Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Nomogram based on immune-inflammatory indicators and age-adjusted charlson comorbidity index score to predict prognosis of postoperative parotid gland carcinoma patients.

BACKGROUND: Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. METHOD: All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. RESULT: The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup. CONCLUSION: The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies.

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma.

OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

Multivariate analysis of prognostic factors in patients with lip squamous cell carcinoma after surgery.

BACKGROUND: Lip squamous cell carcinoma (LSCC) was one of the most common cancer types of head and neck tumors. This study aimed to find more predictors of the prognosis in postoperative LSCC patients. METHODS: A total of 147 LSCC patients between June 2012 and June 2018 were collected from two tertiary care institutions. There were 21 clinicopathological factors included and analyzed in our study. The univariate and multivariate Cox regression analyses were performed to find the independent prognostic factors for predicting progression-free survival (PFS) and overall survival (OS) in postoperative LSCC patients. The role of adjuvant radiotherapy in various subgroups was displayed by Kaplan-Meier plots. RESULTS: The 1-, 3-, and 5-year PFS of postoperative LSCC patients were 88.4%, 70.1%, and 57.8%, respectively. Similarly, the 1-, 3-, and 5-year OS of postoperative LSCC patients were 94.6%, 76.9%, and 69.4%, respectively. The results suggested that postoperative LSCC patients with age at diagnosis ≥ 70 years, grade with moderate or poor differentiate, the American Joint Committee on Cancer (AJCC) stage IV, higher systemic immune-inflammation index (SII), surgical margin < 5, and age-adjusted Charlson Comorbidity Index (ACCI) ≥ 5 tend to have a poorer PFS (all P < 0.05). Besides, postoperative LSCC patients with age at diagnosis ≥ 70 years, AJCC stage IV, higher GPS, higher SII, and ACCI ≥ 5 tend to have a worse OS (all P < 0.05). Additionally, postoperative patients with LSCC in the subgroup of ACCI < 5 and AJCC III-IV stage was more likely to benefit from adjuvant radiotherapy, but not for the other subgroups. CONCLUSION: We identified a series of significant immune-inflammation-related and comorbidity-related clinicopathological factors associated with the prognosis of postoperative LSCC patients by local data from two tertiary care institutions in China, which can be helpful for patients and surgeons to pay more attention to nutrition, inflammation, and complications and finally obtained a better prognosis.

Large-scale separation of alkaloids from Corydalis decumbens by pH-zone-refining centrifugal partition chromatography and their anticomplement activity.

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH50 0.11 and AP50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade.

Whole-genome sequencing-based analysis of antimicrobial resistance, virulence factors, and genetic diversity in Yersinia isolated in Wenzhou, China 2020.

Yersinia spp. vary significantly in their ability to cause diseases that threaten public health. Their pathogenicity is frequently associated with increasing antimicrobial resistance (AMR) and various virulence factors. The aim of the study was to investigate the AMR genes, virulence factors, and genetic diversity of Yersinia strains isolated from meats and fish in Wenzhou in 2020 by using whole-genome sequencing (WGS). A total of 50 isolates were collected. The phylogenetic relationships among the Yersinia species were also analyzed using multilocus sequence typing (MLST), core genome multi-locus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. According to the results, all the strains could be classified into five species, with most isolated from beef, followed by poultry, pork, and fish. AMR genes were identified in 23 strains. And the qnrD1 genes were all located in the Col3M plasmid. Virulence genes, such as yaxA, ystB, pla, and yplA, were also found in the 15 Y. enterocolitica strains. And this study also found the presence of icm/dot type IVB-related genes in one Yersinia massiliensis isolate. MLST analysis identified 43 sequence types (STs), 19 of which were newly detected in Yersinia. Moreover, cgMLST analysis revealed that no dense genotype clusters were formed (cgMLST 5341, 5344, 5346-5350, 5353-5390). Instead, the strains appeared to be dispersed over large distances, except when multiple isolates shared the same ST. Isolates Y4 and Y26 were closely related to strains originating from South Korea and Denmark. This study showed considerable diversity in Yersinia spp. isolated from local areas (Wenzhou City). The data generated in our study may enrich the molecular traceability database of Yersinia and provide a basis for the development of more effective antipathogen control strategies.

College students' influence on COVID-19 vaccination uptake among seniors in China: a protocol of combined cross-sectional and experimental study.

BACKGROUND: College students generally have good knowledge about COVID-19 and may facilitate COVID-19 vaccination in family. The purpose of this study is to understand college students' willingness to persuade their grandparents to initiate COVID-19 vaccination and the effect of their persuasion. METHODS: A combined cross-sectional and experimental study will be conducted online. In the cross-sectional study (Phase I), eligible participants are college students who are aged ≥ 16 years and have at least one living grandparent aged ≥ 60 years who has/have not completed the COVID-19 vaccination. Participants self-complete Questionnaire A to collect information on the socio-demographics of themselves and their grandparents, their knowledge about older adults' COVID-19 vaccination, as well as Health Belief Model (HBM) and Theory of Planned Behavior (TPB) predictor variables. The primary outcome at Phase I is college students' willingness to persuade grandparents to receive COVID-19 vaccines. Those who are willing to persuade grandparents and participate in a follow-up survey will be invited to participate in a randomized controlled trial (Phase II). At Phase II, eligible participants are those who have at least one living grandparent aged ≥ 60 years who completed the COVID-19 initial vaccination series but has/have not received a booster dose. At the baseline, participants self-complete Questionnaire B to collect information on individual grandparents' COVID-19 vaccination status, attitude towards and intention to COVID-19 booster dose. Participants will then be randomly allocated 1:1 to either intervention arm (one-week smartphone-based health education on older adults' COVID-19 vaccination plus two weeks' waiting period) or control arm (three weeks' waiting period). At the end of week three, participants in both arms self-complete Questionnaire C to collect information on their grandparents' COVID-19 vaccination status. The primary outcome at Phase II is the uptake rate of COVID-19 booster dose among grandparents. Secondary outcomes include grandparents' attitude and intention to get a COVID-19 booster dose. DISCUSSION: No previous study had measured the effect of college students' persuasion on COVID-19 vaccination uptake in older adults. Findings from this study will provide evidence for innovative and potentially feasible interventions that further promote COVID-19 vaccination in older adults. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200063240. Registered 2 September 2022.

Nomogram for predicting the preoperative lymph node metastasis in resectable pancreatic cancer.

BACKGROUND: Lymph node metastasis (LNM) is a critical prognostic factor in resectable pancreatic cancer (PC) patients, determining treatment strategies. This study aimed to develop a clinical model to adequately and accurately predict the risk of LNM in PC patients. METHODS: 13,200 resectable PC patients were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database, and randomly divided into a training group and an internal validation group at a ratio of 7:3. An independent group (n = 62) obtained from The First Affiliated Hospital of Xinxiang Medical University was enrolled as the external validation group. The univariate and multivariate logistic regression analyses were used to screen independent risk factors for LNM. The minimum Akaike's information criterion (AIC) was performed to select the optimal model parameters and construct a nomogram for assessing the risk of LNM. The performance of the nomogram was assessed by the receiver operating characteristics (ROC) curve, calibration plot, and decision curve analysis (DCA). In addition, an online web calculator was designed to assess the risk of LNM. RESULT: A total of six risk predictors (including age at diagnosis, race, primary site, grade, histology, and T-stage) were identified and included in the nomogram. The areas under the curves (AUCs) [95% confidential interval (CI)] were 0.711 (95%CI: 0.700-0.722), 0.700 (95%CI: 0.683-0.717), and 0.845 (95%CI: 0.749-0.942) in the training, internal validation and external validation groups, respectively. The calibration curves showed satisfied consistency between nomogram-predicted LNM and actual observed LNM. The concordance indexes (C-indexes) in the training, internal, and external validation sets were 0.689, 0.686, and 0.752, respectively. The DCA curves of the nomogram demonstrated good clinical utility. CONCLUSION: We constructed a nomogram model for predicting LNM in pancreatic cancer patients, which may help oncologists and surgeons to choose more individualized clinical treatment strategies and make better clinical decisions.

