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Abstract Background The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration. Methods To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1β/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB). Results Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1β) signaling pathway. Conclusions These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1β pathway in macrophages. Trial registration Date of registration 09/04/2021 (number: ChiCTR2100045256).

Acidovorax citrulli (Ac) is an important pathogenic bacterium causing bacterial fruit blotch (BFB) in Cucurbitaceae plants and is an important quarantine pest in China. This study was conducted to establish a rapid, convenient, and accurate visual method for detecting A. citrulli. A. citrulli-specific primers and a prober were designed based on the conserved region of the YD-repeat protein gene. Loop-mediated isothermal amplification combined with lateral flow dipstick (LAMP-LFD) was used to establish an assay for the rapid visual detection of A. citrulli by optimizing the reaction temperature and time. The specificity, sensitivity, and performance of the optimized LAMP-LFD assay were evaluated using the genomic DNA of the tested isolates, A. citrulli pure culture, infested seeds, commercial seeds, and leaf samples. The optimal assay temperature and time were 64 °C and 60 min, respectively. The assay specifically detected A. citrulli, and no cross-reactions were observed with the genomic DNA of other closely related species. The detection sensitivity of the LAMP-LFD for detecting pure genomic DNA, the bacterial suspension, bacterial amount on seeds (colony-forming units (CFU)·g−1), and infection rate of seeds (%) were 1 fg·μL−1, 8 CFU·mL−1, 5 CFU·g−1, and 0.05% infestation per reaction, respectively. The positive detection rate of the LAMP-LFD assay was 20–100% in seed samples (n = 1000 seeds) with 0.05–0.1% infestation. The LAMP-LFD assay rapidly and accurately detected A. citrulli in seeds and leaf tissues carrying pathogens. This assay thus offers the advantages of easy operation, rapidity, high specificity and sensitivity, low cost (no need for complex and expensive precision instruments), visualization of detection results, good stability, and strong applicability, which can be used for epidemiological studies and disease management.

Based on the combination of core observation, experimental analysis and testingand geological analysis, the main controlling factors of shale oil enrichment in the Lower Permian Fengcheng Formation in the Mahu Sag of the Junggar Basin are clarified, and a shale oil enrichment model is established. The results show that the enrichment of shale oil in the Fengcheng Formation in the Mahu Sag is controlled by the organic abundance, organic type, reservoir capacity and the amount of migration hydrocarbon in shale. The abundance of organic matter provides the material basis for shale oil enrichment, and the shales containing types I and II organic matters have good oil content. The reservoir capacity controls shale oil enrichment. Macropores are the main space for shale oil enrichment in the Fengcheng Formation, and pore size and fracture scale directly control the degree of shale oil enrichment. The migration of hydrocarbons in shale affects shale oil enrichment. The shale that has expelled hydrocarbons has poor oil content, while the shale that has received hydrocarbons migrated from other strata has good oil content. Lithofacies reflect the hydrocarbon generation and storage capacity comprehensively. The laminated felsic shale, laminated lime-dolomitic shale and thick-layered felsic shale have good oil content, and they are favorable lithofacies for shale oil enrichment. Under the control of these factors, relative migration of hydrocarbons occurred within the Fengcheng shale, which leads to the the difference in the enrichment process of shale oil. Accordingly, the enrichment mode of shale oil in Fengcheng Formation is established as “in-situ enrichment” and “migration enrichment”. By superimposing favorable lithofacies and main controlling factors of enrichment, the sweet spot of shale oil in the Fengcheng Formation can be selected which has great significance for the exploration and development of shale oil.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

