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Spontaneous intracerebral haemorrhage (ICH) is the main presentation in adults with moyamoya disease (MMD), an unusual clinical entity with a poor prognosis. However, optimal management in the acute stage of ICH in patients with MMD remains a challenge. Since minimally invasive surgery (MIS) plus local thrombolysis has emerged as a promising strategy for ICH, we aimed to describe our experience of performing this procedure in this special population in the acute phase, while focusing on its efficacy and safety.The medical data of patients with ICH treated with MIS and local thrombolysis between November 2013 and December 2017 were retrospectively reviewed at our institution. MMD was identified based on the angiographic images. The primary outcome was postoperative intracranial rebleeding. The secondary outcomes were 30-day mortality and 6-month outcome graded using the modified Rankin scale (mRS). Logistic regression was applied to explore independent risk factors for the above outcomes.A cohort of consecutive 337 ICH patients was analysed, of whom 14 (4.15%) were diagnosed with MMD. In total, 36 (11.46%) patients experienced postoperative intracranial rehaemorrhage, of which one patient had MMD. No significant difference was found between the patients with and without MMD regarding postoperative rebleeding (9.09% vs. 11.55%,Our findings suggest that coexistent MMD is not associated with an increased risk of postoperative rebleeding or poor outcome after local thrombolysis for ICH.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is undergoing continuous evolution and convergent mutation, which has led to the rapid emergence of several new variants. These new subvariants carry different mutations in theirreceptor-binding domain (RBD), raising concerns that they may evade neutralizing monoclonal antibodies (mAbs). In this study, we investigated the serum neutralization efficacy of Evusheld (cilgavimab and tixagevimab) antibody cocktails against SARS-CoV-2 Omicron sublineages BA.2, BA.2.75, BA.2.76, BA.5, BF.7, BQ.1.1 and XBB.1.5. Our results show that Evusheld retained neutralizing activity against BA.2, BA.2.75 and BA.5, albeit with somewhat reduced titers. However, the neutralizing activity of Evusheld against BA.2.76, BF.7, BQ.1.1 and XBB.1.5 significantly decreased, with XBB.1.5 showing the greatest escape activity among the subvariants, followed by BQ.1.1, BA.2.76 and BF.7. We also observed that recipients of Evusheld displayed elevated antibody levels in their serum, which efficiently neutralized the original variant, and exhibited different characteristics of infection than those who did not receive Evusheld. These findings provide important guidance for the application of Evusheld in treating SARS-CoV-2 subvariant infections.

This paper focuses on researching the softening resistance performance of Mg alloy under high temperature and the evolution of microstructure during high-temperature treatment. The results showed that, compared with Cu-0.39Cr-0.12Fe alloy, Cu-0.38Cr-0.04Fe-0.08Mg alloy has higher resistance to softening temperature, hardness and conductivity, which were 40 °C, 13 HV, 5% IACS higher than that of Cu-0.39Cr-0.12Fe alloy. Both of the aging precipitated phase of two alloys are nano-Cr phase. Mg can inhibit the growing of nano-Cr phase and the grain recrystallization process significantly. According to 3DAP analysis, the interface structure of Cr/Mg/Cu is formed, which might be the key factor that results in the excellent softening resistance performance of Cu–Cr–Fe–Mg alloy.

The strain of Zika virus (ZIKV) that circulated during the 2015 epidemic in Brazil has been associated with more than 2000 cases of microcephaly from September 2015 through November 2016. The viral genome determines the biology and pathogenesis of a virus and the virus employs its own gene products to evade host immune surveillance, manipulate cellular machineries, and establish efficient replication. Therefore, understanding the functions of virus-encoded protein not only aids the knowledge of ZIKV biology but also guides the development of anti-ZIKV drugs. In this review, we focus on 10 proteins encoded by ZIKV and summarize their functions in ZIKV replication and pathogenesis according to studies published in the past 6 years.

SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.

The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 μm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI2) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA2), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.

Significance Many millions of people take probiotics over the counter, but very little is known about what they do and whether they really work. Here we show that in mice, introducing Bifidobacterium, one of the most commonly used probiotics, not only colonizes the gut, but also alters the entire microbiotic landscape. We previously found that this treatment rescues mice from an otherwise fatal inflammatory syndrome brought on by anti–CTLA-4 antibody, a checkpoint inhibitor that often causes autoimmunity in humans undergoing cancer treatment. Here we show that this is effect is due, at least in part, to the effect of this probiotic treatment on regulatory CD4+ cells, whose metabolic and immune suppressive functions are altered. These CD4+ regulatory T cells are known to be a key mechanism in the control of autoreactivity in the immune system in both mice and humans. Thus, we found a direct connection between probiotic treatment and one of the known principal mechanisms for controlling excess immune responses., Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that Bifidobacterium could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that Bifidobacterium altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10–mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.

α-Synuclein (α-Syn) oligomers play a critical role in the pathogenesis of Parkinson's disease (PD). α-Syn oligomers inducing neuronal death are thought to be associated with the mitochondrial dysfunction and oxidative stress. A chronic PD mouse model was created by daily intragastric administration of rotenone (5 mg/kg, 12 weeks). We analysed the progression of α-Syn aggregates from the gut to the midbrain together with oxidative stress levels and mitochondrial morphology in neurons of the substantia nigra in these mice. Our results showed that α-Syn oligomers were accumulated in the midbrain of the wild-type mice sequentially. The number of dopaminergic neurons was significantly reduced in the rotenone-treated mice. These mice also showed increased reactive oxygen species levels and morphological alterations of mitochondria in the midbrain. These results were reproduced in the α-Syn-transfected SH-SY5Y cells. Collectively, these findings suggest that α-Syn oligomers induce neuronal death at least in part via mitochondrial dysfunction and oxidative stress.

Since the spread of the novel coronavirus (SARS-CoV-2), China has launched an unprecedented fight against the epidemic. At the beginning of the outbreak, China responded quickly by informing the World Health Organization (WHO) and sharing sequence information internationally soon after the draft genome of the virus was revealed by Chinese researchers. China’s effort in transparency, data sharing and quick response for controlling the outbreak was praised by the international community. Although the outbreak is not over yet, the important consideration for this and future outbreaks has aroused wide public discussion. This article is aimed to identify the lessons we could learn from the outbreak and propose suggestions for future improvement from aspects including improving the public health and disease control and prevention system, improving the emergency response mechanism, promoting technological innovation, and increasing medical supplies and reserves. An enhanced holistic system is in urgent need for disease control and prevention through strengthening the public health and disease control and prevention system, improving the emergency response system, building relevant legal system, and establishing a national biosafety system. Future outbreaks might be inevitable, but we can save more lives and avoid much financial loss by effective countermeasures when public health emergency happens.

RSK1, an essential cellular kinase for Kaposi’s sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosphorylation via two separated functional regions: SIMs and amino acid 17–90, respectively, which do not affect each other. Similar to KSHV ORF45, ORF45 of Rhesus Macaque Rhadinovirus has only one SIM and also increases RSK1 SUMOylation in a SIM-dependent manner, while other ORF45 homologues do not have this function. Our work characterized ORF45 as a novel virus encoded SUMO E3 ligase, which is required for ORF45-RSK1 axis-mediated KSHV lytic gene expression.

At steady state, the NOD-like receptor (NLR)-containing pyrin domain (PYD) (NLRP)1 inflammasome is maintained in an auto-inhibitory complex by dipeptidyl peptidases 8 and 9 (DPP8 and DPP9) and is activated by pathogen-encoded proteases after infection. Here, we showed that the open reading frame (ORF)45 protein of the Kaposi's sarcoma-associated herpesvirus activated the human NLRP1 (hNLRP1) inflammasome in a non-protease-dependent manner, and we additionally showed that the Linker1 region of hNLRP1, situated between the PYD and NACHT domains, was required for the auto-inhibition and non-protease-dependent activation of hNLRP1. At steady state, the interaction between Linker1 and the UPA subdomain silenced the activation of hNLRP1 in auto-inhibitory complexes either containing DPP9 or not in a manner independent of DPP9. ORF45 binding to Linker1 displaced UPA from the Linker1-UPA complex and induced the release of the C-terminal domain of hNLRP1 for inflammasome assembly. The ORF45-dependent activation of the NLRP1 inflammasome was conserved in primates but was not observed for murine NLRP1b inflammasomes.

Background: Frail and pre-frail older people often need to take medications. However, factors related to medication adherence among this population remain unclear, warranting further research. This study aims to identify correlates of medication adherence among frail and pre-frail older adults. Methods: From November 2020 to December 2020; a total of 4218 community-dwelling residents aged ≥ 60 years were interviewed by a cross-sectional survey in China. Data on subjects’ general information; medication adherence; and frailty status was obtained via the face-to-face structured questionnaire. Logistic regression models were fitted; separately; to examine these factors linked to medication adherence. Results: We found that 36.2% (n = 1527) and 18.8% (n = 792) of respondents were classified as pre-frail and frail. According to the Morisky scale scores, 66.74% (n = 2815) were found to have adequate medication adherence, and 33.26% (n = 1403) were found to have inadequate medication adherence. Among the pre-frail respondents, age (adjusted odds ratio (AOR) = 1.64; 95% confidence interval (CI): 1.18–2.29, P = 0.003), marital status (AOR = 1.52; 95% CI: 1.04–2.21, P = 0.030), smoking status (AOR = 0.61; 95% CI: 0.37–0.99, P = 0.044), and functional ability (AOR = 0.72; 95% CI: 0.58–0.91, P = 0.006) were significantly related to medication adherence. Among them, advanced age and single were risk factors, which were positively related to the medication adherence of subjects in pre-frailty, while quitting smoking and limited functional ability contributed to improving their medication adherence. In contrast, only age (AOR = 1.77; 95% CI: 1.16–2.69, P = 0.008) was significantly associated with medication adherence among frail subjects. Conclusion: Influencing factors to medication adherence of old people in pre-frailty and frailty have been enriched, which provides a certain reference for promoting medication adherence in this population. Future adherence intervention methods should be designed based on these factors.

Violence behavior recognition is an important research scenario in behavior recognition and has broad application prospects in the field of network information review and intelligent security. Inspired by the long-short-term memory network, we estimate that temporal shift module (TSM) may have more room for improvement in the feature extraction ability of long-term information. In order to verify the above conjecture, we explored based on TSM. After many attempts, it was finally proposed to connect the two TSMs in a cascaded manner, which can expand the receptive field of the model. In addition, an efficient channel attention module was introduced at the front end of the network, which strengthened the model’s spatial feature extraction capabilities. At the same time due to behavior recognition prone to over-fitting, we extended and processed on the basis of some open-source datasets to form a larger violence dataset and solved the problem of over-fitting. The final experimental results show that the algorithm proposed can improve the model’s feature extraction ability of violent behavior in the space and temporal dimension and realize the recognition of violent behavior, which verified the above point of view.

SARS-CoV-2 is the causative agent for the COVID-19 pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin-1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 28 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate Beclin-1-Vps34-Atg14 complex but selectively inhibit Beclin-1-Vps34-UVRAG complex. Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raises the possibility of targeting the autophagic pathway for the treatment of COVID-19.

Viral interfering RNA (viRNA) has been identified from several viral genomes via directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs are loaded onto the Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and initiate the cleavage of target genes. However, the identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity, which requires its histidine residue at the 41st amino acid. Accordingly, the engineered ZIKV-H41R loss-of-function (LOF) mutant virus no longer suppresses Dicer enzymatic activity nor inhibits miRNA biogenesis in NSCs. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected human neural stem cells (NSCs), and miRanda target scanning, we defined 29 ZIKV derived viRNA profiles in NSCs, and established a complex interaction network between the viRNAs and their viral targets. More importantly, we found that viRNA production from the ZIKV mRNA is dependent on Dicer function and is a limiting factor for ZIKV virulence in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs. Therefore, our mapping of viRNAs to their RNA targets paves a way to further investigate how viRNAs play the role in anti-viral mechanisms, and perhaps other unknown biological functions.

Highlights • This study showed high prevalence of psychological disorders and associated factors encompassed all phases of the Chinese COVID-19 epidemic, extending from early in the outbreak to the present remission for the first time. • Our findings raise special concerns about public mental health, especially among non-HCWs involved at the remission stage of the COVID-19 epidemic., Objective : This study aimed to explore the prevalence of psychological disorders and associated factors at different stages of the COVID-19 epidemic in China. Methods : The mental health status of respondents was assessed via the Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI) and the Generalized Anxiety Disorder 7 (GAD-7) scale. Results : 5657 individuals participated in this study. History of chronic disease was a common risk factor for severe present depression (OR 2.2, 95% confidence interval [CI], 1.82-2.66, p

Mesoporous bioactive glasses (MBGs) can be used as carriers for biomolecule delivery with improved functions. Although there are a great number of studies on drug delivery by MBGs, until now little work has been done to investigate the DNA gene transfection effect of MBGs. In this study, radial mesoporous bioactive glasses (rMBGs) were prepared by sol–gel process combined with a micro-emulsion method. The surface was further modified by amino groups in order to improve its affinity for DNA. Our study showed that rMBGs have good apatite-forming ability and cellular biocompatibility. In addition, rMBGs can enter cells in a time- and dose-dependent manner, and mainly localize in the cytoplasm. Agarose gel electrophoresis demonstrated that pOA–EGFP (containing the osteoactivin and the green fluorescent protein fusion gene) can be completely absorbed and protected from DNase I degradation by the aminated rMBGs. Additionally, the plasmid can be successfully expressed in cells transfected by rMBGs.

The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-КB repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.

Graphical abstract, The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called Cas12a-assisted RT-LAMP/AuNP (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/μL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.

We synthetized a series of strontium-substituted submicron bioactive glasses spheres (Sr-SBG, SiO 2 -P 2 O 5 -CaO-SrO) in which strontium was substituted for calcium on a mole percentage basis, then investigated the effect of strontium-substituted amount on morphologies, physicochemical properties, apatite-forming bioactivity of SBG and evaluated the proliferation, differentiation and mineralization of Sr-SBG with different strontium substitution amounts by co-cultured with human dental pulp cells (HDPCs). Results showed that Sr-SBG with different strontium substitution amounts were successfully fabricated and substituting different strontium amounts did not affect the morphology and particle size of SBG. All the Sr-SBG possessed good apatite-forming ability, but substituting a certain amount of strontium for calcium would weaken the apatite-forming ability of SBG. Additionally, all the Sr-SBG extractions promoted proliferation, early odontogenic differentiation and mineralization of HDPCs, however, the cell proliferation, differentiation and mineralization abilities would be reduced when the substituted amount of strontium was excess (15 mol%). This study suggests that Sr-SBG with moderate strontium substitution amounts can be used as a more promising biomaterial for dental repair.

Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy.The seizure was induced by injection of pentylenetetrazol (40mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded. The neuron loss was assessed by immunohistochemistry and TUNEL staining. The expressions of Caspase-3, p75R and TrkA were measured by western blotting.Intranasal NGF significantly reduced the seizure onset and shortened the seizure duration. Intranasal NGF alleviated the neuron loss in the epileptic brain. The number of TUNEL-positive cells in the NGF group was less than that in the control group (P0.05). Overexpression of Caspase-3 and activation of p75R induced by seizure were inhibited by intranasal NGF.Intranasal NGF protected neurons in the epileptic brain by inactivation of p75R/Caspase pathway. Intranasal NGF may be a novel therapeutic strategy for epilepsy.