Circular RNA as new serum metabolic biomarkers in patients with premature ovarian insufficiency.

OBJECTIVE: Quantitative real-time PCR (qPCR) is used to detect the differential expression of circular RNAs in patients of premature ovarian insufficiency (POI), to explore the new biomarkers of POI that can be detected from blood as soon as possible. METHODS: The study collected plasma samples from 30 patients in POI group and 30 normal people group who meet the inclusion criteria, who visited the gynecology clinic of The First Affiliated Hospital of Guangzhou University of Chinese Medicine from July 2019 to December 2020. Then, circRNAs in plasma were extracted for qPCR validation. RESULTS: 1. qPCR technology was performed on hsa_circRNA_008901 and hsa_circRNA_403959, and it was found that the levels of both were considerably downregulated in POI group. Clinical evaluation showed that both hsa_circRNA_008901 and hsa_circRNA_403959 have good diagnostic value for POI. 2. According to miRNA Regulatory Element (MRE) analysis, the predicted target miRNAs of hsa_circRNA_008901 are: hsa-miR-548c-3p, hsa-miR-924, hsa-miR-4677-5p, hsa-miR-6786-3p and hsa-miR-7974; the predicted target miRNAs of hsa_circRNA_403959 are: hsa-miR-1207-5p, hsa-miR-4691-5p, hsa-miR-4763-3p, hsa-miR-6807-5p and hsa-miR-7160-5p. CONCLUSION: Compared with the normal group, the expression levels of hsa_circRNA_008901 and hsa_circRNA_403959 in the POI group were downregulated, suggesting that these two circRNAs may be potential biomarkers of POI. Bioinformatics analysis indicated that hsa_circRNA_008901 and hsa_circRNA_403959 may regulate their binding miRNA through the action form of "molecular sponge", and then regulate the signaling pathway regulated by miRNA, and ultimately affect the disease progression of POI.

Chinese never smokers with adenocarcinoma of the lung are younger and have fewer lymph node metastases than smokers.

BACKGROUND: Lung cancers arising in never smokers have been suggested to be substantially different from lung cancers in smokers at an epidemiological, genetic and molecular level. Focusing on non-small cell lung cancer (NSCLC), we characterized lung cancer patients in China looking for demographic and clinical differences between the smoking and never-smoking subgroups. METHODS: In total, 891 patients with NSCLC, including 841 with adenocarcinoma and 50 with squamous cell carcinoma, were recruited in this study. Association of smoking status with demographic and clinical features of NSCLC was determined, and risk factors for lymph node metastasis and TNM stage were evaluated using Multivariate logistic regression analysis. RESULTS: In patients with adenocarcinoma, never smokers showed a younger age at diagnosis (54.2 ± 12.7vs. 59.3 ± 9.4, padjusted<0.001), a lower risk for lymph node metastasis than smokers (7,6% vs. 19.5%, padjusted<0.001) and less severe disease as indicated by lower percentages of patients with TNM stage of III or IV (5.5% vs. 14.7%, padjusted<0.001 ). By contrast, these associations were not observed in 50 patients with squamous cell carcinoma. Multivariate logistic regression analysis showed that smoking status was a risk factor for lymph node metastasis (OR = 2.70, 95% CI: 1.39-5.31, p = 0.004) but not for TNM stage (OR = 1.18, 95% CI: 0.09-14.43, p = 0.896) in adenocarcinoma. CONCLUSION: This study demonstrates that lung adenocarcinoma in never smokers significantly differ from those in smokers regarding both age at diagnosis and risk of lymph node metastasis, supporting the notion that they are distinct entries with different etiology and pathogenesis.

The Regularity of Stress Shielding in Internal Fixation Characterized by Hydromechanics.

Stress shielding is an important factor in the internal fixation of a fracture. To explore the regularity of stress shielding in internal fixation, a simplified model of a comminuted femoral shaft fracture bridged by a locking plate was established and finite element analysis was performed to analyze the load distribution between the plate and femur from the proximal end of the femur to the fracture line and investigate the stress shielding degree of the plate on the bone. The stress, deformation, and axial compressive force distribution of four internal fixation schemes under compression were obtained, and the stress shielding degrees on each section was calculated. To compare the regularity of stress shielding and flow distribution, the relationship between the compressive force increment and stress shielding degree was established. The normalized curves of compressive force increment with the plate section position were compared with the flow distribution in a Z-type manifold, a parallel pipe system similar to an internal fixation system in structure and working characteristics. For quantitative comparison, the similarity between normalized curves of the compressive force increment and simulated flow distribution was calculated. The regularity of load distribution along the section position of the plate was similar to the flow distribution in the Z-type manifold. Therefore, the flow distribution pattern of the Z-type manifold can be used to characterize the regularity of load distribution in internal fixation. This study provided a new method to characterize the stress shielding degree of a locking plate on bone.

Evaluation of Radiation Response in CoCrFeCuNi High-Entropy Alloys.

CoCrFeCuNi high-entropy alloys (HEAs) prepared by arc melting were irradiated with a 100 keV He+ ion beam. Volume swelling and hardening induced by irradiation were evaluated. When the dose reached 5.0 × 1017 ions/cm2, the Cu-rich phases exhibited more severe volume swelling compared with the matrix phases. This result indicated that the Cu-rich phases were favorable sites for the nucleation and gathering of He bubbles. X-ray diffraction indicated that all diffraction peak intensities decreased regularly. This reduction suggested loosening of the irradiated layer, thereby reducing crystallinity, under He+ ion irradiation. The Nix-Gao model was used to fit the measured hardness in order to obtain a hardness value H0 that excludes the indentation size effect. At ion doses of 2.5 × 1017 ions/cm2 and 5.0 × 1017 ions/cm2, the HEAs showed obvious hardening, which could be attributed to the formation of large amounts of irradiation defects. At the ion dose of 1.0 × 1018 ions/cm2, hardening was reduced, owing to the exfoliation of the original irradiation layer, combined with recovery induced by long-term thermal spike. This study is important to explore the potential uses of HEAs under extreme irradiation conditions.

Association between dietary vitamin A intake from different sources and non-alcoholic fatty liver disease among adults.

Non-alcoholic fatty liver disease (NAFLD) has become an urgent public health issue with high global prevalence, but data on NAFLD are inconsistent. The association of total dietary vitamin A intake with the NAFLD risk was not well documented in previous studies. To explore the relationship between dietary vitamin A intake from different sources and NAFLD risk among American adults. Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. Logistic regression and restricted cubic spline models were used to estimate the relationship between total dietary vitamin A intake and NAFLD risk. 6,613 adult participants were included. After adjusting potential confounders, the odds ratios (ORs) with 95% confidence intervals (CIs) of NAFLD for the highest quartile intake of total vitamin A, preformed vitamin A, provitamin A carotenoids were respectively 0.86 (0.69-1.06), 0.97 (0.74-1.28), and 0.78 (0.61-0.99), compared to the lowest quartile. Stratifying gender and age, provitamin A carotenoids intake was inversely associated with NAFLD risk in females and participants aged < 45 years. Dose-response analysis indicated a linear negative relationship between provitamin A carotenoids intake and NAFLD risk. Provitamin A carotenoids intake was inversely associated with NAFLD, especially in women and those aged < 45 years among adult American.

Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model.

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

[Marrow mesenchymal stem cell transplantation with sodium alginate gel for repair of spinal cord injury in mice].

OBJECTIVE: To investigate the effects of sodium alginate gels on marrow mesenchymal stem cell transplantation for repair of spinal cord injury (SCI) in mice. METHODS: In the present study, effects of different sterilization methods and concentrations of sodium alginate gels were examined. Marrow mesenchymal stem cells (mMSCs) were isolated from mice and cultured. Cells were cultured with sodium alginate gels and MTT assay was applied to determine the cell viability. Mice spinal cord injury was induced by spinal cord transection. mMSCs were transplanted into the cavity of injured spinal cord with sodium alginate gels. The effects of sodium alginate gel were assessed by BMS scales and immunofluorescence staining for NF-200. RESULTS: Compared with liquid form, solid form sodium alginate gel prepared with high pressure vapor sterilization had a better effect on cell viability. SCI mice treated with 10 % sodium alginate gel and mMSCs achieved higher score in BMS scale as well as higher expression of NF-200 compared with the untreated SCI group. CONCLUSION: Sodium alginate gel prepared with solid form sterilization induces mMSCs proliferation and thus can be used as the carrier of stem cell in treatment of SCI.

Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency.

METHODS: A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. RESULTS: A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. CONCLUSION: Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

Investigation of the Mechanism of Zishen Yutai Pills on Polycystic Ovary Syndrome: A Network Pharmacology and Molecular Docking Approach.

