Changes in body-related indices in people exposed to long-term low-dose nuclear radiation / 中国辐射卫生

@#<b>Objective</b> To investigate the effects of low-dose nuclear radiation exposure on the body by analyzing the antioxidant indices, immune indices, lymphocyte proliferation activity, and blood biochemical indices of persons exposed to long-term low-dose nuclear radiation, and to provide a basis for radiation protection and occupational health monitoring. <b>Methods</b> Eighty nuclear radiation workers were selected as the exposure group, and another 30 non-exposure personnel were selected as the control group. In both groups, blood biochemistry, serum total antioxidant capacity (T-AOC), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lymphocyte proliferation activity, proliferating cell nuclear antigen (PCNA), apoptosis factors Bcl-2 and Bax, lymphocyte transformation rate, and lymphocyte micronucleus rate were measured. <b>Results</b> Compared with the control group, T-AOC, GSH-Px, SOD, cell proliferation activity, PCNA, Bcl-2, lymphocyte transformation rate, white blood cell count, and platelet count in the exposure group were significantly decreased, while MDA and Bax were significantly increased (<i>P</i> < 0.05). The lymphocyte micronucleus rate showed no significant difference between the two groups (<i>P</i> > 0.05). <b>Conclusion</b> Long-term low-dose exposure to nuclear radiation has certain effects on related indices of workers, but does not cause significant damage. The personnel exposed to nuclear radiation should enhance the awareness of protection and strengthen scientific protection to reduce radiation damage.

Characterization of entry pathways, species-specific ACE2 residues determining entry, and antibody neutralization evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 variants

The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to lesser extent compared to ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from nine out of ten animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently.

Effect of m-health-based core stability exercise combined with self-compassion training for patients with non-specific chronic low back pain: study protocol for a randomized controlled trial.

BACKGROUND: Non-specific chronic low back pain (NCLBP) has a high incidence, which has a significant impact on a patient's body and mind and is a common condition affecting people's quality of life. Core stability exercise (CSE) is a modestly effective treatment for NCLBP; however, CSE has only been shown to be a useful treatment option in the short term. Many clinical practice guidelines recommend the use of a biopsychosocial framework to guide the management of NCLBP. Self-compassion training (SCT) is a promising psychotherapy treatment option for NCLBP; however, there is still a lack of research on CSE combined with SCT. In this study, we will seek to determine whether CSE combined with SCT is an effective treatment option for patients with NCLBP compared to CSE alone. METHODS: In this study, we will randomize 166 adults with NCLBP to a combined SCT and CSE arm or a CSE alone arm (83 participants per group). Both interventions will consist of four weekly 1.5-h group sessions of CSE supplemented by home practice. The combined group protocol also includes 2 h of SCT before CSE. Interviewers masked to the treatment assignments will assess the outcomes at 4 and 16 weeks post-randomization. The primary outcomes are back pain disability (based on the Roland-Morris Disability Questionnaire) and pain intensity (NRS; average pain, worst pain, average pain) at 16 weeks. DISCUSSION: If SCT is found to enhance the effectiveness of CSE for patients with chronic back pain, the results of the study may promote the development of mind-body therapies for chronic low back pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100042810 . Registered on 21 January 2021.

Spike Protein-independent Attenuation of SARS-CoV-2 Omicron Variant in Laboratory Mice

Despite being more transmissible, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant was found to cause milder diseases in laboratory animals, often accompanied by a lower viral load compared to previous variants of concern. This study revealed the structural basis for a robust interaction between the receptor binding domain of the Omicron spike protein and mouse ACE2. Pseudovirus bearing the Omicron spike protein efficiently utilized mouse ACE2 for entry. By comparing viral load and disease severity among laboratory mice infected by a natural Omicron variant or recombinant ancestral viruses bearing either the entire Omicron Spike or only the N501Y/Q493R mutations in its spike, we found that mutations outside the spike protein in the Omicron variant may be responsible for the observed lower viral load. Together, our results indicated that a post-entry block to the Omicron variant exists in laboratory mice.

