Hepatocellular carcinoma (HCC) is a major public health problem in humans. The imbalance of mitochondrial function has been discovered to be closely related to the development of cancer recently. However, the role of mitochondrial-related genes in HCC remains unclear.

As a well-known cancer-related miRNA, miR-193b-3p is enriched in skeletal muscle and dysregulated in muscle disease. However, the mechanism underpinning this has not been addressed so far. Here, we probed the impact of miR-193b-3p on myogenesis by mainly using goat tissues and skeletal muscle satellite cells (MuSCs), compared with mouse C2C12 myoblasts. miR-193b-3p is highly expressed in goat skeletal muscles, and ectopic miR-193b-3p promotes MuSCs proliferation and differentiation. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) is the most activated insulin signaling gene when there is overexpression of miR-193b-3p; the miRNA recognition element (MRE) within the IGF1BP1 3' untranslated region (UTR) is indispensable for its activation. Consistently, expression patterns and functions of IGF2BP1 were similar to those of miR-193b-3p in tissues and MuSCs. In comparison, ectopic miR-193b-3p failed to induce PAX7 expression and myoblast proliferation when there was IGF2BP1 knockdown. Furthermore, miR-193b-3p destabilized IGF2BP1 mRNA, but unexpectedly promoted levels of IGF2BP1 heteronuclear RNA (hnRNA), dramatically. Moreover, miR-193b-3p could induce its neighboring genes. However, miR-193b-3p inversely regulated IGF2BP1 and myoblast proliferation in the mouse C2C12 myoblast. These data unveil that goat miR-193b-3p promotes myoblast proliferation via activating IGF2BP1 by binding to its 3' UTR. Our novel findings highlight the positive regulation between miRNA and its target genes in muscle development, which further extends the repertoire of miRNA functions.

We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA).

IL-33, which is a crucial modulator of adaptive immune responses far beyond type 2 response, can enhance the function of several T cell subsets and maintain the immune homeostasis. However, the contribution of IL-33 to double negative T (DNT) cell remains unappreciated. Here, we demonstrated that the IL-33 receptor ST2 was expressed on DNT cells, and that IL-33 stimulation increased DNT cells proliferation and survival in vivo and in vitro. Transcriptome sequencing analysis also demonstrated that IL-33 enhanced the biological function of DNT cells, especially effects on proliferation and survival. IL-33 promoted DNT cells survival by regulating Bcl-2, Bcl-xl and Survivin expression. IL-33-TRAF4/6-NF-κB axis activation promoted the transmission of essential division and survival signals in DNT cells. However, IL-33 failed to enhance the expression of immunoregulatory molecules in DNT cells. DNT cells therapy combined with IL-33 inhibited T cells survival and further ameliorated ConA-induced liver injury, which mainly depended on the proliferative effect of IL-33 on DNT cells in vivo. Finally, we stimulated human DNT cells with IL-33, and similar results were observed. In conclusion, we revealed a cell intrinsic role of IL-33 in the regulation of DNT cells, thereby identifying a previously unappreciated pathway supporting the expansion of DNT cells in the immune environment.

Nowadays, bacterial infections are attracting great attention for the research and development of new antimicrobial agents. As one of the quinolones, ciprofloxacin (CI) has a broad-spectrum, strong antibacterial effect. However, the clinical use of ciprofloxacin is limited by drug resistance. Ciprofloxacin carbon dots (CCDs) with enhanced antibacterial activity and copper-doped ciprofloxacin carbon dots (Cu-CCDs) were synthesized by a simple hydrothermal method. The results of structural analysis and antibacterial experiments show that CCDs and Cu-CCDs have effective antibacterial properties by retaining the active groups of ciprofloxacin (-COOH, C-N, and C-F), and Cu-CCDs doped with copper have a better antibacterial effect. In addition, experiments have shown that Cu-CCDs show excellent antibacterial activity against E. coli and S. aureus and have good biocompatibility, which indicates that they have great prospects in clinical applications. Therefore, novel modified copper CCDs with broad-spectrum antibacterial activity, which can be used as antibacterial nanomaterials for potential applications in the field of antibacterial drugs, were synthesized in this study.

The ratio of platelets to lymphocytes (PLR) can serve as a potential biomarker for predicting the prognosis of individuals with acute myocardial infarction (AMI).

This qualitative study evaluates physician training and experience with treatment and prevention services for people who inject drugs (PWID) including medications for opioid use disorder (MOUD) and HIV pre-exposure prophylaxis (PrEP). The Behavioral Model of Healthcare Utilization for Vulnerable Populations was applied as a framework for data analysis and interpretation. Two focus groups were conducted, one with early career physicians (n = 6) and one with mid- to late career physicians (n = 3). Focus group transcripts were coded and analyzed using thematic analysis to identify factors affecting implementation of treatment and prevention services for PWID. Respondents identified that increasing the availability of providers prescribing MOUD was a critical enabling factor for PWID seeking and receiving care. Integrated, interdisciplinary services were identified as an additional resource although these remain fragmented in the current healthcare system. Barriers to care included provider awareness, stigma associated with substance use, and access limitations. Providers identified the interwoven risk factors associated with injection drug use that must be addressed, including the risk of HIV acquisition, notably more at the forefront in the minds of early career physicians. Additional research is needed addressing the medical education curriculum, health system, and healthcare policy to address the addiction and HIV crises in the U.S. South.

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However, Panax notoginseng flower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX-2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL-37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography-tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX-2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.

Leukemia inhibitory factor (LIF) exhibits significant tumor-promoting function, while its cognate receptor (LIFR) is considered to act as either a tumor promoter or suppressor. Dysregulation of LIF and LIFR is associated with the initiation, progression and metastasis of multiple cancer entities. Although increasing numbers of studies are revealing an indispensable critical role of LIFR in tumorigenesis for various different cancers, no systematic analysis of LIFR has appeared thus far.

Recently, immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) monoclonal antibodies (mAbs), have revolutionized the treatment of malignant tumors. Therefore, the number of studies aiming to screen and identify new immune checkpoint molecules for antitumor immunotherapy is increasing. Signaling lymphocytic activation molecule (SLAM) family members are mainly expressed by and regulate the functions of immune cells. Recent studies have shown that several SLAM family members are involved in the regulation of the tumor immune microenvironment and are promising targets for antitumor immunotherapy. Signaling lymphocytic activation molecule family member 8 (SLAMF8) is a type I cell surface glycoprotein and is encoded on chromosome 1q21. To further illustrate the clinical value of SLAMF8 in colorectal cancer (CRC), we retrospectively analyzed the relationship between SLAMF8 expression and the prognosis of CRC patients and the associations between SLAMF8 expression and the expression levels of other SLAM family members and other classic immune checkpoint molecules using The Cancer Genome Atlas (TCGA) data, RNA sequencing data, tissue immunohistochemistry staining, and systematic follow-up analysis. Here, high SLAMF8 expression was associated with poor overall survival (OS) in CRC. The mRNA expression level of SLAMF8 was positively correlated with the expression levels of multiple classic immune checkpoints and other SLAM family members. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the pathways enriched in CRC tissues with high SLAMF8 expression were associated with the regulation of the tumor immune microenvironment.

Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive disorder with poor prognosis. It is caused by pathogenic variants of the ATP binding cassette subfamily B member 4 (ABCB4) gene and usually progresses from chronic cholestasis with or without jaundice to portal hypertension and end-stage liver disease within the first to second decade of life. Few reported PFIC-3 patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Herein, we report a 16-year-old male who was admitted to our hospital due to acute episodes of jaundice and intense pruritus, subsequently progressed to end-stage liver disease. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, drug or liver tumors. Ursodeoxycholic acid and dexamethasone did not relieve his symptoms and he underwent liver transplantation successfully. Targeted next-generation sequencing identified that the patient was a compound heterozygote for two missense mutations (c.959C > T/c.1429C > A) in the ABCB4 gene. The mutation c.1429C > A (p.Q477K) is a novel heterozygous mutation. We constructed a three-dimensional model of this novel pathogenic variant using the SWISS MODEL program and found that the patient's ABCB4 protein is an ATP hydrolysis deficient mutant. The postoperative pathological diagnosis showed intrahepatic cholestasis with progression to cirrhosis. Negative liver tissue immunohistochemistry of MDR3 was found in the explanted liver. The patient was diagnosed with PFIC-3, and his symptoms improved dramatically with liver transplantation. In conclusion, for young patients with acute cholestasis, pruritus, jaundice, growth retardation, and enlargement of the liver and spleen, the possibility of inherited metabolic liver diseases should be considered, detailed medical and family history should be collected, and metabolic screening tests as well as gene tests are necessary for correct diagnosis. Increasing the coverage of PFIC3 is meaningful and thus can improve the current understanding of this disease.

Extensive application of anti-HER2 targeted therapy improves significantly the HER2-positive advanced breast cancer (BC) prognosis, however, it is still difficult to treat brain metastasis. In current study, we explored effective approaches via combining pyrotinib to treat brain metastasis in patients with HER2-positive advanced BC based upon clinical data.

5-Methyladenosine (m5C) is a type of epigenetic modification involved in the progression of various cancers. To investigate the role of m5C-related long non-coding RNAs (lncRNAs) in the prognosis and immune cell infiltration in hepatocellular carcinoma (HCC), we obtained patients' clinical information and transcriptome data of HCC from the Cancer Genome Atlas (TCGA) database. We applied Pearson correlation analysis to construct an m5C-related lncRNA-messenger RNA (mRNA) co-expression network. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were employed to establish an m5C-related lncRNA prognostic risk model. We then verified the model using Kaplan-Meier analysis, principal component analysis, as well as univariate and multivariate Cox analyses. The expression of m5C-related lncRNAs was validated in HCC tissues and different cell lines. Combining the risk score and clinicopathological features, a nomogram was established for predicting the overall survival (OS) of HCC patients. Furthermore, gene set enrichment analysis (GSEA) revealed that some tumor-associated pathways were significantly enriched in the high-risk group. Immune cell infiltration analysis demonstrated that the levels of Treg cells, neutrophils, and M2 macrophages were higher in the high-risk group. In addition, patients with high tumor mutation burden (TMB) had worse OS than those with low TMB. We also assessed the immune checkpoint level and chemotherapeutic agent sensibility. Then in vitro experiments were performed to examine the biological function of MKLN1-AS in HCC cells and found that knockdown of MKLN1-AS suppressed the proliferation, migration, and invasion. In conclusion, m5C-related lncRNAs played a critical role in predicting the prognosis of patients with HCC and may serve as new therapeutic targets for HCC patients.

Plant growth-promoting rhizobacteria (PGPR) are widely used to improve soil nutrients and promote plant growth and health. However, the growth-promoting effect of a single PGPR on plants is limited. Here, we evaluated the effect of applying rhizobium Bradyrhizobium japonicum 5038 (R5038) and two PGPR strains, Bacillus aryabhattai MB35-5 (BA) and Paenibacillus mucilaginosus 3016 (PM), alone or in different combinations on the soil properties and rhizosphere bacterial community composition of soybean (Glycine max). Additionally, metagenomic sequencing was performed to elucidate the profile of functional genes. Inoculation with compound microbial inoculant containing R5038 and BA (RB) significantly improved nodule nitrogenase activity and increased soil nitrogen content, and urease activity increased the abundance of the nitrogen cycle genes and Betaproteobacteria and Chitinophagia in the rhizosphere. In the treatment of inoculant-containing R5038 and PM (RP), significant changes were found for the abundance of Deltaproteobacteria and Gemmatimonadetes and the phosphorus cycle genes, and soil available phosphorus and phosphatase activity were increased. The RBP inoculants composed of three strains (R5038, BA and PM) significantly affected soybean biomass and the N and P contents of the rhizosphere. Compared with RB and RP, RBP consistently increased soybean nitrogen content, and dry weight. Overall, these results showed that several PGPR with different functions could be combined into composite bacterial inoculants, which coordinately modulate the rhizosphere microbial community structure and improve soybean growth.

Burnout is at all-time highs across modern professions. As a typical labor-intensive industry, the high-pressure and task-driven nature of the construction industry makes construction workers more prone to burnout. It is still unclear whether increasing the professionalization level can lessen the many harmful consequences of job burnout on construction workers' employment. Therefore, this study examined the influencing mechanism of professionalization on job burnout in the construction industry. First, a theoretical model based on the conservation of resources (COR) theory was developed with workload, job insecurity, and work-family conflict as moderating variables. A reliable sample of 441 Chinese construction workers were then recruited in the investigation. The data analysis was supported by confirmatory factor analysis (CFA) and structural equation modeling (SEM). The results indicated that: (i) an increase in the professionalization level could be directly effective in alleviating job burnout among construction workers; (ii) workload and work-family conflict could play an independent and continuous mediating role between professionalization and job burnout; and (iii) while job insecurity caused by a low professionalization did not have a direct impact on job burnout, it could have an indirect impact on job burnout through workload and work-family conflict, respectively. This study enriches the literature on job burnout among construction workers, as well as provides a theoretical basis and practical management guidance for Chinese construction companies to alleviate job burnout in workers from a professionalization standpoint.

Atopic dermatitis (AD), characterized by eczema as a chronic pruritic inflammatory skin disease, has become a serious health problem with recurrent clinical episodes. However, current clinical treatments have limited relief and are accompanied by adverse effects. Therefore, there is a necessity to develop new effective drugs for AD treatment. Angelica Yinzi (AYZ) is a classic ancient prescription for nourishing blood, moistening dryness, dispelling wind, and relieving itching. However, its mechanism for alleviating atopic dermatitis remains unknown. Therefore, this study aimed at determining the effects of AYZ and its potential mechanism in alleviating AD-like symptoms.

The COVID-19 pandemic significantly changed society. We aimed to examine the systematic impact of the COVID-19 on injury burden in the United States.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by demyelination and neurodegeneration, for which traditional treatment offers limited relief. Microglial/macrophage modulation plays a critical role in the pathogenesis of MS. Oxygen free radical accumulation can induce axonal and nerve cell damage, and further promote MS development. We created a new recombinant protein based on flagellin from Legionella pneumophila named flagellin A with linked C- and N-terminal ends (FLaAN/C), which is an independent intellectual property of our team. We previously showed that FLaAN/C might mitigate radiation-induced damage by inhibiting inflammatory responses and oxidative stress. However, whether FLaAN/C protects against MS remains unknown. Here, we investigated the anti-inflammatory effects of FLaAN/C on mice with experimental autoimmune encephalomyelitis (EAE) induced by oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). The mice were injected intraperitoneally with FLaAN/C after the onset of clinical symptoms, then clinical behavior scores and changes in body weight were recorded daily. The spinal lumbar spine in model mice was enlarged and accompanied by inflammatory cell infiltration and demyelination that were reversed by FLaAN/C. FLaAN/C also induced microglia/macrophages to generate less pro-inflammatory (CD86, iNOS, and TNF-α), and more anti-inflammatory (CD206, IL-10, and Arginase-1) cytokines. These findings suggesting that FLaAN/C promoted microglial/macrophages polarization from the inflammatory M1 to the anti-inflammatory M2 phenotype. Moreover, FLaAN/C inhibited release of the inflammatory cytokines, TNF-α, IL-8, IL-6, IL-17, and IFN-γ. These results indicated that the anti-inflammatory effect of FLaAN/C was associated with the inhibited generation of reactive oxygen species. FLaAN/C downregulated the expression of phosphorylated NF-κB-p65 and prevented downstream NLRP3 inflammasome-mediated pyroptosis. Collectively, these results indicated that FLaAN/C prevents pyroptosis by inhibiting the ROS/NF-κB/NLRP3 signaling pathway, and promotes the microglial/macrophage M1/M2 polarization that significantly alleviated inflammation in mouse models of EAE. Our findings suggested that FLaAN/C could be a promising candidate for MS therapy.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Increasing studies suggest that mitochondrial dysfunction is closely related to the pathogenesis of AD. Thioredoxin-1 (Trx-1), one of the major redox proteins in mammalian cells, plays neuroprotection in AD. However, whether Trx-1 could regulate the mitochondrial biogenesis in AD is largely unknown. In the present study, we found that Aβ25-35 treatment not only markedly induced excessive production of reactive oxygen species and apoptosis, but also significantly decreased the number of mitochondria with biological activity and the adenosine triphosphate content in mitochondria, suggesting mitochondrial biogenesis was impaired in AD cells. These changes were reversed by Lentivirus-mediated stable overexpression of Trx-1 or exogenous administration of recombinant human Trx-1. What's more, adeno-associated virus-mediated specific overexpression of Trx-1 in the hippocampus of β-amyloid precursor protein/presenilin 1 (APP/PS1) mice ameliorated the learning and memory and attenuated hippocampal Aβ deposition. Importantly, overexpression of Trx-1 in APP/PS1 mice restored the decrease in mitochondrial biogenesis-associated proteins, including adenosine monophosphate -activated protein kinase (AMPK), silent information regulator factor 2-related enzyme 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). In addition, Lentivirus-mediated overexpression of Trx-1 in rat adrenal pheochromocytoma (PC12) cells also restored the decrease of AMPK, Sirt1, and PGC1α by Aβ25-35 treatment. Pharmacological inhibition of AMPK activity significantly abolished the effect of Trx-1 on mitochondrial biogenesis. Taken together, our data provide evidence that Trx-1 promoted mitochondrial biogenesis via restoring AMPK/Sirt1/PGC1α pathway in AD.

Limited knowledge exists on trends in niacin consumption and the prevalence of inadequate intakes in China. Understanding trends and the spatial distribution of the prevalence of inadequate niacin intake is crucial to identifying high-risk areas and sub-populations. The dietary intakes of niacin between 1991 and 2018 were analyzed using the China Health and Nutrition Survey (CHNS) data. The estimated average requirement cut point was applied to estimate inadequacy. The geographic information system's ordinary kriging method was used to estimate the spatial distribution of the prevalence of inadequate niacin intakes. However, between 1991 and 2018, the prevalence of inadequate niacin intake increased from 13.00% to 28.40% in females and from 17.75% to 29.46% in males. Additionally, the geographically significant clusters of high and low prevalence were identified and remained stable over almost three decades. The high prevalence of insufficient niacin intake was more pronounced in Henan and Shandong over 27 years. Further, effective and tailored nutrition interventions are required to address inadequate niacin intake in China.