Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-34a promotes myocardial infarction in rats by inhibiting the activity of SIRT1.

OBJECTIVE To investigate the effect of micro ribonucleic acid (miR)-34a regulating silent information regulator 1 (SIRT1) on myocardial infarction (MI) rats. MATERIALS AND METHODS A total of 30 male, 8-week-old rats were divided into three groups, including: sham group (M group), MI group and MI + miR-34a treatment group (miR group). Tissue morphology in the MI region was observed via hematoxylin-eosin (HE) staining. Myocardial apoptosis in the three groups was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Furthermore, the protein levels of SIRT1, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in myocardial cells were detected via Western blotting. RESULTS Compared with M group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) increased significantly in MI group and miR group (p<0.05), while left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased obviously (p<0.05). The results of HE staining showed that the inflammatory infiltration of myocardial cells and intercellular collagen fibers significantly increased, and the neuronal damage was remarkably aggravated in MI group and miR group when compared with M group (p<0.05). Compared with MI group, myocardial necrosis, inflammatory cell infiltration and intercellular collagen fibers all increased significantly in miR group (p<0.05). Moreover, the results of TUNEL assay revealed that myocardial apoptosis rate in MI group [(21.35±3.12)%] was remarkably higher than that of M group [(9.53±1.17)%]. Meanwhile, it was significantly higher in miR group [(42.38±3.44)%)] than that of MI group, displaying statistically significant differences (p<0.05). The number of apoptotic cells increased obviously in MI group when compared with M group, while it decreased significantly in MI group when compared with miR group (p<0.05). Besides, the protein levels of SIRT1 and Bcl-2 in myocardial tissues in miR group were remarkably lower than those of M group and MI group (p<0.05). Furthermore, the protein level of Bax in miR group was higher than that of M group and MI group, and there were statistically significant differences (p<0.05). CONCLUSIONS Overexpression of miR-34a inhibits the activity of SIRT1, thereby promoting the apoptosis of MI.
Can Leadership Enhance Patient Satisfaction? Assessing the Role of Administrative and Medical Quality

This paper aimed to investigate the relationships between participative leadership (PL), administrative quality (AQ), medical quality (MQ), and patient satisfaction (PS) using the Malcolm Baldrige National Quality Award Healthcare Criteria (MBNQA) criteria. The study further examined the intervening influence of administrative quality and medical quality on the relationship between participative leadership and patient satisfaction. The data was obtained from 123 public sector hospitals in Pakistan. We employed confirmatory factor analysis (CFA) and structural equation modeling (SEM) techniques to test the structural model. From the study results, we found significant and positive relationships between participative, administrative quality, medical quality, and patient satisfaction. In addition, our research found administrative quality and medical quality as potential mediators on PL-PS relation. Adopting participative leadership as an exogenous factor, and both administrative and medical quality as potential mediators of patient satisfaction, provided new insights into MBNQA criteria.
Human Immunodeficiency Virus (HIV) Infection and Use of Illicit Substances Promote Secretion of Semen Exosomes that Enhance Monocyte Adhesion and Induce Actin Reorganization and Chemotactic Migration

Semen exosomes (SE) from HIV-uninfected (HIV−) individuals potently inhibit HIV infection in vitro. However, morphological changes in target cells in response to SE have not been characterized or have the effect of HIV infection or the use of illicit substances, specifically psychostimulants, on the function of SE been elucidated. The objective of this study was to evaluate the effect of HIV infection, psychostimulant use, and both together on SE-mediated regulation of monocyte function. SE were isolated from semen of HIV− and HIV-infected (HIV+) antiretroviral therapy (ART)-naive participants who reported either using or not using psychostimulants. The SE samples were thus designated as HIV−Drug−, HIV−Drug+, HIV+Drug−, and HIV+Drug+. U937 monocytes were treated with different SEs and analyzed for changes in transcriptome, morphometrics, actin reorganization, adhesion, and chemotaxis. HIV infection and/or use of psychostimulants had minimal effects on the physical characteristics of SE. However, different SEs had diverse effects on the messenger RNA signature of monocytes and rapidly induced monocyte adhesion and spreading. SE from HIV infected or psychostimulants users but not HIV−Drug− SE, stimulated actin reorganization, leading to the formation of filopodia-like structures and membrane ruffles containing F-actin and vinculin that in some cases were colocalized. All SE stimulated monocyte chemotaxis to HIV secretome and activated the secretion of matrix metalloproteinases, a phenotype exacerbated by HIV infection and psychostimulant use. SE-directed regulation of cellular morphometrics and chemotaxis depended on the donor clinical status because HIV infection and psychostimulant use altered SE function. Although our inclusion criteria specified the use of cocaine, humans are poly-drug and alcohol users and our study participants used psychostimulants, marijuana, opiates, and alcohol. Thus, it is possible that the effects observed in this study may be due to one of these other substances or due to an interaction between different substances.
Dynorphin‐based “release on demand” gene therapy for drug‐resistant temporal lobe epilepsy

Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease‐modifying treatment strategies of neuropeptides represent promising candidates. Here, we provide the “proof of concept” that gene therapy by adeno‐associated virus (AAV) vector transduction of preprodynorphin into the epileptogenic focus of well‐accepted mouse and rat models for temporal lobe epilepsy leads to suppression of seizures over months. The debilitating long‐term decline of spatial learning and memory is prevented. In human hippocampal slices obtained from epilepsy surgery, dynorphins suppressed seizure‐like activity, suggestive of a high potential for clinical translation. AAV‐delivered preprodynorphin expression is focally and neuronally restricted and release is dependent on high‐frequency stimulation, as it occurs at the onset of seizures. The novel format of “release on demand” dynorphin delivery is viewed as a key to prevent habituation and to minimize the risk of adverse effects, leading to long‐term suppression of seizures and of their devastating sequel.
Evaluation of an Eight-Week Whole-Food Plant-Based Lifestyle Modification Program

Poor diet quality is the leading cause of death both in the United States and worldwide, and the prevalence of obesity is at an all-time high and is projected to significantly worsen. Results from an eight-week group program utilizing an ad-libitum whole-food plant-based dietary pattern, were reviewed. There were 79 participants, all self-referred from the community, including 24 (30.4%) who were already vegetarian or vegan at baseline. Seventy-eight participants (98.7%) completed the eight-week program. Among completers, those with higher BMI at baseline lost a larger percentage of their body weight (total body weight loss of 3.0 ± SD 2.1%, 5.8 ± 2.8%, and 6.4 ± 2.5% for participants who had baseline BMI in normal, overweight, and obese range, respectively). The average weight loss for all the completers was 5.5 ± 3.0 kg (p < 0.0001). Final blood pressure and plasma lipids were reduced compared to baseline (SBP decreased 7.1 ± 15.5 mmHg (p = 0.0002), DBP decreased 7.3 ± 10.9 mmHg (p < 0.0001), total cholesterol decreased 25.2 ± 24.7 mg/dL (p < 0.0001), LDL decreased 15.3 ± 21.1 mg/dL (p < 0.0001)). Twenty-one (26.9%) participants were able to decrease or stop at least one chronic medication compared to two (2.6%) participants who required an increased dose of a chronic medication. Participants who were already vegetarian or vegan at baseline experienced statistically significant weight loss and reductions in total and LDL cholesterol. There was a non-significant trend toward less weight loss in these participants compared to participants who were non-vegetarian at baseline. Reductions in total and LDL cholesterol were not significantly different when comparing vegetarian or vegan and non-vegetarian participants. A whole-food plant-based dietary intervention may provide significant short-term benefits for both non-vegetarian, vegetarian, and vegan individuals.
Evolutionary plasticity in the allosteric regulator-binding site of pyruvate kinase isoform PykA from Pseudomonas aeruginosa

Unlike many other well-characterized bacteria, the opportunistic human pathogen Pseudomonas aeruginosa relies exclusively on the Entner-Doudoroff pathway (EDP) for glycolysis. Pyruvate kinase (PK) is the main “pacemaker” of the EDP, and its activity is also relevant for P. aeruginosa virulence. Two distinct isozymes of bacterial PK have been recognized, PykA and PykF. Here, using growth and expression analyses of relevant PK mutants, we show that PykA is the dominant isoform in P. aeruginosa. Enzyme kinetics assays revealed that PykA displays potent K-type allosteric activation by glucose 6-phosphate and by intermediates from the pentose phosphate pathway. Unexpectedly, the X-ray structure of PykA at 2.4 Å resolution revealed that glucose 6-phosphate binds in a pocket that is distinct from the binding site reported for this metabolite in the PK from Mycobacterium tuberculosis (the only other available bacterial PK structure containing bound glucose 6-phosphate). We propose a mechanism by which glucose 6-phosphate binding at the allosteric site communicates with the PykA active site. Taken together, our findings indicate remarkable evolutionary plasticity in the mechanism(s) by which PK senses and responds to allosteric signals.
Bio-Inspired Representation Learning for Visual Attention Prediction

