Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography.

OBJECTIVE: To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion (LAAO) guided by cardiac computed tomography angiography (CCTA). METHODS: Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched (1:2). Each step of the LAAO procedure in the computed tomography (CT) guidance group (CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA. RESULTS: A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years (P = 0.52), respectively. The procedure duration (45.6 ± 10.7 min vs. 58.8 ± 13.0 min, P < 0.001) and hospital stay (7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group (904.9 ± 348.0 mGy vs. 711.9 ± 211.2 mGy, P = 0.002). There were no significant differences in periprocedural pericardial effusion (3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events (13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up. CONCLUSIONS: CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

Antifeedant, Antifungal Cryptic Polyketides with Six Structural Frameworks from Tea Endophyte Daldinia eschscholtzii Propelled by the Antagonistic Coculture with Phytopathogen Colletotrichum pseudomajus and Different Culture Methods.

The antagonistic coculture with tea phytopathogen Colletotrichum pseudomajus induces antifungal cryptic metabolites from isogenesis endophyte Daldinia eschscholtzii against tea phytopathogens. Sixteen new polyketides with six structural frameworks including ten cryptic ones, named coldaldols A-C (1-3), collediol (5), and daldinrins A-L (10-20 and 23), were found from the coculture of C. pseudomajus and D. eschscholtzii by different culture methods. The unique framework of compounds 11 and 12 featured a benzopyran-C7 polyketone hybrid, and compounds 13-16 were characterized by the novel benzopyran dimer. The structures were determined mainly by spectroscopic methods, including extensive one-dimensional (1D), two-dimensional (2D) NMR, high resolution electrospray ionisation mass spectroscopy (HRESIMS), ECD calculation, and single-crystal X-ray diffraction. The configuration of acyclic compounds 5 and 18 were determined by application of the universal NMR database. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus and Alternaria sp. with MICs of 1-8 µg/mL. Compound 12 had stronger antifungal activity than that of positive drug nystatin. The ether bond at C-4 of the benzopyran derivative increased the antifungal activity. Compounds 4-9 and 11-23 showed antifeedant activities against silkworms with feeding deterrence indices of 15-100% at the concentration of 50 µg/cm2.

Feasibility and safety of the direct current cardioversion at the time of left atrial appendage occlusion for patients with atrial fibrillation.

Background: With an increasing number of patients undergoing left atrial appendage occlusion (LAAO), more attention is being paid to relieving clinical symptoms and improving the quality of life of these patients. For patients with atrial fibrillation (AF), direct current cardioversion (DCCV) is an alternate, nonpharmacological choice to restore sinus rhythm and relieve clinical symptoms. Objectives: The purpose of this study was to assess the feasibility and safety of the DCCV at the time of LAAO for patients with AF. Methods: Forty patients were enrolled in the DCCV group undergoing the DCCV at the time of LAAO. The control group undergoing LAAO alone was formed by 1:1 matching. Results: In the DCCV group, cardioversion was immediately successful in 30 (75%) patients, of which 12 (40%) had AF recurrence at the three-month follow-up. The failed-DCCV group was older (73.70 ± 4.74 vs. 62.20 ± 9.01 years old, P = 0.000), had a faster postcardioversion heart rate (88.80 ± 16.58 vs. 70.97 ± 14.73 times, P = 0.03), and had a higher mean HAS-BLED score (4.00 vs. 3.00, P = 0.01) than the successful-DCCV group. No patients experienced periprocedural pericardial effusion, occluder displacement, device embolism, or >5 mm peridevice leakage. One patient experienced a transient ischemic attack (TIA) in the DCCV group during the follow-up. Conclusions: The DCCV at the time of LAAO is feasible and safe for AF patients with contraindications for catheter ablation or AF recurrence after previous catheter ablation to restore the sinus rhythm and relieve clinical symptoms. The DCCV at the time of LAAO is more likely to succeed for younger patients and patients with lower HAS-BLED scores.

Functional Nucleic Acids-Engineered Bio-Barcode Nanoplatforms for Targeted Synergistic Therapy of Multidrug-Resistant Cancer.

Rational design of multifunctional nanomedicines has revolutionized the therapeutic efficacy of cancers. Herein, we have constructed the functional nucleic acids (FNAs)-engineered nanoplatforms based on the concept of a bio-barcode (BBC) for synergistic targeted therapy of multidrug-resistant (MDR) cancer. In this study, the platinum(IV) prodrug is synthesized to covalently link two kinds of FNAs at a rational ratio to fabricate three-dimensional BBC-like DNA nanoscaffolds, accompanied by the one-pot encapsulation of ZnO nanoparticles (NPs) through electrostatic interaction. The multivalent AS1411 aptamers equipped in ZnO@BBCs facilitate specific and efficient endocytosis into MDR human lung adenocarcinoma cells (A549/DDP). In response to the intracellular environment of A549/DDP cells, such as the lysosome-acidic pH and overexpressed GSH, the ZnO NPs are degraded into Zn2+ ions for generating reactive oxygen species (ROS), while the Pt(IV) prodrugs are reduced into Pt(II) active species by glutathione (GSH), followed by the release of therapeutic DNAzymes for chemotherapy and gene therapy. In particular, the designed system plays an important role in remodeling the intracellular environment to reverse cancer MDR. On the one hand, the depletion of GSH promotes the downregulation of glutathione peroxidase 4 (GPX4) for amplifying oxidative stress and increasing lipid peroxidation (LPO), resulting in the activation of ferroptosis. On the other hand, the silence of early growth response protein 1 (Egr-1) mRNA by Zn2+-dependent DNAzymes directly inhibits the proliferation and migration of MDR cells, which further suppresses the P-glycoprotein (P-gp)-mediated drug efflux. Thus, the proposed nanoplatforms show great promise for the development of versatile therapeutic tools and personalized nanomedicines for MDR cancers.

[New Developments in Research on the Relationship Between Osteoarthritis and Oral-Gut Microbes].

Osteoarthritis (OA) is the most common type of arthritis. The prevalence and the incidence of OA have been continuously growing along with increased life expectancy and the emerging problem of an aging population around the global. Reported findings have confirmed that osteoarthritis is a chronic inflammatory disease and its major risk factors included genetic susceptibility, aging, and environmental factors. However, the pathogenic mechanisms of osteoarthritis remain unclear. Recent studies have shown that oral-gut microbes are associated with the onset and development of osteoarthritis and may provide new targets for osteoarthritis treatment. Herein, we reviewed the latest developments in research on the relationship between oral-gut microbes and the onset and development of osteoarthritis, with a view to creating new perspectives for further elucidation of the pathogenesis of osteoarthritis and exploration of effective treatments in the future.

New AMH cutoff values for warning of decreased ovarian response based on MCL characteristics in young women: a retrospective study using a propensity score-matching analysis.

BACKGROUND: Menstrual cycle length (MCL) and ovarian response varies widely among women of childbearing age. They are provided with anti-Mu¨llerian hormone (AMH) cutoffs for "normal" and "weakened" ovarian responses, which give an early warning of the onset of decreased ovarian response. METHODS: This was a retrospective study in women aged 21 to 35 years with MCLs of 21-35 days receiving in vitro fertilization (IVF) treatment at Center for Reproductive Medicine from October 2018 to October 2021. Intergroup variables were balanced using propensity score matching based on age and BMI, and each case patient (patients with MCLs of 21-25 days) was matched with three control patients (patients with MCLs of 26-35 days). A receiver operating characteristic curve was used to calculate the AMH cutoff values. RESULTS: We included 135 patients with MCLs of 21-25 days and 405 matched control patients with MCLs of 26-35 days who received IVF treatment. The case group had significantly fewer retrieved oocytes, lower AMH values and higher initial and total Gonadotropin (Gn) levels during controlled ovarian hyperstimulation than the control group. The ovarian response began to decrease when AMH was < 3.5 ng/ml in the case group and < 2.7 ng/ml in the control group. CONCLUSION: In young women with MCLs of 21-35 days, short MCL was negatively correlated with AMH values and the number of oocytes retrieved. In patients with MCLs of 21-25 days and 26-35 days, the AMH cutoff values corresponding to the onset of decreased ovarian response were 3.5 ng/ml and 2.7 ng/ml, respectively.

[Effect of Mycobacterium tuberculosis higBA on Bacterial Stress Response and Intracellular Infection and Immunity].

Objective: To investigate the effect of Mycobacterium tuberculosis ( Mtb) higBA on bacterial stress response and intracellular infection and immunity. Methods: The target gene amplified from Mtb H37Rv genome was cloned to the vector and then transferred to Mycobacterium smegmatis ( Ms) to construct a recombinant strain. Stress response experiment and Raw264.7 mouse macrophage infection was carried out with Ms_higBA, the recombinant strain, and Ms_ vec, the vector strain. Tests were conducted to measure bacterial colony forming unit (CFU) and transcriptional levels of cytokines, including interleukin ( IL)-1ß, IL-6, IL-10, IL-12 p40, interferon ( IFN)- γ, tumor necrosis factor ( TNF)- α, and inducible nitric oxide synthase ( iNOS). Results: The recombinant strain, Ms_higBA, was constructed successfully. According to the findings of the stress response experiment, higBA could indeed enhance bacterial survival under certain conditions of in vitro culture. Intracellular infection experiment demonstrated that higBA enhanced bacterial survival in macrophages and influenced the transcriptional level of cytokines. Conclusion: The higBA genes from Mtb play a role in bacterial stress response and intracellular infection and immunity.

Biometric Photoelectrochemical-Visual Multimodal Biosensor Based on 3D Hollow HCdS@Au Nanospheres Coupled with Target-Induced Ion Exchange Reaction for Antigen Detection.

Three-dimensional (3D) hollow photoactive nanomaterials can enhance light capture due to the light scattering benefiting from the unique hollow nanostructures, which contributes to the decrease in energy loss and the electron-hole recombination during the process of photoelectric conversion. Herein, a 3D hollow HCdS@Au nanosphere synthesized by the templated-assisted method and photodeposition is employed to construct a multimodal sensing platform by combining the photoelectrochemical (PEC) biosensor with colorimetric analysis and photothermal imaging. In the presence of target carcinoembryonic antigen (CEA), a sandwich structure is formed on magnetic beads based on the dual-aptamer recognition, followed by the initiation of rolling circle amplification (RCA) to bind numerous CuO-DNA probes. Upon stimulation by chlorhydric acidic, a large number of Cu2+ is released from CuO, which could interact with yellow HCdS@Au on electrode to produce dark CuS by ion exchange. As a result, with increased CEA level, the photocurrent is weakened and the color of electrode interface is changed from yellow to dark, which thus facilitates the PEC and colorimetric detection of CEA. Simultaneously, the formed CuS with highly photothermal effect can achieve qualitative visual analysis of CEA using a portable infrared thermal imager. This work exhibits an excellent performance for sensitive and selective detection of CEA in the dynamic working range from 0.015 to 2.4 ng/mL with a detection limit as low as 3.5 pg/mL. Moreover, the proposed PEC biosensor is successfully applied to CEA determination in human serum, which holds great promise in accurate analysis of biomarkers and early diagnosis of diseases in the clinic.

Intraorbital wooden foreign bodies: case series and literature review.

Intraorbital wooden foreign bodies (IOWFBs) constitute a relatively rare ocular trauma, which occupy a special type of intraorbital foreign bodies (IOFBs). Data regarding IOWFBs must be obtained from case reports or small case series due to their rarity. Here, we reported 5 cases of IOWFBs and reviewed the related literatures, which could provide comprehensive information regarding the clinical manifestations, diagnosis, and surgical treatment of IOWFBs. Combined with the published literature, a total of 51 independent cases were counted after we added 5 cases. Among them, the number of male and female patients was 35 and 16 respectively; the mean age was 27.3±18.2 (range 1-66)y. Obviously, the disorder seemed to occur mainly in young and middle-aged people. Because of the diversity in the clinical manifestations and imaging characteristics of IOWFBs, misdiagnosis and missed diagnosis often occur during the initial visit. Delayed diagnosis may lead to a high risk of orbital infection caused by IOWFBs. Surgery is the treatment of choice for most patients; however, the missed diagnosis and residue of foreign bodies after previous surgery cannot be ignored. Therefore, an accurate diagnosis is governed by the detailed trauma history, careful ocular examination, close observation of clinical manifestations, correct imaging diagnosis [e.g., magnetic resonance imaging (MRI) or computerized tomography (CT)], and timely and completely elimination of IOWFBs.

Associations of soybean products intake with blood pressure changes and hypertension incidence: the China-PAR project.

BACKGROUND: The relationships between dietary intake of soybean products and incident hypertension were still uncertain. This study aimed to illustrate the associations between intake of soybean products with risks of incident hypertension and longitudinal changes of blood pressure in a prospective cohort study. METHODS: We included 67, 499 general Chinese adults from the Project of Prediction for Atherosclerosis Cardiovascular Disease Risk in China (China-PAR). Information about soybean products consumption was collected by standardized questionnaires, and study participants were categorized into the ideal (≥ 125 g/day) or non-ideal (< 125 g/day) group. Hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for incident hypertension were calculated using Cox proportional hazard models. Among participants with repeated measures of blood pressure, generalized linear models were used to examine the relationships between soybean products consumption and blood pressure changes. RESULTS: During a median follow-up of 7.4 years, compared with participants who consumed < 125 g of soybean products per day, multivariable adjusted HR for those in the ideal group was 0.73 (0.67-0.80). This inverse association remained robust across most subgroups while significant interactions were tested between soybean products intake and age, sex, urbanization and geographic region (P values for interaction < 0.05). The mean systolic and diastolic blood pressure levels were 1.05 (0.71-1.39) mmHg and 0.44 (0.22-0.66) mmHg lower among participants in the ideal group than those in the non-ideal group. CONCLUSIONS: Our study showed that intake of soybean products might reduce the long-term blood pressure levels and hypertension incidence among Chinese population, which has important public health implications for primary prevention of hypertension.

[Preliminary Study on the Secretory Performance of Mycobacterium tuberculosis Hypoxic Response Protein 1 (Rv2626c)].

OBJECTIVE: To verify the secretory ability of the hypoxic response protein 1 (HRP1) encoded by Mycobacterium tuberculosis (Mtb) Rv2626c. METHODS: The target gene attached with His tag was amplified from the genome of Mtb standard virulence strain H37Rv. The recombinant plasmid contained the above amplified product was constructed and electroporated into Mycobacterium smegmatis (Ms) (MC 2155) to construct a recombinant strain. Protein expression was induced under heat condition, and the expression of protein from the culture filtrates and the bacterial lysates was detected afterward. The 10 kDa culture filtrate antigen (CFP-10) (Ms) and CFP-10 (Mtb) were used as positive controls, and the cytoplasmic protein heat shock protein 65 (GroEL2) (Mtb) was used as negative controls. RESULTS: The HRP1, GroEL2 (Mtb), CFP-10 (Mtb) and CFP-10 (Ms) were successfully amplified by PCR from recombinant plasmid, and sequencing results of the recombinant plasmid is right, confirming the successful construction of the recombinant plasmid. The recombinant Ms was successfully constructed and it could express the proteins GroEL2 (Mtb), HRP1, CFP-10 (Mtb) and CFP-10 (Ms). The target protein HRP1 was detected in both of the lysate and the culture filtrate of the recombinant strain by Western blot, which was consistent with the positive control CFP-10. The negative control GroEL2 (Mtb) was only detected in the bacterial lysate, but not detected in the culture filtrate. CONCLUSION: The protein HRP1 encoded by Mtb Rv2626c can be secreted out of Ms by the secretion system of Ms. It may be a secreted protein and play an important role in the pathogenesis of Mtb.

Association of cardiovascular diseases with milk intake among general Chinese adults.

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

Beneficial effects of moderate to vigorous physical activity on cardiovascular disease among Chinese adults.

BACKGROUND: In China, lack of evidence remains a significant challenge for the national initiative to promote physical activity (PA). We aimed to quantify the beneficial effects of meeting or maintaining the recommended PA level [150 minutes per week (min/wk) of moderate PA or 75 min/wk of vigorous PA or an equivalent combination] on incident cardiovascular disease (CVD) among Chinese population. METHODS: We included 100,560 participants without history of CVD from three cohorts in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events and its subtypes, including stroke, coronary heart disease, heart failure, and CVD death. RESULTS: During a median follow-up of 7.3 years (range: 6-15 years), 777,163 person-years and 4693 incident CVD events were observed. Compared with participants who were inactive at baseline, the multivariable adjusted HR (95% CI) of developing CVD was 0.74 (0.69-0.79) for those who met recommended moderate to vigorous physical activity (MVPA) level at baseline. Furthermore, the risk of CVD incidence was reduced with increment of MVPA (P trend < 0.001), and the HR (95% CI) of highly-active versus inactive category was 0.62 (0.56-0.68). Compared with individuals who were inactive both at the baseline and follow-up, those keeping active over the period of follow-up had a substantial lower risk of incident CVD with the HR (95% CI) of 0.57 (0.43-0.77). CONCLUSIONS: The findings demonstrated that meeting and maintaining the recommended MVPA level could reduce the cardiovascular risk. Wider adoption of the PA recommendations would have considerable health impacts to the Chinese population.

Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China.

OBJECTIVE: To explore the interactions between pre-pregnancy body mass index (BMI) and age on offspring neuropsychological development from 1 to 24 months in China. METHODS: In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China, between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient (DQ) of children aged from 1 to 24 months. RESULTS: Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains (gross motor, fine motor, adaptive, language, and social; P < 0.001). Age × pre-pregnancy BMI ⪖ 25 kg/m2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m2 (P < 0.01). Multiple comparisons showed pre-pregnancy BMI ⪖ 25 kg/m2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months (P < 0.05). CONCLUSION: This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect (from 1 to 24 months).

