Miracle-dz/UniFAR-FTUs huggingface dataset:
Benefits of different intensities of pulmonary rehabilitation for patients with moderate-to-severe COPD according to the GOLD stage: a prospective, multicenter, single-blinded, randomized, controlled trial

Purpose Pulmonary rehabilitation (PR) is essential to manage patients with COPD. The aim of this study was to investigate the appropriate intensity of PR exercise training for patients with moderate-to-severe COPD. Patients and methods A prospective multicenter randomized controlled trial was conducted from January 2014 to October 2018. The subjects were randomly assigned to three groups with different intensities of PR, according to their maximum oxygen uptake percentage determined by cardiopulmonary exercise testing. After 20 weeks of exercise training, the effects of low-, moderate-, and high-intensity exercise interventions on patients were compared to determine the most appropriate PR prescription. Results For patients with moderate COPD, all the measured parameters were significantly improved in the moderate- and high-intensity PR groups (P<0.01), while there was no significant difference in the frequency of acute exacerbations and the mMRC questionnaire after 20 weeks of PR exercise in the low-intensity PR group. For patients with severe COPD, all variables were also improved in the high-intensity PR group (P<0.05), while the mean differences of pre- and post-PR were lower than those in patients with moderate COPD. Moreover, the Hamilton Anxiety Scale and body mass index showed no significant difference in low-intensity PR group (P>0.05). Conclusion High-intensity PR exercise is helpful for patients with moderate to severe COPD. Moderate COPD patients need to receive intensive PR training; the improvement degrees from PR intervention were higher than those of the severe COPD patients. For patients with severe COPD, high-intensity PR exercise may be more beneficial if patients can tolerate it.
Risk Factors And Epigenetic Markers Of Left Ventricular Diastolic Dysfunction With Preserved Ejection Fraction In A Community-Based Elderly Chinese Population

Purpose Left ventricular diastolic dysfunction with preserved ejection fraction (LVDD-PEF) is an early-stage manifestation but poorly understood in the process of heart failure. This study was designed to investigate risk factors and epigenetic markers for predicting LVDD-PEF. Patients and methods A community-based study in 1568 residents over 65 years was conducted in Shanghai, People’s Republic of China, from June 2014 to August 2015. Echocardiography was performed to diagnose LVDD-PEF. DNA methylation by whole-genome bisulfite sequencing was used to determine those potential epigenetic markers contributing to LVDD-PEF. Results A total of 177 participants (11.3%) were diagnosed with LVDD-PEF, and higher prevalence in females than in males (15.0% vs 6.5%, P<0.001). Multivariate logistic regression analysis indicated that female sex (OR 2.46, 95% CI 1.47–4.13), body mass index (BMI) (OR 1.09, 95% CI 1.04–1.14), pulse pressure (PP) (OR 1.03, 95% CI 1.01–1.05) and carotid intima-media thickness (CIMT) (OR 4.20, 95% CI 1.40–12.55) showed a significant association with LVDD-PEF. Overall, 638 CpG sites were differentially methylated in LVDD-PEF group compared to non-LVDD-PEF group (P<0.001); 242 sites were significantly hypermethylated (covering 238 genes) and 396 sites were significantly hypomethylated (covering 265 genes). Conclusion Our findings found female, BMI, PP, and CIMT were independent predictors for LVDD-PEF in the community-dwelling elderly population. Regulation of DNA methylation might play a crucial role for LVDD-PEF.
Lipidomic characterization of extracellular vesicles in human serum

