Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1–7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to ...identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer–Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson’s disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson’s disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10–15% increase in cell viability of the model cells at 50 μM, while compounds 2 and 4 (100 μM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
As an oncogene, long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) can promote tumor metastasis. Hyperexpression of MALAT1 has been observed in many ...malignant tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism of MALAT1 in HCC remain unclear.
Methods
Thirty human HCC and paracancerous tissue specimens were collected, and the human hepatoma cell lines Huh7 and HepG2 were cultured according to standard methods. MALAT1 and Snail family zinc finger (Slug) expression were measured by real‐time PCR, immunohistochemistry, and western blotting. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay verified the direct interaction between miR‐124‐3p and Slug(SNAI2) or MALAT1. Wound healing and transwell assays were performed to examine invasion and migration, and a subcutaneous tumor model was established to measure tumor progression in vivo.
Results
MALAT1 expression was upregulated in HCC tissues and positively correlated with Slug expression. MALAT1 and miR‐124‐3p bind directly and reversibly to each other. MALAT1 silencing inhibited cell migration and invasion. miR‐124‐3p inhibited HCC metastasis by targeting Slug.
Conclusions
MALAT1 regulates Slug through miR‐124‐3p, affecting HCC cell metastasis. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in HCC.
Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) regulates Slug through miR‐124‐3p, affecting cell migration and cell invasion. Thus, the MALAT1/miR‐124‐3p/Slug axis plays an important role in hepatocellular carcinoma.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is ...required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.
The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on ...intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>10
/mL), respectively, on days 1-6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of
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) and
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) were downregulated (
<
) by AM on day 7, and that the mRNA expressions of
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and
were downregulated (
) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (
) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced
) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.
Abstract
The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human ...assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.
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•A single-layer close packed diamond particles network was constructed.•Diamond/Cu composite thin plate with a sandwiched structure was prepared by press-brazing method.•Thermal and ...mechanical properties were measured and simulated.•Heat dissipation ability of the diamond/Cu composite was increased by 5.7 °C than pure Cu.
High-efficiency heat dissipation is crucial for the reliability and durability of high-power electronics devices. Diamond/copper composites have drawn much attention as promising candidate materials for thermal management due to their high thermal conductivity and tunable coefficient of thermal expansion. In this work, a novel method was proposed to fabricate a thin plate of diamond/copper composite based on the construction of single-layer close packed diamond particles network. The composite with a sandwich structure was prepared by press-brazing method, which is cost-effective for both preparation and post-processing. The microstructures of the composite plate containing diamond, AgCuTi filler and Cu were examined. The influence of diamond particle size on thermal conductivity, coefficient of thermal expansion, and mechanical properties were also experimentally measured and theoretically simulated. The results show that a single-layer close packed diamond particles network is densely brazed between copper layers to form a composite thin plate. The interface TiC layer is in-situ formed between diamond and AgCuTi matrix. With increase in the diamond particle size to 1200 μm, thermal conductivity of 552.7 W⋅m−1⋅K−1, coefficient of thermal expansion of 10.1 × 10-6 K−1, and flexural strength of 204.3 MPa are achieved, which are in agreement with the theoretical simulated results. As a heat spreader substrate, the heat dissipation ability of diamond/Cu composite is increased by 5.7 °C in comparison with pure Cu plate. Finite element analysis and testing of actual scenarios further confirm the excellent thermal performance of the sandwich structured diamond/Cu composite thin plate, making it a prospective candidate for thermal management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Quercetin (Qu) is one of the most abundant flavonoids in the human diet. High concentrations of Qu can easily cause adverse effects and induce inflammation, joint pain and stiffness. In this study, ...Heme was used as a sensitive element and deposited and formed nanorods on a glassy carbon electrode (GCE) for the detection of Qu. The Heme/GCE sensor was characterized using scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. Under optimized conditions, the developed sensor presented a linear concentration ranging from 0.1 to 700 μmol·L
according to the CV and DPV methods. The detection limit for the sensor was 0.134 μmol·L
and its sensitivity was 0.12 μA·μM
·cm
, which were obtained from CV analysis. Through DPV analysis we obtained a detection limit of 0.063 μmol·L
and a sensitivity of 0.09 μA·μM
·cm
. Finally, this sensor was used to detect the Qu concentration in loquat leaf powder extract, with recovery between 98.55-102.89% and total R.S.D. lower than 3.70%. The constructed electrochemical sensor showed good anti-interference, repeatability and stability, indicating that it is also usable for the rapid detection of Qu in actual samples.