Upregulation of SCNN1A Promotes Cell Proliferation, Migration, and Predicts Poor Prognosis in Ovarian Cancer Through Regulating Epithelial-Mesenchymal Transformation.

Background: There is little knowledge about the biological roles and clinical significance of SCNN1A in ovarian cancer. Thus, the objective of this study was to investigate the biological functions and prognosis value of SCNN1A in ovarian cancer to further seek a potential therapeutic target for patients with ovarian cancer. Materials and Methods: First, the expression level of SCNN1A in ovarian cancer samples obtained from ONCOMINE database was determined, and its expression in cell lines was also investigated. Moreover, correlation analysis was performed to determine the relationship between SCNN1A expression and prognosis in ovarian cancer patients according to the data obtained from GEPIA database and Kaplan-Meier plotter website. The biological roles of SCNN1A on cell growth, migration, and invasion were then examined by knockdown of SCNN1A in ovarian cancer cell line SK-OV-3. Ultimately, Western blotting analysis was carried out to investigate the expression of epithelial-mesenchymal transformation markers (including E-cadherin, N-cadherin, Vimentin, and Snail) after silencing SCNN1A. Results: Based on the ONCOMINE-related data and cell lines, SCNN1A was observed to be overexpressed in ovarian cancer samples and cell lines. Survival analysis showed that high expression of SCNN1A was associated with poor overall survival and progression-free survival in ovarian cancer patients. In addition, SCNN1A silence remarkably blocked SK-OV-3 cell growth ability, migration, and invasion potential. Western blotting results showed that SCNN1A silence led to an increase in E-cadherin, whereas a decrease in N-cadherin, Vimentin, and Snail in SK-OV-3 cells. Increased E-cadherin and decreased N-cadherin, Vimentin, as well as Snail inhibited cell invasion of ovarian cancer. Conclusions: SCNN1A might exert crucial roles in cell growth and invasion and migration in ovarian cancer, and might be a potential indicator for prognosis and a therapeutic target for ovarian cancer patients.

Ultrasensitive detection of long non-coding RNAs based on duplex-specific nuclease-actuated cyclic enzymatic repairing-mediated signal amplification.

We develop a new fluorescent method for sensitive detection of long noncoding RNAs (lncRNAs) on the basis of duplex-specific nuclease-actuated cyclic enzymatic repairing-mediated signal amplification. This method exhibits high sensitivity with a detection limit of 0.081 fM, and it can accurately detect the endogenous lncRNA HOTAIR in cancer cells, providing a new approach to study the physiological function of lncRNAs in human diseases.

A study of the application of EZSCAN in pilots and in the general population.

OBJECTIVE: This study aims to evaluate EZSCAN detection in pilots and the general population, and determine the significance of EZSCAN detection in the identification of a pilot's health. METHODS: A total of 87 cases of non-diabetic Air Force pilots (pilot group) and 49 cases from the general population without diabetes were collected. These two groups of subjects underwent EZSCAN detection, as well as the detection of blood glucose, lipid and uric acid levels. RESULTS: Subjects in the pilot group had the highest detection rate of no risk and the lowest detection rate of high risk, while the general population had the highest detection rate of high risk, followed by low risk. The difference in diabetic risk between these two groups were statistically significant (P < 0.01). Various indicators were compared according to different risk levels. In the no risk group, age, BMI and the triglyceride of pilots were lower than in the general population; and the difference was statistically significant (P < 0.05). In high risk group, BMI and blood uric acid of pilots were lower than in the general population; and the difference was statistically significant (P < 0.05). CONCLUSIONS: BMI and blood uric acid are positively correlated to diabetic risk. The EZSCAN detection system can be used for assessment of pilot's diabetic risk, and has certain significance in a pilot's health identification.

Preinduction with bone morphogenetic protein-2 enhances cardiomyogenic differentiation of c-kit+ mesenchymal stem cells and repair of infarcted myocardium.

