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Abstract This paper proposed a frequency reconfigurable antenna that utilizes a multilayer structure of liquid crystal (LC) material. This antenna design incorporates a three-layer stacked structure to create an LC-injected cavity. The inverted microstrip line structure is designed to be in contact with the LC, serving as both a radiating element and a bias electrode. A parasitic patch is placed at the top of the antenna to enhance bandwidth. To prevent interference with DC and RF sources, a bias tee is integrated into the microstrip line input. Experimental results demonstrate that the proposed antenna exhibits excellent impedance matching and stable radiation patterns within the operational frequency range. By comparing the simulated performance of the existing LC antenna with our proposed design, the bandwidth is tripled at a center frequency of 30.3 GHz. In addition, the effective area of the proposed reconfigurable antenna (154 mm2) is 24.6% of the area of the previous reconfigurable antenna (625 mm2).

Abstract Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).

Abstract Adebrelimab, a novel anti‐PD‐L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first‐line treatment for extensive‐stage small‐cell lung cancer in 2023. A two‐compartment model with empirical time‐varying CL for adebrelimab was established based on data from 263 patients receiving body weight‐based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti‐drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non‐responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure–response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight‐based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic.

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Laser direct energy deposition (LDED) exhibits great potential for application in rail repairing due to its low cost and high process automation. However, the martensite transformation accompanied by rapid solidification leads to the decrease in the mechanical properties and threatens the service safety. In this study, the reinforcement strategy of combining cobalt (Co) addition with preheating treatment was investigated systematically by combining thermodynamic calculations with experimental characterization to optimize the microstructure and mechanical properties of U75V steel by LDED. The results indicate that cobalt addition can promote the pearlite percentage by facilitating the leftward shift of the continuous cooling transformation (CCT) curve, and refining the interlamellar spacing. But the martensite start (Ms) temperature will also increase from 206.4 °C to 324.1 °C after 7 wt% Co addition. 350 °C preheating treatment on the substrate can also promote the pearlite transformation by elevating the valley temperature of thermal cycling over Ms, as well as the subsequent decrease in cooling rate, but it is not sufficient to prevent martensite formation. A synergistic reinforcement strategy of 7 wt% Co addition and 350 °C preheating was established, which can effectively suppress the occurrence of martensite in the bottom area of deposition layers and expand the pearlite range in the top area. The bonding strength between the substrate and deposition layers has been elevated by ∼20%, accompanied by the increase in elongation and wear resistance. A mixed mode of adhesive and abrasive wear has transformed into a mode dominated by adhesive wear after optimization.

Abstract Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.

Abstract Parkinson’s disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs are used for homologous targeting to enhance efficacy. In this study, microfluidic electroporation chip prepared mesenchymal stem cell-derived neuron-like cell membrane-coated curcumin PLGA nanoparticles (MM-Cur-NPs) was synthesized and explored therapeutic effect and mechanism in PD. MM-Cur-NPs can protect neuron from damage, restore mitochondrial membrane potential and reduce oxidative stress in vitro. In PD mice, it also can improve movement disorders and restore damaged TH neurons. MM-Cur-NPs was found to be distributed in the brain and metabolized with a delay within 24 h. After 1 h administration, MM-Cur-NPs were distributed in brain with a variety of neurotransmitters were significantly upregulated, such as dopamine. Differentially expressed genes of RNA-seq were enriched in the inflammation regulation, and it was found the up-expression of anti-inflammatory factors and inhibited pro-inflammatory factors in PD. Mechanically, MM-Cur-NPs can not only reduce neuronal apoptosis, inhibit the microglial marker IBA-1 and inflammation, but also upregulate expression of neuronal mitochondrial protein VDAC1 and restore mitochondrial membrane potential. This study proposes a therapeutic strategy provide neuroprotective effects through MM-Cur-NPs therapy for PD.

Abstract Utilizing 32 previously identified S ribonuclease (S-RNase) gene sequences and abundant citrus resources, this study designed specific primers for 10 S-RNase genes. A total of 32 pairs of primers were used to analyze the self-incompatibility genotypes (S-genotypes) of 241 citrus resources, encompassing 105 mandarins, 47 pummelos, 69 oranges, and 20 lemons and citrons. These results provide theoretical guidance for parent selection in production and breeding programs. Among the 215 samples analyzed, two normal S-genotypes were identified, while no S-genotypes were detected in three samples. Notably, 21 samples, primarily citrons, exhibited amplification of only one S-genotype. Additionally, two pummelo samples showed amplification of three S-genotypes each. The integration of S-genotype and selfing phenotype identification revealed five newly discovered self-compatible mutated materials: Changsha ‘Shatian’ pummelo, large-fruited red pummelo, slender leaf ‘Mangshanyegan’, ‘Shatangju’, and W. Murcott. These findings provide valuable resources for investigating the self-compatibility mechanism in citrus.

An in-depth understanding of the fracture behavior and mechanism of metallic shells under internal explosive loading can help develop material designs for warheads and regulate the quantity and mass distribution of the fragments formed. This study investigated the fragmentation performance of a new high-carbon silicon-manganese (HCSiMn) steel cylindrical shell through fragment recovery experiments. Compared with the conventional 45Cr steel shell, the number of small mass fragments produced by the HCSiMn steel shell was significantly increased with a scale parameter of 0.57 g fitted by the Weibull distribution model. The fragmentation process of the HCSiMn shell exhibited more brittle tensile fracture characteristics, with the microcrack damage zone on the outer surface being the direct cause of its high fragmentation. On the one hand, the doping of alloy elements resulted in grain refinement by forming metallographic structure of tempered sorbite, so that microscopic intergranular fracture reduces the characteristic mass of the fragments; on the other hand, the distribution of alloy carbides can exert a ''pinning'' effect on the substrate grains, causing more initial cracks to form and propagate along the brittle carbides, further improving the shell fragmentation. Although the killing power radius for light armored vehicles was slightly reduced by about 6%, the dense killing radius of HCSiMn steel projectile against personnel can be significantly increased by about 26% based on theoretical assessment. These results provided an experimental basis for high fragmentation warhead design, and to some extent, revealed the correlation mechanism between metallographic structure and shell fragmentation.