An immunosuppressive state is regulated by various factors in the tumor microenvironment (TME), including, but not limited to, metabolic plasticity of immunosuppressive cells and cytokines secreted by these cells. We used single‐cell RNA‐sequencing (scRNA‐seq) data and applied single‐cell flux estimation analysis to characterize the link between metabolism and cellular function within the hypoxic TME of colorectal (CRC) and lung cancer. In terms of metabolic heterogeneity, we found myeloid cells potentially inclined to accumulate glutamine but tumor cells inclined to accumulate glutamate. In particular, we uncovered a tumor‐associated macrophage (TAM) subpopulation, APOE+CTSZ+TAM, that was present in high proportions in tumor samples and exhibited immunosuppressive characteristics through upregulating the expression of anti‐inflammatory genes. The proportion of APOE+CTSZ+TAM and regulatory T cells (Treg) were positively correlated across CRC scRNA‐seq samples. APOE+CTSZ+TAM potentially interacted with Treg via CXCL16–CCR6 signals, as seen by ligand–receptor interactions analysis. Notably, glutamate‐to‐glutamine metabolic flux score and glutamine synthetase (GLUL) expression were uniquely higher in APOE+CTSZ+TAM, compared with other cell types within the TME. GLUL expression in macrophages was positively correlated with anti‐inflammatory score and was higher in high‐grade and invasive tumor samples. Moreover, spatial transcriptome and multiplex immunofluorescence staining of samples showed that APOE+CTSZ+TAM and Treg potentially colocalized in the tissue sections from CRC clinical samples. These results highlight the specific role and metabolic characteristic of the APOE+CTSZ+TAM subpopulation and provide a new perspective for macrophage subcluster‐targeted therapeutic interventions or metabolic checkpoint‐based cancer therapies.

As a secondary structural unit locating in the central Jizhong Depression of the Bohai Bay Basin, the formation and evolution of Gaoyang low uplift is closely related to the development of the adjacent Baoding and Raoyang sags. The understanding for the structural characteristics of the Gaoyang low uplift is valuable for the overall study of the extensional deformation system in the central Jizhong Depression. Based on abundant seismic data, the structural characteristics of the Gaoyang low uplift were determined by using structural analysis method. According to drilling data and regional stratigraphic correlation, the age of syndepositional formation and the time of tectonic activity were determined. By compiling balanced sections and analyzing regional tectonic evolution, the genetic mechanism of the Gaoyang low uplift was discussed in this paper. The Gaoyang low uplift is featured by a gentle anticline which narrows from the south to the north, and the west limb of the anticline is steeper than the east counnterpart. Several NW-SE trending faults with large heave and long plane extension distance developed in the east flank of the Gaoyang low uplift, while only a few small-scale faults were developed in the west flank. The age of the oldest syndepositional strata in the southern part of the studied area is the Late Mesozoic, while that in the north is Paleocene. The Gaoyang low uplift is a compound rollover anticline developed in the common hanging wall of the boundary faults on both sides of the central Jizhong Depression, and its formation was mainly controlled by the extension of the boundary faults. The southern Gaoyang low uplift began to develop earlier than the northern part.

Background: Although there is evidence of long-term effects of particulate matter (PM) on cardiovascular diseases (CVD), researches about long-term effects of PM1 on CVD are limited. We aimed to examine the long-term effects and magnitude of PM, especially PM1, on incident CVD in China. Methods: We included 6016 participants aged ≥ 45 years without CVD at baseline in 2011 from the China Health and Retirement Longitudinal Study. Personal PM (PM1, PM2.5, and PM10) concentrations were estimated using geocoded residential address. Generalized linear mixed models and SHapley Additive exPlanation were utilized to calculate the impacts and contributions of PM on CVD. Sensitivity analyses were used to check the robustness. Results: After a follow up of 4-year, 481 (7.99 %) participants developed CVD. Per 10 μg/m3 uptick in 1-year average concentrations of PM1, PM2.5 and PM10 was associated with a 1.20 [95 % confidence interval (CI): 1.05–1.37], 1.13 (95 % CI: 1.11–1.15), and 1.10 (95 % CI: 1.06–1.13) fold risk of incident CVD, respectively. The 2-year average concentrations of PM1, PM2.5 and PM10 were associated with incident CVD, corresponding to a 1.03 (95 % CI: 0.96–1.10), 1.11 (95 % CI: 1.02–1.21), and 1.09 (95 % CI: 1.03–1.15) fold risk, respectively. The SHapley Additive exPlanation values of PM1, PM2.5, and PM10 were 0.170, 0.153, and 0.053, respectively, corresponding to the first, second, and fifth among all air pollutants. Effects of PM1, PM2.5 and PM10 on CVD remained statistically significant in two-pollutant models. The elderly, males, smokers and alcohol drinkers tended to have slightly higher effects, while the differences were not statistically significant (all P-values > 0.05) between subgroups. Conclusion: Long-term exposure to PM1, PM2.5, and PM10 was associated with an increased incidence of CVD. The smaller the particle size, the more important it was for incident CVD indicating that emphasis should be placed on small size of PM.

