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Lepidonotopodinae is a subfamily of Polynoidae endemic to deep-sea chemosynthetic ecosystems around the world. Nevertheless, their species composition and phylogeny have only been systematically studied in hydrothermal vents of the Eastern and Western Pacific. Here, we morphologically and genetically examined worms in Lepidonotopodinae from vents across three Indian Ocean ridges, revealing two new Branchinotogluma species (B. jiaolongae sp. nov. and B. kaireiensis sp. nov.) and two new Levensteiniella species (L. pettiboneae sp. nov. and L. longqiensis sp. nov.). Primary morphological characters distinguishing them from other congeners include the number and arrangement of both pharyngeal papillae and ventral papillae. The reconstructed molecular phylogeny of Lepidonotopodinae supports a monophyletic Levensteiniella , with the two new Indian Ocean species recovered as sisters. As revealed in previous studies, a paraphyletic Branchinotogluma was also found, with the three Indian Ocean species separated into distinct clades with sister-relationships to species from the Mid-Atlantic, Alarcon Rise, and Manus Basin, respectively. This indicates three separate historical invasions to Indian Ocean vents. Our findings increase the number of Indian Ocean Lepidonotopodinae worms to seven, now the most diverse annelid group there, and help to elucidate the biodiversity, distribution, and biogeography of this subfamily in the Indian Ocean. [ABSTRACT FROM AUTHOR]

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein, lead to the functional alteration in both receptor engagement and monoclonal antibody (mAb) recognition. Here, we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion. Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity. However, this weakened effect could be largely compensated by specific epistatic mutations, such as N501Y, thus maintaining the overall ACE2 affinity for the spike protein of all major variants. The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions. Together, this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained, emphasizing the significance of comprehensive assessment of spike mutations. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator‐activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR‐α, PPAR‐β/δ and PPAR‐γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and tumour immune response, and are essential components in tumour progression and metastasis. As such, they have become a target for cancer therapy research. In this review, we discussed the current state of knowledge on the involvement of PPARs in cancer, including their role in tumourigenesis, the impact of PPARs in tumour microenvironment and the potential of using PPARs combinational therapy to treat cancer by targeting essential signal pathways, or as adjuvants to boost the effects of current chemo and immunotherapies. Our review highlights the complexity of PPARs in cancer and the need for a better understanding of the mechanism in order to design effective cancer therapies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) involves degeneration of cells in the brain. Due to insidious onset and slow progression, AD is often not diagnosed until it gets progressed to a more severe stage. The diagnosis and treatment of AD has been a challenge. In recent years, high-throughput sequencing technologies have exhibited advantages in exploring the pathogenesis of diseases. However, the types of cells of the central nervous system are complex and traditional bulk sequencing cannot reflect their heterogeneity. Single-cell sequencing technology enables study at the individual cell level and has an irreplaceable advantage in the study of complex diseases. In recent years, this field has expanded rapidly and several types of single-cell sequencing technologies have emerged, including transcriptomics, epigenomics, genomics and proteomics. This review article provides an overview of these single-cell sequencing technologies and their application in AD. [ABSTRACT FROM AUTHOR]

Background: The various types of ionizing radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases, affecting the status of the aviators to fly. Therefore, it is important to explore the molecular-level changes in the skin during space missions. Objectives: Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression before, during and after space missions. Methods: First, STEM (Short Time-series Expression Miner) software was used to identify the expression patterns of hair follicle genes of astronauts pre-, in- and postflight. Gene Ontology Enrichment Analysis was then performed to explore the gene functions within the module. Protein–protein interaction network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB (Molecular Signatures Database). Results: Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared with preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered on return to the ground, but there are a small number of genes whose expression cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression on entry into space and decreased expression on return to Earth. The genes of this expression pattern were associated with skin development, keratinocyte differentiation and cornification. Ten hub genes were identified as skin-related genes within the module, as well as nine transcription factors and three circadian genes. One hundred and seventy-nine genes decreased in expression after entry into space and increased on return to Earth. By reviewing the literature, we found that four of the genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases. Conclusions: Through bioinformatics analysis, we found that the space environment affects skin keratinocyte differentiation, leading to skin barrier damage and inflammatory responses, and that this effect was decreased after return to Earth. Among 10 International Space Station astronauts studied, 311 genes increased in expression after space entry and decreased after return to Earth. Genes with this expression pattern were associated with skin development, keratinocyte differentiation and cornification. We found that these hub skin-related genes are involved in skin barrier damage and inflammatory responses. [ABSTRACT FROM AUTHOR]

The South China Sea (SCS) basin is hypothesized to host distinct and bathymetrically differentiated fauna due to its semi‐enclosed basin and three‐layer circulation system. To test this hypothesis, three cow falls are artificially deployed at separate depths (655, 1604, and 3402 m) on Zhongnan seamount in the middle SCS, and the associated worms, Sirsoe spp. are selected as targets to explore their diversity, phylogeny, and zonation pattern. Analyses of collected specimens reveal three new Sirsoe species, which were then nominally described and named as S. polita sp. nov. (655 m), S. nanhaiensis sp. nov. (1604 and 3402 m), and S. feitiana sp. nov. (3402 m), and one known species (S. balaenophila lineage II). Metabarcoding analyses on cow‐fall sediments reveal seven additional Operated Taxonomic Units (OTUs) assigned to Sirsoe, increasing the Sirsoe diversity to 10 species/OTUs in the middle SCS. Their distribution along depth shows increasing diversity toward the deeper sites. Phylogenetic inferences recover S. polita closely related to S. alucia from the Southwest Atlantic, forming a lineage deeply divergent from others. The nine deep‐water species/OTUs are scattered in three distinct lineages showing closer phylogenetic relationships between 1604‐ and 3402‐m counterparts. The lineage formed by S. naihaiensis and S. feitiana is distinct from other non‐SCS congeners both morphologically and genetically. These results suggest multiple independent invasions of Sirsoe to the SCS, a new lineage potentially endemic to the SCS, and a strong zonation pattern related to depth, especially between the shallow (655 m) and the deep (1604 and 3402 m) sites. The semi‐enclosed feature combined with the physical structure of the SCS may contribute to such a pattern. This work is registered in ZooBank under: urn:lsid:zoobank.org:pub:317771C8‐42D717‐4765‐A168‐B3BE99B09FBF. [ABSTRACT FROM AUTHOR]

Emergence of various circulating SARS‐CoV‐2 variants of concern (VOCs) promotes the identification of pan‐sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross‐reactive against both SARS‐CoV‐1 and SARS‐CoV‐2 and to search the criterion for bNAbs against all emerging SARS‐CoV‐2, we isolated several SARS‐CoV‐1‐cross‐reactive monoclonal antibodies (mAbs) from a wildtype SARS‐CoV‐2 convalescent donor. These antibodies showed broad binding capacity and cross‐neutralizing potency against various SARS‐CoV‐2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross‐reactive against SARS‐CoV‐1 through their escape mutations. Further evaluation of a series of SARS‐CoV‐1/2‐cross‐reactive bNAbs showed a negative correlation between the neutralizing activities against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron variant. Together, these results suggest the necessity of using cross‐neutralization against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron as criteria for rational design and development of potent pan‐sarbecovirus vaccines and bNAbs. [ABSTRACT FROM AUTHOR]

Recent studies have identified a role for ALKBH7 in the occurrence and progression of cancer, and this protein is related to cellular immunity and immune cell infiltration. However, the prognostic and immunotherapeutic value of ALKBH7 in different cancers have not been explored. In this study, we observed high ALKBH7 expression in 17 cancers and low expression in 5 cancers compared to paired normal tissues. Although ALKBH7 expression did not correlate relatively significantly with the clinical parameters of age (6/33), sex (3/33) and stage (3/27) in the cancers studied, the results of the survival analysis reflect the pan-cancer prognostic value of ALKBH7. In addition, ALKBH7 expression was significantly correlated with the TMB (7/33), MSI (13/33), mDNAsi (12/33) and mRNAsi (13/33) in human cancers. Moreover, ALKBH7 expression was associated and predominantly negatively correlated with the expression of immune checkpoint (ICP) genes in many cancers. Furthermore, ALKBH7 correlated with infiltrating immune cells and ESTIMATE scores, especially in PAAD, PRAD and THCA. Finally, the ALKBH7 gene coexpression network is involved in the regulation of cellular immune, oxidative, phosphorylation, and metabolic pathways. In conclusion, ALKBH7 may serve as a potential prognostic pan-cancer biomarker and is involved in the immune response. Our pan-cancer analysis provides insight into the role of ALKBH7 in different cancers. [ABSTRACT FROM AUTHOR]

The biodiversity of deep-sea hydrothermal vents in the Indian Ocean remains poorly characterised compared with that of their Pacific and Atlantic counterparts. Although the Longqi hydrothermal vent field is the most extensively explored vent site on the ultra-slow-spreading Southwest Indian Ridge, it is still a source of new discoveries. Here, we report and formally describe a new peltospirid snail from Longqi – Lirapex felix sp. nov. Known from only two specimens, it differs from other named Lirapex species by a depressed spire and the lack of coil loosening on the body whorl. Examinations of the external anatomy and radular characteristics agree with its placement in Lirapex, which is also supported by a molecular phylogeny reconstructed using the barcoding fragment of the mitochondrial cytochrome c oxidase I (COI) gene. This is the fifth peltospirid snail known to inhabit the Longqi field, three of which (including Lirapex felix sp. nov.) have been found nowhere else. There is growing evidence that the Longqi field represents a biogeographically unique site among Indian Ocean vents. The discovery of Lirapex felix sp. nov. adds to the unique biodiversity of Longqi field, with implications for conservation in the light of potential deep-sea mining. This work is registered in ZooBank under: [ABSTRACT FROM AUTHOR]

Mammalian orthoreoviruses (MRVs) infect almost all mammals, and there are some reports on MRVs in China. In this study, a novel strain was identified, which was designated as HLJYC2017. The results of genetic analysis showed that MRV HLJYC2017 is a reassortant strain. According to biological information analysis, different serotypes of MRV contain specific amino acid insertions and deletions in the σ1 protein. Neutralizing antibody epitope analysis revealed partial cross-protection among MRV1, MRV2, and MRV3 isolates from China. L3 gene recombination in MRV was identified for the first time in this study. The results of this study provide valuable information on MRV reassortment and evolution. [ABSTRACT FROM AUTHOR]

Objective. Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. Methods. Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl4) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl4 model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results. Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor β1 (TGF-β1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Conclusion. Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-β1-mediated Smad3 and p38 MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea (PED) re-emerged in China in 2010 and is now widespread. Evidence indicates that highly virulent porcine epidemic diarrhea virus (PEDV) strains belonging to genotype G2 caused a large-scale outbreak of diarrhea. Currently, vaccines derived from PEDV classical strains do not effectively prevent infection by virulent PEDV strains, and no specific drug is available to treat the disease. RNA interference (RNAi) is a novel and effective way to cure a wide range of viruses. We constructed three short hairpin RNA (shRNA)-expressing plasmids (shR-N307, shR-N463, and shR-N1071) directed against nucleocapsid (N) and determined their antiviral activities in intestine epithelial cells infected with a classical CV777 strain and LNCT2. We verified that shR-N307, shR-N463, and shR-N1071 effectively inhibited the expression of the transfected N gene in vitro, comparable to the control shRNA. We further demonstrated the shRNAs markedly reduced PEDV CV777 and LNCT2 replication upon downregulation of N production. Therefore, this study provides a new strategy for the design of antiviral methods against coronaviruses by targeting their processivity factors. [ABSTRACT FROM AUTHOR]

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered enteric coronavirus. We have previously shown that the caspase-dependent FASL-mediated and mitochondrion-mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis, which facilitates viral replication. However, the roles of intracellular signaling pathways in SADS-CoV-mediated cell apoptosis and the relative advantages that such pathways confer on the host or virus remain largely unknown. In this study, we show that SADS-CoV induces the activation of ERK during infection, irrespective of viral biosynthesis. The knockdown or chemical inhibition of ERK1/2 significantly suppressed viral protein expression and viral progeny production. The inhibition of ERK activation also circumvented SADS-CoV-induced apoptosis. Taken together, these data suggest that ERK activation is important for SADS-CoV replication, and contributes to the virus-mediated changes in host cells. Our findings demonstrate the takeover of a particular host signaling mechanism by SADS-CoV and identify a potential approach to inhibiting viral spread. • SADS-CoV activated the ERK signaling pathway irrespective of viral replication. • Chemical inhibition and ERK1/2 knockdown markedly impaired SADS-CoV replication. • There were crosstalk between ERK and apoptotic pathways during SADS-CoV infection. • SADS-CoV exploits the ERK cascade to complete successful viral infection. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motor neurons, causing muscle atrophy, bulbar palsy, and pyramidal tract signs. However, the aetiology and pathogenesis of ALS have not been elucidated to date. In this study, a competitive endogenous RNA (ceRNA) network was constructed by analyzing the expression profiles of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) that were matched by 7 ALS samples and 4 control samples, and then a protein-protein interaction (PPI) network was constructed to identify the genes related to ALS. Gene Ontology (GO) was used to study the potential functions of differentially expressed mRNAs (DEmRNAs) in the ceRNA network. For the ALS and control groups, 247177 potential lncRNA-mRNA ceRNA relationship pairs were screened. Analysis of significant relationship pairs demonstrated that the PPI modules formed by the MALAT1-regulated SYNRG, ITSN2, PICALM, AP3B1, and AAK1 genes may play important roles in the pathogenesis of ALS, and these results may help to characterize the pathogenesis of ALS. [ABSTRACT FROM AUTHOR]

• A 4-aa insertion in the COE region of S protein forming an extra alpha helix was firstly identified in PEDV. • A 4-aa insertion in the COE region of S protein may influence the VN antibody reactivity. • PEDV LNsy was a natural recombination between GDS13 and GDS46 strains. In recent years, a novel, highly virulent variant of porcine epidemic diarrhea virus (PEDV) has emerged, causing substantial economic losses to the pork industry worldwide. In this study, a PEDV strain named LNsy was successfully isolated in China. Phylogenetic analysis based on the whole genome revealed that PEDV LNsy belonged to the G2 subtype. For the first time, a unique four amino acids (4-aa) insertion was identified in the COE region of the spike (S) protein (residues 499–640), resulting in an extra alpha helix in the spatial structure of the COE region. To determine changes in virus-neutralization (VN) antibody reactivity of the virus, polyclonal antibodies (PAbs) against the S protein of different subtypes were used in a VN test. Both PAbs against the S protein of the G1 and G2 subtype showed reduced VN reactivity to PEDV LNsy. Further, recombination analyses revealed that PEDV LNsy was the result of recombination between PEDV GDS13 and GDS46 strains at the genomic breakpoints (nt 17,959−20,594 in the alignment) in the ORF1b gene of the genomes. Pathological examination showed gross morphological pathological changes in the gut, including significant villus atrophy and shedding of the infected piglets. These results indicated that a 4-aa insertion in the COE region of the S protein may have partly altered the profiles of VN antibodies and thus it will be important to develop vaccine candidates to resist wild virus infection and to monitor the genetic diversity of PEDV. [ABSTRACT FROM AUTHOR]