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Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC 50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use ( n  = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Transforming growth factor beta (TGF‐β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation‐associated responses. However, the antiviral activities and mechanisms of TGF‐β isoforms, including TGF‐β1, TGF‐β2 and TGF‐β3, remain unclear. Here, we demonstrated that all of the three TGF‐β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF‐β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF‐β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF‐β/SMAD signalling pathway–dependent and TGF‐β/SMAD signalling pathway–independent manners. TGF‐β isoforms showed additional anti‐HCV activities when combined with each other. However, the elevated TGF‐β1 and TGF‐β2, not TGF‐β3, could also induce liver fibrosis with a high expression of type I collagen alpha‐1 and α‐smooth muscle actin in LX‐2 cells. Our results showed a new insight into TGF‐β isoforms in the HCV‐related liver disease progression.

Peroxisome proliferator-activated receptor (PPAR)-γ is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of PPAR-γ in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) proliferation and migration. In the present study, we found PPAR-γ expression was remarkably reduced in RA synovium patient compare with OA and normal, as well as it was low-expression in Adjuvant-induced arthritis (AA). Moreover, inhibition PPAR-γ expression by T0070907 (12.5 μM) or PPAR-γ siRNA could promote FLSs proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, except for TIPM-1. These date indicate that up-regulation of PPAR-γ may play a critical role in RA FLSs. Interestingly, co-incubation FLSs with Pioditazone (25 μM) and over expression vector with pEGFP-N1-PPAR-γ reduced proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, besides TIMP-1. Further study indicates that PPAR-γ may induce activation Wnt/β-catenin signaling. In short, these results indicate that PPAR-γ may play a pivotal role during FLSs activation and activation of Wnt/β-catenin signaling pathway.

Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a suitable substituent at the 9-position might be beneficial for potency. Among them, compound 2d exhibited most potent activities with IC50 values of 7.12–14.8 μM, similar to that of BBR. The effect of 2d was further confirmed in a dose-dependent manner both in RNA and protein level. The mechanism revealed that 2d could inhibit the activation of MEK/ERK signaling pathway. Meanwhile, it could suppress the EV71-induced autophagy by activating AKT and inhibiting the phosphorylation of JNK and PI3KIII proteins. We consider BBR derivatives to be a new family of anti-EV71 agents through targeting host components, with an advantage of broad-spectrum anti-EV71 potency.

As the population ages, intestinal health in the elderly has become a key area of concern, with gut microbiota dysbiosis emerging as a significant issue. This review summarizes the factors influencing dysbiosis and interventions from both traditional Chinese medicine (TCM) and Western medicine, offering a reference for future research. A comprehensive search of global databases up to March 2024 identified 617 original studies on gut microbiota dysbiosis in individuals aged 65 and older. After applying strict PRISMA guidelines, 20 articles met the inclusion criteria. Key findings are summarized in four areas: 1) the definition and mechanisms of dysbiosis, 2) evaluation tools for gut microbiota imbalance, 3) factors contributing to dysbiosis in the elderly, and 4) pharmacological treatments. Both TCM and Western medicine offer unique advantages in managing gut microbiota dysbiosis, and the choice of intervention should be tailored to the individual’s condition. Future research should focus on optimizing integrated TCM and Western medicine approaches to improve outcomes for elderly patients with gut microbiota dysbiosis.

Asparagus (Asparagus officinalis) is a crop with medicinal, horticultural, and nutritional uses. The basic leucine zipper (bZIP) family is a transcription factor family distributed throughout eukaryotes, including plants, and whose members participate in various biological processes, including plant growth, development, flowering, and stress responses. However, a few genome-wide studies of the bZIP family members have been reported. Here, 46 Asparagus bZIP members, named AobZIP01-AobZIP46, were identified from the reference genome via PFAM search and could be divided into 14 subgroups which were shown to be similar via motif and gene structure analysis. The molecular evolution, motif, and gene structure comparative analysis between A. officinalis and Arabidopsis indicated the accuracy of AobZIP member identification. Additionally, the cis-acting elements of the AobZIP members revealed that they might be associated with plant hormones and responses to abiotic stress. The collinear analysis predicted that the function of AobZIP members might be comparable to that of other species. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that AobZIP genes were enriched in the abscisic acid (ABA) pathway. Furthermore, the tissue-specific expression at the seedling stage revealed that root tissue could be used as a target tissue because of its high expression level. The expression of AobZIP genes determined by quantitative real-time PCR under abiotic stress at the seeding stage revealed that some AobZIP members could be candidate genes for plant breeding. This study offers insights for future research in improving the abiotic stress resistance of asparagus utilizing the AobZIP genes.

