Pien-Tze-Huang (PZH) is a well-established Traditional Medicine with beneficial effects against inflammation and cancer. We aim to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota. CRC mouse models were established by azoxymethane plus dextran sulfate sodium (AOM/DSS) treatment or in Apc^min/+ mice, treated with or without PZH (270 and 540mg/kg). Gut barrier function was determined by intestinal permeability assays and transmission electron microscopy (TEM). Fecal microbiota and metabolites were respectively analyzed by metagenomic sequencing and liquid chromatography-mass spectrometry. Germ-free mice or antibiotic-treated mice were used as models of microbiota depletion. PZH inhibited colorectal tumorigenesis in AOM/DSS treated mice and in Apc^min/+ mice in a dose-dependent manner. PZH treatment altered the gut microbiota profile, with an increased abundance of probiotics Pseudobutyrivibrio xylanivorans and Eubacterium limosum, while pathogenic bacteria Aeromonas veronii, Campylobacter jejuni, Collinsella aerofaciens, and Peptoniphilus harei were depleted. Additionally, PZH increased beneficial metabolites taurine and hypotaurine, bile acids, and unsaturated fatty acids and significantly restored gut barrier function. Transcriptomic profiling revealed that PZH inhibited PI3K-Akt, IL-17, TNF, and Cytokine-Chemokine signaling. Notably, the chemopreventive effect of PZH involved both microbiota-dependent and independent mechanisms. Fecal microbiota transplantation (FMT) from PZH-treated mice to germ-free mice partly recapitulated the chemopreventive effects of PZH. PZH components Ginsenoside-F2 and Ginsenoside-Re demonstrated inhibitory effects on CRC cells and primary organoids, and PZH also inhibited tumorigenesis in AOM/DSS-treated germ-free mice. PZH manipulated gut microbiota and metabolites toward a more favorable profile, improves gut barrier function, and suppresses oncogenic and pro-inflammatory pathways, thereby suppressing colorectal carcinogenesis.

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients’ lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1β/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D₃, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.

Background: Genome sequencing has been widely used in plant research to construct reference genomes and provide evolutionary insights. However, few plant species have had their whole genome sequenced, thus restraining the utility of these data. We collected 1,093 samples of vascular plant species growing in the Ruili Botanical Garden, located in southwest China. Of these, we sequenced 761 samples and collected voucher specimens stored in the Herbarium of China National GeneBank. Results: The 761 sequenced samples represented 689 vascular plant species from 137 families belonging to 49 orders. Of these, 257 samples were identified to the species level and 504 to the family level, using specimen and chloroplast sequences. In total, we generated 54 Tb of sequencing data, with an average sequencing depth of 60X per species, as estimated from genome sizes. A reference phylogeny was reconstructed with 78 chloroplast genes for molecular identification and other possible applications. Conclusions: The large dataset of vascular plant genomes generated in this study, which includes both high-depth whole-genome sequencing data and associated voucher specimens, is valuable for plant genome research and other applications. This project also provides insight into the feasibility and technical requirements for “planetary-scale” projects such as the 10,000 Plant Genomes Project and the Earth BioGenome Project.

The primary goal of cattle genomics is the identification of genome-wide polymorphism associated with economically important traits. The bovine genome sequencing project was completed in 2009. Since then, using massively parallel sequencing technologies, a large number of Bos taurus cattle breeds have been resequenced and scanned for genome-wide polymorphisms. As a result, a substantial number of single nucleotide polymorphisms (SNPs) have been discovered across European Bos taurus genomes, whereas extremely less number of SNPs are cataloged for Bos indicus breeds. In this study, we performed whole-genome resequencing, reference-based mapping, functional annotation and gene enrichment analysis of 20 sires representing eleven important Bos indicus (indicine) breeds of Pakistan. The breeds sequenced here include: Sahiwal, Red Sindhi, Tharparkar and Cholistani (tropically adapted dairy and dual purpose breeds), Achai, Bhagnari, Dajal and Lohani (high altitude adapted dual and drought purpose breeds); Dhanni, Hisar Haryana and Gabrali (dairy and light drought purpose breeds). A total of 17.4 billion QC passed reads were produced using BGISEQ-500 next generation sequencing platform to generate 9 to 27-fold genome coverage (average ~16×) for each of the 20 sequenced sires. A total of 67,303,469 SNPs were identified, of which 3,850,365 were found novel and 1,083,842 insertions-deletions (InDels) were detected across the whole sequenced genomes (491,247 novel). Comparative analysis using coding region SNPs revealed a close relationship between the best milking indicine breeds; Red Sindhi and Sahiwal. On the other hand, Bhagnari and Tharparkar being popular for their adaptation to dry and extremely hot climates were found to share the highest number of SNPs. Functional annotation identified a total of 3,194 high-impact (disruptive) SNPs and 745 disruptive InDels (in 275 genes) that may possibly affect economically important dairy and beef traits. Functional enrichment analysis was performed and revealed that high or moderate impact variants in wingless-related integration site (Wnt) and vascular smooth muscle contraction (VSMC) signaling pathways were significantly over-represented in tropically adapted heat tolerant Pakistani-indicine breeds. On the other hand, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) signaling pathways were found over-represented in highland adapted Pakistani-indicine breeds. Similarly, the ECM-receptor interaction and Jak-STAT signaling pathway were significantly enriched in dairy and beef purpose Pakistani-indicine cattle breeds. The Toll-like receptor signaling pathway was significantly enriched in most of the Pakistani-indicine cattle. Therefore, this study provides baseline data for further research to investigate the molecular mechanisms of major traits and to develop potential genomic markers associated with economically important breeding traits, particularly in indicine cattle.

Objectives: Guillain‐Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID‐19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear.Materials and Methods: We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID‐19 and GBS.Results: COVID‐19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein‐protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID‐19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA‐DRB1, HLA‐DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID‐19 and GBS further demonstrated the activation of interleukin‐17 signalling in both conditions.Conclusions: Augmented Th17 cell differentiation and cytokine response was identified in both COVID‐19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID‐19 can increase the risk of GBS.