolved endogeneity issues. To accurately assess the policy effects of WRT, our research constructs a multi-period DID mode that addresses these limitations. New Hydrological Insights for the Regions: This study reveals that WRT significantly improves WUE, with water use per unit of output decreasing by 574.724 units in agriculture, 366.136 units in industry, and 210.770 units overall, demonstrating robustness. The policy effects of WRT require time to materialize, showing both dynamic and spatial sustainability. Technological innovation (TEIN) and water factor mobility (FM) serve as intermediary variables through which WRT optimizes WUE, with TEIN exhibiting a masking effect on WUE improvement. These insights can contribute to improved water resource management globally by guiding the development of tailored water rights policies and strategies that incorporate market mechanisms, foster technological innovation, and improve overall WUE.

T-2 toxin, a trichothecene mycotoxin, is an important environmental pollutant that poses a threat globally to the health of humans and animals. It has been found to induce nephrotoxicity; however, the precise molecular mechanism involved remains unclear. In this study, mice were administered at a single dose of 2 mg/kg body weight T-2 toxin intraperitoneally, and kidney function and ultrastructural observations were assessed after 1 d, 3 d, and 7 d. Histopathological findings revealed that exposure to T-2 toxin caused noticeable tubular degeneration, necrosis and epithelial cell shedding in mouse kidneys. Transmission electron microscopy indicated that exposure to T-2 toxin caused mitochondrial swelling and vacuolization. Transcriptomic data revealed significant differences in the expression of 1122, 58, and 391 genes in kidney tissues 1 d, 3 d, or 7 d after T-2 toxin exposure, respectively. Moreover, after 1 d, the downregulated differentially expressed genes (DEGs) were found to be involved in the cell cycle, p53 signaling, and cellular senescence pathways, while the upregulated DEGs were found to be associated with the ribosomal pathway. Temporal changes in gene expression patterns (i.e., after 3 d and 7 d) and disturbances in cellular metabolism during the recovery period (7 d) were detected in mouse kidneys after exposure to T-2 toxin. In conclusion, this study is the first to provide a comprehensive comparative transcriptomic analysis of T-2 toxin exposure-induced nephrotoxicity-related gene regulation at different time points and to investigate the mechanism underlying the nephrotoxicity of T-2 toxin at the mRNA expression level.

Given its status as the largest water-using sector, it remains pivotal to enhance the water usage efficiency within the agricultural sector to safeguard water resources. The main goal of the Integrated Agricultural Water Pricing Reform (IAWPR) is to encourage water conservation and foster sustainable agricultural development. Nonetheless, achieving sustainable progress in agriculture necessitates a dual focus: not only on the sustainable exploitation of resources but also on upholding the welfare of the population. The impact of the policy on farmers' welfare is not straightforward and requires scientific verification. To this end, the study focuses on the new relationship between IAWPR and farmers' income, exploring its underlying mechanism to broaden the economic benefits of IAWPR. In addition, combining multi-phase Difference-in-Differences (DID) and biennial Malmquist-Luenberger (BML) productivity index overcomes the limitations of traditional measurement methods. The results indicate that the IAWPR has a significant positive impact on farmers, leading to a 31.9% increase in income, and the impact is even more pronounced in the non-farm sector. Furthermore, the IAWPR primarily operates through enhancing agricultural green total factor productivity (AGTFP), where technological change (TC) serves as the principal driving factor of improvements in agricultural efficiency.

