Enhanced secretion of hepatocyte growth factor in human umbilical cord mesenchymal stem cells ameliorates pulmonary fibrosis induced by bleomycin in rats

Umbilical cord mesenchymal stem cells (UCMSCs) are a reportedly promising choice in the treatment of irreversible pulmonary fibrosis and lethal interstitial lung disease with limited drug treatment options. In this study, we investigated the therapeutic efficacy of UCMSCs overexpressing hepatocyte growth factor (HGF), which is considered one of the main anti-fibrotic factors secreted by MSCs. Adenovirus vector carrying the HGF gene was transfected into UCMSCs to produce HGF-modified UCMSCs (HGF-UCMSCs). Transfection promoted the proliferation of UCMSCs and did not change the morphology, and differentiation ability, or biomarkers. Rats were injected with HGF-UCMSCs on days 7 and 11 after intratracheal administration of bleomycin (10 mg/kg). We performed an analysis of histopathology and lung function to evaluate the anti-fibrotic effect. The results showed that HGF-UCMSCs decreased the Ashcroft scores in hematoxylin and eosin-stained sections, the percentage positive area in Masson trichrome-stained sections, and the hydroxyproline level in lungs. Forced expiratory volume in the first 300 m/forced vital capacity was also improved by HGF-UCMSCs. To explore the possible therapeutic mechanism of HGF-UCMSCs, we detected inflammatory factors in the lungs and performed mRNA sequencing in UCMSCs and HGF-UCMSCs. The data indicated that inhibition of interleukin-17 in the lung may be related to the anti-fibrosis of HGF-UCMSCs, and overexpressed HGF probably played a primary role in the treatment. Collectively, our study findings suggested that the overexpression of HGF may improve the anti-fibrotic effect of UCMSCs through directly or indirectly interacting with interleukin-17-producing cells in fibrotic lungs

The feasibility and safety of his-purkinje conduction system pacing in patients with heart failure with severely reduced ejection fraction

ObjectiveThe purpose of this study was to evaluate the feasibility and outcomes of conduction system pacing (CSP) in patients with heart failure (HF) who had a severely reduced left ventricular ejection fraction (LVEF) of less than 30% (HFsrEF).MethodsBetween January 2018 and December 2020, all consecutive HF patients with LVEF < 30% who underwent CSP at our center were evaluated. Clinical outcomes and echocardiographic data [LVEF and left ventricular end-systolic volume (LVESV)], and complications were all recorded. In addition, clinical and echocardiographic (≥5% improvement in LVEF or ≥15% decrease in LVESV) responses were assessed. The patients were classified into a complete left bundle branch block (CLBBB) morphology group and a non-CLBBB morphology group according to the baseline QRS configuration.ResultsSeventy patients (66 ± 8.84 years; 55.7% male) with a mean LVEF of 23.2 ± 3.23%, LVEDd of 67.33 ± 7.47 mm and LVESV of 212.08 ± 39.74 ml were included. QRS configuration at baseline was CLBBB in 67.1% (47/70) of patients and non-CLBBB in 32.9%. At implantation, the CSP threshold was 0.6 ± 0.3 V @ 0.4 ms and remained stable during a mean follow-up of 23.43 ± 11.44 months. CSP resulted in significant LVEF improvement from 23.2 ± 3.23% to 34.93 ± 10.34% (P < 0.001) and significant QRS narrowing from 154.99 ± 34.42 to 130.81 ± 25.18 ms (P < 0.001). Clinical and echocardiographic responses were observed in 91.4% (64/70) and 77.1% (54/70) of patients. Super-response to CSP (≥15% improvement in LVEF or ≥30% decrease in LVESV) was observed in 52.9% (37/70) of patients. One patient died due to acute HF and following severe metabolic disorders. Baseline BNP (odds ratio: 0.969; 95% confidence interval: 0.939–0.989; P = 0.045) was associated with echocardiographic response. The proportions of clinical and echocardiographic responses in the CLBBB group were higher than those in the non-CLBBB group but without significant statistical differences.ConclusionsCSP is feasible and safe in patients with HFsrEF. CSP is associated with a significant improvement in clinical and echocardiographic outcomes, even for patients with non-CLBBB widened QRS

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism

Artificial intelligence : A powerful paradigm for scientific research

Y Artificial intelligence (AI) coupled with promising machine learning (ML) techniques well known from computer science is broadly affecting many aspects of various fields including science and technology, industry, and even our day-to-day life. The ML techniques have been developed to analyze high-throughput data with a view to obtaining useful insights, categorizing, predicting, and making evidence-based decisions in novel ways, which will promote the growth of novel applications and fuel the sustainable booming of AI. This paper undertakes a comprehensive survey on the development and application of AI in different aspects of fundamental sciences, including information science, mathematics, medical science, materials science, geoscience, life science, physics, and chemistry. The challenges that each discipline of science meets, and the potentials of AI techniques to handle these challenges, are discussed in detail. Moreover, we shed light on new research trends entailing the integration of AI into each scientific discipline. The aim of this paper is to provide a broad research guideline on fundamental sciences with potential infusion of AI, to help motivate researchers to deeply understand the state-of-the-art applications of AI-based fundamental sciences, and thereby to help promote the continuous development of these fundamental sciences.Peer reviewe

Gram-Negative Bacterial Sensors for Eukaryotic Signal Molecules

Ample evidence exists showing that eukaryotic signal molecules synthesized and released by the host can activate the virulence of opportunistic pathogens. The sensitivity of prokaryotes to host signal molecules requires the presence of bacterial sensors. These prokaryotic sensors, or receptors, have a double function: stereospecific recognition in a complex environment and transduction of the message in order to initiate bacterial physiological modifications. As messengers are generally unable to freely cross the bacterial membrane, they require either the presence of sensors anchored in the membrane or transporters allowing direct recognition inside the bacterial cytoplasm. Since the discovery of quorum sensing, it was established that the production of virulence factors by bacteria is tightly growth-phase regulated. It is now obvious that expression of bacterial virulence is also controlled by detection of the eukaryotic messengers released in the micro-environment as endocrine or neuro-endocrine modulators. In the presence of host physiological stress many eukaryotic factors are released and detected by Gram-negative bacteria which in return rapidly adapt their physiology. For instance, Pseudomonas aeruginosa can bind elements of the host immune system such as interferon-γ and dynorphin and then through quorum sensing circuitry enhance its virulence. Escherichia coli sensitivity to the neurohormones of the catecholamines family appears relayed by a recently identified bacterial adrenergic receptor. In the present review, we will describe the mechanisms by which various eukaryotic signal molecules produced by host may activate Gram-negative bacteria virulence. Particular attention will be paid to Pseudomonas, a genus whose representative species, P. aeruginosa, is a common opportunistic pathogen. The discussion will be particularly focused on the pivotal role played by these new types of pathogen sensors from the sensing to the transduction mechanism involved in virulence factors regulation. Finally, we will discuss the consequence of the impact of host signal molecules on commensally or opportunistic pathogens associated with different human tissue

HIV-Related Stress Experienced by Newly Diagnosed People Living with HIV in China: A 1-Year Longitudinal Study

This study explored the HIV-related stressors that people living with HIV (PLWH) commonly experience and express as stressful at the time of diagnosis and 1 year later. The factors associated with stress levels and whether social support would moderate the negative effects of stress on psychological health (depressive and anxiety symptoms) were also investigated. Newly diagnosed PLWH were consecutively recruited in this study. Participants rated their stress with the HIV/AIDS Stress Scale at baseline and 1 year later. Social support, depression, and anxiety were also self-reported at both time points. There were significant decreases in stress levels 1 year after diagnosis. Stressors regarding confidentiality, disclosure, emotional distress, fear of infecting others, and excessive attention to physical functions were the most problematic at baseline and 1-year follow-up. A younger age, married status, not living alone, less income, presence of HIV symptoms, and lack of social support were associated with higher levels of stress. No stress-buffering effect of social support on depressive and anxiety symptoms was found in this study. Interventions to reduce stress among PLWH should take into consideration the following priority stressors: confidentiality, discrimination/stigma, serostatus disclosure, distressing emotions, fear of infecting others, and excessive attention to physical functions. More attention should be paid to PLWH with younger age, not living alone, less income, presence of HIV symptoms, and lack of social support

Medication adherence to antiretroviral therapy among newly treated people living with HIV

Abstract Background Free antiretroviral therapy has been implemented in China since 2004, but adherence to antiretroviral therapy among people living with HIV is suboptimal. The effectiveness of antiretroviral therapy is subject to medication adherence, which decreases with prolonged treatment times. The aim of this study was to investigate medication adherence and related factors among people living with HIV with newly initiated antiretroviral therapy. Methods This observational study was conducted in consecutive samples of people living with HIV who had newly initiated antiretroviral therapy. Participants were recruited between March 1, 2013, and August 31, 2014, from the local Center for Disease Control and Prevention and Infectious Disease hospital in a capital city in central China. A standard set of questionnaires was adopted, including the Community Programs for Clinical Research on AIDS Antiretroviral Medications and Self-Report Questionnaire (CPCRA), the Patient Health Questionnaire-9 (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7). T-test, Chi square test and multivariate logistic regression analysis with backward stepwise were performed to explore factors that might influence medication adherence. Results Of the 207 participants, 85.5% of the participants (177/207) were categorized with good adherence, and 14.5% (30/207) with poor adherence. The multivariate logistic regression analyses showed that participants with positive depression (OR = 5.95, 95% CI: 2.34–15.11) and without disclosure of their HIV status to others (OR = 2.62, 95% CI: 1.06–6.50) were more susceptible to poor adherence. Conclusions One-sixth of the participants reported suboptimal medication adherence within the first 6 months. Factors associated with poor adherence included non-disclosure of their HIV status, had positive depression. Tailored interventions, such as effective psychological coping strategies, should be implemented for people living with HIV with newly initiated antiretroviral therapy to improve their medication adherence

Cross-culture validation of the HIV/AIDS stress scale: The development of a revised Chinese version

Background: Being HIV-infected is a stressful experience for many individuals. To assess HIV-related stress in the Chinese context, ameasure with satisfied psychometric properties is yet underdeveloped. This study aimed to examine the psychometric characteristics of a simplified Chinese version of the HIV/AIDS Stress Scale (SS-HIV) among people living with HIV/AIDS in central China. Method: A total of 667 people living with HIV (92% were male) were recruited from March 1 2014 to August 31 2015 by consecutive sampling. A standard questionnaire package containing the Chinese HIV/AIDS Stress Scale (CSS-HIV), the Chinese Patient Health Questionnaire-9 (PHQ-9), and the Chinese Generalized Anxiety Disorder Scale (GAD-7) were administered to all participants, and 38 of the participants were selected randomly to be re-tested in four weeks after the initial testing. Results: Our data supported that a revised 17-item CSS-HIV had adequate psychometric properties. It consisted of 3 factors: emotional stress (6 items), social stress (6 items) and instrumental stress (5 items). The overall Cronbach's α was 0.906, and the test-retest reliability coefficient was 0.832. The revised CSS-HIV was significantly correlated with the number of HIV-related symptoms, as well as scores on the PHQ-9 and GAD-7, indicating acceptable concurrent validity. Conclusion: The 17-item Chinese version of the SS-HIV has potential research and clinical utility in identifying important stressors among the Chinese HIV-infected population and in understanding the effects of stress on adjustment to HIV