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Background Nonalcoholic fatty liver disease (NAFLD) is rarely detected at early stage, and often found when merged with metabolic disorders. Currently, the predictive value of noninvasive indicators for NAFLD with metabolic syndrome (MS) has been rarely reported. Objective To assess the predictive value of monocyte to high-density lipoprotein cholesterol ratio (MHR) for NAFLD with MS in community residents, and to evaluate the associated factors using multivariate regression tree analysis. Methods From June to December 2020, among 9 812 permanent community residents (>45 years) who underwent physical examination in Songjiang District Sijing Community Health Center, 5 727 eligible individuals were selected, including 4 652 with MS, diabetes, hypertension and dyslipidemia and other metabolic disorders〔1 948 with no NAFLD and MS (controls) , 1 248 with NAFLD (NAFLD cases) , 1 456 with both NAFLD and MS (MAFLD cases) 〕, and 1 075 without metabolic disorders (healthy controls) . General data, anthropometric parameters, blood pressure, biochemical parameters and routine blood test results of all participants were collected. Spearman rank correlation analysis was performed to assess the correlation of MHR and lipid accumulation product (LAP) index with NAFLD and MS. ROC analysis was conducted to analyze the optimal cutoff value of noninvasive indicators〔including neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) , lymphocyte to monocyte ratio (LMR) and MHR〕for NAFLD with MS. Factors associated with the predictive value of above-mentioned noninvasive indicators for NAFLD with MS were identified using multivariate regression tree analysis. Results The prevalence rates for metabolic disorders and NAFLD in this group were 76.61% (7 517/9 812) and 27.59% (2 704/9 812) , respectively. The controls, NAFLD cases, MAFLD cases, and healthy controls had significant differences in female ratio, mean age, BMI, waistline, hipline, waist-to-hip ratio, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, HDL-C, total bilirubin, serum uric acid, ALT, AST, ALT/AST ratio, GGT, eGFR, white blood cell count, neutrophil count, monocyte count, lymphocyte count, platelet count, NLR, PLR, LMR, MHR, alcoholic fatty liver disease to NAFLD index, LAP index, and atherogenic index of plasma, and distribution of waistline and BMI, as well as prevalence of hypertension and dyslipidemia (P

This work developed DNA amplifier logic gates (AND-OR, OR-AND, FAN-IN, FAN-OUT, and 4-bit square-root circuits) using a flap endonuclease 1 (FEN1)-catalyzed signal amplification reaction, for the fastest and compact DNA computing. Moreover, the logic circuit can use input strands with concentrations of less than 1 nM, which is more than 100 times lower than the input concentration of other DNA logic circuits, providing a promising methodology for constructing fast and compact DNA computations. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphism (SNP) typing is crucial for drug dosage and disease progression. Therefore, a simple and convenient genotyping assay is essential for personalised medicine. Herein, we developed a non‐invasive, closed‐tube, and visualised method for genotyping. In this method, oral swabs were lysed to directly perform PCR coupled with nested invasive reaction and visualisation based on gold nanoparticle probes in a closed tube. The strategy for genotyping assay depends on the single base recognition property of invasive reaction. This assay allowed quick and simple sample preparation and the detection of 25 copies/μL of CYP2C19*2 and 100 copies/μL of CYP2C19*3 within 90 min. Further, 20 oral swab samples for CYP2C19*2 and CYP2C19*3 were correctly typed, which agreed with pyrosequencing, indicating that this method has great potential for SNP typing in source‐limited regions to guide personalised medicine. [ABSTRACT FROM AUTHOR]

Currently, organic solvents are necessary for the preparation of anionic liposomes for siRNA delivery. The removal of organic solvent is time‐consuming and the residual organic solvent is not only a hidden danger, but also affects the stability of anionic liposomes. Glycerol, which is physiologically compatible and does not need to be removed, is used to promote the dispersion of lipids and the formation of anionic liposomes. Additionally, the preparation process is simple and not time‐consuming. The results showed that anionic liposomes, which were typically spherical with a particle size of 188.9 nm were successfully prepared with glycerol. And with the help of Ca2+, siRNA was encapsulated in anionic liposomes. The highest encapsulation efficiency at 2.4 mM Ca2+ reached 91%. And the formation of calcium phosphate could promote the endosomal escape of siRNA effectively. The results from cell viability showed that the anionic liposomes had no obvious cytotoxicity. It was also verified that anionic liposomes could improve the resistance of siRNA against degradation. Additionally, siRNA delivered by anionic liposomes could play an effective role in knockout. Therefore, anionic liposomes prepared with glycerol will be a safe and effective delivery platform for siRNA and even other nucleic acid drugs. [ABSTRACT FROM AUTHOR]

Background: Characterization of early breast cancer circulating tumor cells (CTCs) may provide valuable information on tumor metastasis. Methods: We used immunomagnetic nanospheres to capture CTCs from the peripheral blood of eight early breast cancer patients and then performed single‐cell RNA sequencing using our proposed bead‐dd‐seq method. Results: CTCs displayed obvious tumor cell characteristics, such as the activation of oxidative stress, proliferation, and promotion of metastasis. CTCs were clustered into two subtypes significantly correlated with the lymph node metastasis status of patients. CTCs in subtype 1 showed a strong metastatic ability because these CTCs have the phenotype of partial epithelial‐mesenchymal transition and enriched transcripts, indicating breast cancer responsiveness and proliferation. Furthermore, DNA damage repair pathways were significantly upregulated in subtype 1. We performed in vitro and in vivo investigations, and found that cellular oxidative stress and further DNA damage existed in CTCs. The activated DNA damage repair pathway in CTCs favors resistance to cisplatin. A checkpoint kinase 1 inhibitor sensitized CTCs to cisplatin in mouse models of breast cancer metastasis. Conclusion: The present study dissects the molecular characteristics of CTCs from early‐stage breast cancer, providing novel insight into the understanding of CTC behavior in breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Brucellosis, caused by Brucella spp., is a major zoonotic public health threat. Although several Brucella vaccines have been demonstrated for use in animals, Brucella spp. can cause human infection and to date, there are no human‐use vaccines licensed by any agency. Recently, methods in vaccine informatics have made major breakthroughs in peptide‐based epitopes, opening up a new avenue of vaccine development. Objectives: The purpose of this article was to identify potential antigenic peptides in Brucella by proteome and peptidome analyses. Methods: Mouse infection models were first established by injection with Brucella and spleen protein profiles were then analysed. Subsequently, the major histocompatibility complex class I or II (major histocompatibility complex [MHC]‐I/II)‐binding peptides in blood samples were collected by immunoprecipitation and peptides derived from Brucella proteins were identified through liquid chromatography–mass spectrometry (LC‐MS/MS). These peptides were then evaluated in a variety of ways, such as in terms of conservation in Brucella and synchronicity in predicted peptides (similarity and coverage), which allowed us to more effectively measure their antigenic potential. Results: The expression of the inflammatory cytokines IL1B and IFN‐γ was significantly altered in the spleen of infected mice and some Brucella proteins, such as Muri, AcpP and GroES, were also detected. Meanwhile, in blood, 35 peptides were identified and most showed high conservation, highlighting their potential as antigen epitopes for vaccine development. In particular, we identified four proteins containing both MHC‐I‐ and MHC‐II‐binding peptides including AtpA, AtpD, DnaK and BAbS19_II02030. They were also compared with the predicted peptides to estimate their reliability. Conclusions: The peptides we screened could bind to MHC molecules. After being stimulated with antigen T epitopes, Memory T cells can stimulate T cell activation and promote immune responses. Our results indicated that the peptides we identified may be good candidate targets for the design of subunit vaccines and these results pave the way for the study of safer vaccines against Brucella. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the relationship between social capital (SC) and hypertension among type 2 diabetes mellitus (T2DM) patients, considering the moderation effects of depressive symptoms. Patients and Methods: A total of 1761 Chinese T2DM patients completed measure scales of social capital and epidemiological survey depression scale (CES-D). The Bootstrap methods PROCESS program is employed to test the moderation model. Results: The prevalence of hypertension among T2DM patients was 39.3%. The SC was negatively correlated with the CES-D score (r=− 0.18, P< 0.01); the SC was also negatively correlated with diastolic blood pressure (r=− 0.05, P< 0.05); and the CES-D score was positively correlated with systolic blood pressure (r=0.05, P< 0.05). Both logistic regression analysis and the Bootstrap method showed that depressive symptoms weakened the protective effect of SC on hypertension, there existed a moderating effect of depressive symptoms on the relationship between SC and hypertension among T2DM patients. Conclusion: Depressive symptoms may be one crucial moderator of the relationship between SC and hypertension in a representative sample of Chinese diabetes patients. The findings indicate that improving SC and mental health may help manage hypertension among T2DM patients. [ABSTRACT FROM AUTHOR]