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Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections.

The activation of interferon (IFN)-regulatory factor-3 (IRF3), characterized by phosphorylation and nuclear translocation of the latent transcription factor, is central to initiating innate antiviral responses. Whereas much has been learned about the upstream pathways and signaling mechanisms leading to IRF3 activation, how activated IRF3 operates in the nucleus to control transcription of IFNs remains obscure. Here we identify EAP30 (a.k.a, SNF8/VPS22), an endosomal sorting complex required for transport (ESCRT)-II subunit, as an essential factor controlling IRF3-dependent antiviral defense. Depletion of EAP30, but not other ESCRT-II subunits, compromised IRF3-dependent induction of type I and III IFNs, IFN-stimulated genes (ISGs) and chemokines by double-stranded RNA or viruses. EAP30, however, was dispensable for the induction of inflammatory mediators of strict NF-κB target. Significantly, knockdown of EAP30 also impaired the establishment of an antiviral state against vesicular stomatitis virus and hepatitis C virus, which are of distinct viral families. Mechanistically, EAP30 was not required for IRF3 activation but rather acted at a downstream step. Specifically, a fraction of EAP30 localized within the nucleus, where it formed a complex with IRF3 and its transcriptional co-activator, CREB-binding protein (CBP), in a virus-inducible manner. These interactions promoted IRF3 binding to target gene promoters such as IFN-β, IFN-λ1 and ISG56. Together, our data describe an unappreciated role for EAP30 in IRF3-dependent innate antiviral response in the nucleus.

Abstract On the basis of subsidence history analysis and balanced cross-section analysis, the vertical uplift/subsidence history and horizontal extension/compression history of the north depression of the south Yellow Sea basin are quantitatively studied. The results show that the tectonic evolution of the north depression of the south Yellow Sea basin since late Cretaceous can be divided into a rifting phase （late Cretaceous to Paleogene） and a post-rifting phase （Neogene to Quaternary）. The rifting phase can be further subdivided into an initial rifting stage （late Cretaceous）, an intensive rifting stage （Paleocene）, a rifting termination stage （Eocene）, and an inversion-uplifting stage （Oligocene）. Together, this division shows the characteristics of an episodic-evolved intracontinental rift-depression basin. The deformation of the north depression of the south Yellow Sea basin since late Cretaceous was mainly fault-related. The horizontal extension and tectonic subsidence were controlled by the activity of faults. The differential evolution of faults also caused variations in local uplift/subsidence movements and the regional heterogeneity in extension. The late Cretaceous initial rifting of the north depression of the south Yellow Sea basin is related to the Pacific-Eurasia convergence. From the Paleocene intensive rifting stage to present, the Pacific-Eurasia convergence and India-Eurasia convergence have played important roles in the evolution of this region.

A cloud-scale WRF simulation was used to investigate the cloud microphysical processes and three-dimensional structure of latent heat budgets in different stages of a mesoscale convective system (MCS) accompanied by heavy rain that occurred in the Guangzhou region of South China. The results enable us to draw the following conclusions: (1) During the development and mature stages, the main heating processes were condensation below 400 hPa and deposition above 400 hPa. The main cooling processes were evaporation and melting. During the dissipation stage, all the microphysical processes were weak. (2) Water vapor condensed into cloud water, and rainwater significantly contributed to all stages of the MCS. (3) During every stage of the MCS, the primary cooling microphysical process was the evaporation of rainwater, which was maximum during the mature stage.

To investigate the effects of electroacupuncture (EA) on the blood-brain barrier permeability and the regulation of matrix metalloproteinases (MMPs) in the mice with Parkinson's disease (PD). Forty-eight C57BL/6 mice were randomly assigned into the normal control (NC) group, the PD model (PD) group, the EA group and the EA + SB-3CT inhibitor group (EA + SB-3CT), with 12 mice in each group. In this experiment, the PD model was established by intragastric administration (IG) with rotenone for 4 wk in the PD group, EA group and EA+SB-3CT group. In the EA + SB-3CT group, 1 h after IG with rotenone, the mice were intraperitoneally injected with MMP-2/9 inhibitor, SB-3CT (25 mg/kg/d). After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting. Compared with the NC group, the behavioral scores increased (P < 0.05), while total time of locomotion, total distance and average speed were reduced (P < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (P < 0.05), Evans blue level in the brain tissue increased (P < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (P < 0.05), whereas MMP-2 and MMP-9 expression was higher (P < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (P < 0.05), while the total time of locomotion, total distance and average speed increased (P < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (P < 0.05), Evans blue level in the brain tissue was lower (P < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was down-regulated (P < 0.05) in the EA group. Compared with the EA group, Evans blue level was reduced (P < 0.05), the protein expression of ZO-1 and occludin was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was further down-regulated (P < 0.05) in the EA+SB-3CT group. EA can effectively ameliorate the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins, ZO-1 and occludin, and down-regulating the expression of matrix metalloporteinases, MMP-2 and MMP-9. The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.

To observe the clinical effect of “scapular heat penetration” technique of acupuncture in treatment of scapulohumeral periarthritis. It was a single-central randomized controlled trial, the participants, outcome assessors and statisticians were blinded. The trial was undertaken in Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, from June 2021 to January 2022. Sixty-seven patients with scalpulohumeral periarthritis were participated. In the control group, the routine acupuncture was given, while in the trial group, the “scapular heat penetration” technique of acupuncture was adopted. The intervention was delivered once every two days, 3 treatments a week; and one course included 9 treatments. Before the 1st treatment and after the 9th treatment, the symptoms and physical signs were observed and recorded in each group. Primary outcome: the score of visual analogy scale (VAS) before treatment and after treatment completion. Secondary outcomes: the range of movement (ROM) of shoulder joint, the score of Japanese Orthopaedic Association (JOA) of shoulder joint and the infrared thermal imaging temperature around the shoulder. A total of 102 cases were collected, 72 cases of them were eligible and 5 cases were withdrawn. Sixty-seven cases were included in analysis. In the within-group comparison, VAS score, ROM and JOA score as well as the shoulder temperature were all ameliorated after 9 treatments in either the trial group or the control group, compared with those before treatment (P < 0.05). In the comparison between two groups, after 9 treatments, VAS score in the trial group was lower than that of the control group (P < 0.05); and the improvements in ROM and shoulder temperature in the trial group were better than those of the control group (P < 0.05). No adverse reactions were found in the two groups. Both the “scapular heat penetration” technique of acupuncture and the conventional acupuncture are effective on scapulohumeral periarthritis. But, regarding the improvements in pain, ROM of shoulder joint, the activity of daily life and shoulder temperature, the “scapular heat penetration” technique of acupuncture is superior to the conventional acupuncture. ChiCTR1900025505

Hepatic ischemia-reperfusion （I/R） injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-At2＇14- prostaglandin J2 （15d-PGJ2） is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti- inflammatory and ceil-protective functions in various types of cells and animal models. In this study we explored the effects of 15d- PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms. A model of segmental （70%） hepatic warm ischemia was established in Balb/c mice, and the pathological changes in serum and liver tissues were detected at 6, 12, and 24 h post-surgery, while 15d-PGJ2 （2.5, 7.5, 15 pg, iv） was administered 30 min prior the surgery. Pretreatment with 15d-PGJ2 （7.5, 15 pg） significantly ameliorated I/R-induced hepatic injury evidenced by dose-dependent reduction of serum ALT and AST levels as well as alleviated tissue damages. 15d-PGJ2 pretreatment significantly decreased the serum TNF-a and IL-113 levels and the hepatic expression of F4/80, a major biomarker of macrophages. 15d-PGJ2 pretreatment upregulated the Bcl-2/Bax ratio, thus reducing the number of apoptotic cells in the livers. 15d-PGJ2 pretreatment considerably suppressed the expression of Beclin-1 and LC3, thus decreasing the number of autophagosomes in the livers. Furthermore, 15d-PGJ2 pretreatment activated Nrf2 and inhibited a ROS/ HIFI~/BNIP3 pathway in the livers. Pretreatment with the PPARy receptor blocker GW9662 （2 pg, ip） partly reversed the protective effects of 15d-PGJ2 on hepatic I/R injury. In conclusion, our results confirm the protective effect of 15d-PGJ2 on hepatic I/R injury, an effect that may rely on a reduction in the activation of Kupffer cells and on activation of the Nrf2 pathway, which lead to inhibition of ROS generation, apoptosis, and autophagy.