Nomograms for predicting overall survival and cancer-specific survival in elderly patients with epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is one of the most fatal gynecological malignancies among elderly patients. We aim to construct two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in elderly EOC patients. METHODS: Elderly patients with EOC between 2000 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Enrolled patients were randomly divided into the training and validation set at a ratio of 2:1. The OS and CSS were recognized as endpoint times. The independent prognostic factors from the multivariate analysis were used to establish nomograms for predicting the 3-, 5- and 10-year OS and CSS of elderly EOC patients. The improvement of predictive ability and clinical benefits were evaluated by consistency index (C-index), receiver operating characteristic (ROC), calibration curve, decision curve (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Finally, the treatment efficacy of surgery and chemotherapy in low-, medium-, and high-risk groups were displayed by Kaplan-Meier curves. RESULTS: Five thousand five hundred eighty-eight elderly EOC patients were obtained and randomly assigned to the training set (n = 3724) and validation set (n = 1864). The independent prognostic factors were utilized to construct nomograms for OS and CSS. Dynamic nomograms were also developed. The C-index of the OS nomogram and CSS nomogram were 0.713 and 0.729 in the training cohort. In the validation cohort, the C-index of the OS nomogram and CSS nomogram were 0.751 and 0.702. The calibration curve demonstrated good concordance between the predicted survival rates and actual observations. Moreover, the NRI, IDI, and DCA curves determined the outperformance of the nomogram compared with the AJCC stage system. Besides, local tumor resection had a higher benefit on the prognosis in all patients. Chemotherapy had a better prognosis in the high-risk groups, but not for the medium- risk and low-risk groups. CONCLUSIONS: We developed and validated nomograms for predicting OS and CSS in elderly EOC patients to help gynecologists to develop an appropriate individualized therapeutic schedule.

Uptake of COVID-19 Vaccination and Its Associated Factors among College Students in China: A Nationwide Cross-Sectional Study.

Our study aims to assess the uptake of COVID-19 vaccination and its associated factors among Chinese college students. A web-based cross-sectional study was conducted from 18 May to 17 June 2022. A total of 3916 participants were included. The coverage of the first dose, complete vaccination and booster vaccination among college students was 99.49%, 81.96% and 79.25%, respectively. College students with an older age (AOR: 0.72, 95% CI: 0.57-0.90), non-medical major (0.47, 0.37-0.61) and studying in north-east China (0.35, 0.22-0.58) were less likely to complete vaccination. Individuals who were female (1.62, 1.35-1.94) and received a recombinant subunit vaccine (8.05, 5.21-12.45) were more likely to complete vaccination. Non-medical students (0.56, 0.43-0.73) and students studying in north-east China (0.28, 0.16-0.49) were less likely to receive a booster dose, while female students (1.51, 1.23-1.85) had a higher likelihood. The main reason for being unvaccinated was "contraindication" (75.00%), and the main reason for not receiving a booster dose was "being too busy to attend to it" (61.37%). This study demonstrated a high adherence to the COVID-19 vaccination policy among Chinese college students. Targeted strategies should be applied to remove barriers to COVID-19 vaccination among college students.

Bicyclol Alleviates Streptozotocin-induced Diabetic Cardiomyopathy By Inhibiting Chronic Inflammation And Oxidative Stress.

PURPOSE: Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. METHODS: A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. RESULTS: We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. CONCLUSION: Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.

Prognostic Value of Temporary Pacemaker Insertion in Patients with Acute Myocardial Infarction in the Era of Percutaneous Coronary Revascularization.

Background: Patients with acute myocardial infarction (AMI) complicated with arrhythmia are not uncommon. Insertion of temporary pacemakers (tPMs) in patients with arrythmia during acute myocardial infarction (AMI) is imperative support therapy. Arrhythmias include high-degree atrioventricular block (AVB), sinus arrest/bradycardia, and ventricular arrythmia storm. To date, no study has evaluated the prognosis of tPMs in patients with AMI complicated with arrhythmia. Especially in the era of thrombolysis or emergency percutaneous coronary intervention (PCI) for coronary artery revascularization, our study was designed to investigate the value of tPMs implantation in cases of AMI complicated with various arrhythmias. Methods: From January 2009 to January 2019, 35,394 patients with AMI, including 62.0% (21,935) with ST-segment elevation myocardial infarction (STEMI) and 38.0% (13,459) with non-ST-segment elevation myocardial infarction (NSTEMI) in four hospitals, were reviewed. A total of 552 patients with AMI associated with arrythmia were included in the cohort. Among the 552 patients, there were 139 patients with tPM insertions. The incidence trend of myocardial infarction complicated with various arrhythmias in the past 10 years was analysed, and the clinical characteristics, in-hospital mortality, postdischarge mortality, composite endpoints of modality, and independent risk factors were compared in patients with and without tPM in the era of coronary artery revascularization. Results: In patients with AMI-associated arrythmia, high-degree AVB was the major cause of tPM insertion (p = 0.045). In the past 10 years, the number of patients with high-degree AVB, tPM implantation, ventricular arrythmia storm, and in-hospital mortality has decreased year by year in the era of coronary artery revascularization. In the tPM group, the culprit vessel was the left main artery, and cardiogenic shock, acute renal injury and high brain natriuretic peptide (BNP) levels were independent risk factors for patients with AMI complicated with arrhythmia. The in-hospital mortality in the tPM group was higher than that in the non-tPM group. The patients with tPM insertion showed better postdischarge survival than patients without tPM insertion. Conclusions: In the era of emergency thrombolysis or PCI, coronary revascularization can ameliorate the prognosis of patients with AMI complicated with various arrhythmias. Temporary pacemaker insertion in patients with AMI complicated with arrhythmia can reduce the postdischarge mortality of these patients.

The Impact of COVID-19 Pandemic on the Clinical Practice Patterns in Atrial Fibrillation: A Multicenter Clinician Survey in China.

The COVID-19 pandemic has severely impacted healthcare systems worldwide. This study investigated cardiologists' opinions on how the COVID-19 pandemic impacted clinical practice patterns in atrial fibrillation (AF). A multicenter clinician survey, including demographic and clinical questions, was administered to 300 cardiologists from 22 provinces in China, in April 2022. The survey solicited information about their treatment recommendations for AF and their perceptions of how the COVID-19 pandemic has impacted their clinical practice patterns for AF. The survey was completed by 213 cardiologists (71.0%) and included employees in tertiary hospitals (82.6%) and specialists with over 10 years of clinical cardiology practice (53.5%). Most respondents stated that there were reductions in the number of inpatients and outpatients with AF in their hospital during the pandemic. A majority of participants stated that the pandemic had impacted the treatment strategies for all types of AF, although to different extents. Compared with that during the assumed non-pandemic period in the hypothetical clinical questions, the selection of invasive interventional therapies (catheter ablation, percutaneous left atrial appendage occlusion) was significantly decreased (all p < 0.05) during the pandemic. There was no significant difference in the selection of non-invasive therapeutic strategies (the management of cardiovascular risk factors and concomitant diseases, pharmacotherapy for stroke prevention, heart rate control, and rhythm control) between the pandemic and non-pandemic periods (all p > 0.05). The COVID-19 pandemic has had a profound impact on the clinical practice patterns of AF. The selection of catheter ablation and percutaneous left atrial appendage occlusion was significantly reduced, whereas pharmacotherapy was often stated as the preferred option by participating cardiologists.

Research Progress on Graphitic Carbon Nitride/Metal Oxide Composites: Synthesis and Photocatalytic Applications.

Although graphitic carbon nitride (g-C3N4) has been reported for several decades, it is still an active material at the present time owing to its amazing properties exhibited in many applications, including photocatalysis. With the rapid development of characterization techniques, in-depth exploration has been conducted to reveal and utilize the natural properties of g-C3N4 through modifications. Among these, the assembly of g-C3N4 with metal oxides is an effective strategy which can not only improve electron-hole separation efficiency by forming a polymer-inorganic heterojunction, but also compensate for the redox capabilities of g-C3N4 owing to the varied oxidation states of metal ions, enhancing its photocatalytic performance. Herein, we summarized the research progress on the synthesis of g-C3N4 and its coupling with single- or multiple-metal oxides, and its photocatalytic applications in energy production and environmental protection, including the splitting of water to hydrogen, the reduction of CO2 to valuable fuels, the degradation of organic pollutants and the disinfection of bacteria. At the end, challenges and prospects in the synthesis and photocatalytic application of g-C3N4-based composites are proposed and an outlook is given.

Molecular Characterization and Phylogenetic Analysis of the 2019 Dengue Outbreak in Wenzhou, China.

In 2019, a dengue outbreak occurred with 290 confirmed cases in Wenzhou, a coastal city in southeast China. To identify the origin of the dengue virus (DENV) from this outbreak, viral RNA was extracted from four serum samples and sequenced for whole genome analysis. Then, phylogenetic analysis, gene mutation, secondary structure prediction, selection pressure analysis, and recombination analysis were performed. DENV strains Cam-03 and Cam-11 were isolated from patients traveling from Cambodia, while ZJWZ-18 and ZJWZ-62 strains were isolated from local patients without a record of traveling abroad. The whole genome sequence of all four strains was 10,735 nucleotides long. Phylogenetic tree analysis showed that the four strains belonged to genotype 1 of DENV-1, but the local Wenzhou strains and imported strains clustered in different branches. ZJWZ-18 and ZJWZ-62 were closely related to strain MF033254-Singapore-2016, and Cam-03 and Cam-11 were closely related to strain AB608788-China : Taiwan-1994. A comparison of the coding regions between the local strains and the DENV-1 standard strain (EU848545-Hawaii-1944) showed 82 amino acid mutations between the two strains. A total of 55 amino acid mutations were found between the coding regions of the local and imported strains. The overall secondary structure of the 3' UTR of the local strains had changed: apparent changes in the head and tail position were observed when compared to DENV-1 standard strain. Furthermore, selection pressure analysis and recombination detection using the 4 isolates and 41 reference strains showed two credible positive selection sites and eight credible recombination events, which warrant further studies. This study may enhance the understanding of viral replication, infection, evolution, virulence, and pathogenicity of DENV.

Cascade targeting codelivery of ingenol-3-angelate and doxorubicin for enhancing cancer chemoimmunotherapy through synergistic effects in prostate cancer.

Immunotherapy has led to an expansion of the treatment of malignancies, but its effect in prostate cancer (PCa) patients is modest. Chemoimmunotherapy is a promising approach that has attracted substantial attention. Although the widely used clinical chemotherapeutic drug doxorubicin (DOX) elicits immunogenic cell death (ICD), its weak ICD effect and the abnormal vasculature of tumors severely limit its efficacy in chemoimmunotherapy. Ingenol-3-angelate (I3A), an emerging antitumor drug with dual chemotherapeutic and immune response-eliciting effects, is expected to exert synergistic effects when administered in combination with DOX. I3A induces the ICD of PCa cells by triggering mitophagy and apoptosis and promotes the normalization of tumor vessels, resulting in sufficient infiltration of immune cells into tumors. A synergistic effect of I3A and DOX was observed in vitro at a molar ratio of 1:4. To codeliver this ratio of I3A and DOX to tumor and ensure their uptake, we designed a dual-targeting delivery system, polylactide-poly(ethylene) glycol-2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate/triphenylphosphonium (PLA-PEG-ACUPA/TPP), which targets prostate-specific membrane antigen (PSMA) and mitochondria. Delivery of these nanomedicines led to inhibited tumor growth and a strong antitumor immune response. This study sheds light on the mitophagic and antiangiogenic mechanisms underlying I3A treatment of PCa and provides a strategy for combining vascular normalization and chemoimmunotherapy for PCa treatment.

Effect of COVID-19 Pandemic on Acute Coronary Syndrome Clinical Practice Patterns: Findings from a Multicenter Clinician Survey in China.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severely affected healthcare systems around the world. This study aimed to investigate the perceptions of cardiologists regarding how the COVID-19 pandemic has affected the clinical practice patterns for acute coronary syndrome (ACS). Methods: A multicenter clinician survey was sent to 300 cardiologists working in 22 provinces in China. The survey collected demographic information and inquired about their perceptions of how the COVID-19 pandemic has affected ACS clinical practice patterns. Results: The survey was completed by 211 (70.3%) cardiologists, 82.5% of whom were employed in tertiary hospitals, and 52.1% reported more than 10 years of clinical cardiology practice. Most respondents observed a reduction in ACS inpatients and outpatients in their hospitals during the pandemic. Only 29.9% of the respondents had access to a dedicated catheter room for the treatment of COVID-19-positive ACS patients. Most respondents stated that the COVID-19 pandemic had varying degrees of effect on the treatment of acute ST-segment elevation myocardial infarction (STEMI), acute non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina. Compared with the assumed non-pandemic period, in the designed clinical questions, the selection of coronary interventional therapy for STEMI, NSTEMI, and unstable angina during the COVID-19 pandemic was significantly decreased (all p < 0.05), and the selection of pharmacotherapy was increased (all p < 0.05). The selection of fibrinolytic therapy for STEMI during the pandemic was higher than in the assumed non-pandemic period (p < 0.05). Conclusions: The COVID-19 pandemic has profoundly affected ACS clinical practice patterns. The use of invasive therapies significantly decreased during the pandemic period, whereas pharmacotherapy was more often prescribed by the cardiologists.

Fis1 phosphorylation by Met promotes mitochondrial fission and hepatocellular carcinoma metastasis.

Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.

Toxic effects of the dinoflagellate Karenia mikimotoi on zebrafish (Danio rerio) larval behavior.

Karenia mikimotoi is a toxic dinoflagellate that forms harmful blooms in coastal waters, threatening aquaculture worldwide. However, we do not know whether K. mikimotoi has a neurotoxic effect on aquatic animal behavior. Thus, this study investigated potential K. mikimotoi neurotoxicity in zebrafish larvae. Cells of K. mikimotoi were collected at the mid-exponential phase from a batch culture to prepare ruptured cell solutions (RCS). At 6 h post-fertilization (hpf), zebrafish embryos were exposed to different RCS concentrations (0, 102, 103, 104, and 2.5 × 104 cells mL-1). After 120 hpf, treated larvae were collected to analyze locomotor behavior; activities of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT); and expression of genes related to neurodevelopment. We found that RCS did not affect survival rate, but significantly decreased larval locomotion, as well as their AChE, SOD, and CAT activity. Additionally, the examination of the day-night behavioral experiment revealed RCS decreased locomotion only at night. Zebrafish larvae were also significantly hypoactive in response to light and sound stimulations. Of the neurodevelopment genes, three (th, neurog1, and neurod1) were downregulated, while two (bdnf and manf) were upregulated. Our study suggests that K. mikimotoi neurotoxicity occurs through causing oxidative damage, as well as disorders in the cholinergic system and nervous system development. The results provide new insight that K. mikimotoi in low abundance did not cause significant lethal effect but still exhibited significant neurotoxicity on aquatic animals.

Sequential receptor-mediated mixed-charge nanomedicine to target pancreatic cancer, inducing immunogenic cell death and reshaping the tumor microenvironment.

Pancreatic cancer (PC) is an aggressive form of cancer with dense stroma and immune-suppressive microenvironment, which are the major barriers for treatment. To address such barriers, this study aimed to develop a sequential receptor-mediated mixed-charge targeted delivery system for PC based on 2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate (ACUPA-) and triphenylphosphonium (TPP+) modified nanomicelles containing ingenol-3-mebutate (I3A), which was named ACUPA-/TPP+-I3A or ACUPA/TPP-I3A. ACUPA/TPP-I3A induced immunogenic cell death (ICD), which significantly increased the number of tumor-infiltrating T lymphocytes, activated adaptive immunity, and achieved superior survival time. I3A, a novel anticancer drug, could induce PC cell necrosis to release damage-associated molecular patterns, thereby activating adaptive immunity. With certain ratios of negatively (ACUPA-) and positively (TPP+) charged ligands, ACUPA/TPP-I3A acquired a negative charge in plasma (pH 7.4, to inhibit aggregation and uptake in the circulation) and was neutral in the acidic tumor microenvironment (pH 5.0-6.0, to overcome electrostatic hindrances and facilitate transcytosis). Furthermore, neovascular endothelium-specific ACUPA enabled rapid transcytosis of ACUPA/TPP-I3A across tumor vessel walls, entering into endosome/lysosomes (pH 4.5-5.0, its charge became positive and exhibited lysosome escape). Then, ACUPA/TPP-I3A selectively targeted mitochondria, which correlated with TPP-mediated effect. Finally, I3A was released to induce ICD that activated adaptive immunity and achieved superior survival time. Therefore, reshaping of the tumor microenvironment and potentiating antitumor immunity using ACUPA-/TPP+-I3A constituted a novel strategy to prolong the survival time.