Visual attention prediction (VAP) is a significant and imperative issue in the field of computer vision. Most of the existing VAP methods are based on deep learning. However, they do not fully take advantage of the low-level contrast features while generating the visual attention map. In this article, a novel VAP method is proposed to generate the visual attention map via bio-inspired representation learning. The bio-inspired representation learning combines both low-level contrast and high-level semantic features simultaneously, which are developed by the fact that the human eye is sensitive to the patches with high contrast and objects with high semantics. The proposed method is composed of three main steps: 1) feature extraction; 2) bio-inspired representation learning; and 3) visual attention map generation. First, the high-level semantic feature is extracted from the refined VGG16, while the low-level contrast feature is extracted by the proposed contrast feature extraction block in a deep network. Second, during bio-inspired representation learning, both the extracted low-level contrast and high-level semantic features are combined by the designed densely connected block, which is proposed to concatenate various features scale by scale. Finally, the weighted-fusion layer is exploited to generate the ultimate visual attention map based on the obtained representations after bio-inspired representation learning. Extensive experiments are performed to demonstrate the effectiveness of the proposed method.
Intensive glucose‐lowering and the risk of vascular events and premature death in patients with decreased kidney function: The ADVANCE trial

To assess the effects of intensive glucose control on the risk of major clinical outcomes according to estimated glomerular filtration rate (eGFR) levels in people with type 2 diabetes. Of 11 140 ADVANCE trial participants, 11 096 with baseline eGFR measurements were included, and classified into three eGFR groups: ≥90 mL/min/1.73 m2; 60 to 89 mL/min/1.73 m2; and < 60 mL/min/1.73 m2. Relative risk reduction of randomized intensive glucose control with regard to the composite outcome of major macro‐ and microvascular events, all‐cause death and cardiovascular death did not significantly vary by eGFR level (P for heterogeneity ≥0.49). The risk of severe hypoglycaemia increased with intensive glucose control; however, this risk did not vary across eGFR groups (P for heterogeneity = 0.83). The risk–benefit profile of intensive glucose control in patients with type 2 diabetes and impaired kidney function appears similar to that observed in those with preserved kidney function.
Lack of the aryl hydrocarbon receptor accelerates aging in mice

The aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild‐type and AhR‐null mice along aging to study the relationship between this receptor and age‐associated inflammation, termed as “inflammaging,” both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR–/– mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when compared with their age‐matched AhR+/+ controls. Importantly, we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging. —Bravo‐Ferrer, I. , Cuartero, M. I. , Medina, V. , Ahedo‐Quero, D. , Peña‐Martínez, C. , Pérez‐Ruíz, A. , Fernández‐Valle, M. E. , Hernández‐Sánchez, C. , Fernández‐Salguero, P. M. , Lizasoain, I. , Moro, M. A. Lack of the aryl hydrocarbon receptor accelerates aging in mice. FASEB J. 33, 12644–12654 (2019). www.fasebj. org
Active Site Architecture and Reaction Mechanism Determination of Cold Adapted β-d-galactosidase from Arthrobacter sp. 32cB

ArthβDG is a dimeric, cold-adapted β-d-galactosidase that exhibits high hydrolytic and transglycosylation activity. A series of crystal structures of its wild form, as well as its ArthβDG_E441Q mutein complexes with ligands were obtained in order to describe the mode of its action. The ArthβDG_E441Q mutein is an inactive form of the enzyme designed to enable observation of enzyme interaction with its substrate. The resulting three-dimensional structures of complexes: ArthβDG_E441Q/LACs and ArthβDG/IPTG (ligand bound in shallow mode) and structures of complexes ArthβDG_E441Q/LACd, ArthβDG/ONPG (ligands bound in deep mode), and galactose ArthβDG/GAL and their analysis enabled structural characterization of the hydrolysis reaction mechanism. Furthermore, comparative analysis with mesophilic analogs revealed the most striking differences in catalysis mechanisms. The key role in substrate transfer from shallow to deep binding mode involves rotation of the F581 side chain. It is worth noting that the 10-aa loop restricting access to the active site in mesophilic GH2 βDGs, in ArthβDG is moved outward. This facilitates access of substrate to active site. Such a permanent exposure of the entrance to the active site may be a key factor for improved turnover rate of the cold adapted enzyme and thus a structural feature related to its cold adaptation.
Biodiversity of Entomopathogenic Fungi in the Soils of South China

The southern part of China, located in tropical and south subtropical areas has unique natural environments, but the distributions of entomopathogenic fungi (EFs) in the soil are not clear. In this research, 198 soil samples were collected from the four Provinces (Autonomous Region) of South China. The results indicated that a total of 292 fungal isolates were obtained from 176 soil samples. Then, based on the morphological and rDNA-ITS sequences analysis, 213 EFs isolates of 19 species in 12 genera were identified. Furthermore, Purpureocillium lilacinum with 75 isolates was recognized as the absolutely dominant EF species, while Isaria javanica, Metarhizium anisopliae, and Beauveria bassiana (respectively with 29, 26, and 26 isolates) were the richer species. The data also indicated that Guangxi Province has the best EFs diversity with the Shannon–Wiener index (SWI) of 2.29, the soils covered with grass had the best EFs diversity with the 2.14 SWI, while the orchard and fallow land had the lowest SWI of 1.52, which suggested that the diversity of plants and insects on ground, as well as the massive application of broad-spectrum fungicides, affect the EFs diversity in the soil. Finally, the rare species, Nectria mauritiicola and Scopulariopsis brumptii were first reported about their entomopathogenic activities against Bemisia tabaci. Our experiment will give new insights to the understanding of EFs distribution characteristics and their biodiversity conservation.
Van der Waals Epitaxy of III‐Nitride Semiconductors Based on 2D Materials for Flexible Applications

