Complement factor H‑related 3 (CFHR3) belongs to the human factor H protein family and is associated with various human diseases, including nephropathy, age‑related macular degeneration and atypical hemolytic uremic syndrome. However, to the best of our knowledge, the role of CFHR3 in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis were performed to determine mRNA and protein expression levels of CFHR3 in HCC and normal adjacent tissue. In addition, CFHR3 was overexpressed in Huh‑7 cells and cell counting kit‑8 assay was used to determine cell viability. Cell proliferation and apoptosis were assessed using flow cytometry, RT‑qPCR and western blotting. The results demonstrated that mRNA (2‑ΔΔCq) and protein expression levels of CFHR3 were significantly lower in tumor tissue compared with in adjacent tissue. Additionally, CFHR3 overexpression decreased cell viability, inhibited cell proliferation and significantly increased apoptosis. It was also identified that CFHR3 could downregulate the expression of Ki67. The results suggested that CFHR3 induced apoptosis by downregulating the expression of survivin and B cell lymphoma 2, upregulating the expression of Bcl‑2‑associated X and promoting caspase‑3 activity. Western blotting revealed that CFHR3 significantly inhibited the protein expression levels of phosphorylated (p)‑phosphoinositide 3‑kinase (PI3K), p‑protein kinase B (Akt) and p‑mammalian target of rapamycin (mTOR). Overexpression of CFHR3 suppressed proliferation and promoted apoptosis of HCC cells by inhibiting the PI3K/Akt/mTOR signaling pathway.
The structure and magnetic properties of Y1-xDyxMn6Sn6 (x = 0-1) compounds have been studied by x-ray diffraction and magnetization measurements. All studied samples crystallize in HfFe6Ge6-type structure (space group P6/mmm). The compound with x = 0 behaves as anti-ferromagnetic behaviour, and the compounds (x = 0.6-1) display ferrimagnetic behaviours in the whole magnetic ordering temperature range. The compounds (x = 0.2-0.4) exhibit a transition from ferrimagnetic to anti-ferromagnetic, then to ferrimagnetic state again with increasing temperature. The magnetization curves of compounds (x = 0.3-1) at 5 K almost saturate at 5 T, and the saturation magnetization Ms decreases with increasing Dy content. The compounds (x = 0-0.3) display field-induced metamagnetic transition, and the threshold field decreases with increasing Dy content. The unit-cell volume V of Y1-xDyxMn6Sn6 (x = 0-1) compounds decreases, and the ordering points increase with increasing Dy content.
Clinical studies have shown that bipolar patients have increased serum uric acid levels. High serum uric acid levels could play a role contributing to high prevalence of metabolic syndrome. Metabolic syndrome is known to increase the risk of developing a number of life threatening diseases including coronary heart disease, hypertension, and type 2 diabetes. This study investigated the association between hyperuricemia and metabolic syndrome and its components in individuals suffering from bipolar disorders. This study recruited 318 inpatients suffering from bipolar disorders from Beijing Hui-Long-Guan Hospital in China and 160 healthy subjects from the same region as the controls. We used National Cholesterol Education Program Adult Treatment Panel III Adapted criteria (NCEP ATP-III A) for the diagnosis of metabolic syndrome. Hyperuricemia was determined as serum uric acid level above 420 μmol/L in men and 360 μmol/L in women (N Engl J Med 359(17):1811–1821, 2008). Among 318 bipolar patients, there was higher prevalence of metabolic syndrome (42.5%) and hyperuricemia (27.7%) than healthy controls (21.9 and 11.9%). Bipolar patients with metabolic syndrome had increased prevalence of hyperuricemia (OR = 3.0, CI95 [1.7–5.4]). Hypertriglyceridemia and larger waist circumference (WC) were associated with hyperunicemia (OR = 1.8, CI95 [1.1–3.1], OR = 1.9, CI95 [1.1–3.4]). Hyperuricemia was associated with metabolic syndrome in bipolar patients (p < 0.001) and especially with hypertriglyceridemia (OR = 1.9, CI95 [1.1–3.1] and increased WC (OR = 2.1 [1.2–4.0]). Bipolar patients over 50 years of age and hyperuricemia were highly prone to develop metabolic syndrome (OR = 14.0, CI95 [5.0–39.0]). Hyperuricemia was highly associated with development of metabolic disorder particularly for aged patients suffering from bipolar disorders. Early prevention of hyperuricemia and metabolic syndrome may lead better life for bipolar patients when they get older.
The hard magnetic properties of melt-spun were studied. A coercivity of and an energy product of at room temperature were obtained for a sample prepared at a wheel speed of ; correspondingly, the size of crystalline grains in these samples is about 38 nm. The mechanism of coercivity is mainly controlled by the nucleation of reversed domains. The phenomenon of remanence enhancement was observed in the melt-spun .
Coronavirus disease-2019 (COVID-19) pandemic has seriously threatened the global public health security and caused a series of mental health problem. Current research focuses mainly on mental health status and related factors in the COVID-19 pandemic among Chinese university students. Data from 11133 participants was obtained through an online survey. The Patient Health Question-9 (PHQ-9) was used to assess depressive symptoms, the Social Support Rate Scale (SSRS) was used to assess social support. We also used 7-item Generalized Anxiety Disorder Scale (GAD-7) to assess anxiety symptoms. Totally, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Awareness of COVID-19, living with family were protective factors that reduced anxiety and depression symptoms. In addition, male, personal COVID-19 exposure, depressive and anxiety symptoms were risk factors for suicidal ideation. Social support, COVID-19 preventive and control measures, prediction of COVID-19 trends, living with family and graduate students are protective factors for reducing suicidal ideation.
Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytes in vitro and in vivo. The ligands derived from GalNAc are compatible with solid-phase oligonucleotide synthesis and deprotection conditions, with synthesis yields comparable to those of standard oligonucleotides. Subcutaneous (SC) administration of siRNA–GalNAc conjugates resulted in robust RNAi-mediated gene silencing in liver. Refinement of the siRNA chemistry achieved a 5-fold improvement in efficacy over the parent design in vivo with a median effective dose (ED50) of 1 mg/kg following a single dose. This enabled the SC administration of siRNA–GalNAc conjugates at therapeutically relevant doses and, importantly, at dose volumes of ≤1 mL. Chronic weekly dosing resulted in sustained dose-dependent gene silencing for over 9 months with no adverse effects in rodents. The optimally chemically modified siRNA–GalNAc conjugates are hepatotropic and long-acting and have the potential to treat a wide range of diseases involving liver-expressed genes.
The excited-state behavior of synthetic DNA dumbbells possessing stilbenedicarboxamide (Sa) linkers separated by short A-tracts or alternating A-T base-pair sequences has been investigated by means of fluorescence and transient absorption spectroscopy. Electronic excitation of the Sa chromophores results in conversion of a locally excited state to a charge-separated state in which one Sa is reduced and the other is oxidized. This symmetry-breaking process occurs exclusively via a multistep mechanism-hole injection followed by hole transport and hole trapping-even at short distances. Rate constants for charge separation are strongly distance-dependent at short distances but become less so at longer distances. Disruption of the A-tract by inversion of a single A-T base pair results in a pronounced decrease in both the rate constant and efficiency of charge separation. Hole trapping by Sa is highly reversible, resulting in rapid charge recombination that occurs via the reverse of the charge separation process: hole detrapping, hole transport, and charge return to regenerate the locally excited Sa singlet state. These results differ in several significant respects from those previously reported for guanine or stilbenediether as hole traps. Neither charge separation nor charge recombination occur via a single-step superexchange mechanism, and hole trapping is slower and detrapping faster when Sa serves as the electron donor. Both the occurrence of symmetry breaking and reversible hole trapping by a shallow trap in a DNA-based system are without precedent.
Peptibody was treated with six proteolytic enzymes (trypsin, chymotrypsin, Asp-N, Glu-C, Lys-C and Lys-N) and digested into amenable peptide fragments for LC-MS analysis. The mass spectrometer used was Q Exactive (Thermo Scientific). For sequencing and peptide-mapping, the data were processed by BiopharmaLynx 1.3 sofware. For molecular weight (MW), the data were calculated through deconvolution by ProMass for XcaliburTM software.
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