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Severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne bunyavirus, causes an emerging viral hemorrhagic fever with a high mortality rate. SFTSV nonstructural protein S (NSs) is a virulence factor that sequesters antiviral proteins into autophagic vesicles for degradation to escape host immune response. SAFA (Nuclear scaffold attachment factor A), an RNA sensor, recognizes viral RNA and is retained in the cytoplasm upon RNA virus SFTSV infection and then activates innate immunity. It is unclear whether NSs mediates the escape of SAFA-mediated antiviral response. Here we showed that SFTSV NSs can inhibit SAFA-dependent antiviral response via autophagy. We used SAFA-NLS (the nuclear localization signal) mutant to transfect SAFA knocked-out MEF cells and found that the cytoplasmic SAFA promoted innate immune response to poly(I:C) stimulating. Importantly, NSs interacted with the AAA+ domain of SAFA and retained SAFA in the cytoplasm thereby suppressing SAFA-mediated antiviral response. Mechanistically, SFTSV NSs degraded cytoplasmic SAFA via SQSTM1/p62-dependent autophagy and sequestered SAFA into autophagic vesicles for degradation through promoting the interaction between SAFA and LC3. In conclusion, our results indicate a novel mechanism of SFTSV NSs to escape host antiviral immune response by recruiting SAFA into autophagic flux for degradation.

Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients’ lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro . The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1 -/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, gro EL, and glt A genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus , 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis , Anaplasma capra , and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis , A. capra , and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the gro EL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and glt A gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides . In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro , while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

One new robustaflavone, (2S,2′′S)-2,3,2′′ ,3′′-tetrahydrorobustaflavone 7,4′,4′′′ -trimethyl ether (1), was isolated from the 75% aqueous EtOH extract of Selaginella uncinata. The structure and absolute configuration of 1 was established by extensive spectroscopic and circular dichroism analyses.

Insulin-like growth factor-binding protein 1 (IGFBP-1), a hypoxia-induced protein, is a member of the IGFBP family that regulates vertebrate growth and development. In this study, full-length IGFBP-1a cDNA was cloned from a hypoxia-sensitive Cyprinidae fish species, the blunt snout bream (Megalobrama amblycephala). IGFBP-1a was expressed in various organs of adult blunt snout bream, including strongly in the liver and weakly in the gonads. Under hypoxia, IGFBP-1a mRNA levels increased sharply in the skin, liver, kidney, spleen, intestine and heart tissues of juvenile blunt snout bream, but recovered to normal levels after 24-hour exposure to normal dissolved oxygen. In blunt snout bream embryos, IGFBP-1a mRNA was expressed at very low levels at both four and eight hours post-fertilization, and strongly at later stages. Embryonic growth and development rates decreased significantly in embryos injected with IGFBP-1a mRNA. The average body length of IGFBP-1a-overexpressed embryos was 82.4% of that of the control group, and somite numbers decreased to 85.2%. These findings suggest that hypoxia-induced IGFBP-1a may inhibit growth in this species under hypoxic conditions.

Histamine is a powerful modulator that regulates blood vessels and blood flow. The effect of histamine on the extracortical vessels has been well described, while much less is known about the effect of histamine on intracortical vessels. In this study, we investigated the effect of histamine on regional cerebral blood flow in rat parietal lobe with laser Doppler flowmetry. The pharmacological characteristics of distinct ways (intracerebroventricular injection, intraperitoneal injection, and cranial window infusion) in applying histamine to the brain were also obtained and compared. Histamine applied in three ways all produced a decrease of rCBF in parietal lobe in a concentration-dependent manner. Cranial window infusion was the most effective way and intraperitoneal injection of L-histidine was the most ineffective, although it is a simple and applied way. To determine which type of receptor takes part in the vessel contraction induced by histamine, H1 receptor antagonist, diphenhydramine, and H2 receptor antagonist, cimetidine, were applied, respectively, before histamine administration. When the injection of cimetidine was conducted in advance, histamine still resulted in a decrease of infusion amount; while the injection of diphenhydramine was conducted in advance, the infusion of blood amount wasn’t changed. These findings indicated that histamine could result in a reduction of rCBF in the rat parietal lobe and this effect of histamine may attribute partly to its combination with H1 receptor.

Insulin-like growth factor-binding protein 1 （IGFBP-1）, a hypoxia-induced protein, is a member of the IGFBP family that regulates vertebrate growth and development. In this study, full-length IGFBP-la cDNA was cloned from a hypoxia-sensitive Cyprinidae fish species, the blunt snout bream （Megalobrama arnblycephala）. IGFBP-la was expressed in various organs of adult blunt snout bream, including strongly in the liver and weakly in the gonads. Under hypoxia, IGFBP-la mRNA levels increased sharply in the skin, liver, kidney, spleen, intestine and heart tissues of juvenile blunt snout bream, but recovered to normal levels after 24-hour exposure to normal dissolved oxygen. In blunt snout bream embryos, IGFBP-la mRNA was expressed at very low levels at both four and eight hours post-fertilization, and strongly at later stages. Embryonic growth and development rates decreased significantly in embryos injected with IGFBP-la mRNA. The average body length of IGFBP-la-overexpressed embryos was 82.4% of that of the contro

MicroRNAs（miRNAs） are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1（Cand1）.Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.

Rapid synthesis of complex molecules via selective functionalization of unactivated carbon–hydrogen bonds is here made easier with the use of removable ‘templates’ that enable the activation of distal bonds. An innovative route to carbon–hydrogen-bond activation The functionalization of unactivated carbon-hydrogen (C–H) single bonds is an efficient and rapid method for the generation of complex molecules from simpler ones. However, it is difficult to achieve selectivity of C–H activation in target molecules possessing multiple inequivalent C–H bonds. These authors report a class of easily removable 'templates' that direct the activation of distal meta-C–H bonds (more than ten bonds away) of a tethered arene. The innovative structures that are generated through this method are extremely hard to access by traditional methods and may provide different avenues for the development of innovative C–H activation reactions. Functionalization of unactivated carbon–hydrogen (C–H) single bonds is an efficient strategy for rapid generation of complex molecules from simpler ones. However, it is difficult to achieve selectivity when multiple inequivalent C–H bonds are present in the target molecule. The usual approach is to use σ -chelating directing groups, which lead to ortho -selectivity through the formation of a conformationally rigid six- or seven-membered cyclic pre-transition state 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 . Despite the broad utility of this approach, proximity-driven reactivity prevents the activation of remote C–H bonds. Here we report a class of easily removable nitrile-containing templates that direct the activation of distal meta -C–H bonds (more than ten bonds away) of a tethered arene. We attribute this new mode of C–H activation to a weak ‘end-on’ interaction 15 between the linear nitrile group and the metal centre. The ‘end-on’ coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta -C–H activation event. In addition, this template overrides the intrinsic electronic and steric biases as well as ortho -directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids).