Uncovering Microbial Composition of the Tissue Microenvironment in Bladder Cancer using RNA Sequencing Data.

Purpose: Bladder cancer (BC) is one of the top 10 common tumors in the world. It has been reported that microbiota can colonize tissues and play important roles in tumorigenesis and progression. However, the current understanding of microorganisms in the BC tissue microenvironment remains unclear. Methods: In this study, we integrated the RNA-seq data of 479 BC tissue samples from seven datasets combined with a range of bioinformatics tools to explore the landscape of microbiome in the BC tissue microenvironment. Results: The pan-microbiome was estimated to surpass 1,400 genera. A total of seven core microbiota (Bacillus, Corynebacterium, Cutibacterium, Escherichia, Halomonas, Pasteurella, and Streptomyces) were identified. Among them, Bacillus was widely distributed in all datasets with a high relative abundance (10.11% of all samples on average). Moreover, some biological factors, including tissue source and tumor grade, were found significant effects on the microbial composition of the bladder tissue. Pseudomonas, Porphyrobacter, and Acinetobacter were enriched in tumor tissues, while Mycolicibacterium and Streptomyces were enriched in patients who showed durable response to BCG therapy. In addition, we established microbial co-occurrence networks and found that the BCG therapy may attenuate the microbiological interactions. Conclusions: This study clearly provided a microbial landscape of the BC tissue microenvironment, which was important for exploring the interactions between microorganisms and BC tissues. The identified specific taxa might be potential biomarkers for BC.

Mapping global zoonotic niche and interregional transmission risk of monkeypox: a retrospective observational study.

BACKGROUND: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. METHODS: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 - 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. RESULTS: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89-6.71), Brazil (3.45, 95% CI: 1.62-7.00) and the United States (2.44, 95% CI: 1.62-3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. CONCLUSIONS: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Leveraging Ligand and Composition Effects: Morphology-Tailorable Pt-Bi Bimetallic Aerogels for Enhanced (Photo-)Electrocatalysis.

Metal aerogels (MAs) are emerging porous materials displaying unprecedented potential in catalysis, sensing, plasmonic technologies, etc. However, the lack of efficient regulation of their nano-building blocks (NBBs) remains a big hurdle that hampers the in-depth investigation and performance enhancement. Here, by harmonizing composition and ligand effects, Pt- and Bi-based single- and bimetallic aerogels bearing NBBs of controlled dimensions and shapes are obtained by facilely tuning the metal precursors and the applied ligands. Particularly, by further modulating the electronic and optic properties of the aerogels via adjusting the content of the catalytically active Pt component and the semiconducting Bi component, both the electrocatalytic and photoelectrocatalytic performance of the Pt-Bi aerogels can be manipulated. In this light, an impressive catalytic performance for electro-oxidation of methanol is acquired, marking a mass activity of 6.4-fold higher under UV irradiation than that for commercial Pt/C. This study not only sheds light on in situ manipulating NBBs of MAs, but also puts forward guidelines for crafting high-performance MAs-based electrocatalysts and photoelectrocatalysts toward energy-related electrochemical processes.

Mechanism of NF-κB Signaling Pathway in Regulating Lung Cancer and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Lung cancer is the leading cause of cancer-related deaths， and standard treatments for lung cancer， including surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， have shown significant clinical effects. However， current available treatment strategies are still unable to cure the disease. Since the majority of lung cancer patients are diagnosed at an advanced stage， surgical options are often lost， and the primary approach is typically a combination of radiotherapy and chemotherapy. However， the adverse reactions associated with these treatments limit their effectiveness and application， and the damage caused to normal tissues is often more severe than that inflicted on the tumor. Currently， traditional Chinese medicine （TCM） has been used as part of combination therapy for cancer treatment due to its unique system of syndrome differentiation， flexible compatibility， and safety and efficacy. TCM prescriptions and single drugs with multiple components and targets can simultaneously regulate multiple pathways. As reported， among numerous pathways involved in the regulation of lung cancer， the nuclear factor-κB （NF-κB） signaling pathway plays a key role in inducing cell transcription and is one of the main pathways involved in the occurrence and development of lung cancer. It can specifically regulate inflammatory responses， cell proliferation， apoptosis， invasion and metastasis， angiogenesis， and multidrug resistance in lung cancer. TCM prescriptions and single drugs can inhibit lung cancer cell proliferation， invasion， and metastasis， induce apoptosis and autophagy in lung cancer cells， suppress angiogenesis， regulate immune function， and treat multidrug resistance by regulating the NF-κB signaling pathway. Therefore， they play a role in intervening in lung cancer. However， there is currently a lack of systematic literature research that comprehensively summarizes and elucidates these aspects in China and abroad. Therefore， it is important to provide a systematic elucidation of the mechanism underlying the regulation of the NF-κB signaling pathway in lung cancer and review TCM interventions in lung cancer based on the NF-κB signaling pathway. This study is expected to provide references for the clinical application of lung cancer therapeutic drugs and the development of new drugs.

Study on the current situation and optimal paths of "physical-medical integration" talents training / 中华医学教育探索杂志

At present, four operating modes have been explored for physical-medical integration in China: hospital health guidance center, sports club health guidance, community health monitoring center and industry-university-research cooperation on the integration of physical and medical services. However, physical-medical integration is still in its infancy, the cultivation of physical-medical integration talents has been a key to the deep development of "physical-medical integration". The researches show that the current training mode of integrative talents mainly focuses on on-the-job training, which is faced with many problems such as serious shortage of specialized talents, imperfect certification system and single talent training mode. It is suggested that the training system, the curriculum system, the public opinion system and the professional standards should be improved so as to realize the scientific and sustainable development of physical-medical talents.

Folic acid supplementation acts as a chemopreventive factor in tumorigenesis of hepatocellular carcinoma by inducing H3K9Me2-dependent transcriptional repression of LCN2.

The effects and mechanisms of folic acid (FA) as a chemopreventive agent for tumorigenesis of hepatocellular carcinoma (HCC) remain unclear. In this study, the QSG-7701, a human normal liver cell line, was cultured in different FA levels (High, Normal or No) for 6 months. Then, the biological characteristics, the expression of main stem cell-like genes or epithelial-mesenchymal transition (EMT) related genes and the tumorigenicity in vivo of cells cultured in different treatment groups were detected. Our results showed that No FA improved the malignant transformation of cells but High FA depressed the malignant transformation. Meanwhile, cells in different treatment groups were mapped by transcriptome sequencing. Then the relativity of increased LCN2 and decreased FA level was identified and confirmed in vitro and vivo. We also revealed that intracellular control of LCN2 would recover the effects of FA on cell proliferation, cell cycle and tumor formation in vitro and vivo. Finally, our studies displayed that increased FA level induced the down-regulation of LCN2 not by DNA hypermethylation of LCN2 promoter but by promoting the level of histone H3 lysine 9 di-methylation (H3K9Me2) in LCN2 promoter. In conclusion, our studies disclosed the chemopreventive effect of FA supplementation on hepatocarcinogenesis, which partial attributed to the inhibition of LCN2 by regulating histone methylation in promoter. Our results provide a potential mechanism of the chemoprevention of FA supplementation on tumorigenesis of HCC and may be helpful in developing treatment target against HCC.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma: a prospective study

OBJECTIVESTo determine the rate of intubation, overall survival, viral clearance, and the development of endogenous antibodies in patients with COVID-19 pneumonia treated with convalescent plasma containing high levels of neutralizing anti-SARS-CoV-2 antibodies. We also aimed to describe the laboratory parameters of the plasma products. DESIGNThis was a phase IIa, single institution, prospective study in adults hospitalized with SARS-CoV-2 pneumonia. SETTINGHackensack University Medical Center, a 770-bed research and teaching hospital located in Bergen County NJ, 11 km from New York City. The study was conducted between April 15 and June 18, 2020. PARTICIPANTS47 hospitalized adult patients were treated: 32 in the non-mechanically ventilated group and 15 in the mechanically ventilated group. All patients had confirmed SARS-CoV-2 pneumonia by radiographic and laboratory evaluation. INTERVENTIONFresh or frozen convalescent plasma from donors with high titers of viral neutralizing antibodies was administered. MAIN OUTCOME MEASURESIncidence of intubation, overall survival, and discharge rate of patients divided in cohorts based on severity of disease. Description of infused plasma characteristics. Evaluation of recipients pre-treatment viral immunity, immunity transfer from convalescent plasma administration, and late immunity 30 and 60 days after treatment. Rates of viral clearance by nasopharyngeal PCR at 10 and 30 days. Outcomes of patients with no pre-treatment immunity. Survival comparison with institutional data for each cohort. RESULTSAnalysis for the non-mechanically ventilated patients showed an intubation rate of 15.6% (95% CI: 5.3%-32.8%) and a day-30 survival rate of 87.5% (28/32; 95% CI:70.2%-96.4%). The overall survival for a comparative group based on institutional data was 66% (675/1023; p=0.012). The rates of negative nasopharyngeal swab by PR-PCR on day+10 and +30 post treatment were 42.9% (95% CI: 24%-63%) and 78% (95% CI: 56%-93%) respectively. Patients mechanically ventilated had a day-30 mortality of 46.7% (95% CI:21.3%-73.4%); the mortality for a comparative group based on institutional data was 68.5% (217/317; p=0.093). The rates of negative nasopharyngeal swab by PR-PCR at day+10 and +30 was 85.7% (95% CI: 42-100%; n=7) and 100% (95% CI: 63-100%; n=8). Seven patients (15%) had no pre-infusion immunity, and all were found to have anti-SARS-CoV-2 neutralizing titers three days post infusion. All evaluable patients were found to have neutralizing antibodies on day+30 (n=30) and on day+60 (n=12) post treatment. There was no difference in outcomes within the ranges of high antiviral neutralizing titers used, mostly greater than 1:1000. There was also no difference between fresh or frozen plasma. The only adverse event was a mild rash in one patient. CONCLUSIONIn this study of adult patients hospitalized with SARS-CoV-2 pneumonia, convalescent plasma was safe and conferred effective transfer of immunity while preserving endogenous immune response. Intubation rates, survival rates compared with institutional data, and viral clearance rates, support the continued evaluation of this antiviral modality. STUDY REGISTRATIONClinicalTrials.gov NTC04343755

Clinical characteristics of postprandial hypotension in elderly patients with coronary heart disease / 中国综合临床

Objective To observe the incidence,clinical characteristics,related factors,adverse events during hospitalization and short-term prognosis of postprandial hypotension (PPH) in elderly patients with coronary heart disease.Methods One hundred and sixty-eight elderly patients with coronary heart disease hospitalized in the Department of Cardiology,Second Hospital of Hebei Medical University from January 2014 to January 2015 were selected as the research subjects.They were monitored by 24 h ambulatory blood pressure monitoring.According to the diagnostic criteria of PPH,they were divided into postprandial hypotension group (PPH group) 34 cases and non-postprandial hypotension group (NPPH group) 134 cases.The clinical characteristics,risk factors related to PPH,occurrence of adverse events and prognosis of all-cause death,cardiovascular and cerebrovascular adverse events were compared between the two groups.Results Among 168 elderly patients with coronary heart disease,thirty-four patients had PPH,and the incidence rate was 20.2％ (34/168).The average systolic blood pressure before meals in PPH group was (139.8± 18.6) mmHg (1 mmHg =0.133 kPa).The proportion of taking calcium antagonists was 50.0％ (17/34) higher than that in NPPH group (127.4± 13.2) mmHg,27.6％ (37/134).The difference between the two groups was statistically significant (t =6.463,x2=6.232,P＜ 0.05).PPH was higher in breakfast and dinner than in lunch;the higher the basal systolic blood pressure level,the higher the incidence of PPH.Logistic regression analysis showed that the basal systolic blood pressure level and age were positively correlated with the occurrence of PPH (r =0.301,r =0.208,P＜ 0.05).Follow-up for 26 months showed that the incidence of all-cause death and cerebrovascular events in PPH group was higher than that in NPPH group (x2 =5.800,11.560,P＜ 0.05).Conclusion The incidence of PPH in elderly patients with coronary heart disease during hospitalization is 20.2％.Breakfast and dinner at three meals are prone to PPH.Older age and high systolic blood pressure level will increase the incidence of PPH.PPH will increase the incidence of mid-term all-cause death and cerebrovascular events.

Study on Preparation and in vitro Release Characteristic of Ursolic Acid/PF 127/TPGS-doxorubicin Mixed Nanomicelles / 中国药房

OBJECTIVE： To prepare Ursolic acid （UA）/Pluronic F127 （PF127）/TPGS-doxorubicin （DOX） mixed nanomicelles， and to characterize it and study its in vitro release behavior. METHODS： UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index， combined with the results of single factor tests， L9（34） orthogonal test was used to optimize drug dosage of UA， molar ratio of PF127 to TPGS， hydration temperature and hydration volume， validation test was performed. On the basis of succinylated TPGS， TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles， the appearance， particle size and critical micelle concentration （PF127/TPGS） were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS： The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg， molar ratio of PF127 to TPGS 3 ∶ 7， hydration temperature 50 ℃， hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00％ （RSD＝0.43％， n＝3）. The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size； average particle size was （115.00±9.42） nm； critical micelle concentration of PF127/TPGS （molecular ratio 3 ∶ 7） was 0.001 3％. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down， compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS： UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size， good stability and good sustained-release effect.

DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas.

Aberrant DNA methylation patterns, which induced by folate deficiency, play important roles in tumorigenesis of colorectal cancer (CRC). Some DNA methylation alterations can also be detected in cell-free DNA (cfDNA) of patients' plasma, making cfDNA an ideal noninvasive circulating biomarker. However, exact DNA methylation alterations induced by folate deficiency in tumorigenesis of CRC and exact potential circulating cfDNA methylation biomarker are still unclear. Therefore, DNA methylation patterns of the normal human colon mucosal epithelial cell line (NCM460), cultured with normal or low folate content, were screened and the DNA hypomethylation of cystathionine-beta-synthase (CBS) promoter was further validated in vitro and vivo. Then, the correlation analysis between folate level, DNA methylation alteration in promoter and expression of CBS was carried out in vitro and vivo. Further, the methylation patterns of CBS promoter in plasma cfDNA were detected and statistically correlated with pathological parameters and clinical outcome. Our study showed that DNA hypomethylation in CBS promoter, induced by folate deficiency, would lead to up-regulation of CBS both in vitro and vivo. Patients with cfDNA hypomethylation of CBS promoter in plasma were correlated with high tumor stage and poor clinical outcome. In addition, cfDNA hypomethylation of CBS promoter in plasma was shown to be an independent prognostic factor for recurrence and cancer-related death in CRC. Our results indicated that DNA hypomethylation of CBS promoter induced by folate deficiency could serve as a potential noninvasive circulating biomarker and may be helpful in developing more effective prognostic markers for CRC.

Methylation-induced loss of miR-484 in microsatellite-unstable colorectal cancer promotes both viability and IL-8 production via CD137L.

Colorectal cancer (CRC) exhibiting MSI (microsatellite instability) represents a well-defined subtype characterized by a deficient mismatch repair pathway and typical clinico-pathological features. Our objective was to identify the entire miRNome and its molecular pathological roles in MSI CRCs. We profiled miRNA expression in MSI CRCs and compared it with MSS counterparts. Microarray and qRT-PCR analysis identified eight miRNAs that could distinguish the MSI status of CRCs. MiR-484 was the most significantly decreased miRNA in MSI CRCs, primarily mediated by the CpG island methylator phenotype. MiR-484 functions as a tumour suppressor to inhibit MSI CRC cell viability in vitro and in vivo. Moreover, miR-484 repressed CD137L expression and thereby attenuated IL-8 production by MSI CRC cells. Our results contribute to a better understanding of the roles of dysregulated miRNAs in the distinct phenotypic features of MSI CRCs and indicate an option for early diagnosis and gene therapy for these patients.

Characterization of the genotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma.

UNLABELLED: Early-onset hepatocellular carcinoma (HCC) accounts for 15%-20% of total HCC cases in Asia, and the incidence is increasing. The low frequency of cirrhosis and poor prognosis of early-onset HCC suggests that its mechanisms may differ from late-onset HCC. Although hepatitis B virus (HBV) infection is epidemiologically associated with HCC, the role of HBV in early-onset HCC remains poorly understood. Here, we report a comparative study of HBV subgenotypes and integration in early- (≤30) and late-onset (≥70) HBV-associated HCC using a novel high-throughput viral integration detection method. We report that HBV B2 is predominantly present in early-onset HCC. HBV integration is a common phenomenon, both in early- and late-onset HCC, which favors integrating into human repeat regions. Moreover, we found a breakpoint in 8q24 located between c-Myc and plasmocytoma variant translocation 1 (PVT1), which was detected in 12.4% (14 of 113) of early-onset HCCs, but only 1.4% (2 of 145) in late-onset HCCs. HBV integrating this site results in c-MYC, PVT1, and microRNA-1204 overexpression in tumors, thereby potentially contributing to the development of early-onset HCC. CONCLUSION: HBV genotype and integration patterns may be distinct in early-onset HCC. Our results may shed light on HCC risk factors in young HBV carriers. Further studies are needed to elucidate at which time in tumor development this integration event occurs and whether it plays an important, causative role in HCC development or progression.

