Matched Redox Kinetics on Triazine-Based Carbon Nitride/Ni(OH)2 for Stoichiometric Overall Photocatalytic CO2 Conversion.

Mismatched reaction kinetics of CO2 reduction and H2O oxidation is the main obstacle limiting the overall photocatalytic CO2 conversion. Here, a molten salt strategy is used to construct tubular triazine-based carbon nitride (TCN) with more adsorption sites and stronger activation capability. Ni(OH)2 nanosheets are then grown over the TCN to trigger a proton-coupled electron transfer for a stoichiometric overall photocatalytic CO2 conversion via "3CO2 + 2H2O = CH4 + 2CO + 3O2." TCN reduces the energy barrier of H2O dissociation to promote H2O oxidation to O2 and supply sufficient protons to Ni(OH)2, whereby the CO2 conversion is accelerated due to the enhanced proton-coupled electron transfer process enabled by the sufficient proton supply from TCN. This work highlights the importance of matching the reaction kinetics of CO2 reduction and H2O oxidation by proton-coupled electron transfer on stoichiometric overall photocatalytic CO2 conversion.

Development of PI3Kγ selective inhibitors: the strategies and application.

The γ isoform of Class I PI3Ks (PI3Kγ) is primarily found in leukocytes and is essential for the function of myeloid cells, as it regulates the migration, differentiation, and activation of myeloid-lineage immune cells. Thus, PI3Kγ has been identified as a promising drug target for the treatment of inflammation, autoimmune disease, and immuno-oncology. Due to the high incidence of serious adverse events (AEs) associated with PI3K inhibitors, in the development of PI3Kγ inhibitors, isoform selectivity was deemed crucial. In this review, an overview of the development of PI3Kγ selective inhibitors in the past years is provided. The isoform selectivity of related drugs was achieved by different strategies, including inducing a specificity pocket by a propeller-shape structure, targeting steric differences in the solvent channel, and modulating the conformation of the Asp-Phe-Gly DFG motif, which have been demonstrated feasible by several successful cases. The insights in this manuscript may provide a potential direction for rational drug design and accelerate the discovery of PI3Kγ selective inhibitors.

Tunable C2 Products via Photothermal Steam Reforming of CO2 over Surface-Modulated Mesoporous Cobalt Oxides.

The conversion of CO2 to high-value products by renewable energy is a promising approach for realizing carbon neutralization, but the selectivity and efficiency of C2+ products are not satisfying. Herein, we report the controllable preparation of highly ordered mesoporous cobalt oxides with modulated surface states to achieve efficient photothermal water-steam reforming of CO2 to C2 products with high activity and tunable selectivity. Pristine mesoporous Co3O4 exhibited an acetic acid selectivity of 96% with a yield rate of 73.44 µmol g-1 h-1. By rationally modifying mesoporous Co3O4 surface states, mesoporous Co3O4@CoO delivered a radically altered ∼100% ethanol selectivity with a yield rate of 14.85 µmol g-1 h-1. Comprehensive experiments revealed that the pH value could strongly influence the selectivity of C2 products over mesoporous cobalt oxides. Density functional theory verified that reduced surface states and rich oxygen vacancies on surface-modified mesoporous cobalt oxides could facilitate further variation of C2 products from acetic acid to ethanol.

MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion.

Mitochondria are double-membraned organelles with variable shapes influenced by metabolic conditions, developmental stage, and environmental stimuli. Their dynamic morphology is a result of regulated and balanced fusion and fission processes. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and the maintenance of membrane potential. Mitofusins are dynamin-related GTPases that are essential for mitochondrial fusion. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via combined oligomerization and GTP hydrolysis. However, the molecular mechanisms of this process remain unknown. Here we present crystal structures of engineered human MFN1 containing the GTPase domain and a helical domain during different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of MFN1 and resembles the 'neck' of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote GTPase domain dimerization in the transition state. Disruption of GTPase domain dimerization abolishes the fusogenic activity of MFN1. Moreover, a conserved aspartate residue trigger was found to affect mitochondrial elongation in MFN1, probably through a GTP-loading-dependent domain rearrangement. Thus, we propose a mechanistic model for MFN1-mediated mitochondrial tethering, and our results shed light on the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders.

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss.

Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica's radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption.

Ethanol Extract of Radix Asteris Suppresses Osteoclast Differentiation and Alleviates Osteoporosis.

Radix Asteris, the root of Aster tataricus L. f., is historically significant in East Asian medicine for treating respiratory conditions. Yet, its implications on bone health remain uncharted. This research investigated the impact of an aqueous ethanol extract of Radix Asteris (EERA) on osteoclast differentiation and its prospective contribution to osteoporosis management. We discerned that EERA retards osteoclast differentiation by inhibiting receptor activator of nuclear factor kappa-B ligand (RANKL) expression and obstructing RANKL-induced osteoclastogenesis. EERA markedly suppressed RANKL-induced expression of NFATc1, a pivotal osteoclastogenic factor, via modulating early RANK signaling. EERA's therapeutic potential was underscored by its defense against trabecular bone degradation and its counteraction to increased body and perigonadal fat in ovariectomized mice, mirroring postmenopausal physiological changes. In the phytochemical analysis of EERA, we identified several constituents recognized for their roles in regulating bone and fat metabolism. Collectively, our findings emphasize the potential of EERA in osteoclast differentiation modulation and in the management of osteoporosis and associated metabolic changes following estrogen depletion, suggesting its suitability as an alternative therapeutic strategy for postmenopausal osteoporosis intertwined with metabolic imbalances.

Overall Carbon-neutral Electrochemical Reduction of CO2 in Molten Salts using a Liquid Metal Sn Cathode.

An overall carbon-neutral CO2 electroreduction requires enhanced conversion efficiency and intensified functionality of CO2 -derived products to balance the carbon footprint from CO2 electroreduction against fixed CO2 . A liquid Sn cathode is herein introduced into electrochemical reduction of CO2 in molten salts to fabricate core-shell Sn-C spheres (Sn@C). An in situ generated Li2 SnO3 /C directs a self-template formation of Sn@C. Benefitting from the accelerated reaction kinetics from the liquid Sn cathode and the core-shell structure of Sn@C, a CO2 -fixation current efficiency higher than 84 % and a high reversible lithium-storage capacity of Sn@C are achieved. The versatility of this strategy is demonstrated by other low melting point metals, such as Zn and Bi. This process integrates energy-efficient CO2 conversion and template-free fabrication of value-added metal-carbon, achieving an overall carbon-neutral electrochemical reduction of CO2 .

M2-phenotype tumour-associated macrophages upregulate the expression of prognostic predictors MMP14 and INHBA in pancreatic cancer.

Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.

Silicate-Mediated Electrolytic Silicon Nanotube from Silica in Molten Salts.

Electrochemical preparation/processing of functional silicon from abundant silica is an ideal protocol to promote sustainability of energy sectors. Such an imperative task is challenged by poor electrical conductivity of Si/SiO2 and inadequate mass diffusion of bulk silicon. Herein, a template-free and one-step preparation of silicon nanotubes (Si-NT) from electrochemical reduction of silica in molten salts is reported. An in situ oriented growth of silicate nanorods (NRs) from silica is clarified as the key step to direct a self-template evolution of Si-NT from silica. The silicate-mediated construction of Si-based NT is versatile and successfully extended to prepare Si-NT/graphite and Tix Siy -NT. Benefitting from fast longitudinal motorways for fast transport of electrons and ions along/inside NTs, an energy consumption 30% lower than industrial silicon production is achieved. When evaluated as anode of lithium ion battery, the Si-NT-based electrodes show outstanding initial Coulombic efficiency and high reversible capacity. The silicate-mediated construction of Si-based NT integrates straightforward preparation and intriguing functionality of Si-based materials, bridging a closed-loop Si-based energy infrastructure.

In Situ Synthesis of CuN4 /Mesoporous N-Doped Carbon for Selective Oxidative Crosscoupling of Terminal Alkynes under Mild Conditions.

The 1,3-conjugated diynes are an important class of chemical intermediates, and the selective crosscoupling of terminal alkynes is an efficient chemical process for manufacturing asymmetrical 1,3-conjugated diynes. However, it often occurs in homogenous conditions and costs a lot for reaction treatment. Herein, a copper catalyzed strategy is used to synthesize highly ordered mesoporous nitrogen-doped carbon material (OMNC), and the copper species is in situ transformed into the copper single-atom site with four nitrogen coordination (CuN4 ). These features make the CuN4 /OMNC catalyst efficient for selective oxidative crosscoupling of terminal alkynes, and a wide range of asymmetrical and symmetrical 1,3-diynes (26 examples) under mild conditions (40 °C) and low substrates ratio (1.3). Density functional theory (DFT) calculations reveal that the aryl-alkyl crosscoupling has the lowest energy barrier on the CuN4 site, which can explain the high selectivity. In addition, the catalyst can be separated and reused by simply centrifugation or filtration. This work can open a facile avenue for constructing single-atom loaded mesoporous materials to bridge homogeneous and heterogeneous catalysis.

CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study.

BACKGROUND: Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS: A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS: The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS: The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis.

Nafamostat, a synthetic serine protease inhibitor, has been used for the treatment of inflammatory diseases such as pancreatitis. Recently, an increasing number of studies have shown the promising antiviral effects of nafamostat for the treatment of coronavirus disease-19 (COVID-19). This study aimed to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and to characterize the pharmacokinetics of nafamostat in rats. Nafamostat in the rat plasma was extracted by solid phase extraction, and 13C6-nafamostat was used as an internal standard. The quantification limit of nafamostat in the rat plasma was 0.5 ng/mL. The LC-MS/MS method was fully validated and applied to characterize the pharmacokinetics of nafamostat in rats. Following intravenous injection (2 mg/kg), nafamostat in the plasma showed a multiexponential decline with an average elimination half-life (t1/2) of 1.39 h. Following oral administration of nafamostat solutions (20 mg/kg) in 10% dimethyl sulfoxide (DMSO) and in 10% DMSO with 10% Tween 80, nafamostat was rapidly absorbed, and the average oral bioavailability was 0.95% and 1.59%, respectively. The LC-MS/MS method and the pharmacokinetic information of nafamostat could be helpful for the further preclinical and clinical studies of nafamostat.

Water Extract of Fritillariae thunbergii Bulbus Inhibits RANKL-Mediated Osteoclastogenesis and Ovariectomy-Induced Trabecular Bone Loss.

Fritillariae thunbergii bulbus has been widely used to treat symptoms of coughs and airway congestion in the chest due to pathological colds and damp phlegm in traditional Chinese medicine. Despite its long history of traditional use, its pharmacological activities on osteoclastogenesis and osteoporosis have not been evaluated. This study investigated the effects of the water extract of Fritillariae thunbergii bulbus (WEFT) on osteoclast differentiation in bone marrow-derived macrophage cells and on ovariectomy (OVX)-induced osteoporosis in mice. We found that WEFT significantly inhibited osteoclastogenesis by downregulating the receptor activator of the NF-κB ligand (RANKL) signaling-induced nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression. In an OVX-induced osteoporosis model, WEFT significantly prevented the OVX-induced trabecular loss of femurs, accompanied by a reduction in fat accumulation in the bone marrow and liver. In addition, WEFT significantly prevented weight gain and gonadal fat gain without recovering uterine atrophy. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, seven alkaloids (peimisine glucoside, yibeissine, peiminoside, sipeimine-glucoside, peimisine, peimine, and peiminine) were identified in WEFT. The results of this study suggest that WEFT can be a potential pharmacological candidate to reduce menopausal osteoporosis and menopause-related symptoms, such as fat accumulation.

Variations in methyl bromide concentration with distance and time during quarantine fumigation.