The snow-shaped distribution network (SDN) is a cable distribution network composed of eight (or six) 10 kV feeders from four (or three) substations in a regular connection. Compared with the traditional 10 kV distribution network, SDN can support a wide range of load transfer among six or eight feeders. Aiming at the problem of load spatial-temporal unbalanced condition caused by the integration of distributed generators (DGs) and different load types in different feeders, this paper proposes a dynamic reconfiguration strategy for load balancing in SDN considering DGs and energy storage system (ESS). Firstly, the basic structure of SDN is analyzed and the power flow model for its dynamic reconfiguration is developed. Secondly, the dynamic reconfiguration optimization model for load balancing in SDN considering DGs and ESS is proposed to utilize the load transfer capability to mitigate the load unbalanced condition and reduce active power loss. Thirdly, the original non-convex model is converted into a mixed-integer second-order cone programming (MISOCP) model by applying the second-order cone relaxation and the big-M method, which is solved by CPLEX solver. Finally, the effectiveness of the proposed model and method are verified by an actual case in Tianjin and IEEE 33-node system. The analysis results show that the proposed method can significantly alleviate the load unbalanced spatial-temporal distribution and improve the economic efficiency by regulating the operation of SDN including ESS optimization and dynamic reconfiguration.

To prevent convulsions and falls of patients in the absence of medical staff, it is crucial to monitor their physical condition in hospital wards. However, several unresolved challenges in human joint recognition remain, such as object occlusion, human self-occlusion and complex backgrounds, resulting in difficulties in its practical application. In this paper, a multi-LiDAR system is proposed to obtain a multi-view human body point cloud. An improved V2V-Posenet model was introduced to detect the actual position of the human joint. In this system, each point cloud was spliced into a full point cloud and voxelized into the model. We also used a random voxel zero setting for data enhancement, constraining the relative length between human joints into a loss function and three-dimensional Gaussian filtering in a heat map for model learning. The improved model exhibited excellent performance in detecting human joints in hospital wards. The experimental results showed that the improved model achieved 91.6 % mean average precision, compared to 80.1 % for the original model and 77.4 % for the comparison algorithm A2J-Posenet. The speed of the improved model meets the requirements for real-time target detection.

Summary: p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.

Morphological adaptation is crucial for animals and robots in navigating unstructured environments. In this article, a quadruped robot with a reconfigurable sprawl posture and posture transformation strategy is proposed, which can transform between different sprawl postures to cope with complex environments and adapt to a dorsal downward fall posture through reverse sprawling. First, the function and structure of the robot are described, including an analysis of the Hawken mechanism's endpoint trajectories and a regional examination of the robot leg's fundamental components, establishing a relationship between the trajectory characteristics and linkage length. Second, the robot posture transformation strategy is analysed, obtaining the geometric dimensional constraints and feasibility regions of the posture transformation. The posture transformation process is quantified, and the robot transformation gait and drive functions are designed. The robot gait and velocity regulation are implemented based on a neural control architecture. Finally, the robot's locomotion and posture transformation are tested using four high‐speed cameras. The results show that the robot can crawl on an inclined surface and continue crawling in a dorsal downward posture post‐fall. Additionally, the robot effectively navigates obstacles and narrow spaces after posture transformation.

Abstract Supramolecular chirality‐mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity‐achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L‐Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L‐Arg) to water‐soluble pillar[5]arene (WP5) are developed through non‐covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D‐Arg nanoparticles show 107 folds stronger binding capability toward phospholipid‐composed liposomes compared with WP5⊃L‐Arg. The enantioselective interaction further triggers the supramolecular chirality‐specific drug accumulation in cancer cells. As a consequence, WP5⊃D‐Arg+DOX+ICG exhibits extremely enhanced chemo‐photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L‐Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio‐application.

Abstract Radar signal sorting is a vital component of electronic warfare reconnaissance, serving as the basis for identifying the source of radar signals. However, traditional radar signal sorting methods are increasingly inadequate and computationally complex in modern electromagnetic environments. To address this issue, this paper presents a novel machine-learning-based approach for radar signal sorting. Our method utilizes SemHybridNet, a Semantically Enhanced Hybrid CNN-Transformer Network, for the classification of semantic information in two-dimensional radar pulse images obtained by converting the original radar data. SemHybridNet incorporates two innovative modules: one for extracting period structure features, and the other for ensuring effective integration of local and global features. Notably, SemHybridNet adopts an end-to-end structure, eliminating the need for repetitive looping over the original sequence and reducing computational complexity. We evaluate the performance of our method through conducting comprehensive comparative experiments. The results demonstrate our method significantly outperforms the traditional methods, particularly in environments with high missing and noise pulse rates. Moreover, the ablation studies confirm the effectiveness of these two proposed modules in enhancing the performance of SemHybridNet. In conclusion, our method holds promise for enhancing electronic warfare reconnaissance capabilities and opens new avenues for future research in this field.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)–PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING–PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING–PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Large-depth and multiscale gradient microstructure in dual-phase Al0.6CoCrFeNi high entropy alloy (HEA) were fabricated by explosion hardening (EH) technique. The gradient microstructure evolution was investigated in detail. The microhardness distribution and tensile properties near EH affected surface were also determined. The formation and strengthening mechanisms of gradient microstructure after EH treatment were subsequently analyzed. Experimental results showed that the multiscale gradient microstructure in terms of grain size, phase morphology, dislocation structure, texture was induced in dual-phase (BCC + FCC) HEA by EH technique. The closer to EH affected surface, the finer grain size, higher dislocation density and stronger texture intensity. The deformation and break of spinodal decomposition and formation of new grain boundaries by dislocation structure contributed to grain refinement and transition of equiaxed grains to dendritic grains from lower area to EH affected surface. After EH treatment, the microhardness generally increased with a maximum increase of ∼67% within 5 mm from EH affected surface, the tensile yield stress increased from 320 MPa to maximum of 700 MPa. The strengthening mechanism is different at various depth positions: near EH affected surface, the main strengthening mechanism is high-density dislocations, stacking faults and grain refinement; in areas relatively far from EH affected surface, only dislocation structure contributed to the strengthening of mechanical properties.

Abstract Recently, owing to the requirements of inference speed, most real-time semantic segmentation networks often have shallow network depth, which limits the receptive field size of the model, leading to the limited acquisition of semantic information and resulting in intraclass inconsistency and ultimately a decrease in segmentation accuracy. Additionally, the shallow network depth also restricts the feature extraction capability of the network, reducing its robustness and ability to adapt to complex scenes. To address these issues, a bilateral network with a rich semantic extractor (RSE) for real-time semantic segmentation (BRSeNet) is presented to perform real-time semantic segmentation. First, to solve the problem of insufficient semantic feature information extraction, an RSE is proposed, which includes a multiscale global semantic extraction module (MGSEM) and a semantic fusion module (SFM). The MGSEM can extract rich global semantics and expand the effective receptive field. Simultaneously, the SFM efficiently integrates multiscale local semantics with multiscale global semantics, resulting in more comprehensive semantic information for the network. Finally, based on the characteristics of detail and semantic branches, a bilateral reconstruction aggregation module is designed to reconstruct the contextual information of detail features, model the interdependencies on semantic feature channels, and enhance feature representation. Comprehensive experiments on the challenging Cityscapes and ADE20K datasets are conducted. The experimental results show that the proposed BRSeNet achieves mean intersection over union of 74.9% and 35.7% at inference speeds of 74 and 65 frames per second, respectively, and ensures a favorable balance between segmentation accuracy and inference speed.

Interfacial solar water evaporation is a reliable way to accelerate water evaporation and contaminant remediation. Embracing the recent advance in photothermal technology, a functional sponge was prepared by coating a sodium alginate (SA) impregnated sponge with a surface layer of reduced graphene oxide (rGO) to act as a photothermal conversion medium and then subsequently evaluated for its ability to enhance Pb extraction from contaminated soil driven by interfacial solar evaporation. The SA loaded sponge had a Pb adsorption capacity of 107.4 mg g−1. Coating the top surface of the SA sponge with rGO increased water evaporation performance to 1.81 kg m−2 h−1 in soil media under one sun illumination and with a wind velocity of 2 m s−1. Over 12 continuous days of indoor evaporation testing, the Pb extraction efficiency was increased by 22.0% under 1 sun illumination relative to that observed without illumination. Subsequently, Pb extraction was further improved by 48.9% under outdoor evaporation conditions compared to indoor conditions. Overall, this initial work shows the significant potential of interfacial solar evaporation technologies for Pb contaminated soil remediation, which should also be applicable to a variety of other environmental contaminants.