Laboratory observation on low molecular heparin for treating high coagulation state in patients with nephrotic syndrome / 重庆医学

Objective To observe the curative effect of low molecular heparin for treating secondary high coagulation state in the patients with nephrotic syndrome(NS) .Methods Total 87 cases of NS in our hospital were divided into the conventional treat‐ment group (n=42) and the low molecular heparin treatment group (n=45) .The routine treatment group was given the prednisone treatment and the low molecular heparin treatment group was treated by low molecular heparin combined with prednisone .The re‐lated indicators of blood coagulation before and after treatment were detected and the clinical curative effects in two groups were an‐alyzed .Results The coagulation related indicators in the conventional treatment group had no statistically significant difference be‐tween before and after treatment (P>0 .05) ,the prothrombin time(PT) and activated partial thrombin time(APTT) after treat‐ment in the low molecular heparin treatment group were significantly extended compared with before treatment ,while the concen‐trations of D‐dimer and fibrinogen were significantly decreased and the concentration of antithrombin Ⅲ was markedly increased compared with before treatment ,showing statistically significant differences between the two groups (P<0 .05);the patients of the low molecular heparin group patients had no bleeding after treatment .Conclusion Low molecular heparin combined with predni‐sone can reduce the secondary high condensation state in NS without bleeding and has a significantly clinical effect .

MicroRNA-23a antisense enhances 5-fluorouracil chemosensitivity through APAF-1/caspase-9 apoptotic pathway in colorectal cancer cells.

Current literature provided information that alteration in microRNA expression impacted sensitivity or resistance of certain tumor types to anticancer treatment, including the possible intracellular pathways. The microRNA-23a (miR-23a)-regulated apoptosis in response to the 5-fluorouracil (5-FU)-induced mitochondria-mediated apoptotic pathway was determined in this study. The miR-23a expression in 5-FU-treated and untreated colon cancer cells and tissues was assessed using real-time PCR analysis. To determine the function of miR-23a in the regulation of 5-FU-induced apoptosis, cell-proliferation, cytotoxicity, and apoptosis analyses were performed. Dual luciferase reporter assay was used to identify the apoptosis-related target gene for miR-23a. The activity of caspases-3, -7, and -9 were also assessed in miR-23a antisense and 5-FU treated tumor cells. A xenograft tumor model was established to evaluate the biological relevance of altered miR-23a expression to the 5-FU-based chemotherapy in vivo. We found that the expression of miR-23a was increased and the level of apoptosis-activating factor-1 (APAF-1) was decreased in 5-FU-treated colon cancer cells compared to untreated cells. The activation of the caspases-3 and 7 was increased in miR-23a antisense and 5-FU-treated colon cancer cells compared to negative control. APAF-1, as a target gene of miR-23a, was identified and miR-23a antisense-induced increase in the activation of caspase-9 was observed. The overexpression of miR-23a antisense up-regulated the 5-FU induced apoptosis in colon cancer cells. However, the miR-23a knockdown did not increase the antitumor effect of 5-FU in xenograft model of colon cancer. This study shows that miR-23a antisense enhanced 5-FU-induced apoptosis in colorectal cancer cells through the APAF-1/caspase-9 apoptotic pathway.

T-2 toxin inhibits mitochondrial function of differentiated murine embryonic stem cells / 中国药理学与毒理学杂志

OBJECTIVE ToexplorethepossiblemechanismoractiontargetsofT-2toxinembryo toxicity by observing the effect of T-2 toxin on mitochondrial function of differentiated murine e mbryonic stemcells(mESCs).METHODS Duringdifferentiationat24,72and120h,ESCswereexposedto T-2 toxin 0.5 μg·L-1 .Meanwhile,mESCs were pre-treated with antioxidant Trolox (200 μmol·L-1 )for 30 min and exposed to T-2 toxin (0.5 μg·L-1 )for 72 h.The mitochondrial ultrasture of differentiated mESCs was observed under a transi mission electrical microscope (TEM).The differentiated ESC mito-chondrial function,including respiratory control ratio (RCR),ATP synthase activity and mitochondrial membranepotential(MMP),wasmeasuredat144hafterdifferentiation.RESULTS Significant decrease of the mitochondrial number,deformation of mitochondrial structure,and lack of complete mito-chodrial crest were observed through TEM in the groups of T-2 toxin exposed for 72 and 1 20 h,respec-tively.Compared with the normal control group,RCR declined by 49.5% and 55.1%,ATP synthase activity decreased by 84.9% and 89.3%,and MMP decreased by 23.2% and 35.2% in T-2 toxin 0.5 μg·L-1 exposure 72 and 1 20 h group,respectively.However,the inhibition of mitochondrial function by T-2 toxin in differentiated mESCs recovered significantly in the presence of the antioxidant Trolox. CONCLUSION T-2toxininducesoxidativestressandinhibitsmESCsmitochondrialfunctionindifferenti-ated mESCs,and ROS-induced mitochondrial malfunction plays an i mportant role in T-2 toxin e mbryonic toxicity mechanis m.

