Comparative Component Analysis of Exons with Different Splicing Frequencies

Transcriptional isoforms are not just random combinations of exons. What has caused exons to be differentially spliced and whether exons with different splicing frequencies are subjected to divergent regulation by potential elements or splicing signals? Beyond the conventional classification for alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs), we have classified exons from alternatively spliced human genes and their mouse orthologs (12,314 and 5,464, respectively) into four types based on their splicing frequencies. Analysis has indicated that different groups of exons presented divergent compositional and regulatory properties. Interestingly, with the decrease of splicing frequency, exons tend to have greater lengths, higher GC content, and contain more splicing elements and repetitive elements, which seem to imply that the splicing frequency is influenced by such factors. Comparison of non-alternatively spliced (NAS) mouse genes with alternatively spliced human orthologs also suggested that exons with lower splicing frequencies may be newly evolved ones which gained functions with splicing frequencies altered through the evolution. Our findings have revealed for the first time that certain factors may have critical influence on the splicing frequency, suggesting that exons with lower splicing frequencies may originate from old repetitive sequences, with splicing sites altered by mutation, gaining novel functions and become more frequently spliced

Bifidobacterium mitigates autoimmune hepatitis by regulating IL-33-induced Treg/Th17 imbalance via the TLR2/4 signaling pathway

The present work aims to evaluate the efficacy of Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules (LCBLECs), a probiotic drug containing Bifidobacterium, in the treatment of autoimmune hepatitis (AIH). In this study, a mouse model of experimental autoimmune hepatitis (EAH) was established to investigate the effects of LCBLECs on AIH. The results showed that LCBLECs improved dysbiosis of gut microbiota, reduced liver injury, restored liver function, and maintained Treg/Th17 balance in EAH mice. In addition, LCBLECs restored Treg/Th17 balance in EAH mice by downregulating IL-33 production. Besides, LCBLECs also suppress IL-33 upregulation in EAH mice by inhibiting the TLR2/4 signaling pathway. Furthermore, LCBLECs also mitigated dysbiosis of gut microbiota and enhanced the efficacy of conventional treatment for AIH patients. To sum up, our findings revealed that LCBLECs exerted therapeutic effects on EAH mice by improving Treg/Th17 imbalance in an IL-33-dependent manner via the TLR2/4 signaling pathway and relieved the clinical symptoms of AIH patients, indicating Bifidobacterium supplementation with LCBLECs might be a potential adjuvant therapy for AIH treatment

Transcriptome analysis of two pepper genotypes infected with pepper mild mottle virus

Pepper mild mottle virus (PMMoV) poses a significant threat to pepper production because it is highly contagious and extremely persistent in soil. Despite this threat, little is known about the molecular processes that underlie plant responses to pepper mild mottle virus. Here, we performed RNA sequencing of tolerant (“17-p63”) and susceptible (“16-217”) pepper genotypes after pepper mild mottle virus or mock inoculation. Viral accumulation in systemic leaves was lower in the pepper mild mottle virus-resistant 17-p63 genotype than in the pepper mild mottle virus-sensitive 16-217 genotype, and infection symptoms were more apparent in systemic leaves of 16-217 than in those of 17-p63 at the same timepoints during the infection process. We identified 2,959 and 2,159 differentially expressed genes (DEGs) in systemic leaves of infected 16-217 and 17-p63, respectively. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes from both genotypes revealed significant enrichment of the MAPK signaling pathway, plant–pathogen interaction, and flavonoid biosynthesis. A number of differentially expressed genes showed opposite trends in relation to stress resistance and disease defense in the two genotypes. We also performed weighted gene co-expression network analysis (WGCNA) of all samples and identified modules associated with resistance to pepper mild mottle virus, as well as seven hub genes. These results identify candidate virus resistance genes and provide insight into pepper defense mechanisms against pepper mild mottle virus

High-efficiency polarization multiplexing metalenses

The polarization multiplexing technique is a well-established method that improves the communication capacity of an optical system. In this paper, we designed orthogonal linear and circular polarization multiplexing metalens using a library of rectangle TiO2 nanostructures. The former can independently focus x- and y-linearly polarized incident lights to designed positions with a focusing efficiency of 53.81% and 51.56%, respectively, whereas the latter with two preset focal points can independently control left and right circularly polarized incident lights with a focusing efficiency of 42.45% and 42.46%, respectively. We also show that both metalenses can produce diffraction-limited focal spots for four polarization states with no obvious distortion, which opens up new applications in polarization imaging and polarization detection

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma

Epidemiological changes and molecular characteristics of Brucella strains in Ningxia, China

ObjectiveHuman brucellosis causes serious public health concerns in Ningxia, China.MethodsThis study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies.ResultsBetween 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that Brucella infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 Brucella strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including B. melitensis bv. 1, bv. 2, bv. 3, B. abortus bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, B. suis bv. 1 and bv. 3, and B. canis. These data highlight the high species/biovars and host diversity of the Brucella population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, B. melitensis, emphasizing the requirement for strengthening surveillance of B. melitensis. Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and MLVA-11, indicating that all strains belong to the East Mediterranean lineage. MLVA cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia.ConclusionThe epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge

Beta-glucan alters gut microbiota and plasma metabolites in pre-weaning dairy calves

The present study aims to evaluate the alterations in gut microbiome and plasma metabolites of dairy calves with β-glucan (BG) supplementation. Fourteen healthy newborn dairy calves with similar body weight were randomly divided into control (n = 7) and BG (n = 7) groups. All the calves were fed on the basal diet, while calves in the BG group were supplemented with oat BG on d 8 for 14 days. Serum markers, fecal microbiome, and plasma metabolites at d 21 were analyzed. The calves were weaned on d 60 and weighed. The mean weaning weight of the BG group was 4.29 kg heavier than that of the control group. Compared with the control group, the levels of serum globulin, albumin, and superoxide dismutase were increased in the BG group. Oat BG intake increased the gut microbiota richness and decreased the Firmicutes-to-Bacteroidetes ratio. Changes in serum markers were found to be correlated with the plasma metabolites, including sphingosine, trehalose, and 3-methoxy-4-hydroxyphenylglycol sulfate, and gut microbiota such as Ruminococcaceae_NK4A214, Alistipes, and Bacteroides. Overall, these results suggest that the BG promotes growth and health of pre-weaning dairy calves by affecting the interaction between the host and gut microbiota

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models

Lycium ruthenicum Murray (LR), known as “black goji berry” or “black wolfberry”, is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina