Cinnamomi cortex extract mitigated monosodium urate-induced acute gouty arthritis in rats through nuclear factor-κB-NOD-like receptor thermal protein domain associated protein 3 signaling pathway.

Cinnamomi cortex was applied to mitigate joint injury since ancient China. However, the effect of Cinnamomi cortex on gouty arthritis (GA) was rarely reported. This study aimed to explore the effect of Cinnamomi cortex on monosodium urate (MSU)-induced acute GA (AGA) in rats, and clarify the underlying mechanism. The results showed that Cinnamomi cortex extract (CE) containing rich polyphenols and flavonoids alleviated joint swelling and inflammation by reducing programmed cell death in MSU-induced AGA rats. Network pharmacology analysis showed that CE's predictive inflammatory pathways included nuclear factor-κB (NF-κB) and necroptosis pathways. CE reduced expression of pyroptosis-related regulators including Gasdermin D and Caspase 1 via regulating NF-κB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway in AGA rats. In conclusion, this study provided a theoretical basis for Cinnamomi cortex applied as a new veterinary medicine to protect against GA.

Universal N2O Reaction Gas To Remove Spectral Interferences of Nonmetallic Impurity Elements by Inductively Coupled Plasma Tandem Mass Spectrometry Analysis of High-Purity Magnesium Alloys.

Using N2O as a universal reaction gas, a new strategy was proposed for the highly sensitive interference-free simultaneous determination of nonmetallic impurity elements in high-purity magnesium (Mg) alloys by ICP-MS/MS. In the MS/MS mode, through O-atom and N-atom transfer reactions, 28Si+ and 31P+ were converted to the oxide ions 28Si16O2+ and 31P16O+, respectively, while 32S+ and 35Cl+ were converted to the nitride ions 32S14N+ and 14N35Cl+, respectively. The ion pairs formed via the 28Si+ → 28Si16O2+, 31P+ → 31P16O+, 32S+ → 32S14N+, and 35Cl+ → 14N35Cl+ reactions by the mass shift method could eliminate spectral interferences. Compared with the O2 and H2 reaction modes, the present approach delivered much higher sensitivity and lower limit of detection (LOD) of the analytes. The accuracy of the developed method was evaluated via standard addition method and comparative analysis by sector field ICP-MS (SF-ICP-MS). The study indicates that in the MS/MS mode, use of N2O as reaction gas can provide interference-free conditions and sufficiently low LODs for analytes. The LODs of Si, P, S, and Cl could reach down to 17.2, 4.43, 10.8, and 31.9 ng L-1, respectively, and the recoveries were in the range of 94.0-106%. The determination results of the analytes were consistent with those obtained by SF-ICP-MS. This study presents a systematic method for the precise and accurate quantification of Si, P, S, and Cl in high-purity Mg alloys by ICP-MS/MS. The developed method provides valuable reference that can be expanded and applied to other fields.

Rapid and efficient isolation platform for plasma extracellular vesicles: EV-FISHER.

Extracellular vesicles (EVs) have found diverse applications in clinical theranostics. However, the current techniques to isolate plasma EVs suffer from burdensome procedures and limited yield. Herein, we report a rapid and efficient EV isolation platform, namely, EV-FISHER, constructed from the metal-organic framework featuring cleavable lipid probes (PO4 3- -spacer-DNA-cholesterol, PSDC). The EV-FISHER baits EVs from plasma by cholesterol and separates them with an ordinary centrifuge. The captured EVs could be released and collected upon subsequent cleavage of PSDC by deoxyribonuclease I. We conclude that EV-FISHER dramatically outperforms the ultracentrifugation (UC) in terms of time (∼40 min vs. 240 min), isolation efficiency (74.2% vs. 18.1%), and isolation requirement (12,800 g vs. 135,000 g). In addition to the stable performance in plasma, EV-FISHER also exhibited excellent compatibility with downstream single-EV flow cytometry, enabling the identification of glypican-1 (GPC-1) EVs for early diagnosis, clinical stages differentiation, and therapeutic efficacy evaluation in breast cancer cohorts. This work portrays an efficient strategy to isolate EVs from complicated biological fluids with promising potential to facilitate EVs-based theranostics.

Pan-Cancer Study of SHC-Adaptor Protein 1 (SHC1) as a Diagnostic, Prognostic and Immunological Biomarker in Human Cancer.

Background: Recent studies highlight the carcinogenesis role of SHC-adaptor protein 1 (SHC1) in cancer initiation, development, and progression. However, its aberrant expression, diagnostic and prognostic value remain unknown in a variety of tumors. Methods: The SHC1 expression profiles were analyzed using GTEx database, TCGA database, Oncomine and CPTAC database. The survival analysis was conducted using GEPIA2, Kaplan-Meier Plotter, UALCAN, and PrognoScan. The diagnostic values of SHC1 were calculated with the "pROC" package in R software. The genetic alteration of SHC1 and mutations were analyzed using cBioPortal. TIMER2 was employed to estimate the correlations between SHC1 expression and tumor-infiltrating immune cells in the TCGA cohort. Enrichment analysis of SHC1 was conducted using the R package "clusterProfiler." Results: SHC1 was ubiquitously highly expressed and closely associated with worse prognosis of multiple major cancer types (all p < 0.05). Further, SHC1 gene mutations were strongly linked to poor OS and DFS in SKCM (all p < 0.05). An enhanced phosphorylation level of SHC1 at the S139 site was observed in clear cell RCC. Additionally, the results revealed SHC1 expression was strongly linked to TMB, MMRs, MSI, TAMs, DNA methylation, m6A RNA methylation, tumor-associated immune infiltration, and immune checkpoints in multiple cancers (all p < 0.05). In addition, the results of the ROC analysis indicated the SHC1 exhibited strong diagnostic capability for KICH (AUC = 0.92), LIHC (AUC = 0.95), and PAAD (AUC = 0.95). Finally, enrichment analysis indicated that SHC1 may potentially involve in the regulation of numerous signaling pathways in cancer metabolism and protein phosphorylation-related functions. Conclusions: These findings highlight that SHC1 plays an important role in the tumor immune microenvironment, and SHC1 has been identified to have prognostic and diagnostic value in multiple cancers. Thus, SHC1 is a potential target for cancer immunotherapy and effective prognostic and diagnostic biomarker.

Prognostic and Diagnostic Values of Semaphorin 5B and Its Correlation With Tumor-Infiltrating Immune Cells in Kidney Renal Clear-Cell Carcinoma.

Background: Semaphorin 5B (SEMA5B) has been described to be involved in the development and progression of cancer. However, the potential diagnostic and prognosis roles and its correlation with tumor-infiltrating immune cells in KIRC have not been clearly reported yet. Methods: The mRNA level of SEMA5B was analyzed via the TCGA and GTEx database as well as the CCLE dataset and verified by GSE53757 and GSE40435 datasets. Meanwhile, the protein level of SEMA5B was analyzed by CPTAC and validated by HPA. The diagnostic value of SEMA5B was analyzed according to the TCGA database and validated by GSE53757, GSE46699, and GSE11024 + GSE46699 datasets. Then, the survival analysis was conducted using GEPIA2. R software (v3.6.3) was applied to investigate the relevance between SEMA5B and immune checkpoints and m6A RNA methylation regulator expression. The correlation between SEMA5B and MMRs and DNMT expression and tumor-infiltrating immune cells was explored via TIMER2. Co-expressed genes of SEMA5B were assessed by cBioPortal, and enrichment analysis was conducted by Metascape. The methylation analysis was conducted with MEXPRESS and MethSurv online tools. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of SEMA5B. Results: SEMA5B was significantly upregulated at both the mRNA and protein levels in KIRC. Further analysis demonstrated that the mRNA expression of SEMA5B was significantly correlated with gender, age, T stage, pathologic stage, and histologic grade. High levels of SEMA5B were found to be a favorable prognostic factor and novel diagnostic biomarker for KIRC. SEMA5B expression was shown to be significantly associated with the abundance of immune cells in KIRC. Also, SEMA5B expression was significantly correlated with the abundance of MMR genes, DNMTs, and m6A regulators in KIRC. Enrichment analysis indicated that the co-expressed genes may involve in crosslinking in the extracellular matrix (ECM). GSEA disclosed that SYSTEMIC_LUPUS_ERYTHEMATOSUS and NABA_ECM_REGULATORS were prominently enriched in the SEMA5B low-expression phenotype. Finally, the methylation analysis demonstrated a correlation between hypermethylation of the SEMA5B gene and a poor prognosis in KIRC. Conclusion: Increased SEMA5B expression correlated with immune cell infiltration, which can be served as a favorable prognostic factor and a novel diagnostic biomarker for KIRC.

Chemical constituents from the stems of Acanthopanax senticosus with their cytotoxic activities.

A new coumestan named 7,5'-dihydroxy-4'-(3''-hydroxy-3''-methyl-trans-isobut-1''-enyl) coumestan (1), together with five known compounds (2-6), was isolated from the EtOAc-soluble extract of the stems of Acanthopanax senticosus. Their structures were elucidated based on extensive spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic activities against four human cancer cells including HepG2, A549, HeLa and MCF-7. Among them, the new compound 1 was found to exhibit significant cytotoxic activity on HeLa cells with IC50 value of 6.5 µM.

Factors Influencing the Low-Temperature Properties of Styrene-Butadiene-Styrene Modified Asphalt Based on Orthogonal Tests.

Styrene-butadiene-styrene (SBS) is widely used in asphalt modification to obtain superior high-temperature performance. Nevertheless, studies on the low-temperature properties of SBS-modified asphalt are not satisfactory. Orthogonal tests are valid in analysing the results. In this paper, the main factors (SBS content, sulfur content, and the addition of rubber processing oil) for improving the low-temperature performance of SBS-modified asphalt were analyzed base on the orthogonal tests. Firstly, the frequency sweep test, bending beam rheometer (BBR) test, and force-ductility test were conducted to evaluate the low-temperature properties of SBS-modified asphalt. Investigation of low-temperature parameters obtained through these tests was conducted base on the orthogonal analysis method. The G-R parameter was abandoned in the analysis of the orthogonal method for the result that the increase of SBS content was negative to the low-temperature properties by the Glover-Rowe (G-R) parameter, which were contrary to the results of BBR and force-ductility tests. Moreover, the other parameters (ΔTc and toughness) sorted according to the orthogonal analysis method indicated the effect on low-temperature performance of the SBS-modified asphalt as SBS content > rubber processing oil > sulfur. As shown above that both SBS and rubber processing oil play a critical role in improving the low-temperature properties of SBS-modified asphalt, for SBS could resist the generation and subsequent propagation of cracks while the rubber processing oil could supplement the maltene loss.

Rheological and Aging Properties of Composite Modified Bitumen by Styrene-Butadiene-Styrene and Desulfurized Crumb Rubber.

Taking advantage of crumb rubber from waste tires to modify bitumen is widely for the environmentally friendly and sustainable development of pavement. This study investigated the modification mechanism, rheological, and aging properties of styrene-butadiene-styrene (SBS)/desulfurized crumb rubber (DCR) composite modified bitumen (SBS/DCRMB). Morphological features and chemical characteristics were assessed by fluorescence intensity measurement and gel permeation chromatography (GPC), respectively, and results demonstrated that the DCR and SBS modifier in SBS/DCRMB had been vulcanized and formed a three-dimensional network structure. Moreover, a comparison of the GPC elution curve showed the residual bitumen hardly changed due to carbon black released from DCR of SBS/DCRMB during the aging process of SBS/DCRMB, and the polymer molecules condensed to larger units. However, the remaining bitumen in SBSMB had changed evidently and the polymer degraded to smaller molecules. Meanwhile the rheological testing results, including multiple stress creep recovery, linear amplitude sweep and bending beam rheometer, declared that the SBS/DCRMB is superior to SBSMB before and after aging.

Characterization of Desulfurized Crumb Rubber/Styrene-Butadiene-Styrene Composite Modified Asphalt Based on Rheological Properties.

