Search

The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection persist months and years after recovery. We conducted an online survey to assess the health condition of convalescents approximately 5 months following the primary infection of SARS-CoV-2. The study recruited 5,510 individuals who were primary infected, 626 participants who had experienced reinfection, and 521 participants who were without infective history. The most common disorders after the primary infection group were fatigue (15.18 %), memory issue (13.13 %), post-exertional malaise (PEM, 11.68 %), and brain fog (11.29 %) at the time of survey. In addition, SARS-CoV-2 infection had an impact on the reproductive systems. In stepwise logistic regression analysis, smoking currently, with background diseases, and outpatient visits in the acute phase could be associated with moderate / severe disorders. Further analysis of different background diseases showed that allergic rhinitis, hyperlipidemia, cardiovascular disease, autoimmune diseases, neurological diseases, and asthma likely increased the risk of moderate/severe disorders. The probability of developing disorders of individuals with SARS-CoV-2 reinfection was higher before the secondary infection than uninfected people. Fatigue, PEM, muscle pain/spasms, chills, joint pain, excessive sweating at rest, headache / dizziness, sore throat or foreign body sensation in the throat, cough, expectoration, dry / painful / watery eyes, loss of appetite and constipation were associated with an increased risk of reinfection. It was essential to undertake further research with enhanced randomization in a larger sample in the community, and to strengthen the validation of the research conclusions. The findings of this study contribute to a deeper understanding of the health recovery process among coronavirus disease 2019 (COVID-19) convalescents. Moreover, the findings help identify characteristic health risk factors associated with convalescents and highlight the risk of moderate / severe disorders and reinfection. Furthermore, the findings also provide valuable guidance and reference for SARS-CoV-2 rehabilitation strategies and the prevention of reinfection, offering insights for scientific recommendations.

SMAD4 deficiency in colorectal cancer (CRC) is highly correlated with liver metastasis and high mortality, yet there are few effective precision therapies available. Here, we show that CCR1+-granulocytic myeloid-derived suppressor cells (G-MDSCs) are highly infiltrated in SMAD4-deficient CRC via CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models, respectively. The excessive TGF-β, secreted by tumor-infiltrated CCR1+-G-MDSCs, suppresses the immune response of cytotoxic T lymphocytes (CTLs), thus facilitating metastasis. Hereby, we develop engineered nanovesicles displaying CCR1 and TGFBR2 molecules (C/T-NVs) to chemotactically target the tumor driven by CCL9/CCR1 axis and trap TGF-β through TGF-β-TGFBR2 specific binding. Chemotactic C/T-NVs counteract CCR1+-G-MDSC infiltration through competitive responding CCL9/CCR1 axis. C/T-NVs-induced intratumoral TGF-β exhaustion alleviates the TGF-β-suppressed immune response of CTLs. Collectively, C/T-NVs attenuate liver metastasis of SMAD4-deficient CRC. In further exploration, high expression of programmed cell death ligand-1 (PD-L1) is observed in clinical specimens of SMAD4-deficient CRC. Combining C/T-NVs with anti-PD-L1 antibody (aPD-L1) induces tertiary lymphoid structure formation with sustained activation of CTLs, CXCL13+-CD4+ T, CXCR5+-CD20+ B cells, and enhanced secretion of cytotoxic cytokine interleukin-21 and IFN-γ around tumors, thus eradicating metastatic foci. Our strategy elicits pleiotropic antimetastatic immunity, paving the way for nanovesicle-mediated precision immunotherapy in SMAD4-deficient CRC.

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a “checkpoint” to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK “checkpoint inhibitor,” for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

Polymer matrix syntactic foams made of hollow glass microspheres (HGMs) and epoxy resin are widely used in underwater vehicles providing buoyancy due to their advantages of low density and high mechanical strength. When HGMs is strong enough, surface modification of HGMs is an effective method to improve the compressive strength of syntactic foams. However, the effects of different surface modifiers on the physical properties of HGMs and the compressive strength of syntactic foams have rarely been systematically studied. It is of great significance to enhance the interfacial strength of syntactic foams. Herein, the T40 HGMs was treated by different modifiers (HCl, NaOH, Li2SiO3, Me3SiONa, KH550, KH560, KH570, and Volan), physical properties of modified HGMs were studied, including true density, angle of repose, isostatic compressive strength, specific surface area, and contact angle. Furthermore, the effects of modified HGMs on the compressive strength of syntactic foams were also studied. The results showed that the compressive strength depend largely on the interface bonding between HGMs and resin matrix. This work can provide some references for mechanical property reinforcement of syntactic foams with high filling ratio and plenty of interface zones.

ABSTRACT: Follicle selection in chicken refers to the process of selecting a follicle to enter hierarchy from a cohort of small yellow follicles (SY) with a diameter of 6 to 8 mm. The follicle being selected will develop rapidly and ovulate. Follicle selection is a key stage affecting chicken egg-laying performance. Our previous study showed that the phosphorylation level of lysine (K)-specific demethylase 1A (LSD1) at serine 54 (LSD1Ser54p) was significantly increased in F6 follicles compared to prehierarchal SY follicles, but its function was unclear. Here, the mechanism of this modification, the effect of LSD1Ser54p dephosphorylation on gene expression profile of chicken hierarchal granulosa cells and the function of fibroblast growth factor 9 (FGF9) that is regulated by LSD1Ser54p were further investigated. The modification of LSD1Ser54p was predicted to be mediated by cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 (GSK3). Treatment of chicken hierarchal granulosa cells with CDK5 inhibitor significantly decreased LSD1Ser54p level (P < 0.05) and LSD1Ser54p interacted with CDK5, suggesting that, in the granulosa cells of chicken hierarchal follicles, LSD1Ser54p modification was carried out by CDK5. When the LSD1Ser54p level decreased in the granulosa cells of chicken hierarchal follicles, both the mRNA expression of FGF9 and α-actinin 2 (ACTN2) and the H3K4me2 level in their promoter regions significantly increased (P < 0.05), indicating that this phosphorylation modification enhanced the demethylation activity of LSD1. Moreover, in chicken hierarchal granulosa cells, overexpression of chicken FGF9 stimulated their proliferation and increased the mRNA expression of hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (Hsd3b) and steroidogenic acute regulatory protein (StAR). This study collectively revealed that phosphorylation of LSD1 at serine 54 by CDK5 enhanced its demethylation activity in chicken ovarian granulosa cells and regulated genes including FGF9 that is engaged in chicken follicle selection.

Summary: Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-β1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-β1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

Summary: Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. Methods: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan–Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. Findings: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48–1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41–0.66, p

The applications and researches of the aerogel in the field of building materials and building energy conservation had been widely concerned due to its excellent thermal insulation properties. However, it has not been paid attention that the potential application values for excellent CO2 adsorption properties of aerogel in building materials. The CO2 adsorption properties of aerogel and the research progress on utilizing SiO2 aerogel in building materials had been reviewed. And the application prospect of the technologies that exploit the CO2 adsorption properties of aerogel and the carbonization technology to prepare SiO2 aerogel-based low-carbon building materials was discussed. It was shown that the type, morphology, and pore structure of aerogel significantly affect the resulting carbon adsorption performance. Amino modification was an effective method for improving the carbon adsorption capacity of aerogel. The performance of aerogel-incorporated cement-based composites could be optimized by improving the performance of binder materials, modifying the aerogel, or preparing new aggregates by loading aerogel into porous materials with higher strength. In addition, it was feasible to prepare new green low-carbon building materials by using aerogel as thermal insulating aggregate and carbon adsorption material, industrial solid wastes rich in alkali metal ions as cementitious materials, and carbonation curing technology. The purpose of this review was to promote the application of CO2 adsorption properties of aerogel in building materials, and enhance the development of low-carbon (or zero-carbon, or negative-carbon) building materials. This is of great significance for reducing carbon emissions in the construction sector and promoting the ''carbon neutrality'' of global.