[Nuclear transfer and reprogramming in fish].

As an important sub-field in the study of animal cloning, fish nuclear transfer was first established in the early 1960s by Chinese embryologists. Due to its advantages, zebrafish has become a unique animal model to study the mystery of reprogramming in nuclear transfer. This article summarizes the history and current situation in fish nuclear transfer technology and discusses the factors that may influence the development of the cloned embryos. A comprehensive understand-ing of the mechanism for epigenetic modification following nuclear transfer, such as genomic DNA methylation and histone acetylation and/or methylation, will likely increase the success rate and eventually lead to the future freedom of cloning technique.

Solution-phase parallel syntheses of herbicidal 1-phenyl-2,4,5- imidazolidinetriones and 2-thioxo-4,5-imidazolidinediones.

In order to find new herbicidally active compounds, a fifteen-member library, focusing on the variation of 3- position substituents of 2,4,5-imidazolidine-trione or 2-thioxo-4,5-imidazolidinedione, was designed and prepared in parallel by the reaction of various ureas or thioureas with oxalyl chloride using solution-phase technology. An interesting and, to the best of our knowledge, unprecedented finding is that a by-product of 1-phenyl-3-propylcarbodiimide was formed during the addition of oxalyl chloride into the solution of 1-phenyl-3-propylthiourea in the presence of triethylamine in dichloromethane. It has been shown that the herbicidal activity of 2,4,5-imidazolidinetriones is about the same as that of their analogous 2-thioxo-4,5-imidazolidinediones. Compound with propyl or isopropyl group at the 3- position of 2,4,5-imidazolidinetrione ring demonstrated good herbicidal activity. The most active compound, 1-(2-fluoro- 4-chloro-5-propargyloxy)-phenyl-3-propyl-2-thioxo-4,5-imidazolidinedione, gave 95% control of the growth of velvetleaf at 200 g/ha in the post-emergence test.

The contribution of the SPINK1 c.194+2T>C mutation to the clinical course of idiopathic chronic pancreatitis in Chinese patients.

BACKGROUND: Recent data suggest that the serine protease inhibitor Kazal type 1 (SPINK1) gene mutation is associated with idiopathic chronic pancreatitis. However, few studies have focused on the serine protease inhibitor Kazal type 1 c.194+2T>C mutation. Therefore, our goal was to study the prevalence and impact of serine protease inhibitor Kazal type 1 mutations on the clinical profile of idiopathic chronic pancreatitis patients in China. METHODS: A retrospective-cohort study of 118 Chinese patients with idiopathic chronic pancreatitis was performed, and genetic tests were carried out to detect SPINK1 mutations. Subjects without pancreatitis were used as controls. In total, 118 idiopathic chronic pancreatitis patients and 100 control subjects were evaluated. RESULTS: The serine protease inhibitor Kazal type 1 c.194+2T>C variant was present in 44.9% of patients with idiopathic chronic pancreatitis. The frequency of diabetes in idiopathic chronic pancreatitis patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (39.6%) was higher than that of patients without the mutation (9.2%). The time to occurrence of diabetes mellitus after idiopathic chronic pancreatitis symptom onset is significantly influenced by the c.194+2T>C mutation (p<0.001). In addition, the mean age of diabetes onset in patients with the serine protease inhibitor Kazal type 1 c.194+2T>C mutation (38.33 ± 9.50) was significantly younger than that of patients without this mutation (49.67 ± 6.74). CONCLUSIONS: The presence of the serine protease inhibitor Kazal type 1 c.194+2T>C mutation seems to be associated with idiopathic chronic pancreatitis and could predispose individuals to pancreatic diabetes onset at an earlier age.

Design and preparation of polyurethane-collagen/heparin-conjugated polycaprolactone double-layer bionic small-diameter vascular graft and its preliminary animal tests / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>People recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft (SDVG) transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique.</p><p><b>METHODS</b>Heparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis.</p><p><b>RESULTS</b>The double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells.</p><p><b>CONCLUSION</b>The double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.</p>

Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease.

Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia.