Establishment of an A/T-Rich Specifically MGB Probe digital droplet PCR Assays Based on SNP for Brucella wild strains and vaccine strains.

In recent years, immunization with the S2 live-attenuated vaccine has been recognized as the most economical and effective strategy for preventing brucellosis in Inner Mongolia, China. However, there are still challenges related to vaccine toxicity and the inability to distinguish between vaccine immunization and natural infection. Therefore, in this study, we developed a digital droplet polymerase chain reaction (ddPCR) assay based on single-nucleotide polymorphism (SNP) loci to identify wild Brucella strains and S2 vaccine strains. The assay demonstrated excellent linearity (R2> 0.99) with a lower detection limit of 10 copies/µL for both wild and vaccine strains. Additionally, the ddPCR assay outperformed the real-time fluorescent quantitative PCR (qPCR) assay in screening 50 clinical samples. We have established an effective and highly sensitive ddPCR assay for Brucella, providing an efficient method for detecting and differentiating wild strains of Brucella from the S2 vaccine strain.

Core concomitant symptoms reported by the patients with breast cancer in postoperative endocrine treatment and the demand for acupuncture therapy： a network-based cross-sectional study. / ä¹³è ºç™Œæœ¯åŽå† åˆ†æ³Œæ²»ç–—æ‚£è€ æŠ¥å‘Šçš„æ ¸å¿ƒä¼´éšç—‡çŠ¶åŠå¯¹é’ˆç¸æ²»ç–—çš„éœ€æ±‚ï¼šä¸€é¡¹åŸºäºŽç½‘ç»œçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the most common concomitant symptoms and the urgent demand of solution in the breast cancer patients undergoing postoperative endocrine treatment, as well as the acceptance and expectation of acupuncture in the patients so as to provide the scientific data for promoting the application of acupuncture in the breast cancer patients. METHODS: Breast cancer patients treated in Tianjin Medical University Cancer Institute and Hospital from January 2022 to March 2023 were randomly selected as the subjects. Using "questionnaire star" website, the questionnaire was conducted to investigate the relevant concomitant symptoms of the patients in postoperative endocrine treatment and the questions related to acupuncture treatment. RESULTS: In this study, 229 questionnaires were distributed and 211 valid ones were collected, with the response rate of 92.1%. Among these patients, the first three common symptoms were sleep disorders (157 cases, 74.4%), hot flashes (138 cases, 65.4%) and joint / muscle pain (118 cases, 55.9%)；the top three symptoms to be solved the most urgently were sleep disorders (131 cases, 62.1%), joint / muscle pain (62 cases, 29.4%) and hot flashes (45 cases, 21.3%). 79.1% of the patients (167 cases) were willing to receive acupuncture treatment because of the high expectations on its potential effect (93%). 20.9% of them (44 cases) refused acupuncture because they were worried not to be treated by the experienced physicians of TCM (52%) or afraid of needling feelings (48%). The average expectation value of acupuncture treatment was 4.02 points (5 points for the total score) among patients willing to receive acupuncture treatment. The main purposes of receiring acupuncture for the patients undergoing endocrine treatment were to strengthen the immune function (92%), reduce the adverse reactions (83%), and improve the physical condition (75%), et al. CONCLUSIONS: Sleep disorder is one of the most concerned symptoms in endocrine treatment for the patients after breast cancer surgery. The patients highly expect for acupuncture treatment even though some patients dislike the needling sensation. How to provide the acceptable and high-quality acupuncture services for cancer patients will be one of the major directions of acupuncture research in the future.

The use of Panax notoginseng saponins injections after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.

Background: As a bioactive metabolite preparation widely used in acute ischemic stroke (AIS), the efficacy and safety of Panax notoginseng saponins injections (PNSI) in patients with AIS after intravenous thrombolysis remain to be evaluated. Methods: This study included randomized controlled trials published before 26 April 2024 in 8 databases. AIS patients who received intravenous thrombolysis were included. The control group receiving conventional treatment and the treatment group receiving additional PNSI. Primary outcomes were selected as mortality, disability, and adverse events. Secondary outcomes were selected as all-cause mortality, improvement of neurological deficit, quality of life, and cerebral injury indicators. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Risk ratio (RR) and mean differences (MD) were calculated for binary variables and continuous variables, respectively, based on a 95% confidence interval (CI). Results: A total of 20 trials involving 1,856 participants were included. None of them reported mortality or disability. There was no significant difference in the adverse events [RR: 1.04; 95% CI: 0.60 to 1.81] and hemorrhagic transformation [RR: 0.99; 95% CI: 0.36 to 2.70] between the two groups. Compared to the control group, the treatment group had a better effect in neurological improvement assessed by National Institutes of Health Stroke Scale [MD: -2.91; 95% CI: -4.76 to -1.06], a better effect in activities of daily living changes in Barthel Index [MD: 9.37; 95% CI: 1.86 to 16.88], and a lower serum neuron-specific enolase level [MD: -2.08; 95% CI: -2.67 to -1.49]. Conclusion: For AIS patients undergoing intravenous thrombolysis, the use of PNSI improved neurological deficits and enhanced activity of daily living in the short term without increasing the occurrence rate of adverse events. However, due to the moderate to very low certainty of evidence, it is advisable to conduct high-quality clinical trials to validate the findings of this study. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=466851, Identifier CRD42023466851.

Insights into the Transmission, Host Range, Genomics, Vaccination, and Current Epidemiology of the Monkeypox Virus.

This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the present vaccination status and strategies to curb the spread of monkeypox. Monkeypox, caused by the Orthopoxvirus known as MPXV, is a zoonotic ailment. MPXV can be transmitted from person to person through respiratory droplets during prolonged face-to-face interactions. While many cases of monkeypox are self-limiting, vulnerable groups such as young children, pregnant women, and immunocompromised individuals may experience severe manifestations. Diagnosis predominantly relies on clinical presentations, complemented by laboratory techniques like RT-PCR. Although treatment is often not required, severe cases necessitate antiviral medications like tecovirimat, cidofovir, and brincidofovir. Vaccination, particularly using the smallpox vaccine, has proven instrumental in outbreak control, exhibiting an efficacy of at least 85% against mpox as evidenced by data from Africa. Mitigating transmission requires measures like wearing surgical masks, adequately covering skin lesions, and avoiding handling wild animals.

Disruption of bacterial biofilms by a green synthesized artemisinin nano-copper nanomaterial.

Bacterial biofilms are associated with antibiotic resistance and account for ∼80% of all bacterial infections. In this study, we explored novel nanomaterials for combating bacteria and their biofilms. Artemisinin nano-copper (ANC) was synthesized using a green synthesis strategy, and its shape, size, structure, elemental composition, chemical valence, zeta potential, and conductivity were characterized using transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, zeta potential, and dynamic light scattering. The results showed that ANC was successfully synthesized utilizing a liquid phase chemical reduction method using chitosan as a modified protectant and l-ascorbic acid as a green reducing agent. The stability of ANC was evaluated using dynamic light scattering. The results showed that the particle size of ANC at different concentrations was comparable to that of the original solution after 7 days of storage, and there was no significant change in the polydispersity index (P > 0.05). The antibacterial effects of ANC on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were determined by disc diffusion and broth dilution methods. The results demonstrated that ANC inhibited and killed E. coli and S. aureus. The effect of ANC on bacterial biofilms was investigated using crystal violet staining, scanning electron microscopy, laser confocal microscopy, and quantitative polymerase chain reaction. The results showed that ANC treatment was able to destroy bacterial biofilms and downregulate biofilm- and virulence-related genes in E. coli (HlyA, gyrA, and F17) and S. aureus (cna, PVL, ClfA, and femB). Green-synthesized ANC possesses excellent antibiofilm properties and is expected to exhibit antibacterial and antibiofilm properties.

Noteworthy impacts of COVID-19 pandemic on cancer screening: A systematic review.

The sudden onset of the coronavirus disease 2019 (COVID-19) in January 2020 has affected essential global health services. Cancer-screening services that can reduce cancer mortality are strongly affected. However, the specific role of COVID-19 in cancer screening is not fully understood. This study aimed to assess the efficiency of global cancer screening programs before and during the COVID-19 pandemic and to promote potential cancer-screening strategies for the next pandemic. Electronic searches in PubMed, Embase, and Web of Science, and manual searches were performed between January 1, 2020 and March 1, 2023. Cohort studies that reported the number of participants who underwent cancer screening before and during the COVID-19 pandemic were included. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Differences in cancer-screening rates were estimated using the incidence rate ratio (IRR). Fifty-five cohort studies were included in this meta-analysis. The screening rates of colorectal cancer using invasive screening methods (Pooled IRR = 0.52, 95% CI: 0.42 to 0.65, p < 0.01), cervical cancer (Pooled IRR = 0.56, 95% CI: 0.47 to 0.67, p < 0.01), breast cancer (Pooled IRR = 0.57, 95% CI: 0.49 to 0.66, p < 0.01) and prostate cancer (Pooled IRR = 0.71, 95% CI: 0.56 to 0.90, p < 0.01) during the COVID-19 pandemic were significantly lower than those before the COVID-19 pandemic. The screening rates of lung cancer (Pooled IRR = 0.77, 95% CI: 0.58 to 1.03, p = 0.08) and colorectal cancer using noninvasive screening methods (Pooled IRR = 0.74, 95% CI: 0.50 to 1.09, p = 0.13) were reduced with no statistical differences. The subgroup analyses revealed that the reduction in cancer-screening rates varied across economies. Our results suggest that the COVID-19 pandemic has had a noteworthy impact on colorectal, cervical, breast, and prostate cancer screening. Developing innovative cancer-screening technologies is important to promote the efficiency of cancer-screening services in the post-COVID-19 era and prepare for the next pandemic.

When DNA-damage responses meet innate and adaptive immunity.

When cells proliferate, stress on DNA replication or exposure to endogenous or external insults frequently results in DNA damage. DNA-Damage Response (DDR) networks are complex signaling pathways used by multicellular organisms to prevent DNA damage. Depending on the type of broken DNA, the various pathways, Base-Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), Non-Homologous End-Joining (NHEJ), Interstrand Crosslink (ICL) repair, and other direct repair pathways, can be activated separately or in combination to repair DNA damage. To preserve homeostasis, innate and adaptive immune responses are effective defenses against endogenous mutation or invasion by external pathogens. It is interesting to note that new research keeps showing how closely DDR components and the immune system are related. DDR and immunological response are linked by immune effectors such as the cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway. These effectors act as sensors of DNA damage-caused immune response. Furthermore, DDR components themselves function in immune responses to trigger the generation of inflammatory cytokines in a cascade or even trigger programmed cell death. Defective DDR components are known to disrupt genomic stability and compromise immunological responses, aggravating immune imbalance and leading to serious diseases such as cancer and autoimmune disorders. This study examines the most recent developments in the interaction between DDR elements and immunological responses. The DDR network's immune modulators' dual roles may offer new perspectives on treating infectious disorders linked to DNA damage, including cancer, and on the development of target immunotherapy.

The role of SARS-CoV-2 ORF7a in autophagy flux disruption: implications for viral infection and pathogenesis.

Although alterations in the autophagy-lysosome pathway have been observed in the SARS-CoV-2 infection and invasion process since the outbreak of the coronavirus disease in 2019, the in-depth mechanism of autophagic and lysosomal reprogramming by SARS-CoV-2 has yet to be well identified. Our recent study unveiled a pivotal role played by the open reading frame 7a (ORF7a) protein in the SARS-CoV-2 genome, particularly in the modulation of macroautophagy/autophagy flux and function during viral infection and pathogenesis. Our study elucidated the underlying molecular mechanisms by which SARS-CoV-2 ORF7a intercepts autophagic flux, evades host autophagy-lysosome degradation, and accelerates viral infection and progeny germination. Furthermore, our study highlights that ORF7a can be a therapeutic target, and glecaprevir may hold potential as a drug against SARS-CoV-2 by targeting ORF7a. The key observations revealed in this study also contribute to a growing understanding of the function of SARS-CoV-2 ORF7a and the mechanisms underlying COVID-2019 treatment.

Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.

Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is verified to be recognized by MARCH1/2/8, which is critical for their blocking activities. Besides, bovine MARCH2 and murine MARCH1 also impair EBOV GP proteolytic processing. Altogether, our findings confirm that MARCH1/2 proteins of different mammalian origins showed a relatively conserved feature in blocking EBOV GP cleavage, which could provide clues for subsequent MARCHs antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.

The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review.

The quick progress of epigenetic study has kindled new hope for treating many cancers. When it comes to RNA epigenetics, the ac4C acetylation modification is showing promise, whereas N-acetyltransferase 10 plays a wide range of biological functions, has a significant impact on cellular life events, and is frequently highly expressed in many malignant tumors. N-acetyltransferase 10 is an acetyltransferase with important biological involvement in cellular processes and lifespan. Because it is highly expressed in many malignant tumors, it is considered a pro-carcinogenic gene. The review aims to introduce NAT10, summarize the effects of ac4C acetylation on tumor growth from multiple angles, and discuss the possible therapeutic targeting of NAT10 and the future directions of ac4C acetylation investigations.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.

SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis.

The coronavirus disease 2019 (COVID-19) continues to pose a major threat to public health worldwide. Although many studies have clarified the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection process, the underlying mechanisms of viral invasion and immune evasion were still unclear. This study focused on SARS-CoV-2 ORF7a (open reading frame-7a), one of the essential open reading frames (ORFs) in infection and pathogenesis. First, by analyzing its physical and chemical characteristics, SARS-CoV-2 ORF7a is an unstable hydrophobic transmembrane protein. Then, the ORF7a transmembrane domain three-dimensional crystal structure model was predicted and verified. SARS-CoV-2 ORF7a localized in the endoplasmic reticulum and participated in the autophagy-lysosome pathway via interacting with p62. In addition, we elucidated the underlying molecular mechanisms by which ORF7a intercepted autophagic flux, promoted double membrane vesicle formation, and evaded host autophagy-lysosome degradation and antiviral innate immunity. This study demonstrated that ORF7a could be a therapeutic target, and Glecaprevir may be a potential drug against SARS-CoV-2 by targeting ORF7a. A comprehensive understanding of ORF7a's functions may contribute to developing novel therapies and clinical drugs against COVID-19.

Baduanjin exercise for chronic non-specific low back pain: protocol for a series of N-of-1 trials.

INTRODUCTION: Chronic non-specific low back pain (CNLBP) is one of the most common health problems worldwide. According to the clinical guideline released by the American College of Physicians, exercise has been recommended for the treatment of chronic LBP. In recent years, traditional Chinese medicine (TCM) is becoming increasingly popular for the management of chronic LBP. Baduanjin exercise is one of the exercise therapies in TCM. N-of-1 trial is a randomised cross-over self-controlled trial suitable for patients with this chronic disease. A series of similar N-of-1 trials can be pooled to estimate the overall and individual therapeutic effects synchronously by hierarchical Bayesian analysis. And N-of-1 trials are considered as a good tool for evaluating the therapeutic effect of TCM. Therefore, this study aims to conduct a series of N-of-1 trials with hierarchical Bayesian analysis for assessing whether Baduanjin exercise is effective and safe for CNLBP. METHODS AND ANALYSIS: This study conducts a series of N-of-1 trials on Baduanjin exercise for the management of CNLBP. Fifty participants will receive 1-3 treatment cycles. They will be randomised into a Baduanjin exercise or waiting list group for a week during the two periods of each treatment cycle. The primary outcome is the 10-point Visual Analogue Scale. The secondary outcomes include the Oswestry Disability Index, the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Short Form Health Survey 12. Statistical analysis will be conducted with WinBUGS V.1.4.3 software. Overall and individual therapeutic effects will be estimated synchronously by hierarchical Bayesian analysis. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics Committee of Tianjin University of TCM (reference number TJUTCM-EC20220005). Our findings will be published in a peer-reviewed journal or international conference. TRIAL REGISTRATION NUMBER: ChiCTR2200063307.

Risk transboundary transmission areas and driving factors of brucellosis along the borders between China and Mongolia.

OBJECTIVE: Brucellosis is a common and neglected zoonotic infectious disease worldwide caused by Brucella. However, transboundary transmissions among countries, particularly those with high incidences, are seldom investigated. In the present study, by taking China and Mongolia as examples, we aim to identify transboundary transmission risk and driving factors of brucellosis along borders. METHODS: 167 brucellosis outbreak locations along the border between China and Mongolia were collected. Wildlife distribution and cross-border activities were mapped. Maximum entropy approach modeling was conducted to predict the potential risk of prevalence of brucellosis with meteorological factors, geographical environment, economic development, living habits et al. The accuracy of the models was assessed by the area under the receiver operating characteristic (ROC) curve (AUC), Kappa test, and correctly classified instances (CCI). RESULTS: The spatial model performed excellent predictive performance with the predictor variables of soils, pastures, goat density, mean precipitation of the wettest month, temperature seasonality, and population density, which with the contribution and permutation important in 27.2 %, 31.9; 23.3 %, 6.8; 18.0 %, 17.2; 11.2 %, 18.1; 10. 3 %, 15.2; 10.0 %, 10.8. The calculated AUC, SD, Kappa, and CCI are 0.870, 0.001, 0.882, and 0.883, respectively. The distribution map of brucellosis showed high-risk areas along the borders. CONCLUSIONS: Our study identified high-risk areas and the driving effect of brucellosis along the borders between China and Mongolia. Moreover, there is the possibility of cross-border wildlife activities in high-risk areas, which increases the risk of cross-border brucellosis transmission. The funding provides clues for cooperative prevention and control of brucellosis by reducing transboundary transmission.

Comparative application of droplet-based digital and quantitative real-time PCR for human brucellosis detection.

We evaluated the diagnostic value of droplet-based digital PCR (dd-PCR) by comparing it with the quantitative real-time PCR (RT-qPCR) for detecting Brucella DNA, 487 whole blood and serum samples collected from suspected human brucellosis, respectively. Sensitivity and specificity were 88.14% and 100% for RT-qPCR; 97.12% and 100% for dd-PCR. The positive rate detected by RT-qPCR and dd-PCR based on the nucleic acid extracted by simultaneous extraction method in serum and blood cells were 56.49% and 62.22%, respectively, which is higher than the commercial kit in 47.74% and 52.77%. Additionally, 32 false-negative samples of chronic patients analyzed by serological tests were positive in the detection from the blood cell nucleic acid. dd-PCR could be considered a valuable tool for detecting Brucella DNA, particularly in false-negative test results. The simultaneous extraction method is complementary to dd-PCR in diagnosing human brucellosis cases at different disease stages, especially in chronic and relapsed stages.

CRISPR-Cas12a test strip (CRISPR/CAST) package: In-situ detection of Brucella from infected livestock.

BACKGROUND: Brucellosis is a common zoonotic disease caused by Brucella, which causes enormous economic losses and public burden to epidemic areas. Early and precise diagnosis and timely culling of infected animals are crucial to prevent the infection and spread of Brucella. In recent years, RNA-guided CRISPR/Cas12a(Clustered Regularly Interspaced Short Palindromic Repeats and its associated protein 12a) nucleases have shown great promise in nucleic acid detection. This research aims to develop a CRISPR/CAST (CRISPR/Cas12a Test strip) package that can rapidly detect Brucella nucleic acid during on-site screening, especially on remote family pastures. The CRISPR/Cas12a system combined with recombinase polymerase amplification (RPA), and lateral flow read-out. RESULTS: We selected the conserved gene bp26, which commonly used in Brucella infection detection and compared on Genbank with other Brucella species. The genomes of Brucella abortus 2308, Brucella suis S2, Brucella melitansis 16 M, and Brucella suis 1330, et al. were aligned, and the sequences were found to be consistent. Therefore, the experiments were only performed on B. melitensis. With the CRISPR/CAST package, the assay of Brucella nucleic acid can be completed within 30 min under isothermal temperature conditions, with a sensitivity of 10 copies/µl. Additionally, no antigen cross-reaction was observed against Yersinia enterocolitica O:9, Escherichia coli O157, Salmonella enterica serovar Urbana O:30, and Francisella tularensis. The serum samples of 398 sheep and 100 cattle were tested by the CRISPR/CAST package, of which 31 sheep and 8 cattle were Brucella DNA positive. The detection rate was consistent with the qPCR results and higher than that of the Rose Bengal Test (RBT, 19 sheep and 5 cattle were serum positive). CONCLUSIONS: The CRISPR/CAST package can accurately detect Brucella DNA in infected livestock within 30 min and exhibits several advantages, including simplicity, speed, high sensitivity, and strong specificity with no window period. In addition, no expensive equipment, standard laboratory, or professional operators are needed for the package. It is an effective tool for screening in the field and obtaining early, rapid diagnoses of Brucella infection. The package is an efficient tool for preventing and controlling epidemics.

The binding profile of SARS-CoV-2 with human leukocyte antigen polymorphisms reveals critical alleles involved in immune evasion.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), astonished the world and led to millions of deaths. Due to viral new mutations and immune evasion, SARS-CoV-2 ranked first in transmission and influence. The binding affinity of human leukocyte antigen (HLA) polymorphisms to SARS-CoV-2 might be related to immune escape, but the mechanisms remained unclear. In this study, we obtained the binding affinity of SARS-CoV-2 strains with different HLA proteins and identified 31 risk alleles. Subsequent structural predictions identified 10 active binding sites in these HLA proteins that may promote immune evasion. Particularly, we also found that the weak binding ability with HLA class I polymorphisms could contribute to the immune evasion of Omicron. These findings suggest important implications for preventing the immune evasion of SARS-CoV-2 and providing new insights for the vaccine design.

Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b+ NCR1+ NKs of tumor microenvironment.

This study was to study the role of methionine enkephalin (menk) in cell invasion and migration as well as NK cells activation of tumor microenvironment in cervical cancer. The results showed that menk inhibited cervical cancer migration and invasion. In addition, we found menk affected epithelial to mesenchymal transition (EMT) related indicators, with increasing E-cadherin level, decreasing N-cadherin and vimentin level. Through in vivo mouse model, we found that menk IFNγ and NKP46 expression was upregulated in tumor tissues by menk compared with controls, while LAG3 expression was inhibited by menk, besides, there was an upregulation of CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer. Therefore, we concluded that menk inhibited cancer migration and invasion via affecting EMT related indicators and activated CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer, laying a theoretical foundation for the further clinical treatment of menk.