A Health Monitoring Model for Circulation Water Pumps in a Nuclear Power Plant Based on Graph Neural Network Observer.

The health monitoring of CRF (circulation water) pumps is essential for prognostics and management in nuclear power plants. However, the operational status of CRF pumps can vary due to environmental factors and human intervention, and the interrelationships between monitoring parameters are often complex. Consequently, the existing methods face challenges in effectively assessing the health status of CRF pumps. In this study, we propose a health monitoring model for CRF pumps utilizing a meta graph transformer (MGT) observer. Initially, the meta graph transformer, a temporal-spatial graph learning model, is employed to predict trends across the various monitoring parameters of the CRF pump. Subsequently, a fault observer is constructed to generate early warnings of potential faults. The proposed model was validated using real data from CRF pumps in a nuclear power plant. The results demonstrate that the average Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE), and Root Mean Square Error (RMSE) of normal predictions were reduced to 1.2385, 0.5614, and 2.6554, respectively. These findings indicate that our model achieves higher prediction accuracy compared to the existing methods and can provide fault warnings at least one week in advance.

Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

Murine exosomal miR-30a aggravates cardiac function after acute myocardial infarction via regulating cell fate of cardiomyocytes and cardiac resident macrophages.

After acute myocardial infarction (AMI), intercellular communication is crucial for maintaining cardiac homeostasis and patient survival. Exosomes secreted by cardiomyocytes serve as carriers for transporting microRNA(miRNAs), participating in intercellular signaling and the regulation of cardiac function. This study aims to investigate the role of exosomal microRNA-30a(miR-30a) during AMI and its underlying mechanisms. AMI was induced by permanent ligation of the left anterior descending (LAD) artery in C57BL/6 mice. The expression of miR-30a in mice was respectively enhanced and inhibited by administering agomiR-30a and antagomiR-30a. Using HL-1 cardiomyocytes and RAW264.7 macrophages for in vitro experiments, HL-1 cardiomyocytes were cultured under hypoxic conditions to induce ischemic injury. Following isolation and injection of exosomals, a variety of validation methods were utilized to assess the expression of miR-30a, and investigate the effects of enriched exosomal miR-30a on the state of cardiomyocytes. After AMI, the level of exosomal miR-30a in the serum of mice significantly increased and was highly enriched in cardiac tissue. Cardiomyocytes treated with agomiR-30a and miR-30a-enriched exosomes exhibited inhibition of cell autophagy, increased cell apoptosis, mice showed an larger myocardial infarct area and poorer cardiac function. Exosomes released from hypoxic cardiomyocytes transferred miR-30a to cardiac resident macrophages, promoting the polarization into pro-inflammatory M1 macrophages. In conclusion, murine exosomal miR-30a exacerbates cardiac dysfunction post-AMI by disrupting the autophagy-apoptosis balance in cardiomyocytes and polarizing cardiac resident macrophages into pro-inflammatory M1 macrophages. Modulating the expression of miR-30a may reduce cardiac damage following AMI, and targeting exosomal miR-30a could be a potential therapeutic approach for AMI.

[Corrigendum] Long non­coding RNA NEAT1 promotes ovarian cancer cell invasion and migration by interacting with miR­1321 and regulating tight junction protein 3 expression.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the cell invasion and migration assay images shown for the A2780 cell line in Figs. 1 and Fig. 3 on p. 3433 and 3435 respectively, the same data panel had apparently been selected to show the results of the si­NEAT1 experiment in Fig. 1 and the si­TJP3 experiment in Fig. 3. After having re­examined their original data, the authors have realized that the image correctly shown for Fig. 1 was inadvertently copied across to Fig. 3. The corrected version of Fig. 3, now correctly showing the data for the si­TJP3 experiment with the A2780 cell line, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 3429­3439, 2020; DOI: 10.3892/mmr.2020.11428].

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Efficacy and Safety of Bariatric Surgery in Dutch People Living with HIV: a Retrospective Matched Cohort Analysis.

