Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Rats ; Animals ; Parkinson Disease ; Rats, Sprague-Dawley ; AMP-Activated Protein Kinases ; Diabetes Mellitus, Type 2 ; Autophagy-Related Protein-1 Homolog

Cadmium(Cd) stress seriously inhibits the growth and development of plants, and Cd is enriched in the human body along the food chain, causing major risks to human health. Ethylene(ETH) is known for its role as a traditional plant hormone that plays a crucial part in various stress responses. However, the precise mechanisms by which ETH regulates plant tolerance to Cd remain unclear. In this study, we observed that treatment with 3 mg L

Blood glucose monitoring is of great significance to diabetic patients, and the development of rapid, accurate and real-time glucose detection technology has become a research hotspot nowadays. This study introduces the concept and classification of the enzyme-free glucose sensor, expounds enzymefree glucose sensor electrode characterization methods and the application progress of different materials in enzyme-free blood glucose sensors. Meanwhile, some problems of enzyme-free glucose sensor existing in the current research and its future application prospects also will be discussed.
Blood Glucose ; Blood Glucose Self-Monitoring ; Electrodes ; Glucose ; Humans ; Monitoring, Physiologic

Aims: Antimicrobial resistance (AMR) is a significant public health concern of modern civilization. The potential risk of AMR is significant in terms of both human and animal health. This study aims to assess the antimicrobial resistance pattern of selected antimicrobials against Escherichia coli of animal, poultry and human origin in the Cumilla district of Bangladesh. Methodology and results: A total of 200 samples were collected from different sources. Isolation and identification of commensal E. coli were performed following standard bacteriological and molecular techniques. Antimicrobial susceptibility testing was performed following the Kirby-Bauer disc diffusion technique. Ampicillin, tetracycline and sulfamethoxazole-trimethoprim resistance genes were detected by polymerase chain reactions (PCR). A total of 152 (76%; 95% confidence interval (CI) 70-81%) E. coli were isolated from cattle, sheep, chicken and human, where 37.5% of isolates were found to be multidrug-resistant (MDR). In the cultural sensitivity test, E. coli showed the highest resistance to sulfamethoxazole-trimethoprim (71%), tetracycline (63%), ampicillin (62%), where gentamicin (23%) showed the lowest resistance, followed by ceftriaxone (26%). The prevalence of resistance genes like blaTEM, tetA, tetB, tetC, sul1 and sul2 were 100%, 95%, 11%, 8%, 58% and 52%, respectively. Conclusion, significance and impact of study The emergence of multidrug-resistant commensal E. coli and resistance genes circulating in animals, poultry and humans limit the treatment options for serious infections.
Escherichia coli ; Drug Resistance, Multiple, Bacterial

In order to provide rationale for selection of good germplasm in Rubus chingii, main effective medicinal ingredients of green fruit such as gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside were measured using UPLC for the samples collected from Chun'an county of Zhejiang province, and such parameters as soluble solid contents of ripe fruit of some samples were also measured to study variation among individuals and correlation. It has been found that there were differences among individuals in the contents of gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside, which ranged from 0.010 2%-0.027 4%, 0.089 5%-0.291 1%, 0.010 5%-0.114 8%, 0.005 8%-0.041 2% and 0.010 9%-0.086 3%, respectively, with a CV of 18.60%, 27.02%, 44.23%, 44.17% and 47.29%, respectively. Gallic acid was positively correlated with ellagic acid, but negatively with kaempferol-3-rutinoside and astragalin significantly. Significantly positive correlation existed between kaempferol-3-rutinoside, astragalin and linden glycoside as well as between ellagic acid and fruit shape index of ripe fruit and between linden glycoside and the content of soluble solids. 51.35% of the individuals had a content of soluble solids more than 15%. Therefore, abundant variations have been found among individuals in effective medicinal ingredients in R. chingii, which shows great potential for selection, but only do 7.61% of the individuals meet the requirement of Chinese pharmacopoeia in terms of the contents of effective medicinal ingredients. Therefore, selection could be first performed in terms of fruit shape index of ripe red fruit, followed by the contents of ellagic acid and kaempferol-3-rutinoside measured. The individuals, in which the contents of effective medicinal ingredients don't meet the requirement of Chinese pharmacopoeia, could be considered for the selection in terms of edible fresh fruit.
Ellagic Acid ; Fruit ; Glycosides ; Humans ; Plant Extracts ; Rubus

The study is aimed to investigate the reproductive biology characteristics of Polygonatum cyrtonema, especially including phenology, flower bud differentiation, flowering timing, floral traits, pollen vigor and stigma receptivity. The results showed that P. cyrtonema forms inflorescence before the leaves spread. In the wild, P. cyrtonema is mainly pollinated by insects such as bumblebees, with a seed setting rate of 65.12%. The seed setting rate of indoor single plant isolation or self-pollination enclosed by parchment paper bag is 0, indicating that it is self-incompatible. In Lin'an city, seedlings begin to emerge from mid-March to early April(the temperature is higher than 7.5 ℃), buds begin to emerge from the end of March to mid-April, and then undergo the full bloom stage from mid-to-late April, and the final flowering stage from the end of April to mid-May. The whole flowering period lasts 36 to 45 days. There are obvious differences in the phenology of different provenances. The flowers come into bloom from the base to the top along the aboveground main axis, which usually contain 4-22 inflorescences with(2-) 4-10(-21) flowers per inflorescence. The flowering pe-riod for a single plant is 26-38 days. The single flower lasts about 20-25 days from budding to opening and withers 2 days after pollination, and then the ovary will gradually expand. If unpollinated, it will continue to bloom for 3-5 days and then wither. Flower development period is significantly related to pollen vigor and stigma remittance. The pollen viability is the highest when the flower is fully opened with anthers gathering on the stigma, and the receptivity is the strongest when the stigma protrudes out of the perianth and secretes mucus. The fruits and seeds ripen in October, and proper shading can ensure the smooth development and maturity of the seeds. This study provides a basis for the hybrid breeding and seed production of P. cyrtonema.
Flowers ; Plant Breeding ; Pollination ; Polygonatum ; Reproduction

Anterograde viral tracers are powerful and essential tools for dissecting the output targets of a brain region of interest. They have been developed from herpes simplex virus 1 (HSV-1) strain H129 (H129), and have been successfully applied to map diverse neural circuits. Initially, the anterograde polysynaptic tracer H129-G4 was used by many groups. We then developed the first monosynaptic tracer, H129-dTK-tdT, which was highly successful, yet improvements are needed. Now, by inserting another tdTomato expression cassette into the H129-dTK-tdT genome, we have created H129-dTK-T2, an updated version of H129-dTK-tdT that has improved labeling intensity. To help scientists produce and apply our H129-derived viral tracers, here we provide the protocol describing our detailed and standardized procedures. Commonly-encountered technical problems and their solutions are also discussed in detail. Broadly, the dissemination of this protocol will greatly support scientists to apply these viral tracers on a large scale.

Petite integration frequency 1 (PIF1) helicases are ubiquitous enzymes which play vital roles in nearly all DNA metabolic processes. In recent years, the biochemical activity and three-dimensional structure of several PIF1 helicases have been reported, but there are few reports on the PIF1 helicase of bacteria living in extreme environments. In this paper, a series of biochemical and biophysical techniques were used to study the Thermodesulfovibrio yellowstonii PIF1 (Ty.PIF1) helicase in many aspects. Ty. PIF1 was obtained with a purity of over 90% and good uniformity using the prokaryotic expression and purification system. Ty.PIF1 is a monomer with a calculated molecular weight of 60 kD in solution. Ty. PIF1 has high thermal stability. The secondary structure remains stable when the temperature is below 65 ℃, and the secondary structure changes only when the temperature is above 70 ℃. The optimal unwinding temperature of Ty.PIF1 in vitro is 45 ℃, which is not the optimal temperature for the survival of thermodesulfovibrio yellowstonii. It indicates that when Ty.PIF1 exerts its enzymatic activity in vivo, it may require the participation of other cofactors. Ty.PIF1 can exert unwinding activity in a wide temperature range (20-55 ℃), and the presence of enzyme activity at 55 ℃ indicates that Ty.PIF1 has heat-resistant properties. Ty.PIF1 prefers to bind to substrates containing ssDNA, but there is certain requirement for the length of the ssDNA, which is at least 4 nt in length. Ty.PIF1 can also bind to the G