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Diabetic cardiomyopathy (DCM), a major risk factor contributing to diabetes-related morbidity and mortality, manifests as a pathophysiologic condition in humans independently of coronary artery disease or hypertension. Several transcription factors intricately participate in the initiation and progression of associated processes. Among these, nuclear factor kappa B (NF-κB), a pleiotropic transcription factor, assumes a crucial role in regulating oxidative stress, inflammatory response, endothelial dysfunction, myocardial fibrosis and hypertrophy, and cardiomyocyte apoptosis in DCM. However, the precise role of NF-κB in DCM remains a subject of ongoing investigation. This article provides a comprehensive review of NF-κB's involvement in several processes associated with DCM.

AbstractBackground The Coronavirus disease 2019 (COVID-19) pandemic has brought a heavy burden to the world, interestingly, it shares many clinical symptoms with systemic lupus erythematosus (SLE). It is unclear whether there is a similar pathological process between COVID-9 and SLE. In addition, we don’t know how to treat SLE patients with COVID-19. In this study, we analyse the potential similar pathogenesis between SLE and COVID-19 and explore their possible drug regimens using bioinformatics and systems biology approaches.Methods The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis.Result Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE.Conclusion COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.

The integration of renewable energy into the power grid poses significant challenges for optimization and scheduling of the power system. In recent years, methods based on deep reinforcement learning have surpassed traditional methods on the high complexity and long-term decision-making of power system optimization and scheduling. However, faced with the inherent uncertainty of renewable energy generation and the different optimization objectives in power system, the deep reinforcement learning methods are unable to effectively address them. This paper proposes a method that combines meta reinforcement learning with multi-agent reinforcement learning to solve the multi-objective two-stage robust optimization of wind/PV/thermal power system. We conducts optimization and scheduling experiments on the IEEE39 bus system. The results indicate that our method not only enhances the robustness of the scheduling strategy, but also outperforms baseline methods in terms of convergence, diversity, and uniformity of the Pareto frontier.

Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

IntroductionAtopic dermatitis (AD) is a common, chronic, recurrent inflammatory skin disease. To date, no meta-analysis have been conducted on the prevalence and risk factors of AD in children aged 1–7 years in Mainland China.MethodsWe conducted a meta-analysis of the prevalence and risk factors of AD among children aged 1–7 years in China. Chinese and English publications were searched in Chinese and English databases on AD epidemiology published between 1999 and 2023. Two researchers independently screened the literature, extracted the data, and evaluated their quality. A meta-analysis was performed using a random-effects model (I2 > 50%) with 95% confidence intervals (CIs) for the forest plots. Data were processed using the RevMan 5.3.ResultsNineteen studies (data from 127,660 samples) met the inclusion criteria. The pooled prevalence of AD in Chinese children aged 1–7 years was 8%. Over the last decade, the prevalence of AD has increased. The prevalence of AD among children in southern China was higher than that in northern China and was the highest at the provincial level in Zhejiang, Shanxi, and Anhui. The prevalence of AD was dependent on the family history of allergy, passive smoking, households with pets, plush toys, and residential area.DiscussionThe prevalence of AD in children (age 1–7 years) in China has increased. Further studies are needed to monitor the prevalence of AD in Chinese children. Therefore, early prevention and screening should be performed for children with a family history of AD, and their living environment should be improved to reduce allergen stimulation, thus reducing the development of AD.

Abstract Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five‐year survival rate for ESCC is still below 20%. Herein, ESCC‐specific DNA aptamers and an innovative aptamer‐modified nano‐system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell‐based systematic evolution of ligands by exponential enrichment (cell‐SELEX). An EA1‐modified nano‐system is developed using a natural egg yolk lipid nanovector (EA1‐EYLNs‐PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1‐EYLNs‐PTX/siEFNA1 nano‐system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer‐modified nano‐systems can deliver drugs and genes with superior tumor‐targeting, potentially revolutionizing targeted therapy in ESCC.

The most prevalent form of colon cancer also ranks high among cancer-related deaths globally. Traditional chemotherapy drugs do not provide sufficient therapeutic efficacy, and advanced colon cancer demonstrates considerable resistance to chemotherapy. As an oral kinase inhibitor, sorafenib (SOR) suppresses the growth of tumour cells, the formation of new blood vessels, and the death of cancer cells. Unfortunately, sorafenib's limited bioavailability, rapid metabolism, and poor solubility have severely limited its clinical use. We developed nanoparticles targeting P-selectin and SOR, with fucoidan (FU) as a ligand. The SOR-CS-FU-NPs were developed by coating polylactide-co-glycolide nanoparticles with chitosan and FU through electrostatic interaction. The SOR-CS-FU-NPs exhibited an average particle diameter of 209.98 ± 1.25 nm and a polydisperse index (PDI) of 0.229 ± 0.022. The SOR-CS-FU nanoparticles exhibited a continuous release pattern for up to 120 h. The SOR-CS-FU nanoparticles exhibited cytotoxicity 8 times greater than free SOR in HCT116 colorectal cancer cells. The cellular absorption of Rhodamine-CS-FU-NPs was three times more than that of free Rhodamine and 19 times greater than that of Rhodamine-CS-NPs. Enhanced reactive oxygen species (ROS) generation and mitochondrial membrane potential damage were also shown in SOR-CS-FU-NPs. An investigation of cell death found that SOR-CS-FU-NPs had an apoptosis index that was 7.5 times greater than free SOR. After that, the SOR-CS-FU-NPs demonstrated a more significant inhibition of cell migration, leading to a wound closure of about 5 %. No toxicity was shown in the non-cancer VERO cell line when exposed to the developed NPs. Taken together, these results provide strong evidence that biocompatible SOR-CS-FU-NPs fabricated effective carriers for the targeted delivery of dasatinib to colorectal cancer.

