We aimed to examine the association of apolipoprotein E (APOE) ɛ4 genotype with neuroimaging markers of Alzheimer's disease: hippocampal volume, brain amyloid deposition and cerebral metabolism.
We ...performed a systematic review and meta-analysis of 14 cross-sectional studies identified in Pubmed from 1996 to 2014 (n=1628). The pooled standard mean difference (SMD) was used to estimate the association between APOE and hippocampal volume and amyloid deposition. Meta-analysis was performed using effect size signed differential mapping using coordinates extracted from clusters with statistically significant difference in cerebral metabolic rate for glucose between APOE ɛ4+ and ɛ4- groups.
APOE ɛ4 carrier status was associated with atrophic hippocampal volume (pooled SMD: -0.47; 95% CI -0.82 to -0.13; p=0.007) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 0.62, 95% CI 0.27 to 0.98, p=0.0006). APOE ɛ4 was also associated with decreased cerebral metabolism, especially in right middle frontal gyrus.
APOE ɛ4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism. Theses associations may indicate the potential role of the APOE gene in the pathophysiology of Alzheimer's disease.
An instrument-free system for point-of-care molecular diagnosis of H1N1 with combined convective PCR and dipstick assay.
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•A complete strategy for instrument-free POC molecular ...diagnosis of H1N1 virus is developed.•A fully disposable chemically-heated thermal processor is developed to heat the capillary tube for convective amplification at 95°C.•A rapid one-step nucleic acid dipstick assay is developed for detection of amplification products by eye without a need for instrumentation.•Sensitive and rapid nucleic acid based H1N1 diagnosis can be obtained with low cost and high convenience especially at the low resource settings.
A simple, convenient, easy-to-use, and low-cost platform for rapid molecular detection of H1N1 virus is designed and implemented based on convective polymerase chain reaction (CPCR) and dipstick assay at the point of care (POC) settings. A fully disposable chemically-heated thermal processor is developed to heat the capillary tube from the bottom at a fixed temperature for amplification without the need for electrical power. Amplification is achieved when reagents in the capillary tube are spontaneously and repeatedly transported through different temperature zones, which significantly shortens the amplification time by eliminating the need for controlled time-domain temperature cycling. A rapid one-step nucleic acid dipstick assay is adopted to facilitate the detection of amplification products with the eye instead of instrumentation. The utility of our POC diagnostic system was demonstrated by detecting H1N1 virus with sensitivity of 1.0 TCID50/mL within 35min. The developed system is particularly desired for resource poor settings, for example, developing countries, outside centralized laboratories, doctor’s offices and homes, to relieve the requirements for laboratory facilities and trained personnel.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In recent years, the risk, such as hypertension, obesity and diabetes mellitus, of cardiovascular diseases has been increasing explosively with the development of living conditions and the expansion ...of social psychological pressure. The disturbance of glucose and lipid metabolism contributes to both collapse of myocardial structure and cardiac dysfunction, which ultimately leads to diabetic cardiomyopathy. The pathogenesis of diabetic cardiomyopathy is multifactorial, including inflammatory cascade activation, oxidative/nitrative stress, and the following impaired Ca
2+
handling induced by insulin resistance/hyperinsulinemia, hyperglycemia, hyperlipidemia in diabetes. Some key alterations of cellular signaling network, such as translocation of CD36 to sarcolemma, activation of NLRP3 inflammasome, up-regulation of AGE/RAGE system, and disequilibrium of micro-RNA, mediate diabetic oxidative stress/inflammation related myocardial remodeling and ventricular dysfunction in the context of glucose and lipid metabolic disturbance. Here, we summarized the detailed oxidative stress/inflammation network by which the abnormality of glucose and lipid metabolism facilitates diabetic cardiomyopathy.
Recently, metal–organic framework (MOF)-based photocatalysts for an efficient CO2 reduction reaction have drawn wide attention in multidisciplinary fields and sustainable chemistry. In this work, a ...series of Cu2+-doped two-dimensional Ti-based MOFs were fabricated by a facile in situ solvothermal method. Cu2+ ions were doped in equal proportions and uniformly dispersed in the crystal structure of the MOF matrix. Interestingly, the doping content of Cu2+ ions and the photocatalytic performance displayed an obvious volcanic relationship, the medium-concentration Cu2+-doped sample (T1-2Cu) held the greatest activity with 100% carbonaceous product (CH4 and CO) formation, and the CH4 production rate was 3.7 μmol g–1 h–1 with 93% electron selectivity. The band structure, local electronic structure, carrier separation kinetics, and CO2 adsorption studies demonstrated that the excellent photocatalytic activity of T1-2Cu benefited from the appropriate amount of Cu2+ ion doping: (1) a doping amount of 2 atom % optimized the conduction band position of the MOF substrate and endowed T1-2Cu with strong reduction potential in thermodynamics, (2) doping Cu2+ ions tuned the local electronic environment around titanium oxide clusters and optimized the generation, separation, and migration processes of photoinduced carriers, and (3) the introduction of Cu2+ ions also provided more accessible active sites and more probabilities for the adsorption and activation of CO2 reactants.
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IJS, KILJ, NUK, PNG, UL, UM
Data on the occurrences of legacy and alternative per- and polyfluoroalkyl substances (PFASs) in glioma are scarce. It remains unclear if PFASs exposure is related to the prevalence of glioma. A ...total of 137 glioma and 40 non-glioma brain tissue samples from patients recruited from the Nanfang Hospital, South China were analyzed for 17 PFAS compounds. Perfluorohexanoic acid, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (FOSA), and 6:2 chlorinated polyfluorinated ether sulfonate were frequently detected (> 60 %) in glioma. The total concentrations (range; median) of 17 PFASs in glioma (0.20–140; 3.1 ng g−1) were slightly higher than those in non-glioma (0.35–32; 2.2 ng g−1), but without statistical significance. The PFAS concentrations in males were statistically higher (p < 0.05) than those in females. Elevated glioma grades were associated with higher concentrations of PFOA, PFOS, and FOSA. Positive correlations were observed between PFAS concentrations (especially for PFOA) and Ki-67 or P53 expression, pathological molecular markers of glioma. Our findings suggested that exposure to PFASs might increase the probability to develop glioma. This is the first case study demonstrating associations between PFASs exposure and brain cancer. More evidences and potential pathogenic mechanisms warranted further investigations.
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•PFASs were commonly detected in glioma and non-glioma human brain tissues.•PFOA concentration positively correlated with glioma grade, Ki-67 and P53 expression.•Glioma is partially ascribed to exposure to legacy and alternative PFASs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AIM: To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio(NLR) in esophageal squamous cell carcinoma(ESCC).METHODS: Data from 371 eligible patients with ESCC who ...had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ2 test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival(CSS) and recurrence-free survival(RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied.RESULTS:The median age of the patients was 57.0years,and 276/371(74.4%)patients were male.The NLR was≤3.0 in 80.1%(297/371)of the patients,and the remaining 19.9%(74/371)had an NLR>3.0.Median postoperative follow-up was 66.0 mointerquartile range(IQR):49.0-76.0 mo,with a follow-up rate of 94%.Follow-up was not significantly different between patients with an NLR≤and>3.0(63.13±1.64 vs 61.52±3.66,P=0.711).However,higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status(P=0.007).A significant,independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS(HR=1.591;P=0.007)and RFS(HR=1.525;P=0.013).Moreover,when patients were stratified by pathological tumor-node-metastasis(TNM)staging,the adverse effects of preoperative serum NLR on CSS(HR=2.294;P=0.008)and RFS(HR=2.273;P=0.008)were greatest in those patients with stageⅢA disease.CONCLUSION:Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients,particularly in patients with stageⅢA disease.
More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and ...its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression.
First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC.
As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration.
Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.
Objectives:
Procalcitonin (PCT) has long been proved as an early diagnostic signal for postoperative outcomes. The purpose of this study is to explore the value of serum procalcitonin levels in ...predicting post-hepatectomy liver failure (PHLF), and further to declarethe relationship between postoperative PCT and short-term prognosis in patients after hepatectomy.
Methods:
Clinical data of patients with hepatocellular carcinoma (HCC) who underwent hepatectomy from June 1st, 2019 to September 31st, 2020 at Shanghai Eastern Hepatobiliary Surgery Hospital had been retrospectively analyzed. Logistic regression analysis was used to evaluate the risk factors related to PHLF. The Kaplan-Meier method was used to calculate the PHLF rate and 30-day survival after surgery.
Results:
A total of 885 patients with complete data were finally included in analysis, 311 of them with elevated serum PCT (≥1 ng/ml). Results of the logistic regression analysis suggested a significant association between PCT and PHLF HR, 95%CI; 3.801 (1.825, 7.917),
p
< 0.001. Other significant risk factors for PHLF included portal hypertension, portal blocking time (>30 min) and blood transfusion (>200 ml). Kaplan-Meier analysis also suggested a higher PHLF rate in elevated PCT patients 9.0% (95% CI, 7.3 to 12.8 VS. 1.9% (95% CI, 1.1–4.3));
p
< 0.001. For secondary outcomes, elevated PCT was also highly associated with postoperative sepsis, ICU admission, 30-day mortality and 3-month mortality.
Conclusion:
Elevated procalcitonin level in patients after hepatectomy is related to higher PHLF rate, with lower 30-day survival and poor short-term postoperative outcomes.
Manipulating topotactic phase transformations via orderly ion transfer in complex oxides ABOx is ubiquitous in advanced applications such as ionotronics, ion-batteries and catalysts. Most of such ...ion-mediated transformations are accomplished by the transfer of oxygen or A-site ions. However, implementing the transformation via the transfer of B-site ions, despite the great challenge to overcome a large cohesive energy, has unique advantage since they host most functional properties of materials. Here, we present a tri-state phase transformation from perovskite (P) to brownmillerite (BM) and to single-layered perovskite (SL) structure via the concerted migration of oxygen and B-site Co-ions in La0.7Sr0.3CoO3 thin films. Ac-STEM, XPS, XAS, PNR, magnetic and electric measurements demonstrated that presented B-site Co-cation transfer is along the CoO4 tetrahedral sub-layer of the BM film, which leads to the reconfiguration of 3d-electrons and spin state in remanent Co ions and causes tremendous changes in magnetic and electric properties: from canted-antiferromagnetic insulator in BM phase to ferromagnetic insulator in SL phase. First-principles calculations revealed that the La3+-doping at A-site largely reduces the cohesive energy of Co-ions in CoO4 and destabilize the CoO4 tetrahedron of BM phase, which explains the formation of Co-ions transfer channel in the CoO4 tetrahedral sub-layer. The present study highlights the effectiveness of regulating topotactic transformation via B-site ions transfer and provides a new pathway for manipulating the topotactic transformation with diverse functionalities.
Tri-state topotactic transformation induced by B-site Co ion transfer was firstly realized in La0.7Sr0.3CoO3 film. A unique transfer channel for Co-ions is demonstrated to be facilitated by the instability of CoO4 due to A-site La-doping. The reconfiguration of 3d-electrons due to Co transfer leads to tremendous changes in magnetic and electric properties. Such new topotactic transformation driven by B-site ion transfer offers opportunity to exploit new types of electrocatalyst with rich functionalities. Display omitted
•Tri-state topotactic transformation induced by B-site Co ion transfer was firstly realized in La0.7Sr0.3CoO3 film.•A unique transfer channel for Co-ions is demonstrated to be facilitated by the instability of CoO4 due to A-site La-doping.•The concerted transfer of Co and O ions drive tremendous changes in magnetic and electric properties.•Such B-site ion transfer provides a new pathway for exploiting electrocatalyst with diverse functionalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The ...efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). Objective. In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/β-catenin signal pathway. Methods. SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson’s trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/β-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. Results. The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, β-catenin, and active β-catenin. Conclusion. Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/β-catenin pathway.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
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