There is a wide variety of extracellular vesicles (EVs) that differ in size and cargo composition. EVs isolated from human plasma or serum carry lipid, protein, and RNA cargo that provides insights to the regulation of normal physiological processes, and to pathological states. Specific populations of EVs have been proposed to contain protein and RNA cargo that are biomarkers for neurologic and systemic diseases. Although there is a considerable amount of evidence that circulating lipids are biomarkers for multiple disease states, it not clear if these lipid biomarkers are enriched in EVs, or if specific populations of EVs are enriched for particular classes of lipid. A highly reproducible workflow for the analysis of lipid content in EVs isolated from human plasma or serum would facilitate this area of research. Here we optimized an MS/MSALL workflow for the untargeted analysis of the lipid content in EVs isolated from human serum. A simple sequential ultracentrifugation protocol isolated three distinct types of serum EVs that were identified based on size, targeted protein, and untargeted lipidomic analyses. EVs in the upper and middle fractions were approximately 140 nm in diameter, while EVs in the pellet were approximately 110 nm in diameter. EVs in the upper most buoyant fractions contained the highest concentration of lipids, were enriched with phospholipids, and immunopositive for the cytoskeletal markers actin, α-actinin, and the mitochondrial protein mitofillin, but negative for the typical EV markers CD63, TSG101, and flotillin. A central fraction of EVs was devoid of cytoskeletal and mitochondrial markers, and positive for CD63, and TSG101, but negative for flotillin. The EV pellet contained no cytoskeletal or mitochondrial markers, but was positive for CD63, TSG101, and flotillin. The EV pellet contained the lowest concentration of most lipids, but was enriched with ceramide. These results provided new insights into the lipid composition of EVs isolated from serum using a simple ultracentrifugation isolation method suitable for lipidomic analysis by mass spectrometry.
Would Colloidal Gold Nanocarriers Present An Effective Diagnosis Or Treatment For Ischemic Stroke?

Introduction This study was conducted to evaluate OX26-PEG-coated gold nanoparticles (GNPs) (OX26@GNPs) as a novel targeted nanoparticulate system on cell survival after ischemic stroke. Materials and methods Dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM) were performed to characterize the OX26@GNPs. The effect of OX26@GNPs on infarct volume, neuronal loss, and necroptosis was evaluated 24 h after reperfusion using 2, 3,5-Triphenyltetrazolium chloride (TTC) staining, Nissl staining and Western blot assay, respectively. Results Conjugation of OX26-PEG to the surface of the 25 nm colloidal gold particles increased their size to 32±2 nm, while a zeta potential change of −40.4 to 3.40 mV remarkably increased the stability of the nanoparticles. Most importantly, OX26@GNPs significantly increased the infarcted brain tissue, while bare GNPs and PEGylated GNPs had no effect on the infarct volume. However, our results indicated an extension of necroptotic cell death, followed by cell membrane damage. Conclusion Collectively, our results showed that the presently formulated OX26@GNPs are not suitable nanocarriers nor contrast agents under oxidative stress for the diagnosis and treatment of ischemic stroke. Moreover, our findings suggest that the cytotoxicity of GNPs in the brain is significantly associated with their surface charge.
Survival Factor Gene FgSvf1 Is Required for Normal Growth and Stress Resistance in Fusarium graminearum

Survival factor 1 (Svf1) is a protein involved in cell survival pathways. In Saccharomyces cerevisiae, Svf1 is required for the diauxic growth shift and survival under stress conditions. In this study, we characterized the role of FgSvf1, the Svf1 homolog in the homothallic ascomycete fungus Fusarium graminearum. In the FgSvf1 deletion mutant, conidial germination was delayed, vegetative growth was reduced, and pathogenicity was completely abolished. Although the FgSvf1 deletion mutant produced perithecia, the normal maturation of ascospore was dismissed in deletion mutant. The FgSvf1 deletion mutant also showed reduced resistance to osmotic, fungicide, and cold stress and reduced sensitivity to oxidative stress when compared to the wild-type strain. In addition, we showed that FgSvf1 affects glycolysis, which results in the abnormal vegetative growth in the FgSvf1 deletion mutant. Further, intracellular reactive oxygen species (ROS) accumulated in the FgSvf1 deletion mutant, and this accumulated ROS might be related to the reduced sensitivity to oxidative stress and the reduced resistance to cold stress and fungicide stress. Overall, understanding the role of FgSvf1 in F. graminearum provides a new target to control F. graminearum infections in fields.
New Approach For Simvastatin As An Antibacterial: Synergistic Effect With Bio-Synthesized Silver Nanoparticles Against Multidrug-Resistant Bacteria