Increasing evidence indicated that mitophagy might play a crucial role in the occurrence and progression of liver diseases. In order to enhance our understanding of the intricate relationship between mitophagy and liver diseases, a comprehensive bibliometric analysis of the existing literature in this field was conducted. This analysis aimed to identify key trends, potential areas of future research, and forecast the development of this specific field. We systematically searched the Web of Science Core Collection (WoSCC) for publications related to mitophagy in liver diseases from 2000 to 2022. We conducted the bibliometric analysis and data visualization through VOSviewer and CiteSpace. The analysis of publication growth revealed a substantial increase in articles published in this field over the past years, indicating mitophagy's growing interest and significance in liver diseases. China and USA emerged as the leading contributors in the number of papers, with 294 and 194 independent papers, respectively. Exploring the mechanism of mitophagy in the initiation and procession of liver diseases was the main content of studies in this field, and Parkin-independent mediated mitophagy has attracted much attention recently. “Lipid metabolism,” “cell death,” “liver fibrosis” and “oxidative stress” were the primary keywords clusters. Additionally, “nlrp3 inflammasome”, “toxicity” and “nonalcoholic steatohepatitis” were emerging research hotspots in this area and have the potential to continue to be focal areas of investigation in the future. This study represents the first systematic bibliometric analysis of research on mitophagy in liver diseases conducted over the past 20 years. By providing an overview of the existing literature and identifying current research trends, this analysis sheds light on the critical areas of investigation and paves the way for future studies in this field.

Heterogeneity is a critical basis for understanding how the tumor microenvironment (TME) contributes to tumor progression. However, an understanding of the specific characteristics and functions of TME subtypes (subTMEs) in the progression of cancer is required for further investigations into single-cell resolutions. Here, we analyzed single-cell RNA sequencing data of 250 clinical samples with more than 200,000 cells analyzed in each cancer datum. Based on the construction of an intercellular infiltration model and unsupervised clustering analysis, four, three, three, and four subTMEs were revealed in breast, colorectal, esophageal, and pancreatic cancer, respectively. Among the subTMEs, the immune-suppressive subTME (subTME-IS) and matrix remodeling with malignant cells subTME (subTME-MRM) were highly enriched in tumors, whereas the immune cell infiltration subTME (subTME-ICI) and precancerous state of epithelial cells subTME (subTME-PSE) were less in tumors, compared with paracancerous tissues. We detected and compared genes encoding cytokines, chemokines, cytotoxic mediators, PD1, and PD-L1. The results showed that these genes were specifically overexpressed in different cell types, and, compared with normal tissues, they were upregulated in tumor-derived cells. In addition, compared with other subTMEs, the expression levels of PDCD1 and TGFB1 were higher in subTME-IS. The Cox proportional risk regression model was further constructed to identify possible prognostic markers in each subTME across four cancer types. Cell-cell interaction analysis revealed the distinguishing features in molecular pairs among different subTMEs. Notably, ligand–receptor gene pairs, including COL1A1-SDC1, COL6A2-SDC1, COL6A3-SDC1, and COL4A1-ITGA2 between stromal and tumor cells, associated with tumor invasion phenotypes, poor patient prognoses, and tumor advanced progression, were revealed in subTME-MRM. C5AR1-RPS19, LGALS9-HAVCR2, and SPP1-PTGER4 between macrophages and CD8+ T cells, associated with CD8+ T-cell dysfunction, immunosuppressive status, and tumor advanced progression, were revealed in subTME-IS. The spatial co-location information of cellular and molecular interactions was further verified by spatial transcriptome data from colorectal cancer clinical samples. Overall, our study revealed the heterogeneity within the TME, highlighting the potential pro-invasion and pro-immunosuppressive functions and cellular infiltration characteristics of specific subTMEs, and also identified the key cellular and molecular interactions that might be associated with the survival, invasion, immune escape, and classification of cancer patients across four cancer types.

Let $ G(a_1, a_2, \ldots, a_k) $ be a simple graph with vertex set $ V(G) = V_1\cup V_2\cup \cdots \cup V_k $ and edge set $ E(G) = \{(u, v)|u\in V_i, v\in V_{i+1}, i = 1, 2, \ldots, k-1\} $, where $ |V_i| = a_i > 0 $ for $ 1\leq i\leq k $ and $ V_i\cap V_j = \emptyset $ for $ i\neq j $. Given two positive integers $ k $ and $ n $, and $ k-2 $ positive rational numbers $ t_2, t_3, \ldots, t_{\lceil k/2\rceil} $ and $ t_2', t_3', \ldots, t_{\lfloor k/2\rfloor}' $, let $ \Upsilon(n; k)_t^{t'} = \{G(a_1, a_2, \ldots, a_k)|\sum_{i = 1}^ka_i = n, a_{2i-1} = t_{i}a_1, a_{2j} = t_j'a_2, i = 2, 3, \ldots, \lceil k/2\rceil, $ $ j = 2, 3, \ldots, \lfloor k/2\rfloor; t = (t_2, t_3, \ldots, t_{\lceil k/2\rceil}), t' = (t_2', t_3', \ldots, t_{\lfloor k/2\rfloor}'); a_s\in N, 1\leq s\leq k\} $, where $ N $ is the set of positive integers. In this paper, we prove that all graphs in $ \Upsilon(n; k)_t^{t'} $ are cospectral with respect to the normalized Laplacian if it is not an empty set.

Peanut (Arachis hypogaea L.), one of the leading oilseed crops worldwide, is an important source of vegetable oil, protein, minerals and vitamins. Peanut is widely cultivated in Asia, Africa and America, and China is the largest producer and consumer of peanut. Genetic engineering has shown great potential to alter the DNA makeup of an organism which is largely hindered by the low transformation and screening efficiency including in peanut. DsRed2 is a reporter gene widely utilized in genetic transformation to facilitate the screening of transformants, but never used in peanut genetic transformation. In this study, we have demonstrated the potential of the red fluorescence protein DsRed2 as a visual reporter to improve screening efficiency in peanut. DsRed2 was firstly expressed in protoplasts isolated from peanut cultivar Zhonhua 12 by PEG, and red fluorescence was successfully detected. Then, DsRed2 was expressed in peanut plants Zhonghua 12 driven by 35S promoter via Agrobacterium tumefaciens-mediated transformation. Red fluorescence was visually observed in calli and regenerated shoots, as well as in roots, leaves, flowers, fresh pod shells and mature seeds, suggesting that transgenic screening could be initiated at the early stage of transformation, and continued to the progeny. Upon screening with DsRed2, the positive plant rate was increased from 56.9% to 100%. The transgenic line was then used as the male parent to be crossed with Zhonghua 24, and the hybrid seeds showed red fluorescence as well, indicating that DsRed2 could be applied to hybrid plant identification very efficiently. DsRed2 was also expressed in hairy roots of Huayu 23 via Agrobacterium rhizogenes-mediated transformation, and the transgenic roots were easily selected by red fluorescence. In summary, the DsRed2 is an ideal reporter to achieve maximum screening efficiency and accuracy in peanut genetic transformation.

Abstract Background Lung squamous cell carcinoma (LSCC) is a form of cancer that is associated with high rates of relapse, poor responsiveness to therapy, and a relatively poor prognosis. The relationship between long non-coding RNA (lncRNA) expression and LSCC patient prognosis remains to be established. Methods In the present study, we discovered that lncRNAs were differentially expressed in LSCC tumor tissues relative to normal control tissues, and we explored the prognostic relevance of these lncRNA expression patterns using data from the Cancer Genome Atlas (TCGA). Results These multidimensional data were analyzed in order to identify lncRNA signatures that were associated with LSCC patient survival outcomes. Kaplan-Meier survival curves revealed prognostic capabilities for three of these lncRNAs (LINC02555, APCDD1L-DT and OTX2-AS1). A Cox regression analysis revealed this three-lncRNA signature to be significantly associated with patient survival. Further GO and KEGG analyses revealed that the predicted target genes of these three lncRNAs were also potentially involved in cancer-associated pathways. Conclusions Together these results thus indicate that this novel three-lncRNA signature can be used to predict LSCC patient prognosis.

With the global epidemic of SARS-CoV-2, it is important to effectively monitor the variation, haplotype subgroup epidemic trends and key mutations of SARS-CoV-2 over time. This is of great significance to the development of new vaccines, the update of therapeutic drugs, and the improvement of detection methods. The AutoVEM tool developed in the present study could complete all mutations detections, haplotypes classification, haplotype subgroup epidemic trends and candidate key mutations analysis for 131,576 SARS-CoV-2 genome sequences in 18 h on a 1 core CPU and 2 GB RAM computer. Through haplotype subgroup epidemic trends analysis of 131,576 genome sequences, the great significance of the previous 4 specific sites (C241T, C3037T, C14408T and A23403G) was further revealed, and 6 new mutation sites of highly linked (T445C, C6286T, C22227T, G25563T, C26801G and G29645T) were discovered for the first time that might be related to the infectivity, pathogenicity or host adaptability of SARS-CoV-2. In brief, we proposed an integrative method and developed an efficient automated tool to monitor haplotype subgroup epidemic trends and screen for the candidate key mutations in the evolution of SARS-CoV-2 over time for the first time, and all data could be updated quickly to track the prevalence of previous key mutations and new candidate key mutations because of high efficiency of the tool. In addition, the idea of combinatorial analysis in the present study can also provide a reference for the mutation monitoring of other viruses.

Objectives: To further reveal the phylogenetic evolution and molecular characteristics of the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on a large number of genomes and provide a basis for the prevention and treatment of SARS-CoV-2. Methods: Various evolution analysis methods were employed. Results: The estimated ratio of the rates of non-synonymous to synonymous changes (Ka/Ks) of SARS-CoV-2 was 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes and nine key specific sites of high linkage, and four major haplotypes were found: H1, H2, H3 and H4. The results of Ka/Ks, detected population size and development trends of each major haplotype showed that H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating that they might have existed for a long time. The H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time, and the frequency of H1 was generally high in Europe and correlated with the death rate (r >0.37), suggesting that these two haplotypes might relate to the infectivity or pathogenicity of SARS-CoV-2. Conclusions: Several key specific sites and haplotypes related to the infectivity or pathogenicity of SARS-CoV-2, and the possible earlier origin time and place of SARS-CoV-2 were indicated based on the evolution and epidemiology of 16,373 SARS-CoV-2 genomes.

Although immunotherapy has achieved good results in various cancer types, a large proportion of patients are limited from the benefits. Hypoxia and metabolic reprogramming are the common and critical factors that impact immunotherapy response. Here, we present current research on the metabolism reprogramming induced by hypoxia on antitumor immunity and discuss the recent progression among preclinical and clinical trials exploring the therapeutic effects combining targeting hypoxia and metabolism with immunotherapy. By evaluating the little clinical translation of the combined therapy, we provide insight into “understanding and regulating cellular metabolic plasticity under the current tumor microenvironment (TME),” which is essential to explore the strategy for boosting immune responses by targeting the metabolism of tumor cells leading to harsh TMEs. Therefore, we highlight the potential value of advanced single-cell technology in revealing the metabolic heterogeneity and corresponding phenotype of each cell subtype in the current hypoxic lesion from the clinical patients, which can uncover potential metabolic targets and therapeutic windows to enhance immunotherapy.

T-cell exhaustion is one of the main reasons of tumor immune escape. Using single-cell transcriptome data of CD8+ T cells in multiple cancers, we identified different cell types, in which Pre_exhaust and exhausted T cells participated in negative regulation of immune system process. By analyzing the coexpression network patterns and differentially expressed genes of Pre_exhaust, exhausted, and effector T cells, we identified 35 genes related to T-cell exhaustion, whose high GSVA scores were associated with significantly poor prognosis in various cancers. In the differentially expressed genes, RGS1 showed the greatest fold change in Pre_exhaust and exhausted cells of three cancers compared with effector T cells, and high expression of RGS1 was also associated with poor prognosis in various cancers. Additionally, RGS1 protein was upregulated significantly in tumor tissues in the immunohistochemistry verification. Furthermore, RGS1 displayed positive correlation with the 35 genes, especially highly correlated with PDCD1, CTLA4, HAVCR2, and TNFRSF9 in CD8+ T cells and cancer tissues, indicating the important roles of RGS1 in CD8+ T-cell exhaustion. Considering the GTP-hydrolysis activity of RGS1 and significantly high mRNA and protein expression in cancer tissues, we speculated that RGS1 potentially mediate the T-cell retention to lead to the persistent antigen stimulation, resulting in T-cell exhaustion. In conclusion, our findings suggest that RGS1 is a new marker and promoting factor for CD8+ T-cell exhaustion and provide theoretical basis for research and immunotherapy of exhausted cells.

Hypoxia is a characteristic of tumor microenvironment (TME) and is a major contributor to tumor progression. Yet, subtype identification of tumor-associated non-malignant cells at single-cell resolution and how they influence cancer progression under hypoxia TME remain largely unexplored. Here, we used RNA-seq data of 424,194 single cells from 108 patients to identify the subtypes of cancer cells, stromal cells, and immune cells; to evaluate their hypoxia score; and also to uncover potential interaction signals between these cells in vivo across six cancer types. We identified SPP1+ tumor-associated macrophage (TAM) subpopulation potentially enhanced epithelial–mesenchymal transition (EMT) by interaction with cancer cells through paracrine pattern. We prioritized SPP1 as a TAM-secreted factor to act on cancer cells and found a significant enhanced migration phenotype and invasion ability in A549 lung cancer cells induced by recombinant protein SPP1. Besides, prognostic analysis indicated that a higher expression of SPP1 was found to be related to worse clinical outcome in six cancer types. SPP1 expression was higher in hypoxia-high macrophages based on single-cell data, which was further validated by an in vitro experiment that SPP1 was upregulated in macrophages under hypoxia-cultured compared with normoxic conditions. Additionally, a differential analysis demonstrated that hypoxia potentially influences extracellular matrix remodeling, glycolysis, and interleukin-10 signal activation in various cancer types. Our work illuminates the clearer underlying mechanism in the intricate interaction between different cell subtypes within hypoxia TME and proposes the guidelines for the development of therapeutic targets specifically for patients with high proportion of SPP1+ TAMs in hypoxic lesions.

Hypersplenism and thrombocytopenia are common complications of liver cirrhosis or thalassemia, but current treatment strategies are limited. This study aimed to evaluate the efficacy and safety of thalidomide in the treatment of hypersplenism and thrombocytopenia in patients with liver cirrhosis or thalassemia. A total of 31 patients with hepatic cirrhosis (n=19) or thalassemia (n=12) diagnosed with hypersplenism and thrombocytopenia (platelet count [PLT]

Abstract Background Transcription factors operate as important switches of transcription networks, and NAC (NAM, ATAF, and CUC) transcription factors are a plant-specific family involved in multiple biological processes. However, this gene family has not been systematically characterized in cotton. Results Here we identify a large number of genes with conservative NAC domains in four cotton species, with 147 found in Gossypium arboreum, 149 in G. raimondii, 267 in G. barbadense and 283 in G. hirsutum. Predicted membrane-bound NAC genes were also identified. Phylogenetic analysis showed that cotton NAC proteins clustered into seven subfamilies and homologous protein pairs showed similar characteristics. Evolutionary property analysis revealed that purifying selection of NAC genes occurred between diploid and polyploid cotton species, and variation analysis showed GhNAC genes may have been subjected to selection and domestication. NAC proteins showed extensive transactivation and this was dependent on the C-terminus. Some development and stress related cis-elements were enriched in the promoters of GhNAC genes. Comprehensive expression analysis indicated that 38 GhNAC genes were candidates for involvement in fiber development, and 120 in stress responses. Gene co-expression network analysis revealed relationships between fiber-associated NAC genes and secondary cell wall (SCW) biosynthesis genes. Conclusions NAC genes were identified in diploid and tetraploid cotton, revealing new insights into their evolution, variation and homology relationships. Transcriptome analysis and co-expression network indicated roles for GhNAC genes in cotton fiber development and stress response, and NAC genes may prove useful in molecular breeding programmes.

Abstract Dysfunction is a common clinical symptom among rehabilitation patients; however, whether there are sex differences in dysfunctions remains unclear. Therefore, this study aimed to explore this issue by examining a large sample of the population with dysfunctional problems. A multi-stage sampling scheme was used to select the rehabilitation outpatients as study participants. A total of 3415 participants from 21 medical institutions in seven cities in China were included in the final analysis. The measurement included general characteristics (age, sex, educational level, marital status, and household income) and disease-related characteristics (dysfunctions, self-care ability, vital signs, disease status, and disease course). The logistic regression was used to analyse the sex difference in dysfunctions among rehabilitation outpatients. Among 3415 rehabilitation outpatients, the mean age of participants was 45.3 years (SD:24.9), and more than half (54.0%) were male. The male patients were more likely to have cognitive impairment (OR = 1.74; 95% CI = 1.42, 2.13), speech disorders (OR = 2.00; 95% CI = 1.62, 2.48), dysphagia (OR = 1.55; 95% CI = 1.12, 2.16), and multiple dysfunctions (OR = 2.00; 95% CI = 1.57, 2.54) than female. Female patients were more likely to have motor dysfunctions (OR = 0.63; 95% CI = 0.50, 0.78). There are sex differences in dysfunctions among rehabilitation outpatients. This sex difference may provide potential clinical value for the treatment of rehabilitation patients.

Abstract Background Relative fat mass (RFM) is a newly developed, sex-specific anthropometric formula designed to estimate total body fat percentage. However, research investigating the correlation between RFM and the risk of non-alcoholic fatty liver disease (NAFLD) remains limited. This study evaluates the association between RFM and the risk of NAFLD within the Japanese population. Methods This study including 14,250 Japanese adults who underwent physical examinations at Murakami Memorial Hospital between 2004 and 2015. We employed binary logistic regression to elucidate the direct relationship between RFM levels and the incidence of NAFLD. Additionally, a generalized additive model (GAM) coupled with smooth curve fitting techniques was utilized to map the non-linear association. Results The cohort had an average age of 43.53 ± 8.89 years, with a male majority of 52.00%. NAFLD was identified in 17.59% of the participants. After adjusting for confounding factors, a significant positive correlation between RFM and NAFLD risk was observed (OR: 1.15, 95%CI: 1.10–1.21, P

Abstract Background This work aims to explore circ_ROBO1’s function in nasopharyngeal carcinoma (NPC). Methods circ_ROBO1 expression in NPC tissues and cell lines was measured. The regulation of circ_ROBO1 and/or miR-324-3p on the proliferation, migration, invasion, and apoptosis of NPC cells was investigated by functional experiments. The interplay between circ_ROBO1, miR-324-3p, and NME1 was explored. Tumor growth and metastasis were studied in mice. Results circ_ROBO1 was overexpressed in NPC. Knockdown of circ_ROBO1 repressed proliferation, migration, and invasion and induced apoptosis of NPC cells. Loss of circ_ROBO1 reduced tumor growth and metastasis in mice. circ_ROBO1 competed with miR-324-3p to upregulate NME1. Lowering miR-324-3p expression impaired the effect of knockdown of circ_ROBO1on NPC cells. Conclusion Overexpressed circ_ROBO1 promotes NPC development by modifying the miR-324-3p/NME1 axis.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by developmental impairments, inattention, motor hyperactivity, and impulsivity. Currently, there is no effective intervention that can completely cure it. One of the pathogenic mechanisms of ADHD involves abnormalities in the norepinephrine (NE) pathway within the prefrontal cortex (PFC). In recent years, transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation technique, has demonstrated promising potential in the treatment of neurological and psychiatric disorders. However, its application in the management of ADHD remains relatively unexplored. Previous studies have shown that taVNS exerts therapeutic effects on attention, cognition, arousal, perception, and behavioral regulation primarily through activating the vagus nerve conduction pathway, specifically targeting the nucleus tractus solitarius - locus coeruleus - NE pathway. These findings have led to the hypothesis that taVNS may be an effective intervention for ADHD, with NE and its pathway playing a pivotal role in this context. Therefore, this review comprehensively examines the correlation between NE pathway alterations in the PFC and ADHD, the mechanism of action of taVNS, and the potential role of the NE pathway in treating ADHD with taVNS, aiming to provide a theoretical foundation for clinical applications.

Granzyme K (GzmK) is a trypsin-like serine protease that functions as a pro-apoptotic protease, has non-cytotoxic functions, and is involved in various physiopathological processes. However, the impact of GzmK on the immunological response of Nile tilapia against bacterial challenge is still poorly explored. In this study, we identified the GzmK gene from Nile tilapia (On-GzmK) and investigated its immunologic roles through in vivo experiments. On-GzmK has an open reading frame of 786 bp and encodes 255 amino acids. On-GzmK has over 60 % genetic similarity with other fish and over 30 % similarity with mammals. Its transcript levels were highest in the liver and vastly increased after being challenged with Streptococcus agalactiae and Aeromonas hydrophila. In vivo experiments implied that On-GzmK might promote inflammatory responses and regulate apoptosis and pyroptosis by participating in the activation of multiple signaling pathways, such as JAK-STAT, MAPK, and NF-κB. The present observations offer additional theoretical support for investigating the processes by which GzmK shields fish against bacterial infections.

Breast cancer is rare in men and is managed using strategies similar to those for breast cancer in women. This study retrospectively analyzed the clinicopathological features, treatment, and survival of male breast cancer (MBC). A total of 66 patients with MBC admitted into Xijing Hospital from August 2006 to March 2024 were reviewed. Data were collected from patients’ hospital records and breast cancer database of Xijing Hospital. The incidence of MBC tended to increase from 2018, with affected individuals being older than those with female breast cancer (FBC). The most common histological type of MBC was invasive carcinoma, with positive hormone receptor status. A total of 62 (93.9%) patients with MBC underwent modified radical mastectomy. Chemotherapy was administered to 39 (59.1%) patients, while endocrine therapy was received by 14 patients (21.2%) and radiotherapy by nine patients (13.6%). Survival analysis indicated that the median overall survival (OS) of patients with MBC was 46.7 months (0.9–184.8 months). As of the latest data, 58 patients (87.9%) with MBC are alive. Factors significantly associated with survival included age (χ 2 = 3.856, p = .050), estrogen receptor (χ 2 = 10.427, p = .005), molecular types (χ 2 = 10.641, p = .031), P63 (χ 2 = 2.631, p