BACKGROUND: Zishen Yutai Pills (ZSYTP) is a prescription based on traditional Chinese medicine used to treat kidney-deficient pattern in traditional Chinese medicine. It is also widely used clinically for the treatment of polycystic ovary syndrome (PCOS) with positive results. This study aims to explore the potential pharmacological mechanism of ZSYTP for the treatment of PCOS by a network pharmacology approach. METHODS: Compounds were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine and TCM Database@ Taiwan, and the corresponding targets were retrieved from PubChem, Swiss Target Prediction, STITCH, and DrugBank. Meanwhile, PCOS targets were retrieved from the GeneCards database, the Online Mendelian Inheritance in Man database, National Center for Biotechnology Information Database, and DrugBank. Subsequently, multiple network construction and gene enrichment analyses were conducted with Cytoscape 3.8.2 software. Based on the previous results in the study, molecular docking simulations were done. RESULTS: 205 active compounds and 478 ZSYTP target genes were obtained after screening by ADME consideration. 1881 disease-related targets were obtained after removing duplicates. 148 intersection target genes between drug and disease targets were isolated. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis highlighted multiple gene functions and different signaling pathways to treat PCOS. Further molecular docking demonstrated the practicality of in vivo action of ZSYTP to a certain extent. CONCLUSIONS: It is possible that the pharmacological effect of ZSYTP on PCOS is linked to the hypoxia-inducible factor 1 (HIF-1) signaling pathway, improving insulin resistance, the variation on gene expression such as RNA splicing, and regulation of mRNA metabolic process. This study paves the way for further research investigating its mechanisms.

Calibration of a Constitutive Model from Tension and Nanoindentation for Lead-Free Solder.

It is challenging to evaluate constitutive behaviour by using conventional uniaxial tests for materials with limited sizes, considering the miniaturization trend of integrated circuits in electronic devices. An instrumented nanoindentation approach is appealing to obtain local properties as the function of penetration depth. In this paper, both conventional tensile and nanoindentation experiments are performed on samples of a lead-free Sn⁻3.0Ag⁻0.5Cu (SAC305) solder alloy. In order to align the material behaviour, thermal treatments were performed at different temperatures and durations for all specimens, for both tensile experiments and nanoindentation experiments. Based on the self-similarity of the used Berkovich indenter, a power-law model is adopted to describe the stress⁻strain relationship by means of analytical dimensionless analysis on the applied load-penetration depth responses from nanoindentation experiments. In light of the significant difference of applied strain rates in the tensile and nanoindentation experiments, two "rate factors" are proposed by multiplying the representative stress and stress exponent in the adopted analytical model, and the corresponding values are determined for the best predictions of nanoindentation responses in the form of an applied load⁻indentation depth relationship. Eventually, good agreement is achieved when comparing the stress⁻strain responses measured from tensile experiments and estimated from the applied load⁻indentation depth responses of nanoindentation experiments. The rate factors ψ σ and ψ n are calibrated to be about 0.52 and 0.10, respectively, which facilitate the conversion of constitutive behaviour from nanoindentation experiments for material sample with a limited size.

Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway.

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

Electroacupuncture exerts neuroprotective effects on ischemia/reperfusion injury in JNK knockout mice: the underlying mechanism.

Simple regulation of c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) pathways is not enough to trigger cell apoptosis. However, activation of the stress activated pathway (JNK/p38 MAPK) together with inhibition of the growth factor activated extracellular signal-regulated kinase (ERK) pathway can promote cell apoptosis. We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury. To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice, mouse models of cerebral ischemia/reperfusion injury were established by Longa's method. Electroacupuncture was conducted at acupoints Chize (LU5), Hegu (LI4), Sanyinjiao (SP6) and Zusanli (ST36) 1.5 hours after ischemia/reperfusion injury for 20 minutes, once a day. The neurological function was evaluated using neurological deficit scores. The expression of phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 (p-p38) in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay. The mRNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction. Electroacupuncture improved neurological function, increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side. Electroacupuncture increased mRNA expression of ERK, but decreased that of p38 in the cerebral cortex and hippocampus on the injured side. In conclusion, electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway, thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.

A novel torsion testing technique for micro-scale specimens based on electromagnetism.

A novel torsion apparatus for micro-scale specimens is developed based on electromagnetism, in which a coil-magnet component is used for actuating and torque measuring. When the current gets through the coil, the torque, produced by Ampere force, can be easily measured by recording the current. A laser displacement sensor is applied to measure the rotation angle. The torque is calibrated using Sartorius BP211D balance. The calibration results demonstrate there is a perfect linear relationship between the torque and the current. The torque capacity is 4.0 × 10(-4) N m with noise-floor of less than 10(-8) N m. The rotation angle capacity is 60° with noise-floor of less than 0.02°. Two sets of copper wire specimens, with diameter of 100 µm and 140 µm, are tested using this apparatus. Experimental results, with good resolution and repeatability, successfully demonstrate the effectiveness of the torsion testing technique for micro-scale specimens.