Stable Cell Clones Harboring Self-Replicating SARS-CoV-2 RNAs for Drug Screen

The development of antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been hampered by the lack of efficient cell-based replication systems that are amenable to high-throughput screens in biosafety level 2 laboratories. Here we report that stable cell clones harboring autonomously replicating SARS-CoV-2 RNAs without S, M, E genes can be efficiently derived from the baby hamster kidney (BHK-21) cell line when a pair of mutations were introduced into the non-structural protein 1 (Nsp1) of SARS-CoV-2 to ameliorate cellular toxicity associated with virus replication. In a proof-of-concept experiment we screened a 273-compound library using replicon cells and identified three compounds as novel inhibitors of SARS-CoV-2 replication. Altogether, this work establishes a robust, cell-based system for genetic and functional analyses of SARS-CoV-2 replication and for the development of antiviral drugs. IMPORTANCESARS-CoV-2 replicon systems that have been reported up to date were unsuccessful in deriving stable cell lines harboring non-cytopathic replicons. The transient expression of viral sgmRNA or a reporter gene makes it impractical for industry-scale screening of large compound libraries using these systems. Here, for the first time, we derived stable cell clones harboring the SARS-CoV-2 replicon. These clones may now be conveniently cultured in a standard BSL-2 laboratory for high throughput screen of compound libraries. This achievement represents a ground-breaking discovery that will greatly accelerate the pace of developing treatments for COVID-19.

SARS-CoV-2 B.1.1.7 infection of Syrian hamster does not cause more severe disease and is protected by naturally acquired immunity

Epidemiological studies have revealed the emergence of multiple SARS-CoV-2 variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality (1). To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and re-infection studies in naive and convalescent Syrian hamsters (>10 months old). Hamsters infected by either a B.1.1.7 variant or a B.1 (G614) variant exhibited comparable viral loads and pathology. Convalescent hamsters that were previously infected by the original D614 variant were protected from disease following B.1.1.7 challenge with no observable clinical signs or lung pathology. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in hamsters and that natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant.

Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2

Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report our efforts to optimize and characterize an HIV-based lentiviral pseudovirus assay for screening neutralizing antibodies for SARS-CoV-2 using a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We assessed different target cells, established conditions that generate readouts over at least a two-log range, and confirmed consistent neutralization titers over a range of pseudovirus input. Using reference sera and plasma panels, we evaluated assay precision and showed that our neutralization titers correlate well with results reported in other assays. Overall, our lentiviral assay is relatively simple, scalable, and suitable for a variety of SARS-CoV-2 entry and neutralization screening assays.

The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13

Biochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting human and the presence of four residues (PRRA) at the S1/S2 site within the Spike protein may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species except mouse to infect 293T cells. Similarly, pseudoviruses bearing spike protein derived from either the bat raTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 Spike displayed distinct effects on pseudoviral entry into different cell types. Strikingly, insertion of PRRA into the raTG13 Spike selectively abrogated the usage of horseshoe bat and pangolin ACE2 but conferred usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and raTG13 spike proteins.

Antibody repertoire induced by SARS-CoV-2 spike protein immunogens

Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody response generated following vaccination by these vaccine modalities. To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). Antibody response was analyzed by ELISA, Surface Plasmon Resonance (SPR) against different Spike proteins in native conformation, and a pseudovirion neutralization assay to measure the quality and function of the antibodies elicited by the different Spike antigens. All three antigens (S1+S2 ectodomain, S1 domain, and RBD) generated strong neutralizing antibodies against SARS-CoV-2. Vaccination induced antibody repertoire was analyzed by SARS-CoV-2 spike Genome Fragment Phage Display Libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD and S2 domains. Furthermore, these analyses demonstrated that surprisingly the RBD immunogen elicited a higher antibody titer with 5-fold higher affinity antibodies to native spike antigens compared with other spike antigens. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease. One Sentence SummarySARS-CoV-2 Spike induced immune response

Effective Heat Inactivation of SARS-CoV-2

In this study, we aimed to evaluate the stability of SARS-CoV-2 under four different heat conditions (37, 42, 56, 60 {degrees}C) and report that the virus is stable at 37 {degrees}C for at least 24 hours. Heating at 56 {degrees}C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.

Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection

The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 {micro}M with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.

DEXH-Box protein DHX30 is required for optimal function of the zinc-finger antiviral protein

The zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by eliminating viral mRNAs in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In this article, we provide evidence that a DEXH box RNA helicase, DHX30, is required for optimal antiviral activity of ZAP. Pull-down and co-immunoprecipitation assays demonstrated that DHX30 and ZAP interacted with each other via their N terminal domains. Downregulation of DHX30 with shRNAs reduced ZAP's antiviral activity. These data implicate that DHX30 is a cellular factor involved in the antiviral function of ZAP.

Imaging Study on Treatment of Femoral Head Bone Defect by the Recombination Vascular Endothelial Grouth Factor (VEGF) and Bone Morphogentic Protein (bBMP) / 实用放射学杂志

C groups and coincidence with pathological changes.After treatment fourth and twelfth weeks,ALP activity,calcium content was higher in group A than group B (?