With the growing interest in bituminous construction materials, desulfurized crumb rubber (CR)/styrene-butadiene-styrene (SBS) modified asphalts have been investigated by many researchers as low-cost environmental-friendly road construction materials. This study aimed to investigate the rheological properties of desulfurized CR/SBS composite modified asphalt within various temperature ranges. Bending beam rheometer (BBR), linear amplitude sweep (LAS), and multiple stress creep recovery (MSCR) tests were performed on conventional CR/SBS composite modified asphalt and five types of desulfurized CR/SBS modified asphalts. Meanwhile, Burgers' model and the Kelvin-Voigt model were used to derive nonlinear viscoelastic parameters and analyze the viscoelastic mechanical behavior of the asphalts. The experimental results indicate that both the desulfurized CR/SBS composite modifier and force chemical reactor technique can enhance the crosslinking of CR and SBS copolymer, resulting in an improved high-, intermediate-, and low-temperature performance of desulfurized CR/SBS composite modified asphalt. Burgers' model was found to be apposite in simulating the creep stages obtained from MSCR tests for CR/SBS composite modified asphalts. The superior high-temperature performance of desulfurized CR/SBS modified asphalt prepared with 4% SBS, 20% desulfurized rubber, and a force chemical reactor time of 45 min contributes to the good high-temperature elastic properties of the asphalt. Therefore, this combination is recommended as an optimal preparation process. In summary, the desulfurization of crumb rubber and using the force chemical reactor technique are beneficial to composite asphalt performance and can provide a new way of utilizing waste tire rubber.

Determination of ultra-trace levels of titanium in human serum using inductively coupled plasma tandem mass spectrometry based on O2/H2 reaction gas.

This study proposes a new strategy to determine ultra-trace Ti in human serum using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). The human serum samples were diluted with 1% (v/v) HNO3, followed by the determination of ultra-trace Ti using ICP-MS/MS. In the MS/MS mode, a small amount of H2 was mixed with O2 (the reaction gas) in a collision reaction cell (CRC) to form an O2/H2 reaction mixture, and then, the conversion of Ti+ to TiO+ was determined by the O2 mass shift method. High concentrations of Ca, S, and P in human serum were ionized in plasma, and the formed Ca+, SO+, and PO + reacted with O2 in CRC to form CaO+, SO2+, and PO2+ to interfere with the determination of TiO+. We employed the mass shift reaction of H2 and oxide ions to eliminate this interference. This method was evaluated using the human serum sample spike recovery experiment and comparative analysis by sector field (SF)-ICP-MS. The results showed that using reaction gas mixture O2/H2 reduced the background equivalent concentration (BEC) of Ti and improved sensitivity. The values determined by this method were consistent with the SF-ICP-MS values, which confirmed its accuracy and reliability. The limit of detection (LOD) of Ti was 0.78-7.20 ng L-1, the recovery was 96.0%-104%, and the relative standard deviation (RSD) was 2.0%-4.2%. This method has solved the problem that the determination of ultra-trace Ti in human serum cannot be accurately determined using O2 reaction mode. It realizes the interference-free and highly sensitive determination of the ultra-trace Ti in samples with high levels of Ca, S, and P and provides a new technique for high-throughput and accurate determination of ultra-trace Ti in human serum.

Diagnostic value and clinical significance of circulating miR-650 and CA211 in detecting of gastric carcinoma.

The present study determined the levels of plasma biomarkers in patients with gastric carcinoma (GC) and investigated their clinical significance and diagnostic value. Between April 2014 and December 2018, 90 patients with GC, 90 patients with precancerous lesions (Pre) and 45 healthy controls (NC) were recruited from the Affiliated Liutie Central Hospital of Guangxi Medical University. Five markers were measured: microRNA-650 (miRNA-650; using reverse transcription-quantitative polymerase chain reaction), and carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA211 and CA50 using electrochemiluminescence. Circulating markers were all upregulated in patients with GC (P<0.05), and CA211 and CA50 were significantly increased in patients with Pre. The miRNA-650 and CA211 had an area under the curve (AUC) of 0.700 (moderate) and 0.866 (high), respectively, in the diagnosis of GC. Differentiation of GC from Pre yielded an AUC of 0.665 (low) and 0.708 (moderate), respectively. The combination model of miRNA-650 and CA211 showed an appropriate value of AUC (0.887) to discriminate the GC patients from the healthy subjects with a sensitivity and specificity of 82.5 and 97.7%. Additionally, differentiating GC from Pre yielded an AUC of 0.767 with a sensitivity of 57.1% and a specificity of 95%, respectively. In terms of clinicopathological features, the expression of miRNA-650 and CA211 in plasma was not associated with the patients' age, sex, Tumor-Node-Metastasis stage, or histological type. In conclusion, plasma miRNA-650 and CA211 is a promising and powerful non-invasive marker for the detection of GC.

Identification of a Five-Autophagy-Related-lncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma.

Although great progresses have been made in the diagnosis and treatment of hepatocellular carcinoma (HCC), its prognostic marker remains controversial. In this current study, weighted correlation network analysis and Cox regression analysis showed significant prognostic value of five autophagy-related long non-coding RNAs (AR-lncRNAs) (including TMCC1-AS1, PLBD1-AS1, MKLN1-AS, LINC01063, and CYTOR) for HCC patients from data in The Cancer Genome Atlas. By using them, we constructed a five-AR-lncRNA prognostic signature, which accurately distinguished the high- and low-risk groups of HCC patients. All of the five AR lncRNAs were highly expressed in the high-risk group of HCC patients. This five-AR-lncRNA prognostic signature showed good area under the curve (AUC) value (AUC = 0.751) for the overall survival (OS) prediction in either all HCC patients or HCC patients stratified according to several clinical traits. A prognostic nomogram with this five-AR-lncRNA signature predicted the 3- and 5-year OS outcomes of HCC patients intuitively and accurately (concordance index = 0.745). By parallel comparison, this five-AR-lncRNA signature has better prognosis accuracy than the other three recently published signatures. Furthermore, we discovered the prediction ability of the signature on therapeutic outcomes of HCC patients, including chemotherapy and immunotherapeutic responses. Gene set enrichment analysis and gene mutation analysis revealed that dysregulated cell cycle pathway, purine metabolism, and TP53 mutation may play an important role in determining the OS outcomes of HCC patients in the high-risk group. Collectively, our study suggests a new five-AR-lncRNA prognostic signature for HCC patients.

Decreased cpg15 augments oxidative stress in sleep deprived mouse brain.

Sleep deprivation (SD) has detrimental effects on the physiological function of the brain. However, the underlying mechanism remains elusive. In the present study, we investigated the expression of candidate plasticity-related gene 15 (cpg15), a neurotrophic gene, and its potential role in SD using a REM-SD mouse model. Immunofluorescent and Western blot analysis revealed that the expression of cpg15 protein decreased in the hippocampus, ventral group of the dorsal thalamus (VENT), and somatosensory area of cerebral cortex (SSP) after 24-72 h of REM-SD, and the oxidative stress in these brain regions was increased in parallel, as indicated by the ratio of glutathione (GSH) to its oxidative product (GSSG). Over-expression of cpg15 in thalamus, hippocampus, and cerebral cortex mediated by AAV reduced the oxidative stress in these regions, indicating that the decrease of cpg15 might be a cause that augments oxidative stress in the sleep deprived mouse brain. Collectively, the results imply that cpg15 may play a protective function in the SD-subjected mouse brain via an anti-oxidative function. To our knowledge, this is the first time to provide evidences in the role of cpg15 against SD-induced oxidative stress in the brain.

Evolution of Rheological Behaviors of Styrene-Butadiene-Styrene/Crumb Rubber Composite Modified Bitumen after Different Long-Term Aging Processes.

In this study, a new type of composite modified bitumen was developed by blending styrene-butadiene-styrene (SBS) and crumb rubber (CR) with a chemical method to satisfy the durability requirements of waterproofing material in the waterproofing layer of high-speed railway subgrade. A pressure-aging-vessel test for 20, 40 and 80 h were conducted to obtain bitumen samples in different long-term aging conditions. Multiple stress creep recovery (MSCR) tests, linear amplitude scanning tests and bending beam rheometer tests were conducted on three kinds of asphalt binders (SBS modified asphalt, CR modified asphalt and SBS/CR composite modified asphalt) after different long-term aging processes, including high temperature permanent deformation performance, resistance to low temperature thermal and fatigue crack. Meanwhile, aging sensitivities were compared by different rheological indices. Results showed that SBS/CR composite modified asphalt possessed the best properties before and after aging. The elastic property of CR in SBS/CR composite modified asphalt improved the ability to resist low temperature thermal and fatigue cracks at a range of low and middle temperatures. Simultaneously, the copolymer network of SBS and CR significantly improved the elastic response of the asphalt SBS/CR modified asphalt at a range of high temperatures. Furthermore, all test results indicated that the SBS/CR modified asphalt possesses the outstanding ability to anti-aging. SBS/CR is an ideal kind of asphalt to satisfy the demand of 60 years of service life in the subgrade of high speed railway.

Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer.

OBJECTIVE: MicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC). MATERIALS & METHODS: The miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed. RESULTS: Elevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC. CONCLUSIONS: Overexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.

Serum Amyloid A is a Novel Inflammatory Biomarker in Polycystic Ovary Syndrome.

BACKGROUND: Serum amyloid A (SAA) is considered a biomarker of inflammation; however, the SAA levels in polycystic ovary syndrome (PCOS) are still uncertain. METHODS: In this study, SAA, glucose, insulin, C-reactive protein (CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone concentrations were measured in 82 women with PCOS and 60 healthy controls. RESULTS: The median concentration of SAA was 5.000 mg/L (IQR: 2.825 - 5.400) in women with PCOS, which was significantly higher than that of controls (3.700 mg/L, IQR: 2.825 - 5.400, p = 0.025). SAA was only positively associated with the CRP (r = 0.303, p = 0.006). No significant association was observed between SAA and body mass index (BMI), total testosterone, or insulin resistance (IR). CONCLUSIONS: SAA levels were increased in women with PCOS, and SAA may be a potential inflammatory biomarker for PCOS.

Decreased Serum Kruppel-Like Factor 7 Level is Positively Associated with Low-Density Lipoprotein Cholesterol Level in Women with Polycystic Ovary Syndrome.

BACKGROUND: Kruppel-like factor 7 (KLF7) is associated with type 2 diabetes and obesity; however, at present the KLF7 level in polycystic ovary syndrome (PCOS) remains unreported. METHODS: In this study, serum KLF7, glucose, insulin, C-reactive protein (CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone concentrations were measured in 65 women with PCOS and 61 healthy controls. RESULTS: Body mass index (BMI) in PCOS and the control group were all < 25 kg/m2. The median concentration of KLF7 was 3.630 ng/mL [interquartile range (IQR): 1.547 - 7.172] in women with PCOS, which was significantly lower than that of controls (5.282 ng/mL, IQR: 3.128 - 11.263, p = 0.003). The KLF7 level was positively correlated with low-density lipoprotein cholesterol (LDL-C) (r = 0.261, p = 0.018). No significant association was observed between KLF7 and the BMI, total testosterone, and insulin resistance (IR). CONCLUSIONS: The KLF7 level decreased in women with PCOS. KLF7 may represent a new therapeutic target in the treatment of PCOS.

[Construction and application of a magnetic and catalytic hairpin assembly-based platform for detecting dual membrane proteins on exosomes].

OBJECTIVE: To construct a magnetic and catalytic hairpin assembly-based platform for detection of dual membrane proteins on exosomes. METHODS: Exosomes in supernatant of breast cancer MDA-MB-231 cell culture were separated, purified and characterized. Super-resolution imaging and Western blotting were performed to confirm the expression of the membrane protein CD63 on the exosomes. Polyacrylamide gel electrophoresis was used to verify the combination of AptEpCAM-T and exosomes. Fluorescence experiments were carried out to test the feasibility of CHA nucleic acid sequence, optimize the reaction conditions, and determine the specificity of the detection platform. RESULTS: Super-resolution imaging and Western blotting showed that breast cancer MDA-MB-231 cell-derived exosomes expressed abundant membrane protein CD63. Polyacrylamide gel electrophoresis indicated that AptEpCAM-T could recognize and bind to exosomes. The results of specificity test showed that the signal-to-noise ratio of the detection platform was 1.10±0.01 for detecting normal human breast epithelial cell-derived exosomes, and was 2.09±0.08 for breast cancer cell-derived exosomes. CONCLUSIONS: Magnetic and catalytic hairpin assembly-based detection platform allows simultaneous detection of two membrane proteins expressed on exosomes and identification of the expressions of membrane proteins on exosomes from different sources.

Development Of A Three-Gene Prognostic Signature For Hepatitis B Virus Associated Hepatocellular Carcinoma Based On Integrated Transcriptomic Analysis.

Integration of public genome-wide gene expression data together with Cox regression analysis is a powerful weapon to identify new prognostic gene signatures for cancer diagnosis and prognosis. Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), however, it remains largely unknown about the specific gene prognostic signature of HBV-associated HCC. Using Robust Rank Aggreg (RRA) method to integrate seven whole genome expression datasets, we identified 82 up-regulated genes and 577 down-regulated genes in HBV-associated HCC patients. Combination of several enrichment analysis, univariate and multivariate Cox proportional hazards regression analysis, we revealed that a three-gene (SPP2, CDC37L1, and ECHDC2) prognostic signature could act as an independent prognostic indicator for HBV-associated HCC in both the discovery cohort and the internal testing cohort. Gene set enrichment analysis showed that the high-risk group with lower expression levels of the three genes was enriched in bladder cancer and cell cycle pathway, whereas the low-risk group with higher expression levels of the three genes was enriched in drug metabolism-cytochrome P450, PPAR signaling pathway, fatty acid and histidine metabolisms. This indicates that patients of HBV-associated HCC with higher expression of these three genes may preserve relatively good hepatic cellular metabolism and function, which may also protect HCC patients from persistent drug toxicity in response to various medication. Our findings suggest a three-gene prognostic model that serves as a specific prognostic signature for HBV-associated HCC.

Soluble cpg15 from Astrocytes Ameliorates Neurite Outgrowth Recovery of Hippocampal Neurons after Mouse Cerebral Ischemia.

The present study focuses on the function of cpg15, a neurotrophic factor, in ischemic neuronal recovery using transient global cerebral ischemic (TGI) mouse model and oxygen-glucose deprivation (OGD)-treated primary cultured cells. The results showed that expression of cpg15 proteins in astrocytes, predominantly the soluble form, was significantly increased in mouse hippocampus after TGI and in the cultured astrocytes after OGD. Addition of the medium from the cpg15-overexpressed astrocytic culture into the OGD-treated hippocampal neuronal cultures reduces the neuronal injury, whereas the recovery of neurite outgrowths of OGD-injured neurons was prevented when cpg15 in the OGD-treated astrocytes was knocked down, or the OGD-treated-astrocytic medium was immunoadsorbed by cpg15 antibody. Furthermore, lentivirus-delivered knockdown of cpg15 expression in mouse hippocampal astrocytes diminishes the dendritic branches and exacerbates injury of neurons in CA1 region after TGI. In addition, treatment with inhibitors of MEK1/2, PI3K, and TrkA decreases, whereas overexpression of p-CREB, but not dp-CREB, increases the expression of cpg15 in U118 or primary cultured astrocytes. Also, it is observed that the Flag-tagged soluble cpg15 from the astrocytes transfected with Flag-tagged cpg15-expressing plasmids adheres to the surface of neuronal bodies and the neurites. In conclusion, our results suggest that the soluble cpg15 from astrocytes induced by ischemia could ameliorate the recovery of the ischemic-injured hippocampal neurons via adhering to the surface of neurons. The upregulated expression of cpg15 in astrocytes may be activated via MAPK and PI3K signal pathways, and regulation of CREB phosphorylation.SIGNIFICANCE STATEMENT Neuronal plasticity plays a crucial role in the amelioration of neurological recovery of ischemic injured brain, which remains a challenge for clinic treatment of cerebral ischemia. cpg15 as a synaptic plasticity-related factor may participate in promoting the recovery process; however, the underlying mechanisms are still largely unknown. The objective of this study is to reveal the function and mechanism of neuronal-specific cpg15 expressed in astrocytes after ischemia induction, in promoting the recovery of injured neurons. Our findings provided new mechanistic insight into the neurological recovery, which might help develop novel therapeutic options for cerebral ischemia via astrocytic-targeting interference of gene expression.