Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Chlorfenapyr is a kind of insecticide widely used in agriculture. Acute chlorfenapyr poisoning has a high mortality rate and there is no effective treatment at present. Poisoning caused by oral chlorfenapyr can lead to multiple organs damage such as heart, brain, muscle and retina. Clinical treatment should remove toxicants from the body early to improve the prognosis. In this paper, the death data of 3 patients with chlorfenapyr poisoning were reported and literature search was conducted to discuss the mechanism and treatment of chlorfenapyr poisoning.

Chlorfenapyr is a kind of insecticide widely used in agriculture. Acute chlorfenapyr poisoning has a high mortality rate and there is no effective treatment at present. Poisoning caused by oral chlorfenapyr can lead to multiple organs damage such as heart, brain, muscle and retina. Clinical treatment should remove toxicants from the body early to improve the prognosis. In this paper, the death data of 3 patients with chlorfenapyr poisoning were reported and literature search was conducted to discuss the mechanism and treatment of chlorfenapyr poisoning.

Objective:To explore the noninvasive diagnosis model and its clinical significance of acute myocardial infarction(AMI) in emergency patients with high-risk chest pain established based on chest pain database.Methods:A total of 467 patients with acute high-risk chest pain admitted to the Affiliated Hospital of Jining Medical University from January 2020 to October 2022 were selected. The patients were divided into AMI group (317 cases) and non-AMI group (150 cases) according to the occurrence of AMI. The clinical data of the two groups were compared, and Lasso regression and Logistic regression were used to analyze the related risk factors of AMI. R language was used to establish a diagnostic model, and concordance index (C-index) was used to evaluate the predictive ability of the model. Calibration curve and decision analysis curve (DCA) were used to verify and evaluate the established model externally.Results:The results of the univariate analysis showed that the proportion of patients with coronary heart disease, respiratory rate, myoglobin, creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I (cTnI), D-dimer, N-terminal pro-brain natriuretic peptide, C- reactive protein, fibrinogen, lactic acid, ST-segment elevation and abnormal ventricular wall movement in the AMI group were higher than those in the non-AMI group: 51.10 % (162/317) vs. 21.33%(32/150), (19.25 ± 2.44) times/min vs. (16.30 ± 2.15) times/min, (270.03 ± 26.59) μg/L vs. (71.44 ± 19.85) μg/L, (30.51 ± 8.22) μg/L vs. (3.22 ± 0.88) μg/L, (4.51 ± 1.38) μg/L vs. (0.04 ± 0.01) μg/L, (1.69 ± 0.51) mg/L vs. (0.32 ± 0.09) mg/L, (2 085.66 ± 561.24) ng/L vs. (964.39 ± 257.40) ng/L, (13.98 ± 4.52) mg/L vs. (7.11 ± 2.26) mg/L, (4.07 ± 0.83) g/L vs. (2.95 ± 0.78) g/L, (2.20 ± 0.49) mmol/L vs. (1.36 ± 0.35) mmol/L, 80.76%(256/317) vs. 16.67% (25/150), 95.27%(302/317) vs. 17.33% (26/150); the platelet count, activited partial thomboplastin time, prothombin time and left ventricular ejection fractionin in the AMI group were lower than those in the non-AMI group: (168.97 ± 29.66) × 10 9/L vs. (230.58 ± 30.57) × 10 9/L, (30.25 ± 4.59) s vs. (33.59 ± 4.16) s, (11.82 ± 0.74) s vs. (13.25 ± 1.02) s, (47.25 ± 5.33)% vs. (58.49 ± 5.07)%, there were statistical differences ( P<0.05). Using 17 variables with P<0.05 in univariate analysis as independent variables, Lasso regression analysis selected 7 predictive variables as coronary heart disease, myoglobin, CK-MB, cTnI, D-dimer, ST segment elevation and abnormal ventricular wall movement. Multivariate Logistic regression analysis showed that coronary heart disease, myoglobin, CK-MB, cTnI, D-dimer, ST-segment elevation and abnormal ventricular wall movement were the related risk factors of AMI ( P<0.05). Hosmer-Lemeshow goodness of fit test showed that the fit was good ( χ2 = 2.56, df = 9, P = 0.860); R language was used to draw the non-invasive diagnosis model of AMI, and the C-index was 0.945, indicated good predictive ability. Calibration curve analysis showed that the calibration degrees of the model establishment population and the external verification population were 0.918 and 0.924, respectively, indicated that the model was in good agreement with the actual observation results. The DCA curve showed that the column graph model for diagnosing AMI had significant positive net benefit and good clinical utility. Conclusions:Coronary heart disease, myoglobin, CK-MB, cTnI, D-dimer, ST-segment elevation and abnormal ventricular wall movement can be used as non-invasive diagnostic markers for AMI in patients with acute high-risk chest pain in emergency department. The prediction performance of the diagnostic model based on the above factors is good.

CD146 Antigen ; immunology ; Fibroblasts ; immunology ; pathology ; Humans ; Scleroderma, Systemic ; drug therapy ; immunology ; pathology

CD146 Antigen ; metabolism ; Humans ; Pericytes ; cytology ; metabolism ; Receptor, Platelet-Derived Growth Factor beta ; metabolism

Animals ; Blood-Brain Barrier ; metabolism ; Ferritins ; metabolism ; Horses ; Mice ; Receptors, Transferrin ; metabolism ; Spleen ; chemistry

Objective To investigate the characteristics of traditional Chinese medical syndrome types of fulminant and epidemic dengue fever patients admitted in Guangzhou and Xishuang banna in the year of 2013,and to ex plore the differences of etiology and pathogenesis, illness, and treatment for the patients in the two regions. Methods We collected the clinical data of 78 cases receiving integrative Chinese and western medicine from 255 patients admitted in Guangzhou Municipal Eighth People’s Hospital, and the clinical data of 39 cases receiving integrative Chinese and western medicine from 120 patients admitted in the People’s Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture in the year of 2013. The traditional Chinese medical syndrome types and the syndrome scores of the total of 117 cases were investigated. The method of phenology was used for the analysis of epidemic time and epidemic region of dengue fever, and the theory of defense-qi-nutrient-blood syndrome differentiation of seasonal febrile diseases was used for the analysis of etiology and pathogenesis of dengue fever. Results ( 1) Dengue fever was epidemic in the first ten days of July and in the middle ten days of November of the year 2013 in Guangzhou region, and was epidemic in the middle ten days of August and the first ten days of October in Xishuangbanna region. The epidemicity of dengue fever in Guangzhou covered the end of summer and the whole autumn, and then disappeared before the coming of winter. In Xishuangbanna , the epidemicity of dengue fever was obvious in autumn, and disappeared in late autumn. ( 2) In the two hospitals, dengue fever patients were dominated by the syndromes of excessive heat in both Qifen and Xuefen, blood stasis blended with toxicity, excessive heat in Qifen, and lingering pathogens in order. (3) Before treatment, the scores of fever were higher in patients of Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital ( P<0.01) . After treatment for 3 days, fever scores were improved in both hospitals (P<0.05 or P<0.01), but the differences between the two hospitals were insignificant (P>0.05) . After treatment for 6 days, fever disappeared in patients of both hospitals. (4) Before treatment, the scores of syndromes were higher in patients of Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital ( P<0.05) . After treatment for 3 days, syndorme scores were improved in both hospitals ( P<0.01) , but the syndrome scores were higher in Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital. After treatment for 6 days, syndrome scores were much improved in patients of both hospitals compared with those after treatment for 3 days (P<0.01) . Conclusion In dengue fever patients admitted in Guangzhou and Xishuangbanna region, the syndrome of excessive heat in both Qifen and Xuefen is the leading type, and then comes blood stasis blended with toxicity. The illness state of patients in Guangzhou region is milder than that of the patients in Xishuangbanna region, the time for symptom relief is about one week, and similar therapeutic effect can be achieved in the two regions .

CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
Animals ; CD146 Antigen ; genetics ; metabolism ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Fibrosarcoma ; metabolism ; pathology ; Male ; Melanoma, Experimental ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B ; metabolism ; Neovascularization, Physiologic ; drug effects ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Retinal Vein ; growth & development ; pathology ; Signal Transduction ; drug effects ; Transplantation, Homologous ; Vascular Endothelial Growth Factor A ; pharmacology ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

FXYD6, FXYD domain containing ion transport regulator 6, has been reported to affect the activity of Na(+)/K(+)-ATPase and be associated with mental diseases. Here, we demonstrate that FXYD6 is up-regulated in hepatocellular carcinoma (HCC) and enhances the migration and proliferation of HCC cells. Up-regulation of FXYD6 not only positively correlates with the increase of Na(+)/K(+)-ATPase but also coordinates with the activation of its downstream Src-ERK signaling pathway. More importantly, blocking FXYD6 by its functional antibody significantly inhibits the growth potential of the xenografted HCC tumors in mice, indicating that FXYD6 represents a potential therapeutic target toward HCC. Altogether, our results establish a critical role of FXYD6 in HCC progression and suggest that the therapy targeting FXYD6 can benefit the clinical treatment toward HCC patients.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Female ; HEK293 Cells ; Humans ; Ion Channels ; antagonists & inhibitors ; metabolism ; Liver Neoplasms ; drug therapy ; metabolism ; Mice, Inbred BALB C ; Mice, Nude ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays