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Summary: Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN.

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists

An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529–0.870, P = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530–0.938, P = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940–0.993, P = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927–0.993, P = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397–0.863, P = .007; CIR: HR: 0.551, 95% CI: 0.353–0.861, P = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424–0.896, P = .011; CIR: HR: 0.617, 95% CI: 0.388–0.979, P = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.

BackgroundThere is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders.MethodThis study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype “All anxiety disorders” to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations.ResultsBidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders.ConclusionOur findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

In this paper, the time fractional Benjamin-Bona-Mahony-Peregrine (BBMP) equation and time-fractional Novikov equation with the Riemann-Liouville derivative are investigated through the use of Lie symmetry analysis and the new Noether's theorem. Then, we construct their group-invariant solutions by means of Lie symmetry reduction. In addition, the power-series solutions are also obtained with the help of the Erdélyi-Kober (E-K) fractional differential operator. Furthermore, the conservation laws for the time-fractional BBMP equation are established by utilizing the new Noether's theorem.

The emergence of distributed energy and prosumers has greatly promoted the reform of the energy market. Blockchain technology provides a very potent solution for distributed energy transactions, however, blockchain technology still develops slowly in the energy field due to the unstable performance of the imperfect system. This paper aims to narrow this gap by the following steps. First, a function-driven integration method is proposed to combine the merit of blockchain distributed ledger and traditional centralized databases. Then a hybrid energy blockchain system architecture is designed, including the blockchain layer, smart contract layer, database layer, and client layer. Further, a peer-to-peer market mechanism considering energy storage arbitrage and fully automated matchmaking is developed on the hybrid blockchain system. The case study proves the effectiveness and safety of the system. The proposed architecture of combined blockchain and database technologies effectively paves the way for constructing a more reasonable and feasible distributed energy trading platform.

Abstract Connected and Autonomous Vehicles (CAVs) are reshaping urban systems, demanding substantial computational support. While existing research emphasizes the significance of establishing physical and virtual infrastructure to facilitate CAV integration, a comprehensive framework for designing CAV-related infrastructure principles remains largely absent. This paper introduces a holistic framework that addresses gaps in current literature by presenting principles for the design of CAV-related infrastructure. We identify diverse urban infrastructure types crucial for CAVs, each characterized by intricate considerations. Deriving from existing literature, we introduce five principles to guide investments in physical infrastructure, complemented by four principles specific to virtual infrastructure. These principles are expected to evolve with CAV development and associated technology advancements. Furthermore, we exemplify the application of these principles through a case study in Oxford, UK. In doing so, we assess urban conditions, identify representative streets, and craft CAV-related urban infrastructure tailored to distinct street characteristics. This framework stands as a valuable reference for cities worldwide as they prepare for the increasing adoption of CAVs.

To explore the effect of different thawing methods on the quality of frozen stripped-walnut kernel, the walnut kernel was soaked in warm water to remove the inner seed coat and then frozen as the test material. The color value, texture, free amino acids, VE, unsaturated fatty acids, rancidity index, volatile composition and microtissue structure of walnut after air thawing at room temperature, microwave thawing, refrigerator thawing at 4 ℃ and room temperature ultrasound thawing were measured. The results showed that the content of total free amino acids, VE, unsaturated fatty acids of stripped-walnut kernel after microwave thawing was higher, and the aroma of roasting was relatively stronger. However, the walnut kernel darkens, the oil oxidation was serious, and the pores between cells were relatively large. The walnut kernel color was the worst after thawing in air at room temperature, and the degree of oxidation was serious. After thawing at 4 ℃ and ultrasonic thawing at room temperature, walnut kernel brightness was higher, the texture was good, the total amount of free amino acids was significantly (P

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets.

Abstract Background Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). Methods The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. Results 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P 0.05). Conclusion TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

Abstract The interfacial morphology of crystalline silicon/hydrogenated amorphous silicon (c-Si/a-Si:H) is a key success factor to approach the theoretical efficiency of Si-based solar cells, especially Si heterojunction technology. The unexpected crystalline silicon epitaxial growth and interfacial nanotwins formation remain a challenging issue for silicon heterojunction technology. Here, we design a hybrid interface by tuning pyramid apex-angle to improve c-Si/a-Si:H interfacial morphology in silicon solar cells. The pyramid apex-angle (slightly smaller than 70.53°) consists of hybrid (111)0.9/(011)0.1 c-Si planes, rather than pure (111) planes in conventional texture pyramid. Employing microsecond-long low-temperature (500 K) molecular dynamic simulations, the hybrid (111)/(011) plane prevents from both c-Si epitaxial growth and nanotwin formation. More importantly, given there is not any additional industrial preparation process, the hybrid c-Si plane could improve c-Si/a-Si:H interfacial morphology for a-Si passivated contacts technique, and wide-applied for all silicon-based solar cells as well.

Under the background of economic globalization, green supply chain management has become a key strategic management tool for enterprises to improve their competitiveness as well as sustainable development. This paper proposes the objective function and constraints in supply chain network optimization based on the policies related to the dual-carbon target and the requirements in the cross-border industrial cooperation model and uses the robust model to solve and realize the establishment of the supply chain network optimization model. The simulation test found that the solving efficiency of this model and the control of carbon emissions are better than the traditional genetic algorithm. Meanwhile, after the optimization of this model, the supplier delivery rate of cross-border enterprise Y can reach 91.28%, which is far beyond the target expectation, and the carbon emission of the enterprise is far below the carbon emission limit, so the green cross-border supply chain network can be realized. The model in this paper can improve the weak link in the green management decision of cross-border supply chain network, strengthen the application of a robust model in the design and optimization of cross-border supply chain network, and provide auxiliary decision-making support for the construction of cross-border supply chain network scientifically and effectively.

Salt stress is a prevailing abiotic stress in nature, with soil salinization becoming a pressing issue worldwide. High soil salinity severely hampers plant growth and leads to reduced crop yields. Hydrogen sulfide (H2S), a gas signal molecule, is known to be synthesized in plants exposed to abiotic stress, contributing to enhanced plant stress resistance. To investigate the impact of sodium hydrosulfide hydrate (NaHS, a H2S donor) on millet’s response to salt stress, millet seedlings were subjected to pretreatment with 200 μM NaHS, followed by 100 mM NaCl stress under soil culture conditions. The growth, osmotic adjustment substances, antioxidant characteristics, membrane damage, and expression levels of related genes in millet seedlings were detected and analyzed. The results showed that NaHS pretreatment alleviated the inhibition of salt stress on the growth of foxtail millet seedlings, increased the proline content and antioxidant enzyme activities, as well as the expression levels of SiASR4, SiRPLK35 and SiHAK23 genes under salt stress. These findings demonstrated that NaHS pretreatment can enhance salt tolerance in foxtail millet seedlings by regulating the content of osmotic adjustment substances and antioxidant enzyme activity, reducing electrolyte permeability, and activating the expression of salt-resistant genes.

Abstract Background The pathogenesis of moyamoya disease (MMD) is unclear. Inflammation and immune imbalance have been identified as potential factors contributing to the occurrence and progression of MMD. However, the specific proteins and metabolites responsible for triggering this process are yet to be established. The purpose of this study is to identify differentially expressed proteins and metabolites in patients with MMD and perform Kyoto Encyclopedia of Genes and Genomes pathway integration analysis to pinpoint crucial proteins and metabolites involved in the disease. Methods We performed untargeted metabolomic and data‐independent acquisition proteomic analyses on the serum samples of individuals with MMD and healthy controls (HC). Results In patients with MMD versus HC, 24 proteins and 60 metabolites, including 21 anionic metabolites and 39 cationic metabolites, which were significantly different, were identified. In patients with MMD, several proteins involved in inflammation and immune metabolism, such as tubulin beta‐6 and complement C4, were found to have significantly altered levels. Similarly, many metabolites involved in inflammation and immune metabolisms, such as dimethyl 4‐hydroxyisophthalate, beta‐nicotinamide mononucleotide, 2‐(3‐(4‐pyridyl)‐1H‐1,2,4‐triazol‐5‐yl)pyridine, and PC (17:1/18:2), were significantly altered. Intriguingly, these proteins and metabolites are involved in the progression of atherosclerosis through immune and inflammatory pathways, although some have never been reported in MMD. Moreover, integrated proteomics and metabolomics studies were conducted to determine shared pathways involving cholesterol metabolism, vitamin digestion, fat digestion, and absorption pathways of proteins and metabolites, which warrant further investigation. Conclusions Significant increases in pro‐inflammatory and immunosuppressive abilities have been observed in patients with MMD, accompanied by significant reductions in anti‐inflammatory and immune regulation. Various metabolites and proteins implicated in these processes have been identified for the first time. These findings hold immense significance for comprehending the pathogenesis of MMD and for the development of future drug therapies.

IntroductionMarine epiphytic diatoms are natural diets for multiple marine invertebrates, including sea cucumbers, sea urchins, etc. They also act as bioindicators in marine waters to assess water quality of coastal ecosystems. Material and methodsWe isolated three strains of Navicula and two strains of Nitzschia from macroalgal epiphytes. Combined concentrations of four macroelements, five trace metals, and three vitamins in f/2 medium were optimized for these diatoms using single-factor and orthogonal tests. Results and discussionThe biomass productivities for 4-L enlarged cultures of the five isolated diatoms in their exclusively optimized f/2 media all increased by nearly 10-fold relative to f/2 medium, and that of Navicula-1 and Nitzschia-2 reached the highest, i.e., 29.52 ± 1.98 and 30.68 ± 2.84 g m-2 d-1, respectively. Moreover, the relative abundance of C20:5n3 in the exclusively optimized f/2 medium-cultured Navicula-1 notably rose by 24%, and that in Nitzschia-2 held stable at > 25%. Thus, Navicula-1 and Nitzschia-2 were screened out with outstanding growth traits and improved fatty acid compositions at high levels of combined nitrogen, phosphorus, iron, and silicon. The two diatoms have potential for becoming quality diets for marine aquaculture, and ideal candidates for effective nutrient removal.