Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.

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Terniopsisyongtaiensis (Podostemaceae), a new species from South East China based on morphological and genomic data.

The new species Terniopsisyongtaiensis X.X. Su, Miao Zhang & Bing-Hua Chen, from Fujian Province, China, is described and illustrated. It is similar to T.heterostaminata from Thailand, but differs in its two fertile stamens, fewer but longer vegetative ramuli, fewer but shorter flowering ramuli, shorter pedicels, capsule-stalk and stamens. The complete chroloplast genome of the new species is 129,074 bp long and has a typical quadripartite structure, including two inverted repeat regions (IRs) of 18,504 bp in length, separated by a large single-copy (LSC) and a small single-copy (SSC) regions of 79,000 bp and 13,066 bp, respectively. The ycf1 and ycf2 genes were lost compared to most higher plants, leading to a substantial reduction in the IR. The phylogenetic analysis using both matK and nrITS revealed that T.yongtaiensis is sister to T.heterostaminata with moderate support, and formed a clade with other Terniopsis species, suggesting that the new species belongs to Tristichoideae.

Identification of Distinct Immune Cell Subsets Associated With Asymptomatic Infection, Disease Severity, and Viral Persistence in COVID-19 Patients.

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

Danxiaorchismangdangshanensis (Orchidaceae, Epidendroideae), a new species from central Fujian Province based on morphological and genomic data.

Danxiaorchismangdangshanensis, a new mycoheterotrophic species from Fujian Province, China, is described and illustrated. The new species is morphologically similar to D.singchiana, but its callus of labellum is a less distinctive Y-shape with three auricles on the apex, four pollinia that are narrowly elliptic in shape and equal in size, and it lacks fine roots. The plastome of D.mangdangshanensis is highly degraded. Phylogenetic analyses distinguished D.mangdangshanensis from its congeners, D.singchiana and D.yangii, with strong support based on nrITS + matK and plastomes, respectively.

Polypleurumchinense (Podostemaceae), a new species from Fujian, China, based on morphological and genomic evidence.

We describe Polypleurumchinense, a new species of Podostemaceae from Yunxiao County, Fujian Province, China, based on morphological and molecular data and the genus Polypleurum is recorded here for the first time from China. Polypleurumchinense has a gross morphology similar to P.longistylosum, but it can be distinguished from the latter by its narrower roots, more numerous and longer leaves, shorter stigmas and more numerous ovules per locule. To distinguish the new Polypleurum species and study its phylogenetic position, its complete plastome was sequenced and characterised. The plastome is 132,110 bp in length, including a pair of inverted repeat regions (IRs) of 20,389 bp divided by the large single-copy (LSC) and small single-copy (SSC) regions of 79,022 bp and 12,310 bp, respectively. The plastome size of P.chinense is relatively smaller compared to most angiosperms due to the absence of the ycf1 and ycf2 genes in the IR regions. The phylogenetic analyses also strongly support the separation of the new species from other taxa.

Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women.

BACKGROUND: Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community-dwelling healthy menopausal women. METHODS: Estimated SMM was derived from whole-body dual-energy X-ray absorptiometry. We performed integrated analyses on whole-genome sequencing, shotgun metagenomic sequencing, and serum short-chain fatty acids (SCFAs), as well as available host SMM measurements among community-dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome-wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one-sample and two-sample Mendelian randomization (MR) analyses, respectively. RESULTS: In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate-producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10-7 ) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10-4 ) and B. virosa (SCC = 0.17, P = 2.4 × 10-4 )]. One-sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two-sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (ß = 0.06, 95% confidence interval 0 to 0.13, P = 0.06). CONCLUSIONS: Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.

CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance.

Porcine reproductive and respiratory syndrome virus (PRRSV) and transmissible gastroenteritis virus (TGEV) are two highly infectious and lethal viruses causing major economic losses to pig production. Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. We found no differences in meat-production or reproductive-performance traits between wild-type and DKO pigs, but detected increased iron in DKO muscle. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Beyond showing that multiple gene edits can be combined in a livestock animal to achieve simultaneous resistance to two major viruses, our study introduces a valuable model for investigating infection mechanisms of porcine pathogenic viruses that exploit pAPN or CD163 for entry.

Pig epidemics are the biggest threat to the pork industry. In 2019 alone, hundreds of billions of dollars worldwide were lost due to various pig diseases, many of them caused by viruses. The porcine reproductive and respiratory virus (PRRS virus for short), for instance, leads to reproductive disorders such as stillbirths and premature labor. Two coronaviruses ­ the transmissible gastroenteritis virus (or TGEV) and the porcine delta coronavirus ­ cause deadly diarrhea and could potentially cross over into humans. Unfortunately, there are still no safe and effective methods to prevent or control these pig illnesses, but growing disease-resistant pigs could reduce both financial and animal losses. Traditionally, breeding pigs to have a particular trait is a slow process that can take many years. But with gene editing technology, it is possible to change or remove specific genes in a single generation of animals. When viruses infect a host, they use certain proteins on the surface of the host's cells to find their inside: the PRRS virus relies a protein called CD163, and TGEV uses pAPN. Xu, Zhou, Mu et al. used gene editing technology to delete the genes that encode the CD163 and pAPN proteins in pigs. When the animals were infected with PRRS virus or TGEV, the non-edited pigs got sick but the gene-edited animals remained healthy. Unexpectedly, pigs without CD163 and pAPN also coped better with porcine delta coronavirus infections, suggesting that CD163 and pAPN may also help this coronavirus infect cells. Finally, the gene-edited pigs reproduced and produced meat as well as the control pigs. These experiments show that gene editing can be a powerful technology for producing animals with desirable traits. The gene-edited pigs also provide new knowledge about how porcine viruses infect pigs, and may offer a starting point to breed disease-resistant animals on a larger scale.

GCY-35/GCY-36-TAX-2/TAX-4 Signalling in O2 Sensory Neurons Mediates Acute Functional Ethanol Tolerance in Caenorhabditis elegans.

Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood. In Caenorhabditis elegans, NPR-1 negatively regulates the development of acute tolerance to ethanol. Here, using in vivo Ca2+ imaging, behavioural tests and chemogenetic manipulation, we show that the soluble guanylate cyclase complex GCY-35/GCY-36-TAX-2/TAX-4 signalling pathway in O2 sensory neurons positively regulates acute functional tolerance in npr-1 worms.

cGMP Signalling Mediates Water Sensation (Hydrosensation) and Hydrotaxis in Caenorhabditis elegans.

Animals have developed the ability to sense the water content in their habitats, including hygrosensation (sensing humidity in the air) and hydrosensation (sensing the water content in other microenvironments), and they display preferences for specific water contents that influence their mating, reproduction and geographic distribution. We developed and employed four quantitative behavioural test paradigms to investigate the molecular and cellular mechanisms underlying sensing the water content in an agar substrate (hydrosensation) and hydrotaxis in Caenorhabditis elegans. By combining a reverse genetic screen with genetic manipulation, optogenetic neuronal manipulation and in vivo Ca(2+) imaging, we demonstrate that adult worms avoid the wetter areas of agar plates and hypo-osmotic water droplets. We found that the cGMP signalling pathway in ciliated sensory neurons is involved in hydrosensation and hydrotaxis in Caenorhabditis elegans.

Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans.

Sensory modulation is essential for animal sensations, behaviours and survival. Peripheral modulations of nociceptive sensations and aversive behaviours are poorly understood. Here we identify a biased cross-inhibitory neural circuit between ASH and ASI sensory neurons. This inhibition is essential to drive normal adaptive avoidance of a CuSO4 (Cu(2+)) challenge in Caenorhabditis elegans. In the circuit, ASHs respond to Cu(2+) robustly and suppress ASIs via electro-synaptically exciting octopaminergic RIC interneurons, which release octopamine (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In addition, ASIs sense Cu(2+) and permit a rapid onset of Cu(2+)-evoked responses in Cu(2+)-sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation among sensory neurons via reciprocal inhibition fine-tunes the nociception and avoidance behaviour.