Background Hypoglycemia is one of the most common complications in patients with DN during hemodialysis. The purpose of the study is to construct a clinical automatic calculation to predict risk of ...hypoglycemia during hemodialysis for patients with diabetic nephropathy. Methods In this cross-sectional study, patients provided information for the questionnaire and received blood glucose tests during hemodialysis. The data were analyzed with logistic regression and then an automated calculator for risk prediction was constructed based on the results. From May to November 2022, 207 hemodialysis patients with diabetes nephropathy were recruited. Patients were recruited at blood purifying facilities at two hospitals in Beijing and Inner Mongolia province, China. Hypoglycemia is defined according to the standards of medical care in diabetes issued by ADA (2021). The blood glucose meter was used uniformly for blood glucose tests 15 minutes before the end of hemodialysis or when the patient did not feel well during hemodialysis. Results The incidence of hypoglycemia during hemodialysis was 50.2% (104/207). The risk prediction model included 6 predictors, and was constructed as follows: Logit (P) = 1.505xhemodialysis duration 8~15 years (OR = 4.506, 3 points) + 1.616xhemodialysis duration 16~21 years (OR = 5.032, 3 points) + 1.504xhaving hypotension during last hemodialysis (OR = 4.501, 3 points) + 0.788xhaving hyperglycemia during the latest hemodialysis night (OR = 2.199, 2 points) + 0.91xdisturbance of potassium metabolism (OR = 2.484, 2 points) + 2.636xserum albumin<35 g/L (OR = 13.963, 5 points)-4.314. The AUC of the prediction model was 0.866, with Matthews correlation coefficient (MCC) of 0.633, and Hosmer-Lemeshow chl.sup.2 of 4.447(P = 0.815). The automatic calculation has a total of 18 points and four risk levels. Conclusions The incidence of hypoglycemia during hemodialysis is high in patients with DN. The risk prediction model in this study had a good prediction outcome. The hypoglycemia prediction automatic calculation that was developed using this model can be used to predict the risk of hypoglycemia in DN patients during hemodialysis and also help identify those with a high risk of hypoglycemia during hemodialysis. Keywords: Diabetic nephropathy, Hemodialysis, Hypoglycemia, Risk prediction
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Taenia hydatigena is a widespread tapeworm of canids (primarily dogs) that causes cysticercosis in ruminants (domestic and wild) and manifests as depression and weakness secondary to various hepatic ...damages and sometimes mortality in young animals, although, commonly encountered cases are asymptomatic. In most taeniids, genetic polymorphism has been found to impact host preferences, distribution, disease epidemiology and management. Recently, we identified two main mitochondrial lineages of T. hydatigena in China, and here, we examined the mitochondrial nad4‐nad5 genes of T. hydatigena from China, Nigeria, Pakistan and Sudan to assess the intraspecies variation of isolates from these countries and also the distribution of the distinct mitochondrial groups. In addition to China, haplogroup B variant was found in Pakistan, while haplogroup A demonstrated a widespread distribution. We then designed a PCR‐restriction fragment length polymorphism (PCR‐RFLP) assay using XmiI (AccI) and RsaI (AfaI) restriction enzymes to differentiate members of both haplogroups. This result provides more molecular evidence supporting the existence of distinct mitochondrial variants of T. hydatigena. The epidemiological significance of these different mitochondrial groups remains to be explored further. The current PCR‐RFLP assay offers a useful molecular approach for investigating the genetic population structure of T. hydatigena in enzootic regions and in identifying/discriminating the different mitochondrial groups (haplogroups A and B).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The wear characteristics of the metal bond diamond tools changes with the grinding process, resulting in affecting the grinding efficiency, tool's life, and surface integrity of the workpiece. In ...this study, the wear evolution of a metal bond diamond tool, for the case of grinding of sapphire, is investigated by using a novel design of the grinding setup. The wear characteristics of the diamond grits and the metal bond at a fixed zone of the grinding tool were examined. In addition, the evolution of the grinding process, the grinding force, the grinding ratio, and the surface integrity of the sapphire were also evaluated. As the material removal volume increases, the number of participating diamond grits, the proportion of micro-fractured diamond grits, and the average diamond grit protrusion height increase during the grinding process. And the proportion of newly exposed diamond grits decreases and the distribution of protrusion height of diamond grits becomes narrower during the grinding process. Consequently, a higher grinding ratio, stable grinding force, and excellent ground surface integrity are achieved positively when the wear of the metal bond diamond tool transforms from the initial stage to the stable stage with the material removal volume of up to 3600 mm3.
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•A novel grinding setup is designed to investigate the wear evolution of fixed zones of diamond tools.•With the increase in material removal volume, the micro-fractured diamond grits increase.•Better grinding performance is obtained during the stable wear stage of the diamond tool.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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