III‐nitride semiconductors have attracted considerable attention in recent years owing to their excellent physical properties and wide applications in solid‐state lighting, flat‐panel displays, and solar energy and power electronics. Generally, GaN‐based devices are heteroepitaxially grown on c‐plane sapphire, Si (111), or 6H‐SiC substrates. However, it is very difficult to release the GaN‐based films from such single‐crystalline substrates and transfer them onto other foreign substrates. Consequently, it is difficult to meet the ever‐increasing demand for wearable and foldable applications. On the other hand, sp2‐bonded two‐dimensional (2D) materials, which exhibit hexagonal in‐plane lattice arrangements and weakly bonded layers, can be transferred onto flexible substrates with ease. Hence, flexible III‐nitride devices can be implemented through such 2D release layers. In this progress report, the recent advances in the different strategies for the growth of III‐nitrides based on 2D materials are reviewed, with a focus on van der Waals epitaxy and transfer printing. Various attempts are presented and discussed herein, including the different kinds of 2D materials (graphene, hexagonal boron nitride, and transition metal dichalcogenides) used as release layers. Finally, current challenges and future perspectives regarding the development of flexible III‐nitride devices are discussed.
A sulfur coordination polymer with wide bandgap semiconductivity formed from zinc(II) and 5-methylsulfanyl-1,3,4-thiadiazole-2-thione.

The sulfur coordination polymer catena-poly[zinc(II)-μ2-bis[5-(methylsulfanyl)-2-sulfanylidene-2,3-dihydro-1,3,4-thiadiazol-3-ido-κ2N3:S]], [Zn(C3H3N2S3)2]n or [Zn2MTT4]n, constructed from Zn2+ ions and 5-methylsulfanyl-1,3,4-thiadiazole-2-thione (HMTT), was synthesized successfully and structurally characterized. [Zn2MTT4]n crystallizes in the tetragonal space group I-4 (No. 82). Each MTT- ligand (systematic name: 5-methylsulfanyl-2-sulfanylidene-2,3-dihydro-1,3,4-thiadiazol-3-ide) coordinates to two different ZnII ions, one via the thione group and the other via a ring N atom, with one ZnII atom being in a tetrahedral ZnS4 and the other in a tetrahedral ZnN4 coordination environment. These tetrahedral ZnS4 and ZnN4 units are alternately linked by the organic ligands, forming a one-dimensional chain structure along the c axis. The one-dimensional chains are further linked via C-H.N and C-H.S hydrogen bonds to form a three-dimensional network adopting an ABAB-style arrangement that lies along both the a and b axes. The three-dimensional Hirshfeld surface analysis and two-dimensional (2D) fingerprint plots confirm the major interactions as C-H.S hydrogen bonds with a total of 35.1%, while 7.4% are C-H.N hydrogen-bond interactions. [Zn2MTT4]n possesses high thermal and chemical stability and a linear temperature dependence of the bandgap from room temperature to 270 °C. Further investigation revealed that the bandgap changes sharply in ammonia, but only fluctuates slightly in other solvents, indicating its promising application as a selective sensor.
Abundance and Antimicrobial Resistance of Three Bacterial Species along a Complete Wastewater Pathway

After consumption, antibiotic residues and exposed bacteria end up via the feces in wastewater, and therefore wastewater is believed to play an important role in the spread of antimicrobial resistance (AMR). We investigated the abundance and AMR profiles of three different species over a complete wastewater pathway during a one-year sampling campaign, as well as including antimicrobial consumption and antimicrobial concentrations analysis. A total of 2886 isolates (997 Escherichia coli, 863 Klebsiella spp., and 1026 Aeromonas spp.) were cultured from the 211 samples collected. The bacterial AMR profiles mirrored the antimicrobial consumption in the respective locations, which were highest in the hospital. However, the contribution of hospital wastewater to AMR found in the wastewater treatment plant (WWTP) was below 10% for all antimicrobials tested. We found high concentrations (7–8 logs CFU/L) of the three bacterial species in all wastewaters, and they survived the wastewater treatment (effluent concentrations were around 5 log CFU/L), showing an increase of E. coli in the receiving river after the WWTP discharge. Although the WWTP had no effect on the proportion of AMR, bacterial species and antimicrobial residues were still measured in the effluent, showing the role of wastewater contamination in the environmental surface water.