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage‐specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage‐specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron‐like state. These neuron‐like cells can be further converted into mature neurons, while single‐cell RNA‐seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties. The authors find that inhibiting mechanical contraction disrupts fibroblast cytoskeleton, promotes YAP/TAZ nuclear exportation, and induces a neuron‐like state which can further maturation. Transcriptomic analysis shows that the cytoskeletal disruption collapses the original expression profile and evokes an intermediate state for neural transdifferentiation. These findings shed light on the underestimated role of the cytoskeleton in maintaining cell identity.

Rhodoterpenoids A‒C ( 1 ‒ 3 ), three new rearranged triterpenoids, together with one new biogenetically related compound, rhodoterpenoid D ( 4 ), were isolated and efficiently elucidated from Rhododendron latoucheae by high-performance liquid chromatography−mass spectrometry−solid-phase extraction−nuclear magnetic resonance (HPLC‒MS‒SPE‒NMR). Compounds 1 and 2 possess an unprecedented skeleton with a 5/7/6/6/6-fused pentacyclic ring system, while compound 3 contains a unique 6/7/6/6/6-fused pentacyclic carbon backbone. Their structures were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) analyses. Plausible biogenetic pathways for 1 ‒ 4 were proposed. Compounds 1 and 4 showed potential activity against herpes simplex virus 1 (HSV-1) with IC 50 values of 8.62 and 6.87  μ M, respectively.

The CCCH(C3H) transcription factor is an important transcription factor in plants in the process of plant development, hormone regulation and under stress. Rose is one of the most important commercial flower crops worldwide. However, there are few reports about the C3H gene of rose and Rosa chinensis Jacq. The reference genome sequence becomes a valuable source of data for the C3H genes in rose (RcC3Hs). We identified 31 encoding members in total, which were distributed on seven chromosomes and clustered into 11 subgroups in R. chinensis. Each subgroup has similar group-specific features including motifs, gene structure, cis-acting elements and collinearity in R. chinensis and two other species (Arabidopsis thaliana and Oryza sativa L). The RcC3Hs' tissue-specific expression by quantitative real-time PCR (qRT-PCR) showed that the expression of RcC3Hs was higher in roots and leaves compared with other tissues. These results provide a theoretical basis for the follow-up exploration of the functions of RcC3Hs and the molecular breeding of rose. Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1901609 .

Hepatitis B virus (HBV) is a global health concern that can cause acute and chronic liver diseases. Thus, there is an urgent need to research novel anti-HBV agents. Our previous reports show that -phenylbenzamide derivatives exert broad-spectrum antiviral effects against HIV-1, HCV, and EV71 by increasing intracellular levels of APOBEC3G (A3G). As A3G is capable of inhibiting the replication of HBV, we screened the -phenylbenzamide derivatives against HBV. In this study, a new derivative, -(4-chlorophenyl)-4-methoxy-3-(methylamino) benzamide (IMB-0523), was synthesized and its anti-HBV activity was evaluated in vitro and in vivo. The acute toxicity and pharmacokinetic profiles of IMB-0523 were also investigated. Our results show that IMB-0523 has higher anti-HBV activity in both wild-type HBV (IC : 1.99 µM) and drug-resistant HBV (IC : 3.30 µM) than lamivudine (3TC, IC : 7.37 µM in wild-type HBV, IC : >440 µM in drug-resistant HBV). The antiviral effect of IMB-0523 against HBV may be due to an increased level of intracellular A3G. IMB-0523 also showed low acute toxicity (LD : 448 mg/kg) in mice and promising PK properties (AUC : 7535.10±2226.73 µg·h/L) in rats. Further, IMB-0523 showed potent anti-HBV activity in DHBV-infected ducks. Thus, IMB-0523 may be a potential anti-HBV agent with different mechanisms than current anti-HBV treatment options.