Effects of dietary berberine on growth performance, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus) fed high-fat diets.

This study aimed to investigate the effects of high-fat diet (HFD) supplemented with berberine on growth, lipid metabolism, antioxidant capacity and lipometabolism-related genes expression of AMPK signaling pathway in juvenile black carp (Mylopharyngodon piceus). Five hundred and forty healthy fish (4.04 ± 0.01 g) were randomly distributed into six groups, and fed six experimental diets: normal-fat diet (NFD, 5% fat), HFD (15% fat), and four HFDs supplemented with graded levels of berberine, respectively. The results showed that, compared with fish fed NFD, HFD had no effects on the growth of fish except for reducing survival rate, whereas HFD caused extensive lipid accumulation, oxidative stress injury and hepatic abnormalities. However, compared with the HFD group, fish fed HFD containing an appropriate berberine (98.26 or 196.21 mg/kg) improved the growth performance, increased hepatic lipid metabolism and antioxidant enzymes activities, and up-regulated the mRNA expression levels of ampk subunits and lipolysis genes such as pparα, cpt-1, acox, atgl and hsl (P < 0.05). Meanwhile, HFD supplemented with an appropriate berberine reduced crude lipid contents in liver and whole-body, decreased serum lipid contents, and ALT and AST activities, and down-regulated the mRNA expression levels of lipogenesis genes such as srebp-1, acc1, gpat, fas and pparγ, and lipid transporter genes such as fatp, fabp and fat/cd36 (P < 0.05). Thus, HFD supplemented with an appropriate berberine could improve growth of black carp, promote lipid metabolism and enhance antioxidant capacity. The lipid-lowering mechanism of berberine might be mediated by activating AMPK pathway, up-regulating lipolysis genes expression, and down-regulating lipogenesis and transport genes expression.

Thermally-Induced Isomerization of Prenucleation Clusters During the Prenucleation Stage of CdTe Quantum Dots.

The evolution of prenucleation clusters in the prenucleation stage of colloidal semiconductor quantum dots (QDs) has remained unexplored. With CdTe as a model system, we show that substances form and isomerize prior to the nucleation and growth of QDs. Called precursor compounds (PCs), the prenucleation clusters are relatively optically transparent and can transform to absorbing magic-size clusters (MSCs). When a prenucleation-stage sample at 25, 45, or 80 °C is dispersed in a mixture of cyclohexane (CH) and octylamine (OTA) at room temperature, either MSC-371, MSC-417, or MSC-448 evolves with absorption peaking at 371, 417, or 448 nm, respectively. We propose that PC-371 forms at 25 °C, and isomerizes to PC-417 at 45 °C and to PC-448 at 80 °C. The PCs and MSCs are quasi isomers. Relatively large and small amounts of OTA favor PC-371 and PC-448 in dispersion, respectively. The present findings suggest the existence of PC-to-PC isomerization in the QD prenucleation stage.

Protease or Clostridium butyricum addition to a low-protein diet improves broiler growth performance.

Low-protein (LP) feeds are used in the poultry industry to combat the increasing consumption of protein resources and reduce environmental pollution caused by excessive nitrogen excretion. Dietary supplementation of protease or Clostridium butyricum increases the growth performance of broilers; however, it is unclear whether they counteract the negative effects of LP diets. The effects of protease and C. butyricum on growth performance, intestinal morphology, anti-oxidant capacity, anti-inflammatory response, and microbial community of broilers have not been studied extensively. Here, 450 healthy 1-day-old Cobb500 broilers were allocated to five groups, according to different diets: basal diet (Control); LP diet (LP; 2% less crude protein than the control); LP diet + 200 g/t HuPro protease (LPH); LP diet + 1.0 × 109 CFU/t C. butyricum (LPC); and basal diet + 200 g/t oxytetracycline (Antibiotic). Supplementing both C. butyricum and protease improved the growth performance of broilers. The supplementation of HuPro protease under low-protein conditions could achieve a breeding effect similar to that of the positive control (Antibiotic). Supplementing C. butyricum could maintain intestinal barrier function, alleviate the inflammatory response, and increase ileal and cecal short-chain fatty acid concentrations. Both C. butyricum and protease altered the bacterial diversity in the cecum, increased Bacteroidetes abundance, and resulted in higher abundance of Rikenellaceae RC9 gut spp. and lower abundance of Alistipes spp. in broilers. This study demonstrates the positive effects of proteases and C. butyricum on broilers and serves as a reference for the selection of appropriate supplementation for broilers in the poultry industry. KEY POINTS: • Low-protein diet had a negative effect on growth performance of broilers. • Protease significantly reduced feed conversion rate. • Clostridium butyricum had positive effects on broilers.