Abstract Cloud environment is a virtual, online, and distributed computing environment that provides users with large-scale services. And cloud monitoring plays an integral role in protecting infrastructures in the cloud environment. Cloud monitoring systems need to closely monitor various KPIs of cloud resources, to accurately detect anomalies. However, due to the complexity and highly dynamic nature of the cloud environment, anomaly detection for these KPIs with various patterns and data quality is a huge challenge, especially those massive unlabeled data. Besides, it’s also difficult to improve the accuracy of the existing anomaly detection methods. To solve these problems, we propose a novel Dynamic Graph Transformer based Parallel Framework (DGT-PF) for efficiently detect system anomalies in cloud infrastructures, which utilizes Transformer with anomaly attention mechanism and Graph Neural Network (GNN) to learn the spatio-temporal features of KPIs to improve the accuracy and timeliness of model anomaly detection. Specifically, we propose an effective dynamic relationship embedding strategy to dynamically learn spatio-temporal features and adaptively generate adjacency matrices, and soft cluster each GNN layer through Diffpooling module. In addition, we also use nonlinear neural network model and AR-MLP model in parallel to obtain better detection accuracy and improve detection performance. The experiment shows that the DGT-PF framework have achieved the highest F1-Score on 5 public datasets, with an average improvement of 21.6% compared to 11 anomaly detection models.

The S(IV)–Fe(II)/PM pretreatment has demonstrated preliminary potential as an effective ultrafiltration (UF) pretreatment technology. However, a comprehensive understanding of its impact on UF membrane fouling control and the dynamic evolution of membrane fouling during prolonged operation is still lacking. In this study, a relatively prolonged fouling experiment was conducted. Results revealed that the S(IV)–Fe(II)/PM pretreatment exhibited superior performance over Al(III) coagulation pretreatment in mitigating the transmembrane pressure difference and addressing both reversible and irreversible membrane fouling. The application of a cluster analysis method to classify membrane fouling evolution stages further confirmed that S(IV)–Fe(II)/PM pretreatment effectively decelerated the rate of membrane fouling evolution. The surface cake layer of UF membranes pretreated with S(IV)–Fe(II)/PM exhibited greater looseness and smoothness. It also showed better results than Al(III) coagulation pretreatment in reducing the accumulation of organic foulants, controlling the Si content and reducing the total microorganisms and live microorganisms in the UF feed water. Variance Partitioning Analysis indicated that the combined contribution of organic, inorganic, and biological foulants was the most significant for UF membranes after S(IV)–Fe(II)/PM pretreatment (50.4%) and UF membranes after Al(III) coagulation pretreatment (70.2%). These findings underscore the efficacy of S(IV)–Fe(II)/PM pretreatment in controlling UF membrane fouling under prolonged operation. HIGHLIGHTS S(IV)/Fe(II)/PM pretreatment efficiently mitigated UF membrane fouling during long-term operation.; S(IV)/Fe(II)/PM pretreatment yielded a long uncontaminated stage and accelerated contaminated stage.; S(IV)/Fe(II)/PM pretreatment suppressed the contribution of organic–inorganic–biological composite fouling.;

Abstract Background This research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC). Methods The data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool. Results SRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib. Conclusion In conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Abstract The rapid advancement of microservice architecture in the cloud has led to the necessity of effectively detecting, classifying, and diagnosing run failures in microservice applications. Due to the high dynamics of cloud environments and the complex dependencies between microservices, it is challenging to achieve robust real-time system fault identification. This paper proposes an interpretable fault diagnosis framework tailored for microservice architecture, namely Multi-scale Learnable Transformation Graph for Fault Classification and Diagnosis(MTG_CD). Firstly, we employ multi-scale neural transformation and graph structure adjacency matrix learning to enhance data diversity while extracting temporal-structural features from system monitoring metrics Secondly, a graph convolutional network (GCN) is utilized to fuse the extracted temporal-structural features in a multi-feature modeling approach, which helps to improve the accuracy of anomaly detection. To identify the root cause of system faults, we finally conduct a coarse-grained level diagnosis and exploration after obtaining the results of classifying the fault data. We evaluate the performance of MTG_CD on the microservice benchmark SockShop, demonstrating its superiority over several baseline methods in detecting CPU usage overhead, memory leak, and network delay faults. The average macro F1 score improves by 14.05%.

Abstract Background Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. Methods We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE−/−) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay. Results miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs. Conclusion These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.

The refinement of bainitic ferrite laths is one of the most critical ways to improve the combination of strength and ductility. However, low-temperature bainitic transformations in the microstructural evolution of carbide-free bainite in high-carbon steels cause challenges for both the manufacture of coils and their application in car bodies. In this study, deformation-induced bainite refinement was proposed for refining bainite and retained austenite laths using a combination of ausforming and austempering in low-carbon low-alloy steel. The deformed austenite supplied more nucleation sites for bainitic transformation and suppressed the thickening of the bainitic ferrite laths by strengthening the surrounding untransformed austenite. A tensile strength of 1283 MPa and total elongation of 23.6% were obtained in the steel with an ausforming strain of 40% before austempering. The significant increase in strength was mainly attributed to the refinement of the bainitic ferrite laths and the high accumulation of dislocations within both the bainitic ferrite and retained austenite. The more stable retained austenite improved the sustainable work-hardening capability via the continuous transformation-induced plasticity effect.

Remote sensing (RS) technologies are extensively exploited by scientists and a vast audience of local authorities, urban managers, and city planners. Coastal regions, geohazard-prone areas, and highly populated cities represent natural laboratories to apply RS technologies and test new methods. Over the last decades, many efforts have been spent on improving Earth’s surface monitoring, including intensifying Earth Observation (EO) operations by the major national space agencies. They oversee to plan and make operational constellations of satellite sensors providing the scientific community with extensive research and development opportunities in the geoscience field. For instance, within this framework, the European Space Agency (ESA) and the Ministry of Science and Technology of China (MOST) have sponsored, since the early 2000s, the DRAGON initiative jointly carried out by the European and Chinese RS scientific communities. This manuscript aims to provide a synthetic overview of some research activities and new methods recently designed and applied and trace the route for further developments. The main findings are related to i) the analysis of flood risk in China, ii) the potential of new methods for the estimation and removal of ground displacement biases in small-baseline oriented interferometric Synthetic Aperture Radar (SAR) methods, iii) the analysis of the inundation risk in low-lying regions using coherent and incoherent SAR methods; and iv) the use of SAR-based technologies for marine applications.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

Osteoporosis (OP)-associated fractures can result in severe morbidity and disability, reduced quality of life, and death. Previous studies have suggested that small noncoding RNAs, for example, small regulatory microRNAs (miRNAs), play a key role in OP by inhibiting target gene expression. Cuproptosis, a recently proposed copper-induced cell death pathway, is linked with OP. Here, we describe the contribution of exosomal miRNAs and cuproptosis to OP. First, we highlight the characteristics of exosomes and roles of exosome-related miRNAs. Next, we discuss the relationship between cuproptosis and OP. Subsequently, we analyze the crosstalk of exosomal miRNAs with cuproptosis in the development of OP. This review aims to investigate a new clinical treatment method for OP.

This is an article in the field of ceramics and composites. In order to explore the resistance of basalt fiber to acid and alkali corrosion, basalt fiber with or without wetting agent was soaked in 3 mol/L sulfuric acid solution and sodium hydroxide solution, respectively, and the mass loss rate, fracture force retention rate and SEM image of fiber surface were tested. The results showed that with the increase of soaking time, the mass loss rate of basalt fiber with infiltrating agent increased from 1.42% to 7.33%, the fracture force retention rate decreased from 95.34% to 66.49%, the mass loss rate of basalt fiber without infiltrating agent increased from 3.69% to 9.40% and the fracture force retention rate decreased from 88.39% to 53.64%. After soaking in sodium hydroxide solution, the mass loss rate of basalt fiber with wetting-agent increased from 0.40% to 5.41%, the fracture force retention rate decreased from 97.37% to 79.82%, the mass loss rate of basalt fiber without wetting-agent increased from 1.50% to 7.08%, and the fracture force retention rate decreased from 93.42% to 69.85%. Both acid-alkaline corrosion cause fiber quality loss, increase fiber surface defects and reduce fiber breaking force.Sulfuric acid solution with the same concentration corrodes basalt fiber more seriously than sodium hydroxide solution. The soaking agent has a protective effect on the fiber and can slow down the corrosion of acid and alkali on the fiber.

Photocatalytic CO2 reduction to produce high value-added carbon-based fuel has been proposed as a promising approach to mitigate global warming issues. However, the conversion efficiency and product selectivity are still low due to the sluggish dynamics of transfer processes involved in proton-assisted multi-electron reactions. Lowering the formation energy barriers of intermediate products is an effective method to enhance the selectivity and productivity of final products. In this study, we aim to regulate the surface electronic structure of Bi2WO6 by doping surface chlorine atoms to achieve effective photocatalytic CO2 reduction. Surface Cl atoms can enhance the absorption ability of light, affect its energy band structure and promote charge separation. Combined with DFT calculations, it is revealed that surface Cl atoms can not only change the surface charge distribution which affects the competitive adsorption of H2O and CO2, but also lower the formation energy barrier of intermediate products to generate more intermediate ∗COOH, thus facilitating CO production. Overall, this study demonstrates a promising surface halogenation strategy to enhance the photocatalytic CO2 reduction activity of a layered structure Bi-based catalyst.

Abstract Background During laparoscopic left hemicolectomy procedures, a previously overlooked consistently thick blood vessel within the gastrocolic ligament near the splenic hilum may contribute to post-operative bleeding complications. The purpose of this study was to investigate the identification and management of the previously overlooked blood vessel. Methods This is a retrospective descriptive study of patients undergoing laparoscopic left colectomy for splenic fexure cancer conducted at a national gastrointestinal surgery centre in China. Consecutive patients with splenic fexure cancer who underwent laparoscopic left colectomy using our“five-step process”(n = 34) between January 2021 and July 2023 were included. Results The vessels can be effectively exposed using the aforementioned “five-step process.” It was observed that the overlooked vessels consistently present in all patients were identified as the omental branch of the left gastroepiploic artery and vein. Conclusion We have identified the origin of previously overlooked blood vessels and recommended a safe method for their management. This may offer advantages to colorectal surgeons performing laparoscopic left colectomy for splenic flexure cancer

Abstract Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1–α-KG–HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.

Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations. However, the integration of molecular risk stratification and treatment guidance for the DCAG regimen has not been well defined. Therefore, this study aimed to investigate the genetic mutations associated with AML and establish appropriate treatment strategies for patients newly diagnosed with AML. Methods: This study analyzed the clinical data and genetic mutations based on next-generation sequencing (NGS) in 124 newly diagnosed patients with AML who received the DCAG regimen at the People's Liberation Army (PLA) General Hospital from January 2008 to August 2020. Factors associated with the cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) in patients newly diagnosed with AML were analyzed. Results: The most adverse prognosis of DCAG-treated patients was observed in those with FLT3-ITD, KIT, PTPN11, GATA2, or IDH1 mutations during univariable analysis, whereas PTPN11 mutation was solely significant in multivariable analysis, with an increased likelihood of CIR (P = 0.001) and reduced LFS duration (P = 0.077). Hyperleukocytosis was maintained as an independent risk factor for increased CIR risk (P = 0.044) and decreased LFS duration (P = 0.042) in multivariable analysis. In this study, we validated the risk classification of patients with AML receiving an epigenetic modifier-based induction regimen across a broad age range. Conclusion: NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.

Abstract Background Accurate estimation of potential evapotranspiration (PET) is the key for studying land-air interaction hydrological processes. Several models are used to estimate the PET based on standardized meteorological data. Although combination-based models have the highest level performance estimation of PET, they require more meteorological data and may therefore be difficult to apply in areas lacking meteorological observation data. Results The results showed significant differences in the spatial trends of PET calculated by different models in China, the Doorenbots–Pruitts model revealed the highest PET (1902.6 mm), and the Kuzmin model revealed the lowest PET (349.6 mm), with the largest difference being 5.5 times. The Romanenko and the Rohwer models were the recommended temperature-based and aerodynamic-based models. On the other hand, the Abtew model was more suitable for arid and semi-arid regions, while the Priestley–Taylor model was more suitable for humid regions. Combination-based models revealed ideal calculation accuracies, among which the Penman–Monteith model was the best option for PET calculation. Conclusions The accuracy range of Romanenko, Rohwer, Abten, Priestley Taylor, and Penman Monteith models improved in MPZ and TCZ is higher than that improved in TMZ and SMZ. This does not mean that the improved models have higher accuracy in MPZ and TCZ than in TMZ and SMZ. On the contrary, the original model performed poorly in MPZ and TCZ, so the improved accuracy was relatively large. The unimproved model was already more suitable in TMZ and SMZ, so the improved accuracy was relatively small. Therefore, regional calibration of the PET models can improve the accuracy and applicability of PET calculation, providing a reference for studying hydrological processes in different climatic zones.

Abstract A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors.

Post-weld heat treatment and rolling deformation are used to improve the mechanical properties of 2195-O Al–Li alloy friction stir welding (FSW) joints, and the effects on the grain structure, precipitation behaviors, hardness distribution, and tensile performance are discussed. Microstructural characterization was conducted using scanning electron microscopy (SEM), electron backscattered diffraction (EBSD), and transmission electron microscopy (TEM). Mechanical properties were measured by hardness test and tensile test. Results show that coarse precipitates are subjected to various degrees of dissolution after FSW. Solution treatment following artificial aging (SAA) and 40% rolling deformation + SAA treatment (R40-SAA) enables the dissolution of coarse precipitates completely and precipitation of strengthening phases (T1 and θ′) in the nugget zone (NZ), thermo-mechanically affected zone and heat-affected zone (HAZ). These strengthening precipitates have little difference in precipitation behavior after SAA and R40-SAA treatment and remain consistent across all regions, resulting in joint hardness change a little between these two joints with a homogeneous distribution. The change in precipitates leads to an increase in hardness and enhances both the SAA joint strength and the R40-SAA joint strength to 503 MPa and 528 MPa (superior to the original joints by 309 MPa and 334 MPa, respectively), respectively. The SAA joints fracture in the NZ resulting from the development of AGG, and develop an intergranular fracture morphology with an elongation of 4.2%. The R40-SAA joints have an elongation of 7.2% due to the generation of uniformly fine grains in the NZ, and fail in the HAZ exhibiting a brittle fracture mechanism.

To address the limited wear resistance attributed to the insufficient initial mechanical properties observed in high manganese steel (HM) wear behavior, we introduced nitrogen (N) to modulate precipitation behavior, thereby elevating material mechanical properties and wear resistance, and this was further enhanced through aging treatments. Due to the nitrogen addition, the precipitates transformed from MC to M(C, N), concurrently triggering a substantial increase and refinement in precipitates. As a result, nitrogenous high manganese steel (NHM) exhibited improved strength, toughness, and work-hardening capacity. The enhancements amounted to 67–77 MPa in yield strength and 5.3–9.3 % in elongation, with these improvements becoming more pronounced after extending the aging treatment. Under impact abrasive wear conditions, the NHM demonstrated the development of a stable work-hardened layer. The NHM hardened layer rapidly reached a depth of 4–6 mm, effectively resisting abrasive embedding and suppressing matrix abrasion. This transitioned the primary wear mechanisms from cutting and plowing to plastic deformation and micro-spalling. Additionally, NHM's great uniformity and toughness-plasticity played a crucial role in preventing the initiation and propagation of fatigue cracks and fatigue sheds.

Abstract The next generation of high-capacity, multi-task optical informatics requires sophisticated manipulation of multiple degrees of freedom (DoFs) of light, especially when they are coupled in a non-separable way. Vector beam, as a typical non-separable state between the spin and orbital angular momentum DoFs, mathematically akin to entangled qubits, has inspired multifarious theories and applications in both quantum and classical regimes. Although qubit rotation is a vital and ubiquitous operation in quantum informatics, its classical analogue is rarely studied. Here, we demonstrate the logical rotation of vectorial non-separable states via the uniform self-assembled chiral superstructures, with favorable controllability, high compactness and exemption from formidable alignment. Photonic band engineering of such 1D chiral photonic crystal renders the incident-angle-dependent evolution of the spatially-variant polarizations. The logical rotation angle of a non-separable state can be tuned in a wide range over 4π by this single homogeneous device, flexibly providing a set of distinguished logic gates. Potential applications, including angular motion tracking and proof-of-principle logic network, are demonstrated by specific configuration. This work brings important insight into soft matter photonics and present an elegant strategy to harness high-dimensional photonic states.

Abstract For classical waves, phase matching is vital for enabling efficient energy transfer in many scenarios, such as waveguide coupling and nonlinear optical frequency conversion. Here, we propose a temporal quasi-phase matching method and realize robust and complete acoustical energy transfer between arbitrarily detuned cavities. In a set of three cavities, A, B, and C, the time-varying coupling is established between adjacent elements. Analogy to the concept of stimulated Raman adiabatic passage, amplitudes of the two couplings are modulated as time-delayed Gaussian functions, and the couplings’ signs are periodically flipped to eliminate temporal phase mismatching. As a result, robust and complete acoustic energy transfer from A to C is achieved. The non-reciprocal frequency conversion properties of our design are demonstrated. Our research takes a pivotal step towards expanding wave steering through time-dependent modulations and is promising to extend the frequency conversion based on state evolution in various linear Hermitian systems to nonlinear and non-Hermitian regimes.

Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

Abstract Constructing heterojunctions with vacancies has garnered substantial attention in the field of piezo‐photocatalysis. However, the presence of interfacial vacancies can serve as charge‐trapping sites, leading to the localization of electrons and hindering interfacial charge transfer. Herein, dual oxygen vacancies in the NiFe‐layered double hydroxide and Bi2MoO6−x induced interfacial bonds have been designed for the piezo‐photocatalytic N2 oxidation to NO3−. Fortunately, it achieves sensational nitric acid production rates (7.23 mg g−1 h−1) in the absence of cocatalysts and sacrificial agents, which is 6.03 times of pure Bi2MoO6 that under ultrasound and light illumination. Theoretical and experimental results indicate that interfacial bonds act as “charge bridge” and “strain center” to break the carrier local effect and negative effects with piezocatalysis and photocatalysis for promoting exciton dissociation and charge transfer. Moreover, the strong electronic interaction of the interfacial bond induces internal reconstruction under ultrasound for promoting the local polarization and adsorption of N2, which accelerates the fracture of the N≡N bonds and reduces the activation energy of the reaction. The research not only establishes a novel approach for optimizing the combined effects of piezo‐catalysis and photocatalysis, but also achieves equilibrium between the synergistic impacts of vacancies and heterojunctions.

China’s oases are the center of human life and economic development for tens of millions of inhabitants in drylands. However, oases have experienced a significant expansion of cropland during the past three decades, which has resulted in rapidly increasing agricultural water demand and increasing water shortages in the region. Although crop switching is recognized as a promising strategy for improving the sustainability of agricultural production, little is known about how much it can improve the sustainability of oasis cropping systems and whether there are trade-offs among multiple sustainability goals. Here, we used a crop-water-use model, data on crop production and nutrient content, observational data on streamflow, and oasis land-use data to assess the impacts of different crop switching scenarios on water demand, nutrient supply, and income. The results showed that oasis agricultural water demand increased from 28.5 km3 to 41.1 km3 between 1987 and 2017, with 74.6 % of the oasis counties experiencing increasing agricultural water stress. By replacing all crops with those having the lowest water demand in each respective county, the demand for irrigation can be reduced by 23.1 %, and the demand for groundwater reduced by as much as 72.8 %. Crop switching scenarios that also consider crop species diversity, in which replacing the highest water demand crops with alternative crops (those with the lowest water demands, highest protein production, or highest calorie production) in each county can effectively reduce irrigation water demand (8.5–12.9 % for streamflow and 32.7–43.3 % for groundwater), while increasing protein (21.3–35.8 %) and calorie (27.5–42.7 %) production as well as income (1.4–2.4 %). Our research provides potential solutions to effectively alleviate the conflict between agricultural development and the environment in oasis regions.

Abstract Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non‐coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation. In this study, lncRNA sequencing (lncRNA seq) is conducted on five pairs of HBV‐positive and HBV‐negative liver tissue. Through analysis, HOXA‐AS2 (HOXA cluster antisense RNA 2) is identified as a significantly upregulated lncRNA in HBV‐infected livers. Further experiments demonstrate that HBV DNA polymerase (DNA pol) induces HOXA‐AS2 after establishing persistent high‐level HBV replication. Functional studies reveal that HOXA‐AS2 physically binds to cccDNA and significantly inhibits its transcription. Mechanistically, HOXA‐AS2 recruits the MTA1‐HDAC1/2 deacetylase complex to cccDNA minichromosome by physically interacting with metastasis associated 1 (MTA1) subunit, resulting in reduced acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) associated with cccDNA and subsequently suppressing cccDNA transcription. Altogether, the study reveals a mechanism to self‐limit HBV replication, wherein the upregulation of lncRNA HOXA‐AS2, induced by HBV DNA pol, can epigenetically suppress cccDNA transcription.

ObjectiveIn the double-blind, phase III, placebo-controlled RUBY randomized clinical trial, dostarlimab plus carboplatin-paclitaxel significantly increased survival among patients with primary advanced or recurrent endometrial cancer (EC). We conducted a cost-effectiveness analysis of dostarlimab in combination with chemotherapy in these patients stratified by mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) subgroups from the perspective of a United States payer.Materials and methodsA Markov model with three states was employed to simulate patients who were administered either dostarlimab in combination with chemotherapy or chemotherapy based on the RUBY trial. Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model.ResultsIn dMMR EC, the combination of dostarlimab and chemotherapy achieved an additional 5.48 QALYs at an incremental cost of $330,747 compared to chemotherapy alone, resulting in an ICER of $60,349.30 per QALY. In pMMR EC, there were 1.51 additional QALYs gained at an extra cost of $265,148, yielding an ICER of $175,788.47 per QALY. With a 15.2% discount on dostarlimab, the ICER decreased to $150,000 per QALY in the pMMR EC. The univariate sensitivity analysis revealed that the cost of dostarlimab, utility of progression-free survival (PFS), and progressive disease (PD) had the most significant impacts on the outcomes. Probabilistic sensitivity analysis revealed that dostarlimab had a 100% likelihood of being considered cost-effective for patients at a WTP threshold of $150,000 per QALY for dMMR EC, whereas this likelihood was only 0.5% for pMMR EC.ConclusionDostarlimab in combination with chemotherapy was cost-effective for primary advanced or recurrent dMMR EC from the perspective of a United States payer at a WTP threshold of $150,000 per QALY, but not for pMMR EC. Lowering the prices of dostarlimab could potentially enhance the cost-effectiveness of treatment for pMMR EC.

Radiometers and Wearable biosensors, as vital parts of the realm of quantum medicine, are becoming popular for their ability to continuously and immediately provide physiological data through single-cell spectroscopy, brain imaging, and noninvasive monitoring of biochemical markers in various neuroimaging and biofluids such as sweat, tears, and interstitial fluid. Various biosensing, microfluidic sampling, and transport technologies have been combined, made smaller, and incorporated with flexible materials to improve ease of use and comfort. Enhancing the understanding of the connections between noninvasive biofluids and blood analyte levels is crucial for improving the reliability of wearable biosensors. This review discusses the noninvasive monitoring of biomarkers such as hormones and metabolites utilizing electrochemical and optical biosensors, single-cell spectroscopy, and brain imaging. Increasing the number of biomarkers for monitoring will need further on-body bio affinity testing and various sensing devices. Large-scale validation studies with many participants are necessary to use wearable biosensors in therapeutic settings. Wearable biosensor technology's ability to quickly and accurately detect real-time physiological data in therapy might significantly impact our daily routines

Brain glioma, which is highly invasive and has a poor prognosis, is the most common primary intracranial tumor. Several studies have verified that the extent of resection is a considerable prognostic factor for achieving the best results in neurosurgical oncology. To obtain gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of existing devices, it is imperative to develop a real-time image-guided resection technique to offer reliable functional and anatomical information during surgery. At present, the application of intraoperative ultrasound (IOUS) has been indicated to enhance resection rates and maximize brain function preservation. IOUS, which is promising due to its lower cost, minimal operational flow interruptions, and lack of radiation exposure, can enable real-time localization and precise tumor size and form descriptions while assisting in discriminating residual tumors and solving brain tissue shifts. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound (CEUS), three-dimensional ultrasound (3DUS), noninvasive ultrasound (NUS), and ultrasound elastography (UE), could assist in achieving GTR in glioma surgery. This article reviews the advantages and disadvantages of IOUS in glioma surgery.

ObjectiveTo review our single-institution experience in the surgical management of foramen magnum tumors via a far-lateral approach using an oblique straight incision.MethodsFrom October 2023 to January 2024, four cases of tumors in the foramen magnum area treated at the Capital Medical University-affiliated XuanWu hospital neurosurgery department were involved in this study. All cases were managed with a far-lateral approach using an oblique straight incision. We retrospectively reviewed the clinical and imaging data, as well as the surgical strategies employed.ResultsThree cases of foramen magnum meningiomas and one case of glioma of the ventral medulla. All cases underwent a far-lateral approach using an oblique straight incision; all cases had a gross total resection, and the wounds healed well without cerebral fluid leakage or scalp hydrops. Except for one case of right foramen magnum meningioma, which had dysphagia and pneumothorax, the other cases were without any postoperative complications.ConclusionA far-lateral approach using an oblique straight incision can preserve muscle integrity and minimize subcutaneous exposure, allowing for complete anatomical reduction of muscles. This craniectomy method is simple and replicable, making it worthy of further clinical practice.

A Ground Coupled Heat Pump (GCHP) is a highly energy efficient heating, ventilation, and air conditioning (HVAC) system that utilises the ground as the heat source when heating and as the heat sink when cooling. This paper investigates GCHP systems with horizontal Ground Heat Exchangers (GHEs) in the rural industry, exemplifying the technology for poultry (chicken) sheds in Australia. This investigation aims to provide an Artificial Neural Network (ANN) model that can be used for GCHP design at various locations with different climates. To this extent, a Transient System Simulation Tool (TRNSYS) model for a typical horizontal GHE applied in a rural farm was first verified. Using this model, over 700,000 hourly performance data items were obtained, covering over 80 different yearly loading patterns under three different climate conditions. The simulated performance data was then used to train the ANN. As a result, the trained ANN can predict the performance of GCHP systems with identical (multiple) GHEs even under climatic conditions (and locations) that have not been specifically trained for. Unlike other works, the newly introduced ANN model is accurate even with limited types of input data, with high accuracy (less than 5% error in most cases tested). This ANN model is 100 times computationally faster than TRNSYS simulations and 10,000 times faster than finite element models.

Rationale: Cryostimulation involves using water environments and low temperatures as intervention mediums, with main methods including CWI (cold water immersion), CWT (contrast water therapy), and WBC (whole-body cryostimulation). Previous systematic reviews focused on the effect of cryostimulation on muscle fatigue and sports performance. However, studies on the selection of different cryostimulation methods and their intervention effects present inconsistent results. Introduction: To systematically review and methodologically appraise the quality and effectiveness of existing intervention studies that the effects of various cryostimulation methods, including CWI, CWT, and WBC, on exercise performance and fatigue recovery. Methods: Following PRISMA guidelines, we conducted searches in PubMed, Embase, The Cochrane Library, Web of Science, and EBSCO databases to gather randomized controlled trials or self-controlled trials involving CWI/CWT/WBC and their effects on exercise performance or fatigue recovery. The search period ranged from November 2013 to November 2, 2023. Literature screening was performed using EndNote X9.1, and the quality of included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis was conducted using RevMan 5.3 software. Results: This study included a total of 18 articles, included a total of 499 healthy participants, comprising 479 males and 20 females. Among them, participants underwent cryostimulation, including 102 using CWT, using CWI, and 58 using WBC. Compared to the control group, cryostimulation can significantly alleviate muscle pain intensity (SMD -0.45, 95% CL -0.82 to 0.09, P = 0.01). Specifically, CWI significantly reduced muscle pain intensity (SMD = −0.45, 95% CI: 0.820.09, P = 0.01), WBC significantly decreased C-reactive protein levels (SMD = −1.36, 95% CI: 2.350.36, P = 0.008). While, CWT showed no significant differences from the control group in exercise performance and fatigue recovery indicators (P > 0.05). Conclusion: Cryostimulation can significantly reduce muscle pain intensity and perceived fatigue. Specifically, CWI significantly alleviates muscle pain intensity, WBC significantly lowers markers of inflammation caused by fatigue after exercise, in contrast, CWT does not significantly improve exercise performance and fatigue recovery. After exercise, compared with rest, using cryostimulation may have more noticeable benefits for muscle fatigue and muscle pain, with recommendations prioritizing WBC and CWI particularly for addressing inflammation and muscle pain. However, all cryostimulation may have no significant influence on exercise performance.

Abstract Developing non‐precious‐metal electrocatalysts that can operate with a low overpotential at a high current density for industrial application is challenging. Heterogeneous bimetallic phosphides have attracted much interest. Despite high hydrogen evolution reaction (HER) performance, the ordinary oxygen evolution reaction (OER) performance hinders their practical use. Herein, it is shown that Fe‐doping reverses and enlarges the interfacial electrical field at the heterojunction, turning the H intermediate favorable binding sites for HER into O intermediate favorable sites for OER. Specifically, the self‐supported heterojunction catalysts on nickel foam (CoP@Ni2P/NF and Fe‐CoP@Fe‐Ni2P/NF) are readily synthesized. They only require the overpotentials of 266 and 274 mV to drive a large current density of 1000 mA cm−2 (j1000) for HER and OER, respectively. Furthermore, a water splitting cell equipped with these electrodes only requires a voltage of 1.724 V to drive j1000 with excellent durability, demonstrating the potential of industrial application. This work offers new insights on interfacial engineering for heterojunction catalysts.

ObjectiveThis study aimed to explore the correlation between serum potassium (K+) concentration upon admission and the presence of the Island Sign (IS) in cranial CT scans of patients diagnosed with Hypertensive Intracerebral Hemorrhage (HICH), including the potential presence of a non-linear relationship.MethodsThis investigation constituted a single-center cross-sectional study. We systematically gathered comprehensive general clinical characteristics, biological indicators, and imaging data from a cohort of 330 patients diagnosed with HICH. These patients received treatment within the neurosurgery department of Chongqing Emergency Medical Center during the period spanning from July 1, 2018, to July 7, 2023. Our primary objective was to scrutinize the potential connection between serum K+ concentration upon admission and the presence of the IS observed in cranial CT scans. To meticulously address this inquiry, we employed logistic regression modeling, thereby meticulously evaluating the correlation aforementioned. Moreover, in order to delve deeper into the intricacies of the relationship, we extended our analysis by employing a smoothed curve-fitting model to meticulously authenticate the potential non-linear interrelation between these two critical variables.ResultsIn this investigation, a total of 330 patients diagnosed with HICH were ultimately enrolled, exhibiting an average age of 58.4 ± 13.1 years, comprising 238 (72.1%) males and 92 (27.9%) females. Among these participants, 118 individuals (35.7%) presented with the IS upon admission cranial CT scans, while 212 patients (64.3%) did not exhibit this characteristic. Upon comprehensive multifactorial adjustments, a non-linear association was uncovered between serum K+ concentration and the presence of IS. Notably, an inflection point was identified at approximately 3.54 mmol/L for serum K+ concentration. Prior to the patient’s serum K+ concentration reaching around 3.54 mmol/L upon admission, a discernible trend was observed—every 0.1 mmol/L increment in serum K+ concentration was associated with an 8% decrease in the incidence of IS (OR: 0.914, 95% CI: 0.849–0.983, p = 0.015).ConclusionThe findings of this study underscore a negative association between reduced serum K+ concentration upon admission and the occurrence of the IS on cranial CT scans among patients diagnosed with hypertensive cerebral hemorrhage. Furthermore, this negative correlation appears to manifest within the realm of a non-linear relationship. This study elucidates the potential significance of serum K+ concentration levels among patients with HICH, highlighting the role they play. Moreover, the maintenance of a physiological equilibrium in serum K+ concentrations emerges as a conceivable protective factor for individuals within the stroke population.

The CRISPR-associated endonuclease Cas12a has become a powerful genome-editing tool in biomedical research due to its ease of use and low off-targeting. However, the size of Cas12a severely limits clinical applications such as adeno-associated virus (AAV)-based gene therapy. Here, we characterized a novel compact Cas12a ortholog, termed EbCas12a, from the metagenome-assembled genome of a currently unclassified Erysipelotrichia. It has the PAM sequence of 5'-TTTV-3' (V = A, G, C) and the smallest size of approximately 3.47 kb among the Cas12a orthologs reported so far. In addition, enhanced EbCas12a (enEbCas12a) was also designed to have comparable editing efficiency with higher specificity to AsCas12a and LbCas12a in mammalian cells at multiple target sites. Based on the compact enEbCas12a, an all-in-one AAV delivery system with crRNA for Cas12a was developed for both in vitro and in vivo applications. Overall, the novel smallest high-fidelity enEbCas12a, this first case of the all-in-one AAV delivery for Cas12a could greatly boost future gene therapy and scientific research.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation.Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model.Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959).Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

Abstract Rainbands are essential to tropical cyclones (TCs), significantly affecting TC structure and intensity change. High‐resolution synthetic aperture radar (SAR) imagery can capture the footprints of rainbands caused by rain‐induced sea surface roughness modification. Using 464 SAR TC images, we investigated the rainband‐occurrence probability of TCs under different hemispheres, local times (LTs), intensities, and ocean basins. Results show that the rainband‐occurrence probability is highest in the downshear‐left quadrant for Northern Hemisphere TCs (downshear‐right quadrant for Southern Hemisphere TCs). For Northern Hemisphere TCs, the rainband‐occurrence probability is overall higher in the early morning (LT), and the peak region of rainband‐occurrence probability appears farther from the TC center in the evening (LT). Compared with weak TCs, the rainband‐occurrence probability becomes higher for strong TCs in the Northern Hemisphere. Furthermore, TCs have a higher rainband‐occurrence probability in the Northwest Pacific than in the North Atlantic and Northeast Pacific.

BackgroundLong QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H Member 2 (KCNH2) gene are known to cause Long QT syndrome through an autosomal dominant inheritance pattern. However, as of now, there have been no reports of any KCNH2 variant leading to Long QT syndrome exhibiting incomplete penetrance that is influenced by gender.MethodsWhole-exome sequencing (WES) was conducted on the proband to identify pathogenic variants. Subsequently, Sanger sequencing was employed to validate the identified likely pathogenic variants in all family members.ResultsWe analyzed a pedigree spanning three-generations afflicted by Long QT syndrome. WES revealed a novel KCNH2 missense variant (p.Val630Gly, c.1889 T>G) as the causative factor for the family’s phenotype. Within this family, all three male carriers of the KCNH2 variant carriers exhibited the Long QT syndrome phenotype: one experienced sudden death during sleep, another received an implantable cardioverter defibrillator (ICD), and a younger man displayed a prolonged QTc interval without any instances of syncope or malignant arrhythmia to date. Interestingly, the middle-aged female carrier showed no Long QT Syndrome phenotype. However, her offspring, diagnosed with Turner syndrome (45, X) and also a carrier of this variant, experienced frequent syncope starting at 12 years old and was diagnosed with Long QT syndrome, leading to an ICD implantation when she was 15 years old. These observations suggest that the manifestation of Long QT syndrome associated with this KCNH2 variant exhibits incomplete penetrance influenced by gender within this family, indicating potential protective mechanisms against the syndrome in females affected by this variant.ConclusionOur investigation has led to the identification of a novel pathogenic KCNH2 variant responsible for Long QT syndrome within a familial context characterized by gender-selective, incomplete penetrance. This discovery highlights a unique pathogenic inheritance pattern for the KCNH2 gene associated with Long QT syndrome, and could potentially shed light on the distinct penetrance behaviors and patterns of the KCNH2 gene. This discovery broadens our exploration of the KCNH2 gene in cardiac arrhythmias, highlighting the intricate genetic dynamics behind Long QT syndrome.

PurposeThe overall distribution pattern of intramuscular nerves and the regions with the highest spindle abundance in deep cervical muscles have not been revealed. This study aimed to reveal neuromuscular compartmentalization and localize the body surface position and depth of the center of the region of highest muscle spindle abundance (CRHMSA) in the deep cervical muscles.MethodsThis study included 36 adult cadavers (57.7 ± 11.5 years). The curved line joining the lowest point of the jugular notch and chin tip was designated as the longitudinal reference line (line L), and the curved line connecting the lowest point of the jugular notch and acromion was designated as the horizontal reference line (line H). Modified Sihler’s staining, hematoxylin–eosin staining and computed tomography scanning were employed to determine the projection points (P) of the CRHMSAs on the anterior surfaces of the neck. The positions (PH and PL) of point P projected onto the H and L lines, and the depth of each CRHMSA, and puncture angle were determined using the Syngo system.ResultsThe scalenus posterior and longus capitis muscles were divided into two neuromuscular compartments, while the scalenus anterior and longus colli muscles were divided into three neuromuscular compartments. The scalenus medius muscle can be divided into five neuromuscular compartments. The PH of the CRHMSA of the scalenus muscles (anterior, medius, and posterior), and longus capitis and longus colli muscles, were located at 36.27, 39.18, 47.31, 35.67, and 42.71% of the H line, respectively. The PL positions were at 26.53, 32.65, 32.73, 68.32, and 51.15% of the L line, respectively. The depths of the CRHMSAs were 2.47 cm, 2.96 cm, 2.99 cm, 3.93 cm, and 3.17 cm, respectively, and the puncture angles were 87.13°, 85.92°, 88.21°, 58.08°, and 77.75°, respectively.ConclusionPresent research suggests that the deep cervical muscles can be divided into neuromuscular compartments; we recommend the locations of these CRHMSA as the optimal target for administering botulinum toxin A injections to treat deep cervical muscle dystonia.