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.

In the context of the rapid development of Internet of Things (IoT) technology and the extensive proliferation of the global Internet, the authenticity of data has become a focal point of societal demand. It plays a decisive role in enhancing the quality of decision-making and operational efficiency. However, the storage and authenticity verification of large-scale IoT real-time data present unprecedented technical challenges. Faced with the inherent data security risks of traditional centralized cloud storage, blockchain technology reveals its unique potential for solutions with its inherent immutability and decentralization. Nevertheless, current blockchain-based data storage solutions are still restricted by high costs and inefficiency. To address these challenges, this paper innovatively proposes the BI-TSFID framework, which leverages the benefits of Ethereum and IPFS and optimizes the Merkle Tree structure and verification mechanisms. The BI-TSFID framework adopts a strategy of on-chain data summary storage and off-chain computation. This approach provides IoT with efficient and reliable data storage, reduces operational costs, and simplifies the verification process. This research has improved the data computation efficiency by refining the structure of the Merkle Tree and analyzed its optimal branch number. Additionally, the study introduces a sampling-based data integrity verification method that significantly reduces resource consumption during the verification process. Experimental results show that the solutions proposed in this paper effectively enhance the efficiency and security of IoT data management and provide valuable guidance for the theory and practice of real-time data storage and verification, further promoting the development and innovation in the related technological fields.

Background While anti-programmed cell death protein-1 (PD-1) monotherapy has shown effectiveness in treating lung cancer, its response rate is limited to approximately 20%. Recent research suggests that abnormal lipid metabolism in patients with lung adenocarcinoma may hinder the efficacy of anti-PD-1 monotherapy.Methods Here, we delved into the patterns of lipid metabolism in patients with The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and their correlation with the immune microenvironment’s cellular infiltration characteristics of the tumor. Furthermore, the lipid metabolism score (LMS) system was constructed, and based on the LMS system, we further performed screening for potential agents targeting lipid metabolism. The mechanism of MK1775 was further validated using RNA sequencing, co-culture technology, and in vivo experiments.Results We developed an LSM system and identified a potential sensitizing agent, MK1775, which targets lipid metabolism and enhances the effects of anti-PD-1 treatment. Our results demonstrate that MK1775 inhibits tumor progression by influencing lipid crosstalk between tumor cells and tumor-associated macrophages and CD8+T cells, thereby increasing the effectiveness of anti-PD-1 treatment. Further, we found that MK1775 inhibited the phosphatidylinositol 3-kinase(PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, which on one hand downregulated FASN-mediated synthesis of fatty acids (FAs) to inhibit fatty acid oxidation of tumor-associated macrophages, and on the other hand, promoted IRF-mediated secretion of CXCL10 and CXCL11 to facilitate the infiltration of CD8+ T cells.Conclusions These findings emphasize the important role of lipid metabolism in shaping the complex tumor microenvironment. By manipulating the intricate intricacies of lipid metabolism within the tumor microenvironment, we can uncover and develop promising strategies to sensitize immunotherapy, potentially revolutionizing cancer treatment approaches.

BackgroundCognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients.MethodsSixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA

Summary: DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1—a component of the E3 ligase complex involved in HIV regulation—is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.

More and more evidence has showed that low glycaemic index (GI) diet was a benefit to the Type 2 Diabetes Mellitus (T2DM). However, the detailed mechanism was not clear. Here, we detected the effects of low-GI diet on the HFD/STZ-induced T2DM rats model. Our results showed that low-GI diet significantly decreased triglyceride and glucose level in the serum of T2DM rats, and increased the level of insulin and C-peptide in T2DM rats. Besides, low-GI diet also increased Bacteroidota at the phylum level. And at the genus level, low-GI diet promoted the proliferation of the abundance of Turicibacter, Lactobacillus, Desulfovibrio, Prevotellaceae, Lachnospiraceae, Monoglobus, Xylanophilum and Roseburia. Moreover, we also found that low-GI diet significantly improved the contents of valeric acid, acetic acid, propionic acid, isobutyric acid, butyric acid, 2-methylbutyrate, isovaleric acid, 4-methylvaleric acid and hexanoic acid; upregulated the levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and G protein-coupled receptor 41 (GPR41); and increased the numbers of L-cells (P