Objective: To evaluate the feasibility and effectiveness of dual fluorescence laparoscopy in the localization of ureteral stricture and its blood supply，and to provide a new idea for the treatment of complex ureteral stenosis，thus helping doctors to improve the efficiency of ureteral reconstruction surgery. Methods: Our team developed a dual fluorescence laparoscopic system，which could simultaneously identify the ureter stricture by intra-ureteral injection of methylene blue (MB) and assess the blood supply of the ureteral stumps by intravenous injection of indocyanine green (ICG). Results: The clinical data of 3 patients who underwent lingual mucosa ureteroplasty using dual fluorescence laparoscopy in Zhongnan Hospital of Wuhan University were retrospectively analyzed.All operations were successful，without conversion to open surgery.The operation time was 144，132 and 163 minutes，respectively.The length of harvested lingual mucosa graft was 2.0，2.8 and 3.5 cm，respectively.No intraoperative or postoperative complications occurred.Eight weeks after operation，ureterography showed that the ureter was unobstructed. Conclusion: Dual fluorescence laparoscopy is safe and feasible in the repair of complex ureteral stricture with lingual mucosa graft，which provides a new idea for complex ureteral reconstruction.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

ObjectiveUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze the differences in chemical components between raw products and wine-processed products of Polygonatum cyrtonema rhizome. MethodUPLC-Q-Exactive Orbitrap MS was used to analyze the chemical compositions of P. cyrtonema rhizome before and after processing， and the effective response ions were extracted after raw data processing， and the differential compounds before and after processing were screened combined with multivariate statistical analysis and according to the conditions of variable importance in the projection（VIP） value>1， P<0.05， fold change（FC）>2 or FC<0.5， based on the retention time， quasi-molecular ions， fragment ions and other information， the components were identified in combination with the control products and the literature， and the significant difference compounds were identified by clustering thermal analysis and relative quantitative analyzed， in order to clarify the change rule of the main components in P. cyrtonema rhizome before and after processing. ResultA total of 72 differential constituents between raw products and wine-processed products were identified， including 15 alkaloids， 12 organic acids， 12 amino acids， 6 flavonoids， 4 saccharides and 23 others. There were a total of 18 significantly different components， among which 13 compounds， including L-malic acid， lactic acid and 9，12，13-trihydroxy-10-octadecenoic acid， showed an increasing trend in content after wine processing， 5 compounds such as trans-3-indoleacrylic acid， L-arginine， D-tryptophan， showed a decreasing trend after processing. ConclusionThe chemical components of P. cyrtonema rhizome are significantly different before and after processing， mainly organic acids， saccharides， amino acids， flavonoids and alkaloids， which can lay the foundation for the in-depth study of the processing mechanism of Polygonati Rhizoma.

Studies have shown that Humanin protein plays a neuroprotective role in the process of anti-Alzheimer's disease in a variety of ways.This review introduces the latest research progress on the neuroprotective effect of Humanin protein in Alzheimer's disease from the aspects of the discovery,structural characteristics,neuroprotective mechanism of Humanin and the structure and function of its new homologous secretory peptide Rattin.

In order to meet the market demand for the fast and accurate genetic detection of African swine fever virus(ASFV),a new method for EIS-qPCR detection was established with a rapid,high sensitivity,and pollution prevention.Primers and probes for a duplex qPCR were designed based on the conserved region of ASFV virus p72 gene and the endogenous internal standard(EIS)cytb gene sequence in pigs.An anti-contamination system was established with uracil DNA N-gly-cosylase enzyme in the reaction system.The results showed that the method can finish the rapid qPCR detection of ASFV within 30 min with a minimal detection limit of 4.12 copies/μL.Moreo-ver,the method only detected the ASFV p72 gene,and no amplifications of classical swine fever vi-rus(CSFV),pseudorabies virus(PRV),porcine parvo virus(PPV),porcine reproductive and re-spiratory syndrome virus(PRRSV)and porcine circovirus type 2(PCV2)were observed.Repeti-tive results showed a coefficient of variation below 2％.With strong anti-pollution capacity,the method can effectively eliminate false-positive amplification caused by low-dose aerosol pollution.Detection results of 146 clinical samples showed a 100％consistence with the results of the com-mercial ASFV detection kit.Compared with similar technologies,the EIS-qPCR established in this study was faster,sensitive,and suitable for the rapid diagnosis of ASFV infection in the early stage,which provided the tool for the monitoring and precise prevention and control of African swine fever.

BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
Animals ; Mice ; Calcium/metabolism* ; Cysteine Endopeptidases/metabolism* ; Myocardial Reperfusion Injury/metabolism* ; Myocardium/metabolism* ; Myocytes, Cardiac/metabolism* ; Proteins/metabolism* ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics*

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

Objective:To investigate the correlation between neutrophil/lymphocyte ratio (NLR) combined with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and severity of coronary lesions in patients with acute coronary syndrome (ACS).Methods:Patients who were diagnosed with ACS due to chest pain and received emergency coronary angiography in the First Affiliated Hospital of University of Science and Technology of China and the Affiliated Hospital of Anhui Medical University from January 2017 to June 2020 were enrolled in the final analysis. The data of gender, age, body mass index (BMI), past history, emergency blood routine indicators [neutrophil (NEU), lymphocyte (LYM), monocyte (MON), eosinophil (EOS), basophil (BAS), red blood cell (RBC), mean corpuscular volume (MCV), blood red cell distribution width (RDW), mean platelet volume (MPV), platelet volume distribution width (PDW)], blood lipid index [triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, very low-density lipoprotein cholesterol (VLDL-C)], and coronary angiography were collected. The results of coronary angiography were evaluated by the Gensini score. According to the Gensini score, the patients were divided into the control group (Gensini score = 0, 55 cases) and the study group (Gensini score > 0, 889 cases), and then the patients in the study group were divided into the low-Gensini-score group (Gensini score < 66, 419 cases) and the high-Gensini-score group (Gensini score ≥ 66, 470 cases). The differences in the general baseline data of the four groups were compared, and the correlation between the statistically significant data and the Gensini score was linearly analyzed, and then the combined diagnostic factors (NLR combined with LDL-C/HDL-C ratio) were obtained by Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of NLR combined with LDL-C/HDL-C ratio in predicting the severity of coronary artery lesions in patients with ACS. Finally, multivariate linear regression analysis was used to establish the predictive model between NLR combined with LDL-C/HDL-C ratio and Gensini score.Results:A total of 944 patients were finally included. The differences in gender, age, BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, RDW, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C ratio between the control group and the study group were statistically significant. The differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, TG, TC, HDL-C, LDL-C, NLR and LDL-C/HDL-C ratio between the low-Gensini-score group and the high-Gensini-score group were statistically significant. Linear regression analysis showed that compared with other indicators, the correlation between NLR, LDL-C/HDL-C ratio and Gensini score was stronger in the study group ( r values were 0.634 and 0.663, respectively, both P < 0.05). Binary Logistic regression analysis of the indicators related to Gensini score showed that NEU, LYM, HDL-C and LDL-C were independent risk factors for coronary stenosis in patients with ACS [odds ratio ( OR) were 0.189, 10.309, 13.993, 0.251, 95% confidence intervals (95% CI) were 0.114-0.313, 4.679-22.714, 3.402-57.559, 0.121-0.519, respectively, all P < 0.05]. ROC curve analysis showed that NLR combined with LDL-C/HDL-C ratio had higher predictive value in predicting the severity of coronary lesions in ACS patients [area under the ROC curve (AUC) was 0.952, 95% CI was 0.93-0.969], when the cutoff value was -3.152, the sensitivity was 98.20%, and the specificity was 81.60%. According to the results of multivariate linear regression analysis, the prediction model between NLR, LDL-C/HDL-C ratio and Gensini score was established, and the formula was Gensini score = -7.772+15.675×LDL-C/HDL-C ratio+8.288×NLR ( R2 = 0.862). Conclusion:There is a significant correlation between emergency NLR combined with LDL-C/HDL-C ratio and Gensini score in patients with ACS at admission, which has a certain predictive value for the severity of coronary artery stenosis in patients with ACS, and can be used as a predictor for evaluating the severity of coronary artery disease.