Thymoquinone is the main active monomer extracted from black cumin and has anti-inflammatory, antioxidant and anti-apoptotic functions. However, the protective effects of thymoquinone on cardiovascular function in diabetes remain to be fully elucidated. The present study aimed to investigate the molecular mechanisms underling the beneficial effects of thymoquinone on the cardiovascular function in streptozotocin-induced diabetes mellitus (DM) rats. Supplement thymoquinone may recover the insulin levels and body weight, inhibit blood glucose levels and reduce the heart rate in DM-induced rats. The results indicated that the heart, liver and lung to body weight ratios, in addition to the blood pressure levels, were similar for each experimental group. Treatment with thymoquinone significantly reduced oxidative stress damage, inhibited the increased endothelial nitric oxide synthase protein expression and suppressed the elevation of cyclooxygenase-2 levels in DM-induced rats. In addition, thymoquinone significantly suppressed the promotion of tumor necrosis factor-α and interleukin-6 levels in the DM-induced rats. Furthermore, administration of thymoquinone significantly reduced caspase-3 activity and the promotion of phosphorylated-protein kinase B (Akt) protein expression levels in DM-induced rats. These results suggest that the protective effect of thymoquinone improves cardiovascular function and attenuates oxidative stress, inflammation and apoptosis by mediating the phosphatidylinositol 3-kinase/Akt pathway in DM-induced rats.

Periostin is an extracellular matrix protein involved in fibrosis. The present study investigated the importance of periostin in hypertension-induced myocardial fibrosis. Rats were randomly divided into either the normal group (0.4% NaCl diet; n=8) or hypertension group (8% NaCl diet; n=8). For 36 weeks, the blood pressure and heart rate of the rats were monitored. At week 36, the hearts were extracted for further analysis. Masson's staining and western blotting were performed to determine the levels of periostin protein expression, oxidative stress and fibrosis. In addition, fibroblasts were isolated from adult rats and cultured in vitro, and following treatment with angiotensin II (Ang II) and N-acetyl-L-cysteine (NAC), western blotting, immunofluorescence and 2′,7′ dichlorodihydrofluorescin staining were performed to examine reactive oxygen species production, and periostin and α-smooth muscle actin (α-SMA) expression levels. The results demonstrated that periostin expression and oxidative stress were increased in hypertensive hearts compared with normal hearts. The in vitro experiments demonstrated that Ang II upregulated the expression levels of periostin and α-SMA compared with the control, whereas, pretreatment with NAC inhibited oxidative stress, periostin and α-SMA expression in fibroblasts. In conclusion, the results of the current study suggested that oxidative stress-induced periostin is involved in myocardial fibrosis and hypertension. The present study demonstrated that periostin inhibition may be a promising approach for the inhibition of hypertension-induced cardiac remodeling.

Pumpkin plants showing symptoms of witches' broom (PuWB) were observed in Xinjiang Uyghur autonomous region, China, in September 2018. A phytoplasma was detected in symptomatic plants by PCR amplifying portions of the 16S ribosomal and tuf genes. In addition, the phylogeny based on these genes sequencing indicated that the PuWB strain clusters with 'Candidatus Phytoplasma solani' (subgroup 16SrXII-A). Furthermore, based on in silico and in vitro restriction fragment length polymorphism analyses, the PuWB phytoplasma was confirmed as a 'Ca. P. solani'-related strain. This was the first record of the occurrence of phytoplasma presence in pumpkins in China, and the first record of 16SrXII phytoplasma infecting pumpkins in the world.