PURPOSE: Obesity is rising among people with HIV (PLWH), sparking interest in bariatric surgery (BS) for this group. Yet, large-scale comparative research on BS outcomes in PLWH is lacking. METHODS: We performed a retrospective, matched cohort analysis in PLWH and HIV uninfected controls. Subjects were retrieved from the Dutch Audit for Treatment of Obesity (DATO) registry. Matching (1:7 ratio) included age (± 5-years), sex, body-mass index (BMI) of ± 3 kg/m2, surgery type, and associated health problems (AHPs) at baseline. The primary endpoint was total weight loss percentage (%TWL) ≥ 20% achieved at 1-year post-BS. Secondary endpoints were cumulative %TWL achieved at 2-years post-BS, a reported remission or improvement in AHPs post-BS, and surgical complications, both at 1-year post-BS. Comparisons were performed using conditional logistic regression. RESULTS: Twenty-seven PLWH and 168 controls were included. At 1-year post-BS, 89% PLWH achieved ≥ 20%TWL, compared to 94% of controls (p = 0.4). Cumulative %TWL at 2-years post-BS were 82% and 92% in PLWH and controls, respectively (p = 0.2). Improvement rates in hypertension and type 2 diabetes mellitus were 50% and 86% in PLWH, versus 87% and 87% in controls. Full remission occurred in 20% and 71% of PLHIV, versus 49% and 44% of controls, respectively. No improvement or remission was observed for dyslipidaemia in PLHIV compared to 54% improvement and 29% remission in controls. Surgical complications were 0% in PLHIV and 13% (n = 21) in controls. CONCLUSION: Efficacy and safety outcomes of BS were similar between PLWH and controls except for the lack of improvement in dyslipidaemia in PLWH.

Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

The mechanism of target regulating of miR-421 to Menin/Caspase-3 pathway for depression / 实用医学杂志

Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression.Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide(LPS),and depressive behavior was detected by glucose preference test and open-field test.miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats.TargetScan database and mi RDB database were used to predict the target genes of miR-421.Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes.The impact of over-expression and inhibition of miR-421 on target genes was observed,then the influence of over-expression and inhibition of target genes on downstream factors was observed,and the related mechanism of miR-421 on depression was explored.Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats(P<0.001),Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats(P<0.001).Binding targets of Menin and miR-421 were predicted by TargetScan database,and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay.Menin expression was down-regulated while miR-421 was overexpressed(P<0.001),whereas it was up-regulated as miR-421 was inhibited(P<0.001).qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased(P<0.001),and IL-1β expression in the hippo-campus was significantly increased(P<0.01).When the expression of Menin was inhibited,the expressions of Caspase-3,NF-κB and IL-1β were increased(P<0.001),while the expressions of Caspase-3,NF-κB and IL-1β were decreased when Menin was overexpressed(P<0.001).Conclusions Inhibition of miR-421 expression can increase Menin expression,decrease Caspase-3 content,and reduce neuroinflammatory response,thereby improving depressive symptoms.

A controlled clinical study of two types of thoracoscopic precision segmentectomy for determining interseg-mental plane / 局解手术学杂志

Objective To compare the application effects of simple artery ligation and modified inflation-deflation method in determining the lung intersegment plane during thoracoscopic precision segmentectomy.Methods A total of 80 patients who underwent thoracoscopic precision segmentectomy in our hospital from August 2021 to February 2023 were prospectively included and divided into the observation group and the control group by random number table method,with 40 cases in each group.Patients in the observation group were determined the lung intersegment plane by simple artery ligation,while patients in the control group were determined the lung intersegment plane by modified inflation-deflation method.The perioperative related indexes,lung function indexes,postoperative complications and follow-up of patients between the two groups were compared.Results The operative time and blood loss of patients in the observation group were significantly shorter/lower than those in the control group(P<0.05).There was no significant difference in the time to reveal the interseg-mental planes, total drainage volume after operation, indwelling time of drainage tube, postoperative hospital stay or lung segmentectomy distribution of patients between the two groups (P>0. 05). The percentage of forced vital capacity to the predicted values (FVC％pred) and percentage of forced expiratory volume in 1 second to the predicted values (FEV1％pred) after operation of patients in the two groups were significantly decreased compared with those before operation (P<0. 05), and FVC％pred and FEV1％pred after operation of patients in the observation group were significantly higher than those in the control group (P<0. 05). There was no statistically significant difference in the occurrence of postoperative complications of patients between the two groups (P>0. 05). There was no death, local recurrence or distant metastasis occurred in all patients during follow-up. Conclusion Compared with the modified inflation-deflation method, the application of simple artery ligation to determine the intersegment plane during thoracoscopic precision segmentectomy has significant advantages such as simple operation, less injury, and less impact on the lung function of patients, which is a feasible and effective technique, with high safety.

Clinical Study on Oral Use of Jiawei Puji Xiaodu Granules Combined with External Application of Xiaozhong Sanjie Ointment in the Treatment of Acute Tonsillitis in Children / 广州中医药大学学报

Objective To evaluate the clinical efficacy of oral use of Jiawei Puji Xiaodu Granules(mainly composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Taraxaci Herba,Violae Herba,Schizonepetae Herba,Arctii Fructus,Gleditsiae Spina,Paeoniae Radix Rubra,Moutan Cortex,and Phragmitis Rhizoma)combined with external application of Xiaozhong Sanjie Ointment(mainly composed of Scutellariae Radix,Coptidis Rhizoma,Phellodendri Chinensis Cortex,and Gleditsiae Spina,etc.)in the treatment of acute tonsillitis in children,and to observe their effects on the immune function and related inflammatory indexes of the patients.Methods A total of 116 children with acute tonsillitis of heat stagnation in the lung and stomach type were randomly divided into the control group and the observation group,with 58 cases in each group.The control group was treated with Cefixime Dispersible Tablets,while the observation group was treated with Jiawei Puji Xiaodu Granules for oral use and Xiaozhong Sanjie Ointment for external application.Both groups were treated for 14 days and then were followed-up for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,white blood cell(WBC)count,T lymphocyte subset CD3+,CD4+,CD8+ and CD4+/CD8+ levels,and serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6)and C-reactive protein(CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and time for the disappearance of clinical symptoms were compared between the two groups,and the occurrence of adverse reactions and the recurrence of tonsillitis in the two groups were monitored at the same time.Results(1)During the trial,there were 8 cases falling off in the control group but none case falling off in the observation group,and eventually 50 cases in the control group and 58 cases in the observation group completed the full course of treatment.(2)After 14 days of treatment,the total effective rate of the observation group was 98.28%(57/58),while that of the control group was 90.00%(45/50).The intergroup(tested by rank sum test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the time for the disappearance of sore throat,time for the disappearance of purulent spots,time for subsiding fever and time for the tonsils recovering to normal in the observation group were all significantly shorter than those in the control group(P＜0.05).(4)After treatment,the scores of primary and secondary symptoms and the overall symptom scores in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction of the scores in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the levels of T lymphocyte subset CD3+,CD4+ and CD4+/CD8+ in the two groups were significantly higher(P＜0.05)while the level of CD8 + was significantly lower(P＜0.05)than those before treatment,and the increase in the levels of CD3+,CD4+ and CD4+/CD8+ and the reduction of the CD8+ level of the observation group were significantly superior to those of the control group(P＜0.05).(6)After treatment,the levels of WBC,TNF-α,IL-1β,IL-6 and CRP in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the treatment period,no skin allergy,nausea,vomiting or other gastrointestinal adverse reactions occurred in the two groups,which showed a high degree of safety.(8)The 6-month follow-up showed that the recurrence rate of tonsillitis in the observation group was 5.17%(3/58),which was significantly lower than that of 24.00%(12/50)in the control group,and the difference was statistically significant(χ2 = 8.330,P＜0.05).Conclusion The efficacy of Jiawei Puji Xiaodu Granules combined with Xiaozhong Sanjie Ointment exert notable curative effect for children with acute tonsillitis of heat stagnation in the lung and stomach type.The combined therapy can significantly shorten the duration of the disease,improve the clinical symptoms of the children and effectively reduce the recurrence rate of tonsillitis.The therapeutic mechanism may be related to the enhancement of the immune function and the inhibition of inflammatory response.

Engineering electronic structures and optical properties of a MoSi2N4 monolayer via modulating surface hydrogen chemisorption.

Recently, a MoSi2N4 monolayer has been successfully synthesized by a delicately designed chemical vapor deposition (CVD) method. It exhibits promising (opto)electronic properties due to a relatively narrow bandgap (∼1.94 eV), high electron/hole mobility, and excellent thermal/chemical stability. Currently, much effort is being devoted to further improving its properties through engineering defects or constructing nanocomposites (e.g., van der Waals heterostructures). Herein, we report a theoretical investigation on hydrogenation as an alternative surface functionalization approach to effectively manipulate its electronic structures and optical properties. The calculation results suggested that chemisorption of H atoms on the top of N atoms on MoSi2N4 was energetically most favored. Upon H chemisorption, the band gap values gradually decreased from 1.89 eV (for intrinsic MoSi2N4) to 0 eV (for MoSi2N4-16H) and 0.25 eV (for MoSi2N4-32H), respectively. The results of optical properties studies revealed that a noticeable enhancement in light absorption intensity could be realized in the visible light range after the surface hydrogenation process. Specifically, full-hydrogenated MoSi2N4 (MoSi2N4-32H) manifested a higher absorption coefficient than that of semi-hydrogenated MoSi2N4 (MoSi2N4-16H) in the visible light range. This work can provide theoretical guidance for rational engineering of optical and optoelectronic properties of MoSi2N4 monolayer materials via surface hydrogenation towards emerging applications in electronics, optoelectronics, photocatalysis, etc.

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in patients worldwide. Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC. It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC. Here, we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients. We found that DMRTA1 was extremely upregulated in the non-pathologic complete response (non-pCR) group. The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression, which could increase cisplatin sensitivity in ESCC. Additionally, suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells. Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2, which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback. Therefore, DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

Secular Trends in Gastric and Esophageal Cancer Attributable to Dietary Carcinogens From 1990 to 2019 and Projections Until 2044 in China: Population-Based Study.

BACKGROUND: Little is known about trends in or projections of the disease burden of dietary gastric and esophageal cancer (GEC) in China. OBJECTIVE: We aim to report GEC deaths and disability-adjusted life years (DALYs) from 1990 to 2019, predict them through 2044, and decompose changes in terms of population growth, population aging, and epidemiological changes. METHODS: We retrieved dietary GEC data from the Global Burden of Disease (GBD) online database and used joinpoint regression and age-period-cohort models to analyze trends in dietary GEC deaths and DALYs from 1990 to 2019 in China. We used a Bayesian age period cohort model of integrated nested Laplace approximations to predict the disease burden of GEC through 2044 and obtained the estimated population of China from 2020 to 2050 from the Global Health Data Exchange website. Finally, we applied a recently developed decomposition method to attribute changes between 2019 and 2044 to population growth, population aging, and epidemiological changes. RESULTS: The summary exposure values and age-standardized rates decreased significantly from 1990 to 1999, with percentage changes of -0.06% (95% CI -0.11% to -0.02%) and -0.05% (95% CI -0.1% to -0.02%), respectively. From 1990 to 2019, for dietary esophageal cancer, the percentage change in age-standardized mortality rate (ASMR) was -0.79% (95% CI -0.93% to -0.58%) and the percentage change in age-standardized DALY rate (ASDR) was -0.81% (95% CI -0.94% to -0.61%); these were significant decreases. For dietary stomach cancer, significant decreases were also observed for the percentage change in ASMR (-0.43%, 95% CI -0.55% to -0.31%) and the percentage change in ASDR (-0.47%, 95% CI -0.58% to -0.35%). In addition, data from both the joinpoint regression and annual percentage change analyses demonstrated significantly decreasing trends for the annual percentage change in ASMR and ASDR for GEC attributable to dietary carcinogens. The overall annual percentage change (net drift) was -5.95% (95% CI -6.25% to -5.65%) for dietary esophageal cancer mortality and -1.97% (95% CI -2.11% to -1.83%) for dietary stomach cancer mortality. Lastly, in 2044, dietary esophageal cancer deaths and DALYs were predicted to increase by 192.62% and 170.28%, respectively, due to age structure (121.58% and 83.29%), mortality change (76.81% and 92.43%), and population size (-5.77% and -5.44%). In addition, dietary stomach cancer deaths and DALYs were predicted to increase by 118.1% and 54.08%, with age structure, mortality rate change, and population size accounting for 96.71% and 53.99%, 26.17% and 3.97%, and -4.78% and -3.88% of the change, respectively. CONCLUSIONS: Although the predicted age-standardized rates of mortality and DALYs due to dietary GEC show downward trends, the absolute numbers are still predicted to increase in the next 25 years due to rapid population aging in China.

Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells.

DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity. Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect. Natural products are a rich source of lead compounds for drug discovery, including anti-tumor drugs. In this study, we found that narciclasine (NCS), an amaryllidaceae alkaloid, is a novel inhibitor of topoisomerase I (topo I). Our data demonstrated that NCS inhibited topo I activity and reversed its unwinding effect on p-HOT DNA substrate. However, it had no obvious effect on topo II activity. The molecular mechanism of NCS inhibited topo I showed that NCS did not stabilize topo-DNA covalent complexes in cells, indicating that NCS is not a topo I poison. A blind docking result showed that NCS could bind to topo I, suggesting that NCS might be a topo I suppressor. Additionally, NCS exhibited a potent anti-proliferation effect in various cancer cells. NCS arrested the cell cycle at G2/M phase and induced cell apoptosis. Our study reveals the antitumor mechanisms of NCS and provides a good foundation for the development of anti-cancer drugs based on topo I inhibition.

Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. METHODS: Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). RESULTS: The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice.

BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

3D ZnII-Based coordination polymer: Synthesis, structure and fluorescent sensing property for nitroaromatic compounds.

A water-stable ZnII-based coordination polymer (CP) with excellent photophysical behavior, namely [Zn2L(atez)(H2O)2] (compound 1; H3L = 4-(2',3'-dicarboxylphenoxy); atez = 5-aminotetrazole), was successfully prepared by the solvothermal reaction of Zn ions with a π-conjugated and semi-rigid multicarboxylate ligand H3L in the presence of N-containing linker atez. Compound 1 displays a hierarchically pillared three-dimensional (3D) (3,4,5)-connected (4·62) (42·64) (43·64·83) net which is based on two-dimensional (2D) multicarboxylate- ZnII layers strutted by the atez ligands. Sensing investigations of compound 1 reveal that this material can selectively and sensitively detect nitroaromatic compounds in water suspension through fluorescence quenching effect. In particular, it is worth noting that it shows highly specific detection of nitrobenzene (NB) and 2,4,6-trinitrophenol (TNP) with remarkable quenching constants (KSV = 7.5 × 104 M-1 for NB and KSV = 1.9 × 105 M-1 for TNP) and low limit of detection (LOD = 0.93 µM for NB and LOD = 0.36 µM for TNP). Investigations reveal that the probable mechanisms for such sensing processes are the concurrent presence of fluorescence resonance energy transfer (FRET) as well as photoinduced electron transfer (PET) between the CP and nitroaromatic molecules. This work not only offers an effective route to improve the application of fluorescent CPs but also provide one novel probable fluorescence probe for nitroaromatic compounds.

Nitrogen-doped hollow carbon@tin disulfide as a bipolar dynamic host for lithium-sulfur batteries with enhanced kinetics and cyclability.

Lithium-sulfur batteries (LSBs) are promising next-generation electrochemical energy storage systems owing to high theoretical specific capacity (1675 mAh/g) and low cost. However, the shuttling effect of soluble polysulfides with slow conversion kinetics has deferred their commercial applications. The feasible design and synthesis of composite cathode hosts offer a promise solution to improving their electrochemical performances. In this work, tin disulfide (SnS2) nanosheets were anchored on nitrogen-doped hollow carbon with mesoporous shells, forming a bipolar dynamic host ("SnS2@NHCS"). It can efficiently confine the polysulfides and promote their conversion during (dis)charge. The as-assembled LSBs delivered a high capacity, superior rate and cyclability. This work presents a new view on the exploration of novel composite electrode materials for various rechargeable batteries with emerging applications.