Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To analyze the composition and function of residual cells in pre-transplantation human thymic slices by single-cell transcriptomics sequencing(scRNA-seq),and established a quality assessment method for thymic slices based on the expression levels of molecular markers in the culture supernatant.Methods The discarded thymus from 18 patients with congenital heart disease undergoing surgical treatment in Department of Cardiothoracic Surgery of Children's Hospital Affiliated to Chongqing Medical University from May 2023 to January 2024 were collected and prepared into thymic slices.After the slices were cultured in vitro for 14 d,scRNA-seq was employed to identify the residual cell types,and gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis was performed to analyze the biological function of the residual cells.Then based on the literature concerning thymic slice culture,the molecular markers indicating thymocyte function were screened out.ELISA was applied to detect the changes in protein levels of molecular markers in the supernatant.Receiver operating characteristic(ROC)curve was plotted and assess the value of the molecular markers in the supernatant in evaluating the quality of thymic slices with area under the curve(AUC).Then,the qualified and unqualified thymic slices determined by our obtained molecular markers were transplanted subcutaneously into male nude mice(6～8 weeks old,weighing 14～17 g),respectively,and the male nude mice without transplantation of the thymic slices served as control group.Flow cytometry and histologic analysis were utilized to observe the immune reconstitution after transplantation.Results ① scRNA-seq identified 11 cell types in thymic slices,dominated with epithelial cells,fibroblasts,and T cells.GO and KEGG enrichment analysis showed that epithelial cells were involved in enrichment entries related to chemotaxis,epithelial cell development,cell matrix adhesion and tight junction;fibroblasts were involved in enrichment entries related to extracellular matrix,epithelial cell proliferation,negative regulation of cell migration,and regulation of actin cytoskeleton;T cells were mainly related to T cell differentiation,regulation of T cell activation,T cell apoptosis,and T cell receptor signaling.② Molecular markers,CCL19,CCL21,CXCL12,CXCL16,IL16 and SELL were identified to indicate thymocyte function.Compared with the levels of the first day,the protein secretions of CCL19,CCL21,CXCL12 and CXCL16 were significantly increased during in vitro culture(P<0.05),while the protein secretions of IL16 and L-selectin(protein form of SELL)were significantly decreased(P<0.05).The combined predictor Pre1 from subset of cytokines(IL16 and L-selectin)had the highest value in the quality assessment of thymic slices after 1 d of culture(AUC=0.883),and the combined predictor Pre2 from subset of cytokines(CCL19,CCL21,CXCL12 and CXCL16)had the highest value in the quality assessment after 14 d of culture(AUC=0.948).③ Transplantation in nude mice indicated that the qualified thymic slices could develop to thymus structure in vivo,and effectively increase the proportion of T cells in peripheral blood(P<0.01),while the unqualified thymic slices could not obtain the reconstitution of T cell development.Conclusion The main residual component cells in thymic slices are epithelial cells,fibroblasts and T cells.IL16 and L-selectin can be used as potential indicators to determine the quality of donor thymic samples.CCL19,CCL21,CXCL12 and CXCL16 can effectively evaluate the quality of thymic slices before transplantation.

Purpose To observation the relationship be-tween the β-catenin/Slug signal specific inhibitor FH535 and EMT,and to explore the role of LPCAT1 in regulating the inva-sion,metastasis,and growth of cervical cancer cells.Methods Hela cells were transfected with sh-NC and sh-LPCAT1,and SiHa cells were transfected with Vector group and LPCAT1 over-expression plasmid.SiHa cells were divided into control group(Con),LPCAT1 group,LPCAT1+FH535 group and FH535 group.The proliferation of cervical cancer cells was detected by CCK-8 analysis and colony formation test.The metastasis and invasion ability of cervical cancer cells were detected by wound healing test and Transwell test.Western blot was used to analyze the expression of LPCAT1,β-catenin/Slug signaling pathway and EMT-related proteins in cells.Results Compared with Vector group,the cell viability,colony number,migration and invasion number of SiHa cells in LPCAT1 group increased signif-icantly(P＜0.05).Compared with sh-NC group,the cell via-bility,colony number,migration and invasion number of Hela cells in sh-LPCAT1 group decreased significantly(P＜0.05).Compared with LPCAT1 group,the levels of Wnt4(1.18±0.05 vs 0.80±0.06),β-catenin(1.05±0.08 vs 0.77±0.05),Slug(1.13±0.06 vs 0.28±0.02),Cyclin D1(0.99±0.06 vs 0.44±0.02),N-cadherin(0.91±0.07 vs 0.46±0.03)and vimentin(0.95±0.06 vs 0.49±0.03)in SiHa cells in LPCAT1+FH535 group decreased significantly(P＜0.05),and the level of E-cadherin(0.44±0.03 vs 0.58±0.03)in-creased significantly(P＜0.05).In addition,compared with LPCAT1 group,the number of colonies(224±15 vs 146±11),migration(85±3vs51±4)and invasive(166±10 vs 90±5)cells of SiHa cells in LPCAT1+FH535 group decreased signifi-cantly(P＜0.05).Conclusion The increase of LPCAT1 ex-pression may promote the metastasis and progress of CC by acti-vating β-catenin/Slug signaling pathway,and LPCAT1 may be a potential marker for predicting CC metastasis.

Objective To explore the correlation between the immune related adverse(irAEs)reactions in patients treated with pembrolizumab and traditional Chinese Medicine(TCM)constitution.Methods A total of 110 patients diagnosed with non-small cell lung cancer for the first time were selected.When receiving pembrolizumab immunotherapy for the first time,a general information questionnaire,a TCM constitution classification and judgment scale,an immune related adverse reaction follow-up record book,and a patient's self-perception diary were used to investigate and analyze the TCM syndrome and adverse reactions of the patients.Results Among non-small cell lung cancer patients,there were more than four TCM constitutions,with 48 cases(43.64%)having a calm constitution,20 cases(18.18%)having a biased constitution,30 cases(27.27%)having a yang deficiency constitution,and 12 cases(10.91%)having a yin deficiency constitution.Qi deficiency and Yang deficiency were more prone to fatigue,while Yang deficiency was more prone to rash;Qi deficiency and Yin deficiency were more prone to itching;Yang deficiency was more prone to diarrhea;Non-small cell lung cancer patients with mild constitution were less prone to immune related adverse reactions.Conclusion TCM constitution is related to irAEs,which could predict the occurrence of immune related adverse reactions from the perspective of TCM constitution and intervene in adverse reactions early.

Background: and Purpose To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). Methods: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. Results: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4–53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8–15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. Conclusion TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Objective:To explore the status and influencing factors of participation in cardiac rehabilitation of cardiovascular nurses.Methods:This is a cross-sectional study. From January to February 2022, a total of 3 047 cardiovascular nurses in members of China Cardiovascular Health Alliance were selected as research objects by convenience sampling method. General data questionnaire and Cardiovascular Nurses Participated in the Cardiac Rehabilitation Questionnaire (CNPCRQ) were used to investigate cardiovascular nurses. Multiple linear regression analysis was used to investigate the influencing factors of participation in cardiac rehabilitation of cardiovascular nurses. A total of 3 047 questionnaires were distributed in this study, and 2 704 valid questionnaires were effectively received, with an effective recovery rate of 88.74%.Results:The total score of CNPCRQ of cardiovascular nurses was (93.23±31.58), which was at a moderate level. Multiple linear regression analysis results showed that age, education, professional title, hospital location, hospital level, position type and hospital type were the influencing factors of participation in cardiac rehabilitation of cardiovascular nurses.Conclusions:The status of participation in cardiac rehabilitation of cardiovascular nurses in China needs to be improved. Role and job content of cardiovascular nurses should be further clarified, and cardiac rehabilitation knowledge and skills training should be strengthened in the future, so as to promote the profession development of cardiac rehabilitation and improve patients' health outcomes.

Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.

Objective To evaluate the quality of the clinical trial literatures published on the treatment of COVID-19 with TCM, find out the shortcomings and put forward corresponding suggestions, in order to promote TCM against COVID-19. Methods "COVID-19", "New Coronavirus Pneumonia", "TCM", "Chinese Medicine", "Clinical Trial", "Lianhua Qingwen", "Huoxiang Zhengqi", "Jinhua Qinggan", and other keywords were used to search relevant literatures in CNKI and PubMed database. Among the all the screened relevant literatures on the treatment of COVID-19 with TCM, the literature quality was assessed according to evaluation criteria of clinical trial literatures. Results A total of 463 papers related to the treatment of COVID-19 with TCM were obtained. 440 papers on theoretical research on the network pharmacology mechanism of Chinese medicine treatment of COVID-19 were excluded. Among the 23 articles included in the quality analysis, there are 3 randomized controlled studies, 1 multi-center prospective randomized controlled trial, 2 disease case report trials, and 5 uncontrolled single arm studies, 5 controlled trials and 7 retrospective studies. In the period of more than half a year, although many clinical trial documents of TCM for the treatment of COVID-19 have been published, the clinical trial design reflected in most TCM clinical trials were not standardized. There are problems in "randomness and rationality", such as no control group, no randomization design, only case studies, no blinding method in controlling bias, and insufficient objectivity in the evaluation criteria of efficacy. All of these need to be improved. Conclusion The treatment of new coronavirus pneumonia with TCM still requires more and standardized clinical trial verifications and publications to generate strong evidence-based results, such as adding control groups, increasing sample size, and using blinding methods to increase the credibility of clinical trials.

Objective To investigate the occupational life status and occupational related stress factors of young hospital pharmacists, and to promote the healthy development of young pharmacists. Methods Questionnaire was designed and released on-line through Wenjuan Star APP. Demographic characteristic information, occupational stress and stress management data were obtained. Data were processed with SPSS. Results About sixty percent of 289 questionnaire respondents complained of occupational stress (178 respondents). Gender, education level, hospital grade, and job position had no significant effect on occupational stress difference. However, different age group showed different occupational stress. Pharmacist at the age of 31-35 complained more stress than the other age group. Pharmacist with high title complained more stress than the lower titles. Conclusion More than half of young pharmacists suffer from the high occupational stress, and various intervention measures should be taken to relieve the stress.

Objective To investigate the rationality and efficacy of enhanced recovery after surgery (ERAS) in liver transplant recipients. Methods Clinical data of 465 liver transplant recipients were retrospectively analyzed. All recipients were divided into the ERAS group (n=163) and control group (n=302) according to whether they received ERAS. The severity of disease in the ERAS group was worse than that in the control group. Operation situations including the operation time, anhepatic phase and intraoperative blood transfusion volume of the liver transplant recipients were observed and recorded. Postoperative recovery conditions including the length of intensive care unit (ICU) stay, total length of hospital stay, total ventilator removal time at postoperative 28 d and postoperative re-intubation rate were recorded. The survival rates at 90 d, 180 d and 1 year after liver transplantation were calculated. The influencing factors of survival rate of liver transplant recipients were analyzed. Results The anhepatic phase in the ERAS group was 45 (39, 53) min, significantly longer than 40 (32, 48) min in the control group (P < 0.05). The volume of erythrocyte infusion in the ERAS group was 10 (7, 13) U, significantly less than 18 (10, 28) U in the control group (P < 0.05). The length of postoperative ICU stay and total length of hospital stay in the ERAS group were 135 (84, 212) h and 24 (18, 33) d, significantly shorter than 154 (103, 253) h and 34 (20, 50) d in the control group (both P < 0.05). Total ventilator removal time at postoperative 28 d was 26 (25, 27) d, significantly longer than 26 (23, 27) d in the control group (P < 0.05). The postoperative re-intubation rate in the ERAS group was 11.0%, significantly lower than 20.8% in the control group (P < 0.05). The 90 d, 180 d and 1-year survival rates in the ERAS group were 92.8%, which were significantly higher than 81.1%, 78.1% and 75.7% in the control group (all P < 0.05). ERAS and operation time were the independent influencing factors of survival rate of liver transplant recipients (both P < 0.05). Conclusions ERAS after liver transplantation can improve the survival rate of recipient, shorten the length of hospital stay, reduce the re-intubation rate and accelerate the rehabilitation after liver transplantation.