This study proposes a novel colorimetric method based on the ultraviolet/visible spectrophotometry-colorimetric method (UV/Vis-CM) for detecting and quantifying total triterpenoids in traditional Chinese medicine. By incorporating the colourants 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid, triterpenoid compounds colour development became more sensitive, and the detection accuracy was significantly improved. 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid were incorporated in a 1:3 vol ratio at room temperature to react with the total triterpenes for 25 min, incorporated to an ice bath for 5 min, and then detected at the optimal absorption wavelength. The accuracy and reliability of this method were verified by comparison with high-performance liquid chromatography and four other colorimetric methods. Additionally, this approach has the advantages of not requiring heating during operation, high sensitivity, short usage time, low solvent usage, and low equipment costs. This study not only offers a reliable method for detecting total triterpenes in traditional Chinese medicine but also offers a rapid detection tool for on-site testing and large-scale screening, laying a foundation for the modernization of traditional Chinese medicine research, quality control, and drug development.

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Drawing upon Hofstede's cultural model, this study establishes a framework for examining the factors influencing citizens' continuous use of e-government websites. This paper, employing quantile regression, reveals that collectivism, masculinity, long-term orientation, and constraint culture exhibit varying degrees of influence on different levels of continuous use of China's e-government websites. Moreover, it has been observed that masculine culture exerts a limiting effect on the continuous use of e-government websites by the Chinese public, but this restriction diminishes beyond the 50th percentile of continuous usage level. In contrast, constraint-oriented culture consistently influences the Chinese public's continuous usage behavior of e-government websites. Both collectivist culture and long-term orientation culture demonstrate their impact on the continuous use of e-government websites among the Chinese public once a certain threshold of continuous usage level is achieved. In light of these findings, the study suggests that the government should pay attention to the cultural aspects of e-government websites and provide culturally adaptive e-government services to better meet the public's needs and expectations.

Background: Central compartment atopic disease (CCAD) is a subtype of chronic rhinosinusitis (CRS). Research focusing on the endoscopic sinus surgery (ESS) outcomes of CCAD is limited. This study aimed to evaluate the outcomes of ESS in CCAD and compared to 2 following subtypes: chronic rhinosinusitis with nasal polyps (CRSwNP) and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Methods: This case-control study enrolled patients with bilateral CRSwNP who underwent ESS and had at least 1 year of follow-up. Patients were classified into CCAD, CRSwNP/CC, and CRSwNP NOS. The demographic data, preoperative disease severity, and surgery outcomes, including CRS control status, endoscopic score, and symptom scores at 1 year postoperatively, were collected. We defined well controlled and partly controlled as appropriate disease control. Results: This study screened 259 patients and enrolled 138 patients with complete medical records and 1-year follow-up (CCAD N = 51, CRSwNP/CC N = 55, CRSwNP NOS N = 32). Among them, appropriate disease control was achieved in 84.3% of patients (43/51) in the CCAD group, 69.1% (38/55) in the CRSwNP/CC group, and 93.7% (30/32) in the CRSwNP NOS group (P = 0.029). Then we performed post-hoc analysis using appropriate disease control and uncontrolled. There was a significant difference between CRSwNP/CC and CRSwNP NOS (P = 0.007), but no significant difference compared CCAD group to CRSwNP/CC group (P = 0.065) and CRSwNP NOS group (P = 0.199). There were significant differences in endoscopic E-score among groups (P

ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

Summary: Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

Summary: Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5′-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.

Circulating miRNA expression is most commonly measured by qRT-PCR, however, the lack of a suitable endogenous control hinders people from evaluating the accurate changes in miRNA expression levels and developing the non-invasive biomarkers. In this study, we aimed to screen the specific, highly stable endogenous control in esophageal squamous cell carcinoma (ESCC) to overcome the obstacle. We selected “housekeeping” miRNAs according to the published database and initially acquired 21 miRNAs. Subsequently, we screened these miRNAs using GSE106817 and TCGA datasets according to specific inclusion criteria and evaluated the suitability of “candidate” miRNAs. Among these miRNAs, the average abundance of miR-423-5p was relatively high in serum. Notably, miR-423-5p expression in serum showed no significant difference between ESCC patients and healthy controls (n = 188, P = 0.29). Moreover, among these miRNAs, miR-423-5p was the most stable miRNA using the NormFinder algorithms. Overall, these results indicate that miR-423-5p, as a novel and optimal endogenous control, could be used to quantify circulating miRNAs in ESCC.

Mink has been identified as an animal with susceptibility to SARS-CoV-2 and also as the only animal with evidence to transmit the virus back to humans. Thus, the surveillance of viruses among high-density farmed minks has a significant meaning for the control of zoonotic emerging diseases in humans. Within anal swabs of minks that died of unknown causes in a mink farm, mink calicivirus (MCV) and mammalian orthoreovirus (MRV) were detected and simultaneously observed within MDCK cell culture from the sample of the same lethal mink. The parallel isolation was successfully performed by utilizing cell lines from different host sources with distinct viral sensitivities, i.e. Mv.1.Lu and Vero-E6 and the two viruses were independently separated. The prevalence of the virus among the minks and its genomic characteristics were investigated through deep sequencing technology. Phylogenetic analysis of the viral genome showed a close relationship of the newly isolated MCV-GCCDC8-2020 with MCV strains belonging to the genus Vesivirus, but with unique mutations derived from the major structural protein (VP1). The reovirus MRV-GCCDC9-2020 isolated from the same mink belongs to serotype 3 mammalian orthoreovirus and genome analysis showed a potential reassortment derived from reoviruses in different species. This study provides a beneficial reference on viral co-infection within disease investigation in farmed minks and raises the concern for the virus surveillance among the high-density fed animal farms.

This study aims to evaluate the biosafety awareness of laboratory staff working on pathogens detection in seven Centers for Disease Control and Prevention and support these staff's biosafety management and training. A total of 208 laboratory staff from seven provincial CDCs were chosen by stratified random sampling to undergo a self-administered questionnaire survey. The collected data were analyzed using SPSS 22.0. The overall average biosafety awareness of the CDC laboratory staff involved in pathogen detection was 82.5 points. The average biosafety awareness score was the highest in health monitoring (92.63 points) and the lowest in risk assessment and control (41.6 points). Among the seven provincial CDCs, the Guizhou Provincial Center for Disease Control and Prevention laboratory staff showed the lowest average biosafety awareness score (74.3 points). The team who worked for 5–14 years were more likely to score above the passing score (≥88 points; corrected OR 0.400, 95%CI: 0.168–0.951) than the staff with less than five years of work experience. In addition, the mid-level and junior-level staff, as well as the lower position ones were more likely to score below the passing score (

Coronavirus disease 2019 (COVID-19) pandemic has spread in 220 countries/regions to wreak havoc to human beings around the world. At present, the second wave of COVID-19 has begun in many European countries. The complete control of COVID-19 is very urgent. Although China quickly brought the virus under control, there have been eight sporadic outbreaks in China since then. Both in Xinfadi of Beijing and Dalian outbreak of COVID-19, environmental swab samples related to imported cold chain food were tested nucleic acid positive for SARS-CoV-2. In this outbreak in Qingdao, we directly isolated SARS-CoV-2 from the cod outer package's surface swab samples. This is the first time worldwide, SARS-CoV-2 were isolated from the imported frozen cod outer package's surface, which showed that imported frozen food industry could import SARS-CoV-2 virus.

Senile osteoporosis (SOP) is widely regarded as one of the typical aging-related diseases due to a decrease in bone mass and the destruction in microarchitecture. The inhibition of mitophagy can promote bone marrow mesenchymal stem cells (BMSCs) senescence, and increasing studies have shown that interventions targeting BMSCs senescence can ameliorate osteoporosis, exhibiting their potential for use as therapeutic strategies. Sirtuin-3 (Sirt3) is an essential mitochondria metabolic regulatory enzyme that plays an important role in mitochondrial homeostasis, but its role in bone homeostasis remains largely unknown. This study seeks to investigate whether advanced glycation end products (AGEs) accumulation aggravated BMSCs senescence and SOP, and explored the mechanisms underlying these effects. We observed that AGEs significantly aggravated BMSCs senescence, as well as promoted mitochondrial dysfunction and inhibited mitophagy in a concentration-dependent manner. In addition, this effect could be further strengthened by Sirt3 silencing. Importantly, we identified that the reduction of Sirt3 expression and the mitophagy were vital mechanisms in AGEs-induced BMSCs senescence. Furthermore, overexpression of Sirt3 by intravenously injection with recombinant adeno-associated virus 9 carrying Sirt3 plasmids (rAAV-Sirt3) significantly alleviated BMSCs senescence and the formation of SOP in SAMP6. In conclusion, our data demonstrated that Sirt3 protects against AGEs-induced BMSCs senescence and SOP. Targeting Sirt3 to improve mitophagy may represent a potential therapeutic strategy for attenuating AGEs-associated SOP.

Farrerol, an important bioactive constituent of rhododendron, exhibits broad activities such as anti-oxidative and anti-inflammatory effects. Recent studies showed that farrerol possesses neuroprotective activity, however, the mechanism has not been reported. The aim of the present study was to investigate the protective effect of farrerol on β-amyloid (Aβ)-induced mouse microglial BV-2 cells and the underlying mechanism. BV-2 cells were pretreated with farrerol for 1 h and then subjected to Aβ. MTT assay was performed to measure the mitochondrial metabolic activity in BV-2 cells. The production of reactive oxygen species (ROS) and malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected to reflect oxidative stress status. The secretion and mRNA levels of interleukin (IL)-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA and qRT-PCR. The expressions of NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD (P) H: quinone oxidoreductase 1 (NQO1), and Kelch-like ECH-associated protein 1 (Keap1) were measured by western blot. Our results showed that farrerol improved mitochondrial metabolic activity in Aβ-induced BV-2 cells. Aβ induced the production of ROS and MDA, and inhibited the SOD activity and the expression of SOD1 and SOD2 mRNA, while the effects were attenuated by farrerol. Farrerol also inhibited the induction effect of Aβ on IL-6, IL-1β, and TNF-α. In addition, farrerol enhanced the activation of Nrf2/Keap1 pathway in Aβ-induced BV-2 cells. Knockdown of Nrf2 by small interfere RNA (siRNA) targeting Nrf2 (si-Nrf2) abolished the protective effect of farrerol on Aβ-induced BV-2 cells. In conclusion, farrerol attenuated Aβ-induced oxidative stress and inflammation in BV-2 cells through enhancing the activation of Nrf2/Keap1 pathway. The findings indicated that farrerol could be considered as a therapeutic approach for the treatment of Alzheimer’s disease (AD).

As one kind of tetracycline antibiotics, oxytetracycline (OTC) residues in animal-derived foods can do serious harm to human health. Though aptasensors for the detection of OTC are widely reported, label-free electrochemical aptasensor with low cost, simple preparation and good applicability should be further explored to meet the current urgent needs. In this study, a label-free electrochemical aptasensor for OTC determination was designed. The detection was based on specific recognition by the aptamer covalently-bound on the sensing interface via diazonium coupling reaction, which was verified by computer simulation. Experiment results showed that the differential pulse voltammetry (DPV) current response of the constructed electrochemical aptasensor was linear with the logarithm of OTC concentration in the range of 1.0 × 10−9 g mL−1–1.0 × 10−4 g mL−1 (R2 = 0.9897) with the limit of detection of 2.29 × 10−10 g mL−1. The proposed aptasensor indicated good selectivity, reproducibility and stability, which could be attributed to the stable modification of aptamer on the sensing interface. The OTC in the milk sample was detected by the spiked recovery method, and good results were obtained, with the recovery rate being 87.0%-99.3%. The proposed label-free electrochemical aptasensor can provide methods for low-cost, accurate and rapid detection of antibiotic residues.

There are plenty of evidences to show that combining of chemotherapy and immunotherapy should be a very potent anti-cancer therapeutic method. In this research, we evaluated the anti-tumor activity of doxorubicin prodrug combined with erythrocyte membrane-enveloped polymer nano-vaccine against tumor in vitro and in vivo. We also analyzed the immune cell populations to investigate the effect in the tumor microenvironment and explored the inhibitory of lung metastasis. Our study showed that chemo-immunotherapy could inhibit the growth of melanoma tumor in mice. This combination approach promoted a stronger immune response by up-regulating the expression of dendritic cells and cytotoxic T cells in lymph nodes and increased the secretion of cytokines. It also restricted the immunosuppressive environment through inhibiting expression of regulatory T cells. It suggested that combination of prodrug and nano-vaccine achieved better anti-tumor effect than monotherapy, which should be widely valued and further studied to establish in a more economical and efficient way, expected to apply in the future clinical practice of cancer treatment.

The electrical conductivity of the oil film is a key property of electrowetting displays (EWD) and its evolution probably correlates to the device lifetime. In this report, we fabricate an EWD device and measure its electrical impedance spectrum. The experimental results inform on the electrical resistivity of the oil film, as revealed by comparison with numerical simulations based on an equivalent electrical circuit model. Wide distribution in the oil-film resistance has to be incorporated into the model to reproduce the measured impedance spectrum precisely, which supports previous work indicative of pixel-to-pixel variation in the oil film electrical conductivity. Our work demonstrates that one can conveniently characterize the oil film resistance and its non-uniformity using electrical impedance spectroscopy.

Objective: The present study aimed to determine whether postoperative fractionated radiotherapy, at a total dose of 35 Gy, affected expanded polytetrafluoroethylene (ePTFE) graft anastomotic stoma healing and neointima formation. Methods: The subrenal abdominal aortas of 20 mongrel dogs were replaced with an ePTFE graft. The dogs were randomly divided into either a radiotherapy or nonradiotherapy control group. Grafts were harvested at 4 or 8 weeks after surgery. Hematoxylin–eosin staining, and immunohistochemistry tests for proliferating cell nuclear antigen (PCNA) and CD34 were undertaken to analyze the anastomotic healing and neointima formation. Results: The patency rate of grafts was 100% in each group. No disunion, rupture, or aneurysm was observed in the anastomotic stoma. Eight weeks after surgery, the graft neointima and anastomotic vessel wall of the radiotherapy group were significantly thinner than those of the control group (p

Objective: We investigated the safety and efficacy of the Numen coil compared with the Axium coil in the treatment of intracranial aneurysms., Methods: Because CATCH (Coil Application Trial in China) is a prospective randomized controlled open-label noninferiority trial conducted in 10 centers across China, patients who fulfilled the inclusion and exclusion criteria were randomized 1:1 to either a test group (Numen) or a control group (Axium). The primary outcome was based on successful aneurysm occlusion at 6 months follow-up, whereas secondary outcomes included technical success, the recanalization and retreatment rates, and the rate of serious adverse events (SAEs) at 6 months and 12 months follow-up., Results: Between August 2017 and December 2019, 350 patients presenting with 350 aneurysms were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 91.18% for the test group compared with 91.85% in the control group, with a difference of -0.68% (P = 0.8419), and the overall mortality during the 30-day follow-up period was 1.19% and 1.81% in the test and control group, respectively, showing no significant difference between the 2 groups (P = 0.6837), whereas the SAE incidence during the 12-month follow-up period was 12.50% and 17.47% in the test and control groups, respectively, which was not statistically significant (P = 0.2222)., Conclusions: This trial showed that the Numen coil was noninferior to the Axium coil in terms of intracranial aneurysm embolization and can be considered as a safe and effective coil for treating patients with intracranial aneurysm in clinical practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)