Background Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections. Methods Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by Fusarium oxysporum (AgNPbio) in combination with simvastatin against reference and multidrug-resistant bacterial strains. Results Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL−1 against MRSA. AgNPbio with a size of 77.68± 33.95 nm and zeta potential −34.6 ± 12.7 mV showed an MIC of 0.212 mg mL−1 against S. aureus including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNPbio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNPbio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNPbio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA. Conclusion Our results indicate that the combination of AgNPbio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNPbio are required, with the same antibacterial activity.
Photoluminescent And Self-Assembled Hyaluronic Acid-Zinc Oxide-Ginsenoside Rh2 Nanoparticles And Their Potential Caspase-9 Apoptotic Mechanism Towards Cancer Cell Lines

Background Zinc oxide nanoparticles (ZnO NPs) are used in modern cancer therapy based on their specific target, efficacy, low toxicity and biocompatibility. The photocatalytic performance of Zinc oxide (ZnO) nanocomposites with hyaluronic acid (HA) was used to study anticancer properties against various human cancer cell lines. Methods Zinc oxide (ZnO) nanocomposites functionalized by hyaluronic acid (HA) were prepared by a co-precipitation method (HA-ZnONcs). The submicron-flower-shaped nanocomposites were further functionalized with ginsenoside Rh2 by a cleavable ester bond via carbodiimide chemistry to form Rh2HAZnO. The physicochemical behaviors of the synthesized ZnO nanocomposites were characterized by various analytical and spectroscopic techniques. We carried out 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the toxicity of Rh2HAZnO in various human cancer cells (A549, MCF-7, and HT29). Furthermore, to confirm the apoptotic effects of Rh2HAZnO and to determine the role of the Caspase-9/p38 MAPK pathways by various molecular techniques such as RT-PCR and Western blotting. Furthermore, Rh2HAZnO induced morphological changes of these cell lines, mainly intracellular reactive oxygen species (ROS) were observed by ROS staining and nucleus by Hoechst staining. Results We confirmed that Rh2HAZnO exhibits the anti-cancer effects on A549 lung cancer, HT29 colon cancer, and MCF7 breast cancer cells. Moreover, intracellular reactive oxygen species (ROS) were observed in three cancer cell lines. Rh2HAZnO induced apoptotic process through p53-mediated pathway by upregulating p53 and BAX and downregulating BCL2. Specifically, Rh2HAZnO induced activation of cleaved PARP (Asp214) in A549 lung cancer cells and upregulated Caspase-9/phosphorylation of p38 MAPK in other cell lines (HT29 and MCF-7). Furthermore, Rh2HAZnO induced morphological changes in the nucleus of these cell lines. Conclusion These results suggest that the potential anticancer activity of novel Rh2HAZnO nanoparticles might be linked to induction of apoptosis through the generation of ROS by activation of the Caspase-9/p38 MAPK pathway.
Long Noncoding RNA HCP5 Regulates Pancreatic Cancer Gemcitabine (GEM) Resistance By Sponging Hsa-miR-214-3p To Target HDGF

Background Gemcitabine (GEM) is one of the most widely chemotherapy drugs in PC. However, the chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. lncRNA may play an essential role in PC and serve as a prognosis biomarkers in PC with GEM-resistance. In our study, we aim to investigate the role of lncRNA HCP5 in PC. Materials and methods QRT-PCR detected the expression of lncRNA HCP5. The effects of knockdown lncRNA HCP5 on the proliferation, migration, invasion, cell apoptosis and autophagy were investigated in GEM-resistance PC cells. Bioinformatic analysis, luciferase reporter assay and RNA immunoprecipitation assay were performed to predict for potential miRNAs that can interact with lncRNA HCP5 and mRNAs that can interact with miR-214-3p. Results Our study revealed that lncRNA HCP5 expression was upregulated in PC tissues, especially increased expression in GEM-resistant PC tissues and GEM-resistant PC cells. Wound healing, Transwell assays, flow cytometry, Western blot, luciferase reporter assay and RNA immunoprecipitation (RIP) results demonstrated lncRNA HCP5 acted as a ceRNA to regulate GEM-resistance PC cells' proliferation, invasion, migration, cell apoptosis and autophagy by targeting HDGF via miR-214-3p. Conclusion Our results revealed that lncRNA HCP5 is highly expressed in HCC, and development of GEM-resistance PC cells involving the processes of proliferation, invasive, migration, cell apoptosis and autophagy through the miR-214-3p/HDGF axis. Targeting lncRNA HCP5 may improve gemcitabine-based therapeutic efficacy.
Diffusion Tensor Imaging And Tractography In Autistic, Dysphasic, And Healthy Control Children

Background: Diffusion tensor imaging (DTI) is a powerful tool for investigating brain anatomical connectivity. The aim of our study was to compare brain connectivity among children with autism spectrum disorders (ASD), developmental dysphasia (DD), and healthy controls (HC) in the following tracts: the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Methods: Our sample consisted of 113 children with a mean age 8.7±2.2 years (77 boys, 36 girls), divided into three subgroups: ASD (n=39), DD (n=36), and HC (n=38). The International Classi ﬁ cation of Diseases, 10th ed. was used to make clinical diagnoses. DTI images were collected using a 1.5 T Phillips Achieva MR imaging system. Results: Detailed analyses of fractional anisotropy (FA) revealed signi ﬁ cant differences among the in right but not in the UF. Post-hoc analyses revealed three patterns of FA differences among the groups: (1) in the right AF, right IFOF, and right ILF, FA was signi ﬁ cantly lower in the ASD group compared to the DD and HC groups; however, there was no difference in FA between DD and HC; (2) in the left AF and left IFOF, FA was signi ﬁ cantly lower in the ASD than in the HC group, but there were no differences between DD vs HC nor DD vs ASD; and (3) in the left ILF, no difference in FA was seen between ASD and DD, but FA in both was signi ﬁ cantly lower than in the HC. Conclusion: Microstructural white matter properties differed between ASD vs DD and HC subjects. The tract where FA impairment in ASD and DD subjects was the most similar was the left ILF.
Utility of Big Data in Predicting Short-Term Blood Glucose Levels in Type 1 Diabetes Mellitus Through Machine Learning Techniques

Machine learning techniques combined with wearable electronics can deliver accurate short-term blood glucose level prediction models. These models can learn personalized glucose–insulin dynamics based on the sensor data collected by monitoring several aspects of the physiological condition and daily activity of an individual. Until now, the prevalent approach for developing data-driven prediction models was to collect as much data as possible to help physicians and patients optimally adjust therapy. The objective of this work was to investigate the minimum data variety, volume, and velocity required to create accurate person-centric short-term prediction models. We developed a series of these models using different machine learning time series forecasting techniques suitable for execution within a wearable processor. We conducted an extensive passive patient monitoring study in real-world conditions to build an appropriate data set. The study involved a subset of type 1 diabetic subjects wearing a flash glucose monitoring system. We comparatively and quantitatively evaluated the performance of the developed data-driven prediction models and the corresponding machine learning techniques. Our results indicate that very accurate short-term prediction can be achieved by only monitoring interstitial glucose data over a very short time period and using a low sampling frequency. The models developed can predict glucose levels within a 15-min horizon with an average error as low as 15.43 mg/dL using only 24 historic values collected within a period of sex hours, and by increasing the sampling frequency to include 72 values, the average error is reduced to 10.15 mg/dL. Our prediction models are suitable for execution within a wearable device, requiring the minimum hardware requirements while at simultaneously achieving very high prediction accuracy.
Dual Inhibitors of 8-Oxoguanine Surveillance by OGG1 and NUDT1.

Oxidative damage in DNA is one of the primary sources of mutations in the cell. The activities of repair enzymes 8-oxoguanine DNA glycosylase (OGG1) and human MutT Homolog 1 (NUDT1 or MTH1), which work together to ameliorate this damage, are closely linked to mutagenesis, genotoxicity, cancer, and inflammation. Here we have undertaken the development of small-molecule dual inhibitors of the two enzymes as tools to test the relationships between these pathways and disease. The compounds preserve key structural elements of known inhibitors of the two enzymes, and they were synthesized and assayed with recently developed luminescence assays of the enzymes. Further structural refinement of initial lead molecules yielded compound 5 (SU0383) with IC50 (NUDT1) = 0.034 M, IC50 (OGG1) = 0.49 M. The compound SU0383 displayed low toxicity in two human cell lines at 10 M. Experiments confirm the ability of SU0383 to increase sensitivity of tumor cells to oxidative stress. Dual inhibitors of these two enzymes are expected to be useful in testing multiple hypotheses regarding the roles of 8-oxo-dG in multiple disease states.
The Clinical Value of HSP60 in Digestive System Cancers: a Systematic Review and Meta-Analysis.

BACKGROUND Heat shock protein 60 has been reported to have a high diagnostic value for digestive system cancers. We sought to systematically evaluate the diagnostic value of HSP60 in patients with gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC). METHODS Relevant literature was adopted from the online databases. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were pooled using random effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to express the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software. RESULTS We merged 12 studies in a meta-analysis, including 1 GC, 5 CRC, and 6 HCC. Overall, the pooled sensitivity, specificity, and DOR to predict GC/CRC/HCC patients were 70%, 71%, and 8.49, respectively, corresponding to an AUC of 0.81. In subgroup analysis, the 82% specificity prompted a more advanced diagnostic accuracy for diagnosing CRC than HCC. CONCLUSIONS HSP60 was an advanced biomarker for digestive system cancers and its abnormal expression might have implications for early diagnosis in screening of GC/CRC/HCC.
Draft Genome Sequences of 12 Monophasic Salmonella enterica subsp. enterica Serotype Typhimurium 1,4,[5],12:i:− Strains Isolated from Wild Griffon Vultures in Eastern Spain

Monophasic Salmonella enterica subsp. enterica serovar Typhimurium is one of the most common zoonotic pathogens. Salmonella species reside in a wide variety of hosts, including wild animals. Thus, we report here the genome sequences of 12 monophasic S. Typhimurium strains isolated from healthy wild vultures to gain better insight into their epidemiology and host-pathogen interactions. ABSTRACT Monophasic Salmonella enterica subsp. enterica serovar Typhimurium is one of the most common zoonotic pathogens. Salmonella species reside in a wide variety of hosts, including wild animals. Thus, we report here the genome sequences of 12 monophasic S. Typhimurium strains isolated from healthy wild vultures to gain better insight into their epidemiology and host-pathogen interactions.
Increased arrhythmia susceptibility in type 2 diabetic mice related to dysregulation of ventricular sympathetic innervation.

BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have a greater risk of developing life-threatening cardiac arrhythmias. Since the underlying mechanisms and potential influence of diabetic autonomic neuropathy are not well understood, we aimed to assess the relevance of a dysregulation in cardiac autonomic tone. METHODS AND RESULTS Ventricular arrhythmia susceptibility was increased in Langendorff-perfused hearts isolated from mice with T2DM (db/db). Membrane properties and synaptic transmission were similar at cardiac postganglionic parasympathetic neurons from diabetic and control mice; however, a greater asynchronous neurotransmitter release was present at sympathetic postganglionic neurons from the stellate ganglia of db/db mice. Western blot analysis showed a reduction of tyrosine hydroxylase (TH) from the ventricles of db/db mice, which was confirmed with confocal imaging as a heterogeneous loss of TH-immunoreactivity from the left ventricular wall but not the apex. In-vivo stimulation of cardiac parasympathetic (vagus) or cardiac sympathetic (stellate ganglion) nerves induced similar changes in heart rate in control and db/db mice and the kinetics of pacing-induced Ca2+ transients, recorded from isolated cardiomyocytes, were similar in control and db/db cells. Antagonism of cardiac muscarinic receptors did not affect the frequency or severity of arrhythmias in db/db mice, but sympathetic blockade with propranolol completely inhibited arrhythmogenicity. CONCLUSION Collectively, these findings suggest that the increased ventricular arrhythmia susceptibility of type 2 diabetic mouse hearts is due to dysregulation of the sympathetic ventricular control.