In vitro embryonic technology is crucial for improving farm animal reproduction but is hampered by the poor quality of oocytes and insufficient development potential. This study investigated the relationships among changes in the gut microbiota and metabolism, serum features, and the follicular fluid metabolome atlas. Correlation network maps were constructed to reveal how the metabolites affect follicular development by regulating gene expression in granulosa cells. The superovulation synchronization results showed that the number of follicle diameters from 4 to 8 mm, qualified oocyte number, cleavage, and blastocyst rates were improved in the dairy heifers (DH) compared with the non-lactating multiparous dairy cows (NDC) groups. The gut microbiota was decreased in Rikenellaceae_RC9_gut_group, Alistipes, and Bifidobacterium, but increased in Firmicutes, Cyanobacteria, Fibrobacterota, Desulfobacterota, and Verrucomicrobiota in the NDC group, which was highly associated with phospholipid-related metabolites of gut microbiota and serum. Metabolomic profiling of the gut microbiota, serum, and follicular fluid further demonstrated that the co-metabolites were phosphocholine and linoleic acid. Moreover, the expression of genes related to arachidonic acid metabolism in granulosa cells was significantly correlated with phosphocholine and linoleic acid. The results in granulosa cells showed that the levels of PLCB1 and COX2, participating in arachidonic acid metabolism, were increased in the DH group, which improved the concentrations of PGD2 and PGF2α in the follicular fluid. Finally, the expression levels of apoptosis-related proteins, cytokines, and steroidogenesis-related genes in granulosa cells and the concentrations of steroid hormones in follicular fluid were determinants of follicular development. According to our results, gut microbiota-related phosphocholine and linoleic acid participate in arachidonic acid metabolism in granulosa cells through the gut–follicle axis, which regulates follicular development. These findings hold promise for enhancing follicular development and optimizing oocyte quality in subfertile dairy cows.

Computer vision (CV) techniques have been widely studied and applied in the shipping industry and maritime research. The existing literature has primarily focused on enhancing image recognition accuracy and precision for water surface targets by refining CV models themselves. This paper introduces innovative methods to further improve the accuracy of detection and recognition using CV models, including using ensemble learning and integrating shipping domain knowledge. Additionally, we present a novel application of CV techniques in the maritime domain, expanding the research perspective beyond the traditional focus on the accurate detection and recognition of water surface targets. Specifically, a novel solution integrating a CV model and the transfer learning method is proposed in this paper to address the challenge of relatively low-speed and high-charge internet services on ocean-going vessels, aiming to improve the online video viewing experience while conserving network resources. This paper is of importance for advancing further research and application of CV techniques in the shipping industry.

With the widespread integration of distributed resources, optimizing the operation of urban distribution networks faces challenges including uneven source-load-storage distribution, fluctuating feeder power flows, load imbalances, and network congestion. The urban snow-shaped distribution network (SDN), characterized by numerous intra-station and inter-station tie switches, serves as a robust framework to intelligently address these issues. This study focuses on enhancing the safe and efficient operation of SDNs through a two-phase optimal scheduling model that coordinates source-network-load-storage. In the day-ahead scheduling phase, an optimization model is formulated to minimize operational costs and mitigate load imbalances. This model integrates network reconfiguration, energy storage systems (ESSs), and flexible load (FL). During intra-day scheduling, a rolling optimization model based on model predictive control adjusts operations using the day-ahead plan to minimize the costs and penalties associated with power adjustments. It provides precise control over ESS and FL outputs, promptly correcting deviations caused by prediction errors. Finally, the proposed model is verified by an actual example of a snow-shaped distribution network in Tianjin. The results indicate significant improvements in leveraging coordinated interactions among source-network-load-storage, effectively reducing spatial-temporal load imbalances within feeder clusters and minimizing the impact of prediction inaccuracies.

Western Sichuan Yi suancai contains a group of highly functional microorganisms in an alpine and high-altitude ecological environment. Due to its unique salt-free fermentation process, it is nutritious and has a crispy texture. Six periods were established during fermentation: day 0, day 2, day 5, day 8, day 11, and day 14. The results showed that the antioxidant capacity and organic acid content increased during the fermentation process, while the pH gradually decreased, indicating that suancai from the later periods was better for supplementing the human body with acid substances and eliminating free radicals. Twenty-six flavour compounds were identified, including alcohols, esters, ketones, and acids. Ethyl alcohol, 3-methyl-1-butanol, ethyl methanoate, and acetic acid were the main contributors to the flavour, imparting floral and fruity notes to the suancai. Five dominant bacterial genera (Lactobacillus, Leuconostoc, Weissella, Klebsiella, and unclassified_o__Lactobacillales) were identified via high-throughput sequencing during the fermentation process, and there were nine dominant fungal genera (Dipodascaceae_gen_Incertae_sedis, Mucor, Pichia, unclassified__f__Dipodascaceaet, Cyberlindnera, Diutina, Trichosporon, Saccharomycopsis, and Wickerhamomyces). Correlation analysis showed that the antioxidant capacity was positively correlated with genera such as Lactobacillus, Mucor, and Alternaria, indicating that these microorganisms have important roles in enhancing the antioxidant properties of suancai. Meanwhile, some genera, such as Microbacterium, Herbaspirillum, Mortierella, and Sampaiozyma, promote the synthesis of alcohols, esters, acids, and ketones. This study revealed the interactions between microorganisms and metabolites during the fermentation of western Sichuan Yi suancai and provided a scientific basis for further understanding the fermentation mechanism of traditional suancai and improving the fermentation process.

Abstract Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high‐sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe2+‐GOx gel using a photothermal‐enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double‐bonded adamantane (Ada) interacts with the host‐guest effect of graphene oxide and the double‐bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G′) of the gel increased from 130 to 330 Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self‐healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe2+‐GOx + NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial‐infected diabetic wounds.

3D laser scanning is widely used in modeling industrial scenes, involving crucial steps like point cloud (PC) data preprocessing and extracting modeling targets from scattered points. Extracting target PC data from larger scenes is more challenging than from smaller settings. To efficiently obtain high-quality scene data and modeling targets, we introduce an innovative approach with the adaptive density-based voxel grid filtering algorithm and a probability statistics histogram method during preprocessing. We also propose a novel method for automatic extraction of target PC data using the adjacent feature plane constraint (AFPC) clustering technique. Initially, we capture height characteristics of the target object's PC through experiential and statistical height attributes. Points corresponding to each height are then clustered based on the PC's density distribution using the density-based spatial clustering of applications with noise algorithm. The intersection of these results optimizes the position of the target object's extraction bounding box, achieving seamless automatic object extraction. Experimental results validate the effectiveness of our preprocessing methodology, with F1 scores of 97.7 % and 97.3 % for the 220 kV and 500 kV areas, respectively. Furthermore, our novel extraction method demonstrates the ability to autonomously and directly extract electrical equipment from substation PC data.

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Osteoarthritis (OA) has been considered non-reversible as articular cartilage wears down with limited repair capacity. Enhanced chondrocyte hypertrophy and increased type X collagen gene (COL10A1) expression have been associated with OA. Therefore, regulators controlling collagen X expression and chondrocyte hypertrophy may play a role in OA intervention. Here, we investigated how Distal-less homeobox 5 (DLX5), the distal-less homeobox family member, controls murine Col10a1 gene expression and chondrocyte hypertrophy in chondrogenic cell models and its role in a murine OA model. Through qRT-PCR and Western blot analyses, we detected significantly increased levels of COL10A1 and DLX5 in hypertrophic MCT and ATDC5 cells compared to their proliferative stage. Forced expression of Dlx5 further increases, while knockdown of Dlx5 decreases COL10A1 expression in hypertrophic MCT cells. We have performed dual-luciferase reporter and ChIP assays and demonstrated that DLX5 promotes reporter activity through direct interaction with Col10a1 cis-enhancer. We established a murine OA model and detected markedly increased COL10A1 and DLX5 in the articular cartilage and subchondral bone of the OA mice compared with the controls. Notably, forced overexpression of DLX5 in hypertrophic MCT cells up-regulates RUNX2, and adjacent DLX5 and RUNX2 binding sites have previously been found within the Col10a1 cis-enhancer. Together, our data suggest that DLX5 may cooperate with RUNX2 to control cell-specific Col10a1 expression and chondrocyte hypertrophy and is involved in OA pathogenesis.

Abstract Iron-based catalysts are promising candidates for advanced oxidation process-based wastewater remediation. However, the preparation of these materials often involves complex and energy intensive syntheses. Further, due to the inherent limitations of the preparation conditions, it is challenging to realise the full potential of the catalyst. Herein, we develop an iron-based nanomaterial catalyst via soft carbon assisted flash joule heating (FJH). FJH involves rapid temperature increase, electric shock, and cooling, the process simultaneously transforms a low-grade iron mineral (FeS) and soft carbon into an electron rich nano Fe0/FeS heterostructure embedded in thin-bedded graphene. The process is energy efficient and consumes 34 times less energy than conventional pyrolysis. Density functional theory calculations indicate that the electron delocalization of the FJH-derived heterostructure improves its binding ability with peroxydisulfate via bidentate binuclear model, thereby enhancing ·OH yield for organics mineralization. The Fe-based nanomaterial catalyst exhibits strong catalytic performance over a wide pH range. Similar catalysts can be prepared using other commonly available iron precursors. Finally, we also present a strategy for continuous and automated production of the iron-based nanomaterial catalysts.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving “full coverage” treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Background: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. Materials and Methods: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. Results: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. Conclusions: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

Trueperella pyogenes can cause various infections in the organs and tissues of different livestock (including pigs, cows, goats, and sheep), including mastitis, endometritis, pneumonia, or abscesses. Moreover, diseases induced by T. pyogenes cause significant economic losses in animal husbandry. In recent large-scale investigations, T. pyogenes has been identified as one of the main pathogens causing endometritis in lactating cows. However, the main treatment for the above-mentioned diseases is still currently antibiotic therapy. Understanding the impact of endometritis associated with T. pyogenes on the fertility of cows can help optimize antibiotic treatment for uterine diseases, thereby strategically concentrating the use of antimicrobials on the most severe cases. Therefore, it is particularly important to continuously monitor the prevalence of T. pyogenes and test its drug resistance. This study compared the uterine microbiota of healthy cows and endometritis cows in different cattle farms, investigated the prevalence of T. pyogenes, evaluated the genetic characteristics and population structure of isolated strains, and determined the virulence genes and drug resistance characteristics of T. pyogenes. An amount of 186 dairy cows were involved in this study and 23 T. pyogenes strains were isolated and identified from the uterine lavage fluid of dairy cows with or without endometritis.

AIM: To elucidate the relationship between macular sensitivity and time in range (TIR) obtained from continuous glucose monitoring (CGM) measures in diabetic patients with or without diabetic retinopathy (DR). METHODS: This was a cross-sectional study including 100 eyes of non-DR patients and 60 eyes of DR patients. An advanced microperimetry was used to quantitate the retinal mean sensitivity (MS) and fixation stability in central macula. TIR of 3.9-10.0 mmol/L was evaluated with CGM. Pearson coefficient analysis and multiple linear regression analysis were used to assess the correlation between TIR and retinal sensitivity. RESULTS: In a comparison of non-DR patients, significant differences (P0.05). A multivariable linear regression analysis was performed to prove that TIR and SDBG were both independent risk factors for MS reduction in the DR group. CONCLUSION: TIR is correlated with retinal MS reduction in DR patients, suggesting a useful option for evaluating DR progression.

Abstract Charcot-Marie-Tooth disease(CMT) is a hereditary peripheral neuropathy, characterized by progressive distal hypoesthesia and amyotrophia. CMT is characterized by an X- linked recessive inheritance pattern. The apoptosis-inducing factor mitochondria associated-1 (AIFM1) is the main pathogenic gene of the X-linked recessive Charcot-Marie-Tooth disease-4 with or without cerebellar ataxia (CMTX4), also known as Cowchock syndrome. In this study, we enrolled a family with CMTX from the southeast region of China and identified a novel AIFM1 variant (NM_004208.3: c.931C>G; p.L311V) using whole exon sequencing technology. The results of our study may also be useful for genetic counseling, embryo screening of in vitro fertilization embryos, and prenatal genetic diagnosis.

Abstract Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation. Extrinsic serine is transported into MKs through SLC38A1 and downregulates SVIL via SAM-mediated tri-methylation of H3K9, ultimately leading to the impairment of megakaryopoiesis. Inhibition of serine utilization or treatment with TPO enhances megakaryopoiesis and thrombopoiesis and suppresses MM progression. Together, we identify serine as a key metabolic regulator of thrombocytopenia, unveil molecular mechanisms governing MM progression, and provide potential therapeutic strategies for treating MM patients by targeting thrombocytopenia.

Background Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. Methods The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. Results WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. Conclusion IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC.

Cadmium (Cd) is a highly toxic heavy metal that can severely hinder plant growth and development. Tomato is one of the most important economical crops in the world, and its quality and safety are closely related to human health. Therefore, it is important to elucidate the molecular mechanisms involved in tomato plant responses to Cd stress. In this study, tomato plants were treated with or without 100 μM Cd2+ in hydroponic culture for 3 days. Transcriptional changes in tomato roots and shoots were examined by transcriptome sequencing techniques. A total of 1,123 differentially expressed genes (DEGs) were identified in roots and 159 DEGs were identified in shoots after Cd treatment, including 15 DEGs were upregulated and 24 DEGs were downregulated in both roots and shoots. KEGG enrichment analysis showed that DEGs in the roots and shoots under Cd stress were significantly enriched in the glutathione metabolism pathway, sulfur metabolism pathway, phenylpropanoid biosynthesis, plant-pathogen interaction cutin pathway, suberine and wax biosynthesis pathway, and photosynthesis-antenna proteins pathway. 15 DEGs were further validated by quantitative real-time RT-PCR, including ABC transporter genes, WRKY transcription factors, and NAC transcription factors, among others. This study will provide a theoretical basis for further research on the molecular mechanisms involved in tomato responses to Cd stress, and genetic improvement of Cd tolerance.

BackgroundAs a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML.MethodsFirst, we extracted the mRNA expression profiles of bone marrow samples from an AML cohort from The Cancer Genome Atlas database and employed Cox regression analysis to select prognostic hub genes associated with lipid metabolism and immunity. We then constructed a prognostic signature with hub genes significantly related to survival and validated the stability and robustness of the prognostic signature using three external datasets. Gene Set Enrichment Analysis was implemented to explore the underlying biological pathways related to the risk signature. Finally, the correlation between signature, immunity, and drug sensitivity was explored.ResultsEight genes were identified from the analysis and verified in the clinical samples, including APOBEC3C, MSMO1, ATP13A2, SMPDL3B, PLA2G4A, TNFSF15, IL2RA, and HGF, to develop a risk-scoring model that effectively stratified patients with AML into low- and high-risk groups, demonstrating significant differences in survival time. The risk signature was negatively related to immune cell infiltration. Samples with AML in the low-risk group, as defined by the risk signature, were more likely to be responsive to immunotherapy, whereas those at high risk responded better to specific targeted drugs.ConclusionsThis study reveals the significant role of lipid metabolism- and immune-related genes in prognosis and demonstrated the utility of these signature genes as reliable bioinformatic indicators for predicting survival in patients with AML. The risk-scoring model based on these prognostic signature genes holds promise as a valuable tool for individualized treatment decision-making, providing valuable insights for improving patient prognosis and treatment outcomes in AML.

Wetlands in the arid zone of northwest China have ecological values such as climate regulation, water conservation, and biodiversity maintenance. However, in the context of global warming and economic development, the degree of natural and human interference in the wetlands has been increasing, and wetland health problems are becoming increasingly severe. The current comparative research on the ecosystem health evaluation of natural and constructed wetlands and their sustainable development in the arid zone of northwest China is not perfect, so we selected the natural (Dunhuang Xihu Wetland) and constructed wetlands (Suzhou District Wetland) as research objects. The ecosystem health evaluation system has been developed from 5 levels of the drive, pressure, state, impact, and response (DPSIR). The ecological health status and impact factors were evaluated for the two wetlands using socioeconomic data combined with remote sensing technology from 2000 to 2019. The results showed that 1) the ecological health of natural and constructed wetlands was in a medium healthy state, and the ecological health values of the wetlands showed a trend of decreasing and then increasing from 2000 to 2019, with 2005 as the turning point. The ecological health status of natural wetlands (0.46) was better than that of constructed wetlands (0.42). 2) The main reasons for the degradation of constructed wetlands (-3.20%) were the urban population expansion and blind agricultural reclamation of wetlands, while the degradation of natural wetlands (-6.45%) was dominated by extreme climatic conditions and overuse of water resources. These results provide case support and a theoretical basis for the conservation management and sustainable development of wetland ecosystems in the arid zone.

Adenoid hypertrophy is a pathological condition characterized by the enlargement of the adenoids in children, which may lead to various problems. The conventional manual measurement is time-consuming and subject to subjective errors. Previous automated methods based on landmark detection in X-ray images have shown reliability. However, these methods neglect global features, making it difficult to locate landmarks accurately and thus affecting adenoid-to-nasopharyngeal (AN) ratio estimation when migrating to MRI images. In this paper, we first apply a deep-learning method to automatically assess adenoid hypertrophy in MRI images. We propose an adenoid network (ADNet) to capture local and global features near landmarks to achieve accurate landmark localization. Specifically, ADNet uses an encoder-decoder architecture where we employ a depthwise separable convolution-based encoder to extract local features and then employ an adaptive convolution-based decoder to capture global features. We collected a dataset of 500 cephalometric MRI images to train and evaluate the performance of the proposed model. Our experimental results demonstrate that our network achieves state-of-the-art performance with an average radial error of 4.85 pixels for landmark detection, an average successful detection rate of 96% within 15 pixels, and an error of 0.026 for the calculated AN ratio.

In order to realize the effective separation of palladium from high-level liquid waste (HLLW), a ligand-supported adsorbent (NTAamide(C8)/SiO2-P) was prepared by the impregnation method in a vacuum. The SiO2-P carrier was synthesized by in situ polymerization of divinylbenzene and styrene monomers on a macroporous silica skeleton. The NTAamide(C8)/SiO2-P adsorbent was fabricated by impregnating an NTAamide(C8) ligand into the pore of a SiO2-P carrier under a vacuum condition. The adsorption performance of NTAamide(C8)/SiO2-P in nitric acid medium has been systematically studied. In a solution of 0.2 M HNO3, the distribution coefficient of Pd on NTAamide(C8)/SiO2-P was 1848 mL/g with an adsorption percentage of 90.24%. With the concentration of nitric acid increasing, the adsorption capacity of NTAamide(C8)/SiO2-P decreases. Compared to the other 10 potential interfering ions in fission products, NTAamide(C8)/SiO2-P exhibited excellent adsorption selectivity for Pd(II). The separation factor (SFPd/other metals > 77.8) is significantly higher than that of similar materials. The interference of NaNO3 had a negligible effect on the adsorption performance of NTAamide(C8)/SiO2-P, which maintained above 90%. The adsorption kinetics of Pd(II) adsorption on NTAamide(C8)/SiO2-P fits well with the pseudo-second order model. The Sips model is more suitable than the Langmuir and Freundlich model for describing the adsorption behavior. Thermodynamic analysis showed that the adsorption of Pd(II) on NTAamide(C8)/SiO2-P was a spontaneous, endothermic, and rapid process. NTAamide(C8)/SiO2-P also demonstrated good reusability and economic feasibility.