Methyl bromide (MB) is a highly toxic and ozone-depleting substance and should be replaced. Worker exposure to high MB concentrations during fumigation has been previously reported. However, variations in MB concentration as a function of distance from fumigated objects or of time after degassing have not been reported so far. In this study, air samples were collected at various distances from fumigated objects (oranges, wood in containers, and wood in tarpaulin) during injection and degassing and analyzed via gas chromatography according to the Occupational Safety and Health Agency method. In addition, MB concentrations were directly measured over time using a gas detector during degassing. Non-linear regression analysis of the logarithmically transformed data indicated a clear decrease in MB concentration with distance as well as time. Non-linear regression models were constructed to describe the decrease in MB concentration with distance from the objects and with time during degassing (P < 0.05 for all models). The results of this study could aid in establishing appropriate safety guidelines, and hence, in preventing risks related to MB exposure.

[Longitudinal Study of the Association Between Handgrip Strength and Chronic Disease Multimorbidity among Middle-aged and Older Adults].

OBJECTIVE: To investigate the potential association between multimorbidity and the handgrip strength of middle-aged and older adults. METHODS: The baseline (2011) and second-round follow-up (2015) data of China Health and Retirement Longitudinal Study (CHARLS) were used. Adults≥40 were selected as the subjects of the study. Variables incorporated in the study included handgrip strength, chronic disease prevalence, demographic variables, and health behavior variables. Generalized estimating equations were used to analyze the longitudinal association between handgrip strength and multimorbidity. RESULTS: A total of 28 368 middle-aged and older adults were included in the baseline and follow-up samples, with an average age of (59.1±9.7) years old, the oldest being 96 while the youngest being 40. Among them, 6 239 were male, accounting for 47.3%. In the second-round follow-up, 9 186 baseline respondents and 5 994 new respondents were covered, reaching a total of 15 180 respondents. Compared with the baseline, a higher proportion of the second-round follow-up respondents were female ( P=0.033) and were older ( P<0.001). From the baseline to the second-round follow-up, Q1, the lowest grip strength category, increased from 23.4% to 26.6%, while Q4, the highest grip strength category, decreased from 26.5% to 21.2%. The prevalence of having more than three chronic diseases increased from 18.2% to 24.2% and the prevalence of having more than five chronic diseases increased from 3.3% to 6.2%. After adjusting for confounding variables, the interaction items of handgrip strength and time showed statistical significance. After stratification by gender, the interaction items of male handgrip strength and follow-up time were statistically significant in both models ( P<0.05). The marginal effect graph of the interactive item showed that the multimorbidity prevalence of respondents with lower handgrip levels grew faster with age. Individual effect analysis showed that the correlation between handgrip strength and multimorbidity was not statistically significant at baseline, but the follow-up done four years afterwards showed statistical significant correlation between handgrip strength and multimorbidity. CONCLUSION: Respondents with lower baseline handgrip strength are associated with increasingly higher risk of multimorbidity over time. Handgrip strength can be used as an effective screening tool for middle-aged and older adults in China to identify those at higher risks of multimorbidity of chronic diseases.

[A Study of the Relationship Between Job Satisfaction and Work Engagement of Physicians in Public Hospitals].

OBJECTIVE: To understand the level of job satisfaction and work engagement of physicians in public hospitals, to analyze the interaction between job satisfaction and work engagement, and to discuss how each dimension of job satisfaction affects work engagement so as to provide information and reference for improving the level of work engagement of physicians in public hospitals. METHODS: Covering 6 public hospitals in Sichuan (3 tertiary-level hospitals and 3 secondary-level hospitals), 638 questionnaires were obtained from physicians through convenient sampling for data description and analysis. Pearson correlation method was used to analyze the correlation between job satisfaction and work engagement, and multiple linear stepwise regression method was used to analyze work engagement and the influencing factors of each dimension. RESULTS: With regard to job satisfaction, physicians showed high levels of satisfaction in personal safety (3.77±0.87), leadership identification and support (3.59±0.77), and job pressure (3.51±0.81). The mean points of work engagement and each dimension were as follows: total mean points of work engagement (4.02±0.99), dedication (4.21±1.13), absorption (4.19±1.08) and vigor (3.63±1.04). In job satisfaction, salary and benefits, work environment, social recognition, organizational management, leadership identification and support are positively correlated to work engagement and all dimensions. In job satisfaction, 5 dimensions, including social recognition, leadership recognition and support, work achievement, personal safety and organizational management, had a significant influence on work engagement and all dimensions. CONCLUSION: Emphasis on the high-level needs for recognition and self-actualization of doctors, doctor-patient communication, and personal development of doctors may improve doctors' job satisfaction and work engagement.

Radiomics Based on MRI as a Biomarker to Guide Therapy by Predicting Upgrading of Prostate Cancer From Biopsy to Radical Prostatectomy.

BACKGROUND: Biopsy Gleason score (GS) is crucial for prostate cancer (PCa) treatment decision-making. Upgrading in GS from biopsy to radical prostatectomy (RP) puts a proportion of patients at risk of undertreatment. PURPOSE: To develop and validate a radiomics model based on multiparametric magnetic resonance imaging (mp-MRI) to predict PCa upgrading. STUDY TYPE: Retrospective, radiomics. POPULATION: A total of 166 RP-confirmed PCa patients (training cohort, n = 116; validation cohort, n = 50) were included. FIELD STRENGTH/SEQUENCE: 3.0T/T2 -weighted (T2 W), apparent diffusion coefficient (ADC), and dynamic contrast enhancement (DCE) sequences. ASSESSMENT: PI-RADSv2 score for each tumor was recorded. Radiomic features were extracted from T2 W, ADC, and DCE sequences and Mutual Information Maximization criterion was used to identify the optimal features on each sequence. Multivariate logistic regression analysis was used to develop predictive models and a radiomics nomogram and their performance was evaluated. STATISTICAL TESTS: Student's t or chi-square were used to assess the differences in clinicopathologic data between the training and validation cohorts. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated. RESULTS: In PI-RADSv2 assessment, 67 lesions scored 5, 70 lesions scored 4, and 29 lesions scored 3. For each sequence, 4404 features were extracted and the top 20 best features were selected. The radiomics model incorporating signatures from the three sequences achieved better performance than any single sequence (AUC: radiomics model 0.868, T2 W 0.700, ADC 0.759, DCE 0.726). The combined mode incorporating radiomics signature, clinical stage, and time from biopsy to RP outperformed the clinical model and radiomics model (AUC: combined model 0.910, clinical model 0.646, radiomics model 0.868). The nomogram showed good performance (AUC 0.910) and calibration (P-values: training cohort 0.624, validation cohort 0.294). DATA CONCLUSION: Radiomics based on mp-MRI has potential to predict upgrading of PCa from biopsy to RP. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5 J. Magn. Reson. Imaging 2020;52:1239-1248.

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis.

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and -9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.

[Epidemiology, Treatment, and Epidemic Prevention and Control of the Coronavirus Disease 2019: a Review].

This review summarizes the ongoing researches regarding etiology, epidemiology, transmission dynamics, treatment, and prevention and control strategies of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and pandemic H1N1 virus. SARS-CoV-2 may be originated from bats, and the patients and asymptomatic carriers are the source of epidemic infection. The virus can be transmitted human-to-human through droplets and close contact, and people at all ages are susceptible to this virus. The main clinical symptoms of the patients are fever and cough, accompanied with leukocytopenia and lymphocytopenia. Effective drugs have been not yet available thus far. In terms of the prevention and control strategies, vaccine development as the primary prevention should be accelerated. Regarding the secondary prevention, ongoing efforts of the infected patients and close contacts quarantine, mask wearing promotion, regular disinfection in public places should be continued. Meanwhile, rapid detection kit for serological monitoring of the virus in general population is expected so as to achieve early detection, early diagnosis, early isolation and early treatment. In addition, public health education on this disease and prevention should be enhanced so as to mitigate panic and mobilize the public to jointly combat the epidemic.

STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant progression of gastric cancer cells via mTOR signal-mediated inhibition of autophagy.

BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student's t-test (two-tailed). RESULTS: We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker.