Aerobic exercise has shown beneficial effects in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the regulatory mechanism is not turely clear. Therefore, we aim to clarify the possible mechanism by investigating the effects of aerobic exercise on NAFLD and its mitochondrial dysfunction.

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.

High-altitude environments dramatically influenced the genetic evolution of vertebrates. However, little is known about the role of RNA editing on high-altitude adaptation in non-model species. Here, we profiled the RNA editing sites (RESs) of heart, lung, kidney, and longissimus dorsi muscle from Tibetan cashmere goats (TBG, 4500 m) and Inner Mongolia cashmere goats (IMG, 1200 m) to reveal RNA editing-related functions of high-altitude adaptation in goats. We identified 84,132 high-quality RESs that were unevenly distributed across the autosomes in TBG and IMG, and more than half of the 10,842 non-redundant editing sites were clustered. The majority (62.61%) were adenosine-to-inosine (A-to-I) sites, followed by cytidine-to-uridine (C-to-U) sites (19.26%), and 32.5% of them had a significant correlation with the expression of catalytic genes. Moreover, A-to-I and C-to-U RNA editing sites had different flanking sequences, amino acid mutations, and alternative splicing activity. TBG had higher editing levels of A-to-I and C-to-U than IMG in the kidney, whereas a lower level was found in the longissimus dorsi muscle. Furthermore, we identified 29 IMG and 41 TBG population-specific editing sites (pSESs) and 53 population-differential editing sites (pDESs) that were functionally involved in altering RNA splicing or recoding protein products. It is worth noting that 73.3% population-differential, 73.2% TBG-specific, and 80% IMG-specific A-to-I sites were nonsynonymous sites. Moreover, the pSESs and pDESs editing-related genes play critical functions in energy metabolisms such as ATP binding molecular function, translation, and adaptive immune response, which may be linked to goat high-altitude adaptation. Our results provide valuable information for understanding the adaptive evolution of goats and studying plateau-related diseases.

Infectious laryngotracheitis (ILT) and Newcastle disease (ND) are two important avian diseases that have caused huge economic losses to the poultry industry worldwide. Newcastle disease virus (NDV) has been used as a vector in the development of vaccines and gene delivery. In the present study, we generated a thermostable recombinant NDV (rNDV) expressing the glycoprotein gB (gB) of infectious laryngotracheitis virus (ITLV) based on the full-length cDNA clone of the thermostable TS09-C strain. This thermostable rNDV, named rTS-gB, displayed similar thermostability, growth kinetics, and pathogenicity compared with the parental TS09-C virus. The immunization data showed that rTS-gB induced effective ILTV- and NDV-specific antibody responses and conferred immunization protection against ILTV challenge in chickens. The efficacy of rTS-gB in alleviating clinical signs was similar to that of the commercial attenuated ILTV K317 strain. Furthermore, rTS-gB could significantly reduce viral shedding in cloacal and tracheal samples. Our study suggested that the rNDV strain rTS-gB is a thermostable, safe, and highly efficient vaccine candidate against ILT and ND.

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.

Although miR-27b-3p has been evidenced to regulate the proliferation, apoptosis, and differentiation of a variety of mammalian cell types, its actions and mechanisms on ovarian cell steroidogenesis remains largely unknown in both mammalian and avian species. In this study, we aimed to determine the expression profiles of miR-27b-3p in granulosa cell layers during goose ovarian follicle development and to reveal its actions on estrogen (E2) secretion of goose granulosa cells as well as the underlying regulatory mechanisms. It was observed that miR-27b-3p was ubiquitously expressed throughout follicle development but exhibited much higher levels in hierarchical- than in prehierarchical follicles. In cultured granulosa cells from the fourth through second largest preovulatory (F4-F2) follicles of goose, up- and downregulation of miR-27b-3p by using its mimic and inhibitor significantly decreased and increased E2 secretion, respectively. Meanwhile, the mRNA levels of STAR and CYP19A1 were significantly reduced while those of CYP11A1 and 3βHSD were elevated in the mimic-transfected granulosa cells. By comparison, downregulation of miR-27b-3p enhanced the mRNA levels of STAR but had no significant effects on those of CYP19A1, CYP11A1, and 3βHSD. Results from bioinformatic prediction and luciferase reporter assay demonstrated that CYP1B1 was a downstream target of miR-27b-3p. Although the siRNA-mediated downregulation of CYP1B1 did not significantly change E2 secretion by goose granulosa cells, it reduced the mRNA levels of STAR and CYP19A1 as well as those of LKB1 and AMPKα, which are involved in the AMPK signaling pathway. Taken together, these data suggest that miR-27b-3p plays an inhibitory role in E2 secretion by goose F4-F2 granulosa cells, at least in part, by targeting CYP1B1 through the AMPK signaling pathway.

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.

African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs of all breeds and ages, caused by African swine fever virus (ASFV). Due to the absence of a safe and efficacious vaccine, accurate laboratory diagnosis is critical for the control of ASF prevention. The p30 protein is immunogenic and stimulates a high level of antibody response to ASFV infection. We developed a panel of 4 monoclonal antibodies (mAbs) against p30 protein, and mAb-2B4 showed the highest percent of inhibition (PI) of 70% in the solid phase blocking ELISA (bELISA). Epitope mapping revealed the mAb-2B4 recognized the epitope of aa 12-18 of p30, which is conserved among various ASFV genotypes. Subsequently, a competitive enzyme-linked immunosorbent assay (cELISA) was established using HRP-labeled mAb-2B4. The cutoff for discrimination between 98 negative sera and 40 positive sera against ASFV was determined by plotting a receiver operating characteristic (ROC) curve. It yielded the area under the curve (AUC) of 0.998, and a diagnostic specificity of 97.96% and a sensitivity of 97.5% were achieved when the cutoff value was determined at 37.1%. Furthermore, the results showed an excellent repeatability of the established cELISA and no cross-reaction to antisera against six other pig pathogens. Additionally, the cELISA detected a titer of 1:256 in the positive standard serum. Overall, mAb-2B4 showed a conserved epitope and high ability to be inhibited by positive sera in ASFV antibody detection. The cELISA based on HRP-labeled mAb-2B4 offers an alternative to other assays for a broader diagnostic coverage of ASFV infection.

Renal cell carcinoma (RCC) is a common malignant tumor in the elderly, with an increasing trend in recent years. We aimed to construct a nomogram of cancer-specific survival (CSS) and overall survival (OS) in elderly patients with nonmetastatic renal cell carcinoma (nmRCC).

Substantial ultrafine zinc particles exist in air pollutions. The level of Zn concentrations in serum and tissue could affect patients with myocardial infarction (MI). The aim of the study is to investigate the change of cardiac functions and peripheral hemodynamics in MI rats after long-term inhalation of ultrafine Zn particles. Coronary artery ligation surgery was performed to induce MI in Wistar rats. The inhalation of ultrafine Zn particles was carried out for 6 weeks after the operation. Physiological and hemodynamic measurements and computational biomechanics analysis were demonstrated in eight groups of rats at postoperative 4 and 6 weeks. There was no statistical significance between shams and shams with inhalation of ultrafine Zn particles. There were significant impairments of cardiac and hemodynamic functions in MI rats. In comparison with MI rats, the inhalation of ultrafine Zn particles for 4 weeks slowed down the progression from MI to heart failure, but the inhalation for 6 weeks accelerated the process. The long-term inhalation of ultrafine zinc particles induced excessive accumulation of zinc in serum and tissue, which deteriorated cardiac and hemodynamic dysfunctions in MI rats. The findings suggested the importance for regulating Zn intake of MI patients as well as looking at ways to lower zinc concentrations in air pollutions.

Myocardial infarction (MI) is characterized by coronary artery occlusion, ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Therefore, it is urgent to explore the potential mechanism of myocardial injury during the MI process to develop effective therapies for myocardial cell rescue.

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.

Quinoa (Chenopodium quinoa Willd.) is a herb within the Quinoa subfamily of Amaranthaceae, with remarkable environmental adaptability. Its edible young leaves and grains are rich in protein, amino acids, microorganisms, and minerals. Although assessing the effects of fertilization on quinoa yield and quality has become an intensive area of research focus, the associated underlying mechanisms remain unclear. As one of the three macro nutrients in plants, potassium has an important impact on plant growth and development. In this study, extensive metabolome and transcriptome analyses were conducted in quinoa seedlings 30 days after fertilizer application to characterize the growth response mechanism to potassium.  RESULTS: The differential metabolites and genes present in the seedlings of white and red quinoa cultivars were significantly enriched in the photosynthetic pathway. Moreover, the PsbQ enzyme on photosystem II and delta enzyme on ATP synthase were significantly down regulated in quinoa seedlings under potassium deficiency. Additionally, the differential metabolites and genes of red quinoa seedlings were significantly enriched in the arginine biosynthetic pathway.

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).

The molecular mechanisms of acute otitis media (AOM) development, and the intercellular crosstalk within the multicellular ecosystem of AOM, are not clear.

Hepatoblastoma as the most prevalent hepatic malignancy in children, its etiology remains unclear. N6-Methyladenosine (m6A) modification which can modify various physiological processes, plays a critical role in tumorigenesis. Methyltransferase-like 14 (METTL14), an important component of the m6A methyltransferase complex, remains elusive during hepatoblastoma occurrence and development. We explored the relationship between METTL14 gene polymorphisms (rs1064034 T > A, rs298982 G > A, rs62328061 A > G, rs9884978 G > A, and rs4834698 T > C) and hepatoblastoma susceptibility from 313 patients and 1446 controls. The role of METTL14 polymorphisms in hepatoblastoma was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Of the included subjects, 308 patients and 1444 controls were successfully genotyped. We did not find any significant correlation between the risk of hepatoblastoma and the five potentially functional METTL14 polymorphisms individually. However, the presence of 4-5 risk genotypes exhibited a significant increased hepatoblastoma risk (adjusted OR = 1.32, 95% CI = 1.03-1.69, P = 0.031) compared to those carriers with 0-3 risk genotypes. Furthermore, the stratified analysis demonstrated that the rs1064034 AA genotype, rs62328061 AG/GG genotypes, rs4834698 TC/CC genotypes, and 4-5 risk genotypes were related to hepatoblastoma susceptibility in certain subgroups. The expression quantitative trait loci (eQTL) analysis revealed that rs1064034 T > A and rs4834698 T > C were correlated with the expression levels of METTL14 and its surrounding genes. Prospectively, these findings suggested that METTL14 polymorphisms may correlation with hepatoblastoma susceptibility and provide a fresh insight into the genetic underpinnings of m6A modification in hepatoblastoma.

Background: Few comprehensive lifestyle intervention programmes have been investigated on overweight and obese adults in China. This study was to evaluate the effect of a 36-month weight management programme on weight loss and its maintenance among overweight and obese patients in Ningbo, China. Methods: Adults with BMI ≥24kg/m2 enrolled in this programme, including nutritional, physical activity, psychological and endocrinological counselling sessions, from July 2015 to January 2020. Adults participated in face-to-face counselling sessions and group-based education. Then, participants joined 21-day intensive programme using Bohe health APP and WeChat group to get personal advice of nutrition and lifestyle. In the end, participants were requested to join 33-month follow-ups including face-to-face counselling and personal advice on WeChat group. The main outcome was to evaluate the changes in weight at each followup from baseline weight. Results: In total, 692 adults participated in this entire weight management programme. During follow-ups, 579, 475, 299, 219, and 135 adults participated at 3, 6, 12, 24, and 36 months, respectively. All participants had a significant initial weight loss at 3 months, then maintained the weight loss during 33-month follow-ups. At 36 months, 11.0%, 6.4%, and 3.5% of all participants achieved 5%, 10%, and 15% weight loss from the baseline weight, respectively. Adjusted weight at 36 months was significantly reduced from the baseline weight in both sex (-7.2 kg). Conclusion: This weight management programme is suggested to benefit to reduce initial body weight and maintain long-term weight loss among overweight and obese adults.

Porcine Epidemic Diarrhea (PED) is a highly contagious intestinal disease which mostly caused by Porcine Epidemic Diarrhea Virus (PEDV). The PED has caused huge economic losses to the pig industry all over the world and a valid PEDV vaccine is needed to prevent the infection. In this study, we constructed expression plasmid based on the spike (S) gene of the epidemic PEDV strain. The recombinant eukaryotic S (Se) and prokaryotic S (Sp) subunit proteins were expressed and purified as vaccine antigens. We designed a new subunit vaccine based on S proteins, adjuvanted with layered double hydroxide (LDH). The results indicated that the LDH adjuvanted subunit vaccines induced a better immune effect in terms of antibody level and cellular immune response. In conclusion, this study showed a new design of a PEDV subunit vaccine with nanotechnology and demonstrated the potential for its clinical application.

Ovarian cancer is one of the common malignant tumors of female reproductive organs, which seriously threatens the life and health of women. Resistance to chemotherapeutic drugs for ovarian cancer is the root cause of recurrence in most patients. The purpose of this study is to determine the differentially expressed genes of platinum resistance in ovarian cancer, and to screen out molecular targets and diagnostic markers that could be used to treat ovarian cancer platinum resistance.

The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.