The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

In order to detect the environmental data of isolated cabin under various environmental conditions,a negative pressure cabin environment detector for aviation was developed,which was composed of a shell,a differential pressure transmitter,a pressure sensor,a carbon dioxide concentration sensor,an oxygen concentration sensor,a temperature and humidity sensor,a data processing module,a liquid crystal display(LCD)screen and USB data interface.It could environmental data such as carbon dioxide concentration,oxygen concentration,temperature,humidity,pressure difference between cabin and outside the cabin and air pressure outside the cabin in real time,the data processing module collected and processed the data,the data and data change curves was displayed in real time by the LCD screen,and the detection data was extracted through the USB data interface.When used in aviation environment,the detector could work continuously without fault for no less than 300 hours,and the average fault repair time was about 30 minutes,with good performance and high detection accuracy,which can provide convenience for the environmental data detection of negative pressure cabins,and is worthy of popularization.

Bioluminescence is a widespread phenomenon in nature, and luminescent organisms can be found both on land and in the ocean. Among them, luciferase based bioluminescence systems have been widely studied, inspiring the exploration of genetic and epigenetic aspects and the development of a series of related assays for in vivo and in vitro studies. This paper summarizes the recent developments of luciferase based bioluminescence assays in terms of bioluminescence systems, types of luciferases, and the development and application of luciferase bioluminescence assays.

Objective:To investigate the effects of cognitive types on dual-task paradigm gait performance in patients with stroke.Method:Using a cross-sectional study design, patients with stroke were trained with single task walking and dual-task walking with four different cognitive tasks (spontaneous speech [SS], serial counting backward [SCB], word list generation (WLG), and auditory Stroop [AS]). A three-dimensional gait and motion analysis system were used to record and analyze gait data, and calculate dual-task effect (DTE) for different cognitive tasks, and compare the differences in spatiotemporal parameters and DTE of gait analysis under different states.Results:A total of 35 patients with stroke (aged 61.0±2.5 years) were included, among which 27 were males (77.1%). There were 25 patients with ischemic stroke (71.4%) and 10 patients with hemorrhagic stroke (28.6%). Compared with single task walking, patients had decreased gait speed, shorter step length on the affected side, and a larger support phase ratio of the unaffected to the affected side during SCB dual task and SS dual task (all P<0.05), and the difference was more obvious during SCB dual task ( P<0.05). Compared with single task walking, patients had a reduced swing phase ratio of the unaffected to the affected side during SCB dual task (all P<0.05). The DTEs of gait speed, step length of the affected side, and the support phase ratio of the unaffected to the affected side during SCB dual task and SS dual task were significantly greater than those during WLG dual task and AS dual task ( P<0.05). The DTEs of gait speed and step length of the affected side during SCB dual task were significantly greater than that during SS dual task (all P<0.05). The DTE of the swing phase ratio of the unaffected to the affected side during SCB dual task was significantly greater than that during other types of cognitive tasks (all P<0.05). Conclusion:Different cognitive tasks had different effects on gait performance during dual-task walking in patients with stroke, and the degree of dual-task interference was associated with specific task types.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Gene editing tools with nucleases as the main component have now implemented programmable targeted mutagenesis or insertion or deletion of mammalian genomes.From zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas system to safer and more accurate Cas9 fusion protein gene editing tools and other nuclease gene editing tools, this paper systematically describes the development and evolution of gene editing, with detailed introduction to the development and optimization of next-generation gene editing tools, and a prospect of the clinical application of and challenges for gene editing tools.

Objective:To investigate the pathogenesis and prognosis of transformation of primary myelofibrosis (PMF) to B-cell acute lymphoblastic leukemia (B-ALL).Methods:The diagnosis and treatment process of a patient transferred from PMF to B-ALL in Affiliated Tumor Hospital of Zhengzhou University in November 2018 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 64-year-old female, she was initially diagnosed with PMF, and then she developed B-ALL 17 months later after receiving treatment of prednisone, danazole, levamisole, aspirin, thalidomide and jaktinib. After induction therapy, the patient received 8 months of continuous remission, and then the reexamination showed relapse. There was no remission after reinduction therapy. The patient gave up treatment and was discharged 2 months later. JAK2 V617F gene mutation was positive before and after leukemia transformation.Conclusions:The patients with transformation of PMF to B-ALL have poor clinical prognosis and short survival time. The possible mechanism of its transformation may be related to additional genetic events or certain high-risk genes. However, the specific mechanism is still unclear, and further investigation of the etiology is needed to seek targeted treatment.

Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.

Objective:To explore the relationship between the expression of neuropilin-1 (NRP-1) on Treg cells and its ligands semaphorins-3A (Sema3A) , transforming growth factor-β 1 (TGF-β 1) as well as the balance of type 1 helper T cells (Th 1) and type 2 helper T cells (Th 2) cells. Methods:This study enrolled 62 patients with immune thrombocytopenia (ITP; 33 and 29 newly diagnosed and chronic ITP, respectively) from March 2014 to May 2015. Consequently, 30 healthy people in the same period were selected as the normal control group. The expression of NRP-1 in Treg cells was detected via flow cytometry. The Sema3A, TGF-β 1, IFN-γ, and IL-4 levels in plasma were detected by enzyme-linked immunosorbent assay. The real-time polymerase chain reaction technique was used to detect the mRNA expression levels of NRP-1, Sema3A, and TGF-β 1. The one-way analysis of variance and independent sample t-test was used for comparison between three and two groups, respectively. Correlations among the mRNA expression levels of NRP-1, Sema3A, and TGF-β 1 were assessed via Spearman correlation coefficients. Results:Treg cells in the newly diagnosed ITP group significantly increased compared with those in the chronic ITP and normal control groups. The expression of NRP-1 decreased[ (0.15 ± 0.03) %, (0.33 ± 0.15) %, and (0.46 ± 0.06) %; P<0.01], the plasma Sema3A level increased[ (8.10 ± 1.32) μg/L, (7.41±1.30) μg/L, and (2.88±0.82) μg/L; P<0.01], and the plasma TGF-β 1 level decreased[ (16.50±3.36) μg/L, (35.17±10.26) μg/L, and (41.00±10.02) μg/L; P<0.01]. Moreover, the level of plasma IFN-γ increased[ (17.21+2.80) ng/L, (10.23+1.59) ng/L, and (8.18+3.27) ng/L; P<0.01], and the ratios of Th 1/Th 2 (IFN-γ/IL-4) increased (1.29±0.30, 0.72±0.16, and 0.61±0.27; P<0.01) . The mRNA expressions of NRP-1 and Sema3A in the newly diagnosed ITP and chronic ITP groups were lower than that in the normal control group ( P<0.01) . Consequently, the NRP-1 mRNA expression was positively correlated with Sema3A and TGF-β 1 mRNA expression in the newly diagnosed ITP group. Conclusion:NRP-1 played an essential role in the pathogenesis of ITP.

The corona virus disease 2019 (COVID-19) caused by the new coronavirus (SARS-CoV-2) has spread rapidly around the world,posing a serious threat to the public"s health. As of September 30,2020,the number of infected people in the world has reached 33 million,causing more than 1 million deaths. Normalized nucleic acid detection methods based on lab have long turnaround time and high cost. Therefore,there is an urgent need to develop a convenient method to detect SARS-CoV-2,so as to achieve rapid testing and timely control of the epidemic when resources are limited.This review summarizes the point-of-care testing (POCT) methods developed for SARS-CoV-2 in terms of extraction,amplification and detection,and briefly introduces commercial POCT instruments that integrate these three steps,in order to provide references for emergency response and rapid deployment of COVID-19 and other emerging infectious diseases.