Plasma Long Non-Coding RNA Expression Profiles in Patients with Rheumatoid Arthritis.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. METHODS: The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. RESULTS: Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. CONCLUSIONS: We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.

The clinical value of hematological markers in rheumatoid arthritis patients treated with tocilizumab.

BACKGROUND: Emerging evidence indicates that some hematological markers have critical value in evaluating treatment response. This study was performed to determine the clinical value of hemoglobin (Hb), platelet (Plt), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: Fifty-two RA patients receiving TCZ were recruited and followed for 6 months. The values of abovementioned hematological markers were collected. Clinical disease activity index (CDAI) and disease activity score based on 28 joints (DAS28)-ESR were calculated. Correlation analysis was conducted by calculating Pearson's correlation coefficient. The change in disease activity between groups according to the baseline level of hematological markers was compared by t test. RESULTS: Significant correlation between change in NLR (△NLR), change in PLR (△PLR), and change in CDAI (△CDAI) was found (△NLR: r = 0.30, P = 0.03; △PLR: r = 0.31, P = 0.03). The change in Plt (△Plt) was correlated with change in DAS28-ESR (△DAS28-ESR) (r = 0.36, P = 8.24 × 10-3 ). Greater improvement in CDAI was seen in patients categorized into Plt high group (t = 2.06, P = 0.04), NLR high group (t = 2.15, P = 0.04), and PLR high group (t = 2.41, P = 0.02) compared with the contrast group. CONCLUSION: Our study demonstrated that △Plt, △NLR, and △PLR could be used to monitor the clinical response to TCZ. RA patients with high baseline levels of Plt, NLR, and PLR achieved more improvement, indicating these hematological markers might be utilized to guide TCZ treatment.

Real-Time Change Point Detection with application to Smart Home Time Series Data.

Change Point Detection (CPD) is the problem of discovering time points at which the behavior of a time series changes abruptly. In this paper, we present a novel real-time nonparametric change point detection algorithm called SEP, which uses Separation distance as a divergence measure to detect change points in high-dimensional time series. Through experiments on artificial and real-world datasets, we demonstrate the usefulness of the proposed method in comparison with existing methods.

LBH mRNA Expression and Polymorphisms in Patients with Rheumatoid Arthritis.

Background: This study was performed to determine the mRNA expression levels of limb-bud and heart (LBH) in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA), and to assess the associations of LBH rs7579944 and rs906868 polymorphisms with RA in a Chinese population. Methods: Real-time transcription-polymerase chain reaction analysis was used to determine the LBH mRNA expression in PBMCs from 53 patients with RA and 58 healthy controls, and LBH rs7579944 and rs906868 polymorphisms were genotyped in 328 RA patients and 449 healthy controls. Results: The LBH mRNA expression levels were significantly decreased in RA patients compared with healthy controls (p = 0.02). However, non-significant correlation between LBH mRNA expression in PBMCs and ESR (r = 0.14, p = 0.36), CRP (r = 0.17, p = 0.27) or DAS28-ESR (r = 0.23, p = 0.12) was found. There was no significant difference in neither genotype (p = 0.90) nor allele (p = 0.97) distribution of the LBH rs7579944 polymorphism between RA patients and healthy controls. The relationships between the major allele T of LBH rs7579944 polymorphism and the risk of RA under dominant and recessive model were examined, whereas non-significant evidence was found. Similarly, a non-significant signal was detected for the association of LBH rs906868 polymorphism with RA. Conclusions: Decreased expression of LBH mRNA in PBMCs might contribute to the pathogenesis of RA.

Metagenome-assembled genome reveals species and functional composition of Jianghan chicken gut microbiota and isolation of Pediococcus acidilactic with probiotic properties.

BACKGROUND: Chickens are one of the most widely farmed animals worldwide and play a crucial role in meat and egg production. Gut microbiota is essential for chickens' health, disease, growth, and egg production. However, native chickens such as Jianghan chickens have better meat and egg production quality than centralized chickens, their intestinal microbial diversity is richer, and the potential gut microbial resources may bring health benefits to the host. RESULTS: The bacterial species composition in the gut microbiota of Jianghan chickens is similar to that of other chicken breeds, with Phocaeicola and Bacteroides being the most abundant bacterial genera. The LEfSe analysis revealed significant differences in species composition and functional profiles between samples from Jingzhou and the other three groups. Functional annotation indicated that the gut microbiota of Jianghan chickens were dominated by metabolic genes, with the highest number of genes related to carbohydrate metabolism. Several antibiotic resistance genes (ARGs) were found, and the composition of ARGs was similar to that of factory-farmed chickens, suggesting that antibiotics were widely present in the gut microbiota of Jianghan chickens. The resistance genes of Jianghan chickens are mainly carried by microorganisms of the Bacteroidota and Bacillota phylum. In addition, more than 829 isolates were selected from the microbiota of Jianghan chickens. Following three rounds of acid and bile tolerance experiments performed on all the isolated strains, it was determined that six strains of Pediococcus acidilactici exhibited consistent tolerance. Further experiments confirmed that three of these strains (A4, B9, and C2) held substantial probiotic potential, with P. acidilactici B9 displaying the highest probiotic potential. CONCLUSIONS: This study elucidates the composition of the intestinal microbiota and functional gene repertoire in Jianghan chickens. Despite the absence of antibiotic supplementation, the intestinal microbial community of Jianghan chickens still demonstrates a profile of antibiotic resistance genes similar to that of intensively reared chickens, suggesting resistance genes are prevalent in free-ranging poultry. Moreover, Jianghan and intensively reared chickens host major resistance genes differently, an aspect seldom explored between free-range and pastured chickens. Furthermore, among the 829 isolates, three strains of P. acidilatici exhibited strong probiotic potential. These findings provide insights into the unique gut microbiota of Jianghan chickens and highlight potential probiotic strains offering benefits to the host. Video Abstract.

The Indoor Predictability of Human Mobility: Estimating Mobility with Smart Home Sensors.

Analyzing human mobility patterns is valuable for understanding human behavior and providing location-anticipating services. In this work, we theoretically estimate the predictability of human movement for indoor settings, a problem that has not yet been tackled by the community. To validate the model, we utilize location data collected by ambient sensors in residential settings. The data support the model and allow us to contrast the predictability of various groups, including single-resident homes, homes with multiple residents, and homes with pets.

Clinical analysis of 175 cases of vaginal intraepithelial neoplasia.

OBJECTIVE: To evaluate the risk factors related to vaginal intraepithelial neoplasia (VaIN) severity. STUDY DESIGN: This retrospective study included patients with histologically confirmed VaIN diagnosed at Hubei Provincial Maternal and Child Health Hospital, China, between January 2017 and October 2021. The primary outcomes were persistence, remission, progression, and recurrence. Multiple ordinal logistic regression analysis was used to analyze the risk factors of VaIN severity. RESULTS: A total of 175 patients were included, 135 (77.1%) with VaIN 1, 19 (10.9%) with VaIN 2, and 21 (12%) with VaIN 3. Patients with VaIN 3 were older than those with VaIN1 2 (P < 0.001). The ratio of patients with concomitant cervical lesions increased with VaIN grade (23.7%, 47.4%, and 47.6% for VaIN 1, 2, and 3, respectively). The proportion of patients with intraepithelial neoplasia (CIN) 3 increased with the VaIN grade (3.1%, 44.5%, and 80% for VaIN 1, 2, and 3, respectively, respectively; all P < 0.001). In patients with VaIN 1, 19.4% had regression (spontaneous regression in 90.5%) and 80.6% underwent laser ablation (regression in 93.1%). In patients with VaIN 2 and 3, 3.1% showed no regression, 53.1% underwent laser ablation (regression in 76.4%), and 73.8% underwent excision (regression in 78.7%). Age (OR = 1.05, 95 %CI: 1.01-1.10, P = 0.010) and concomitant cervical lesion (OR = 6.99, 95 %CI: 2.31-21.12, P = 0.001) were independent risk factors for the severity of VaIN. CONCLUSION: Age and cervical lesions might be the risk factors for VaIN severity.

Foxo3a-Mediated DNMT3B Impedes Cervical Cancer Cell Proliferation and Migration Capacities through Suppressing PTEN Promoter Methylation.

OBJECTIVE: Cervical cancer is linked with the constitutive activation of growth factors and gene mutations-induced pro-survival signaling pathways. Herein, we purposed to explore the possible molecular mechanism of Foxo3a-mediated DNMT3B in the proliferation and migration of cervical cancer cells via mediating the PTEN promoter methylation. METHODS: Foxo3a expression in cervical cancer was tested by qRT-PCR and western blot experiments. The cervical cancer cell biological functions with overexpression of Foxo3a were evaluated by CCK-8 assay, Transwell experiment, and flow cytometry, respectively. MS-PCR was utilized for testing the PTEN methylation levels, and ChIP experiment was implemented for evaluating the enrichment of DNMT3B in the PTEN promoter region and the binding of Foxo3a and DNMT3B. The PTEN methylation and interference with Foxo3a expression were performed in cervical cancer cells, and then their impacts on cervical cancer cell biological functions were observed. RESULTS: FOXO3a was expressed at a low level in cervical cancer, and its overexpression contributed to a reduction in cell proliferative, migratory and invasive capabilities, and an elevation in apoptosis rate. Foxo3a blocked its methylation with the PTEN promoter by repressing DNMT3B activity. Upon treatment with methyltransferase inhibitor (5-aza-dc), the malignant phenotypes of cervical cancer cells were diminished. 5-aza-dc neutralized the impacts of silencing Foxo3a on malignant phenotypes. CONCLUSION: This research underlines that Foxo3a blocks its methylation with the PTEN promoter by inhibiting DNMT3B activity, which subsequently impedes cervical cancer cell progression.

Evaluation of cholesterol transformation abilities and probiotic properties of Bacteroides dorei YGMCC0564.

Hypercholesterolemia, a risk factor for cardiovascular disease (CVD), often requires therapeutic agents with varying degrees of side effects. This has created a need for safe and natural alternatives such as medications or functional foods that can improve lipid metabolism and reduce cholesterol levels. In recent years, Next-generation probiotics (NGPs) have recently emerged as a potential solution, offering distinct mechanisms compared to traditional probiotics. Among the NGPs, Bacteroides, a dominant bacterial genus in the human gut, has gained significant attention due to its prevalence, ability to break down plant polysaccharides, and production of short-chain fatty acids (SCFAs). Recent evidence has demonstrated that Bacteroides effectively reduces cholesterol levels, prevents obesity, and lowers the risk of CVD. However, research on Bacteroides is currently limited to a few species, leaving rooms for exploration of the beneficial functions of different species in this genus. In this study, we isolated 66 Bacteroides strains, including 9 distinct species, from healthy adults' fecal samples. By comparing their ability to assimilate cholesterol, we found that the transformation ability was not specific to any particular species. Notably, Bacteroides dorei YGMCC0564 revealed superior cholesterol-lowering capabilities and bile salt hydrolase (BSH) activity in vitro, surpassing that of Lactobacillus GG (LGG). YGMCC0564 exhibited favorable probiotic characteristics, including high survival rate in vitro simulation of gastrointestinal digestion, excellent adhesion ability, susceptibility to antibiotics, absence of hemolysis or virulence genes, and substantial production of SCFAs. The strain also demonstrated remarkable bile salt deconjugation activities and upregulation of the BT_416 gene associated with cholesterol, providing insights into a possible molecular mechanism underlying its cholesterol-reducing activity. These findings establish YGMCC0564 as a promising NPG candidate for improving cardiovascular health.