BACKGROUND: Preclinical and clinical trails show that c-kit+ cardiac stem cells can differentiate towards cardiovascular cells and improve cardiac function after myocardial infarction (MI). However, survival and differentiation of the engrafted stem cells within ischemic and inflammatory microenvironment are poor. METHODS: c-Kit+ cells were isolated from mesenchymal stem cells (MSCs) of rat bone marrow. Reliability of preinduction with bone morphogenetic protein-2 (BMP-2) in promotion of survival and differentiation of c-kit+ MSCs was assessed in vitro and after transplantation. RESULTS: c-Kit+ MSCs have a potential to differentiate towards cardiomyocytes. BMP-2 promotes proliferation, migration and paracrine of the cells, and protects the cells to survive in the hypoxic condition. After induction with 10 ng/mL BMP-2 for 24 h, the cells can differentiate into cardiomyocytes at four weeks. The electrophysiological characteristics of the differentiated cells are same as adult ventricular cardiomyocytes. In rat MI models, cardiac function was improved, the size of scar tissue was reduced, and regeneration of the myocardium and microvessels was enhanced significantly at four weeks after transplantation of BMP-2-preinduced cells. The survived cells and cardiomyocytes differentiated from the engrafted cells were increased greatly. CONCLUSION: The results suggest that transient treatment with BMP-2 can induce c-kit+ MSCs to differentiate into functional cardiomyocytes. Preinduction with BMP-2 enhances survival and differentiation of the cells. BMP-2-primed cells promote repair of the infarcted myocardium and improvement of cardiac function. Transplantation of BMP-2-preinduced c-kit+ MSCs is a feasible strategy for MI therapy.

Label-Free Sensitive Detection of DNA Methyltransferase by Target-Induced Hyperbranched Amplification with Zero Background Signal.

DNA methyltransferases (MTases) may specifically recognize the short palindromic sequences and transfer a methyl group from S-adenosyl-l-methionine to target cytosine/adenine. The aberrant DNA methylation is linked to the abnormal DNA MTase activity, and some DNA MTases have become promising targets of anticancer/antimicrobial drugs. However, the reported DNA MTase assays often involve laborious operation, expensive instruments, and radio-labeled substrates. Here, we develop a simple and label-free fluorescent method to sensitively detect DNA adenine methyltransferase (Dam) on the basis of terminal deoxynucleotidyl transferase (TdT)-activated Endonuclease IV (Endo IV)-assisted hyperbranched amplification. We design a hairpin probe with a palindromic sequence in the stem as the substrate and a NH2-modified 3' end for the prevention of nonspecific amplification. The substrate may be methylated by Dam and subsequently cleaved by DpnI, producing three single-stranded DNAs, two of which with 3'-OH termini may be amplified by hyperbranched amplification to generate a distinct fluorescence signal. Because high exactitude of TdT enables the amplification only in the presence of free 3'-OH termini and Endo IV only hydrolyzes the intact apurinic/apyrimidinic sites in double-stranded DNAs, zero background signal can be achieved. This method exhibits excellent selectivity and high sensitivity with a limit of detection of 0.003 U/mL for pure Dam and 9.61 × 10-6 mg/mL for Dam in E. coli cells. Moreover, it can be used to screen the Dam inhibitors, holding great potentials in disease diagnosis and drug development.

Verticillium dahliae manipulates plant immunity by glycoside hydrolase 12 proteins in conjunction with carbohydrate-binding module 1.

Glycoside hydrolase 12 (GH12) proteins act as virulence factors and pathogen-associated molecular patterns (PAMPs) in oomycetes. However, the pathogenic mechanisms of fungal GH12 proteins have not been characterized. In this study, we demonstrated that two of the six GH12 proteins produced by the fungus Verticillium dahliae Vd991, VdEG1 and VdEG3 acted as PAMPs to trigger cell death and PAMP-triggered immunity (PTI) independent of their enzymatic activity in Nicotiana benthamiana. A 63-amino-acid peptide of VdEG3 was sufficient for cell death-inducing activity, but this was not the case for the corresponding peptide of VdEG1. Further study indicated that VdEG1 and VdEG3 trigger PTI in different ways: BAK1 is required for VdEG1- and VdEG3-triggered immunity, while SOBIR1 is specifically required for VdEG1-triggered immunity in N. benthamiana. Unlike oomycetes, which employ RXLR effectors to suppress host immunity, a carbohydrate-binding module family 1 (CBM1) protein domain suppressed GH12 protein-induced cell death. Furthermore, during infection of N. benthamiana and cotton, VdEG1 and VdEG3 acted as PAMPs and virulence factors, respectively indicative of host-dependent molecular functions. These results suggest that VdEG1 and VdEG3 associate differently with BAK1 and SOBIR1 receptor-like kinases to trigger immunity in N. benthamiana, and together with CBM1-containing proteins manipulate plant immunity.