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The COVID‐19 coronavirus is now spreading worldwide. Its pathogen, SARS‐CoV‐2, has been shown to use angiotensin‐converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS‐CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age‐dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. A shockingly common enrichment of viral infection pathways was found among ACE2 anti‐expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID‐19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general. This study revealed the negative correlation of high basal ACE2 level with CoVID‐19 severity/fatality at the population level and its anticorrelation with virus infection pathway expression levels, upregulation by sex hormones and suppression by inflammatory cytokine at the molecular level.

Background Plants have evolved the ability to produce specialized metabolites as a defense mechanism against biotic and abiotic stressors, with flavonoid-mediated defense responses playing a crucial role in this process. Diverse flavonoids are present in various rice-grown resources, and they confer tolerance to different environmental conditions, including high temperature stress. Elucidating the differences in these flavonoids is essential for breeding improved rice varieties with enhanced tolerance to adverse environments. In a previous study, we isolated a dominant rice mutant generated by T-DNA insertion and christened it rolled and erect leaf 1 (hereafter rel1 -D), initially identified for its enhanced tolerance to drought stress and its involvement in the regulation of leaf rolling and erectness. In this study, we utilized ZH11 and the rel1 -D mutant as experimental materials to compare the expression profiles of genes and metabolites involved in the flavonoid pathway and high-temperature tolerance. Result In our previous study, we generated a dominant mutant rel1 -D in the ZH11 rice background via T-DNA insertion. Upon exposure to high-temperature stress followed by a recovery period, we observed that all ZH11 plants succumbed to the stress, whereas nearly 50% of the rel1 -D mutants survived. Comprehensive transcriptomic and metabolomic analyses revealed 1,184 differentially expressed genes (DEGs) and 126 differentially abundant metabolites (DAMs) between the two genotypes. Notably, the majority of these differentially expressed genes and metabolites were enriched in the phenylalanine and flavonoid biosynthetic pathways in the rel1 -D mutant. Specifically, the expression levels of key genes involved in flavonoid biosynthesis, including OsCHI , OsF3H , OsFLS , OsCHS , OsPAL , and Os4CL , were significantly upregulated in rel1 -D, resulting in elevated levels of flavonoid compounds. Furthermore, we constructed a correlation network integrating phenotypic traits with the identified genes and metabolites. Our analysis indicated that the metabolism of flavonoids and phenolic compounds in leaves was positively correlated, whereas both were negatively correlated with yield-related traits. Conclusion Potential genes regulated by ROLLED AND ERECT LEAF1 ( REL1) and flavonoid metabolites were identified. REL1 may affect the accumulation of flavonoid metabolites by regulating the expression of key genes in the flavonoid biosynthesis pathway to influence the heat tolerance of rice.

This study aimed to investigate the role of purple tomato anthocyanin (PTA) in autophagy induced by chromium(VI) in a chicken hepatocellular carcinoma cell line (LMH cells). LMH cells were exposed to Cr(VI), PTA, and Cr(VI) + PTA. The changes in endoplasmic reticulum (ER) stress, autophagy, related proteins, and COX-2 were detected. Results showed that the cell viability was reduced after Cr(VI) treatment, and the decrease was also restrained by 3-MA or PTA. Levels of ER stress-related proteins (GRP78/Bip and PERK) and COX-2 increased after Cr(VI) treatment, which resulted in an increase in autophagy-related proteins (Beclin1 and LC3-II), inhibition of autophagy pathway protein mTOR, and degradation of autophagy-related protein p62, leading to excessive autophagy and cell damage. Meanwhile, the changes of these indicators induced by Cr(VI) were alleviated by PTA. In conclusion, our study suggested that Cr(VI) can induce excessive autophagy in LMH cells, while PTA can ameliorate Cr(VI)-induced autophagy by inhibiting ER stress.

Dairy cows are highly susceptible to mastitis caused by Klebsiella pneumoniae, and treating these infections poses a challenge due to the resistance of the bacterium to common antibiotics. This study aimed to evaluate the safety of W. cibaria SDS2.1 and investigate its protective effects against K. pneumoniae-induced mastitis. The safety of W. cibaria SDS2.1 was assessed through comprehensive analyses, including antibiotic resistance profiling, hemolysis assays, cell cytotoxicity tests, and whole-genome sequencing. Furthermore, its ability to protect against cellular and tissue damage caused by K. pneumoniae-induced mastitis was evaluated using both in vitro and in vivo models. Our results revealed that W. cibaria SDS2.1 was non-hemolytic, non-cytotoxic, and significantly inhibited the growth of K. pneumoniae (p < 0.05). Additionally, W. cibaria SDS2.1 effectively reduced the adhesion and invasion of K. pneumoniae. In the K. pneumoniae-induced mouse mastitis model, W. cibaria SDS2.1 significantly reduced myeloperoxidase (MPO) activity, mammary tissue damage, and the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) (p < 0.05). In K. pneumoniae-infected bovine mammary epithelial cells (bMECs), W. cibaria SDS2.1 significantly decreased lactate dehydrogenase (LDH) release, indicating reduced cellular damage. These findings demonstrate that W. cibaria SDS2.1 exhibits anti-inflammatory properties in experimental models, suggesting its potential role in mitigating K. pneumoniae-induced mastitis.

Steroid-induced osteonecrosis of femoral head (SONFH) is one of the most common bone disorders in humans. Statin treatment is beneficial in preventing the development of SONFH through anti-inflammation effects and inhibition of the glucocorticoid receptor (GR). However, potential mechanisms of statin action remain to be determined. In this study, pulse methylprednisolone (MP) treatment was used to induce SONFH in broilers, and then MP-treated birds were administrated with simvastatin simultaneously to investigate the changes in cartilage homeostasis. Meanwhile, chondrocytes were isolated, cultured, and treated with MP, simvastatin, or GR inhibitor in vitro. The changes in serum homeostasis factors, cell viability, and expression of GR were analyzed. The results showed that the morbidity of SONFH in the MP-treated group increased significantly compared with the simvastatin-treated and control group. Furthermore, MP treatment induced apoptosis and high-level catabolism and low-level anabolism in vitro and vivo, while simvastatin significantly decreased catabolism and slightly recovered anabolism via inhibiting GR and the hypoxia-inducible factor (HIF) pathway. The GR inhibitor or its siRNA mainly affected the catabolism of cartilage homeostasis in vitro. In conclusion, the occurrence of SONFH in broilers was related to the activation of GR and HIF pathway, and imbalance of cartilage homeostasis. Simvastatin and GR inhibitor maintained cartilage homeostasis via GR and the HIF pathway.

Enterotoxigenic Escherichia coli (ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective mechanisms of Nar against ETEC infection in porcine intestinal epithelial cells (IPEC-J2). ETEC infection induced oxidative stress and ferroptosis in IPEC-J2 cells by elevating intracellular iron content and ROS accumulation, increasing MDA levels, downregulating SOD activity and GPX4 expression, and upregulating the transcription of CHAC1 and SLC7A11. In contrast, Nar suppressed ETEC-induced ferroptosis of IPEC-J2 cells by inhibiting the SLC7A11/GPX4 pathway. Specifically, Nar mitigated mitochondrial damage, reduced intracellular iron levels and ROS accumulation, and ultimately reversed the oxidative stress. Network pharmacology and molecular docking identified heat-shock protein 90 (HSP90) as a potential target of Nar. Overexpression and knockdown experiments revealed that ETEC-induced ferroptosis was mediated by upregulation of HSP90, while the protective effects of Nar against ETEC-induced ferroptosis were dependent on the downregulation of HSP90. In conclusion, Nar targets host HSP90 to protect IPEC-J2 cells from ferroptosis caused by ETEC infection. This study demonstrates that Nar is a potent antioxidant natural compound with potential for preventing ETEC-induced intestinal damage.

Related studies have shown that chromium (Cr) is toxic to cells, and hydrogen can protect cells by regulating endoplasmic reticulum (ER) stress and autophagy. However, there are few reports on the protective effects of hydrogen on heavy metal-induced cell damage. The objective of this study was to investigate the protection of hydrogen-rich medium (HRM) on Cr(VI)-induced ER stress and autophagy in DF-1 cells. Therefore, HRM were pretreated for 30 min before Cr(VI) treatment, and detected the autophagy and ER stress-related indicators to determine the role of HRM. The results showed that HRM could reduce the cell damage caused by Cr(VI), and 3-methyladenine (3-MA) could protect cells by inhibiting over autophagy. HRM can reverse the changes of ER stress- and autophagy-related indexes caused by Cr(VI), and inhibit the excessive autophagy caused by Cr(VI). In conclusion, HRM can protect cells from damage induced by Cr(VI), and play a role by inhibiting ER stress-mediated autophagy.

In this study, a novel oral vaccine of recombinant ( ) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed. In the current study, the gp85 protein of ALV-J was expressed on the surface of with the surface-display motif, , by constructing a shuttle vector . Surface localization of the fusion protein was verified by western blotting and flow cytometry. Subsequently, Specific Pathogen Free Hy-Line Brown layer chickens were orally vaccinated with the recombinant and presented with high levels of serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) titers in bile and duodenal-mucosal fluid. After challenged with ALV-J of a 3 × 10 50% tissue culture infective dose (TCID50), serum samples of the chickens were collected and viremia was analyzed. Results showed that, compared to the and PBS control group, the recombinant group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection. These results indicate that oral immunization with the recombinant provided an effective means for eliciting protective immune response against early ALV-J infection.

As an application of the Legendrian singularity theory, we classify the bifurcations of a holonomic first-order differential equation with a complete integral. The equations satisfy that the one-parameter integral diagrams are R+-simple and stable. Using this result, the parametric differential equation models in electrical power systems and engineering can be studied.

Background Wearable smart watches provide large amount of real-time data on the environmental state of the users and are useful to determine risk factors for onset and progression of myopia. We aim to evaluate the efficacy of machine learning algorithm in differentiating indoor and outdoor locations as collected by use of smart watches. Methods Real time data on luminance, ultraviolet light levels and number of steps obtained with smart watches from dataset A: 12 adults from 8 scenes and manually recorded true locations. 70% of data was considered training set and support vector machine (SVM) algorithm generated using the variables to create a classification system. Data collected manually by the adults was the reference. The algorithm was used for predicting the location of the remaining 30% of dataset A. Accuracy was defined as the number of correct predictions divided by all. Similarly, data was corrected from dataset B: 172 children from 3 schools and 12 supervisors recorded true locations. Data collected by the supervisors was the reference. SVM model trained from dataset A was used to predict the location of dataset B for validation. Finally, we predicted the location of dataset B using the SVM model self-trained from dataset B. We repeated these three predictions with traditional univariate threshold segmentation method. Results In both datasets, SVM outperformed the univariate threshold segmentation method. In dataset A, the accuracy and AUC of SVM were 99.55% and 0.99 as compared to 95.11% and 0.95 with the univariate threshold segmentation (p < 0.01). In validation, the accuracy and AUC of SVM were 82.67% and 0.90 compared to 80.88% and 0.85 with the univariate threshold segmentation method (p < 0.01). In dataset B, the accuracy and AUC of SVM and AUC were 92.43% and 0.96 compared to 80.88% and 0.85 with the univariate threshold segmentation (p < 0.01). Conclusions Machine learning algorithm allows for discrimination of outdoor versus indoor environments with high accuracy and provides an opportunity to study and determine the role of environmental risk factors in onset and progression of myopia. The accuracy of machine learning algorithm could be improved if the model is trained with the dataset itself.