Multi-Person Activity Recognition in Continuously Monitored Smart Homes.

Activity recognizers are challenging to design for continuous, in-home settings. However, they are notoriously difficult to create when there is more than one resident in the home. Despite recent efforts, there remains a need for an algorithm that can estimate the number of residents in the house, split a time series stream into separate substreams, and accurately identify each resident's activities. To address this challenge, we introduce Gamut. This novel unsupervised method jointly estimates the number of residents and associates sensor readings with those residents, based on a multi-target Gaussian mixture probability hypothesis density filter. We hypothesize that the proposed method will offer robust recognition for homes with two or more residents. In experiments with labeled data collected from 50 single-resident and 11 multi-resident homes, we observe that Gamut outperforms previous unsupervised and supervised methods, offering a robust strategy to track behavioral routines in complex settings.

Multiscale Characteristics and Drivers of the Bundles of Ecosystem Service Budgets in the Su-Xi-Chang Region, China.

Managing ecosystem services (ESs) to meet human needs is critical to achieving sustainable development in rapidly urbanizing regions. Identifying ES budget bundles and analyzing their drivers at a multiscale level can facilitate management decision-making; however, further research is required in areas undergoing rapid urbanization. This study quantified the supply, demand, and budgets of six typical ESs at the county, township, and village scales in the Su-Xi-Chang region in 2020. Additionally, the influence of natural environmental and socioeconomic factors on ES budget bundles was investigated based on K-means cluster analysis and the Geodetector model. The results showed that ESs on all three scales showed a mismatch between supply and demand. The similarity in the spatial pattern of supply, demand, and budgets of ESs at the township and village scales was higher than that at the township and county scales. The location and area of surplus, balance, and deficit varied with scale. We found that population density and the proportion of impervious surfaces are the main factors influencing the formation of the ES budget bundles at different scales. In addition, the diversity and degree of interpretation of drivers varied with scale. We believe that focusing on the overall situation on a large scale and implementing precise management on a small scale can make management decisions more effective. This study can provide a scientific basis for the sustainable utilization of ESs in the Su-Xi-Chang region, and the research results and methods can provide a reference for similar studies in other rapidly urbanizing areas in the world.

Intelligent Simulation of Water Temperature Stratification in the Reservoir.

In order to fully make use of limited water resources, humans have built many water conservancy projects. The projects produce many economic benefits, but they also change the natural environment. For example, the phenomenon of water temperature stratification often occurs in deep reservoirs. Thus, effective ways are needed to predict the water temperature stratification in a reservoir to control its discharge water temperature. Empirical formula methods have low computational accuracy if few factors are considered. Mathematical model methods rely on large amounts of accurate hydrological data and cost long calculation times. The purpose of the research was to simulate water temperature stratification in a reservoir by constructing an intelligent simulation model (ISM-RWTS) with five inputs and one output, determined on the basis of artificial neural networks (ANN). A 3D numerical model (3DNM) was also constructed to provide training samples for the ISM-RWTS and be used to test its simulation effect. The ISM-RWTS was applied to the Tankeng Reservoir, located in the Zhejiang province of China, and performed well, with an average error of 0.72 °C. Additionally, the Intelligent Computation Model of Reservoir Water Temperature Stratification (ICM-RWTS) was also discussed in this paper. The results indicated that the intelligent method was a powerful tool to estimate the water temperature stratification in a deep reservoir. Finally, it was concluded that the advantages of the intelligent method lay in its simplicity of use, its lower demand for hydrological data, its well generalized performance, and its flexibility for considering different input and output parameters.

The Interaction Mechanism of Fiscal Pressure, Local Government Behavioral Preferences and Environmental Governance Efficiency: Evidence from the Yangtze River Delta Region of China.

In environmental governance, local governments are the main actors, and their behavioral preferences between economic growth competition (EGC) and environmental regulation (ER) affect the inputs and outputs of environmental governance. Most studies discuss the relationship between government behaviors and the environment from the fiscal decentralization perspective, with few studies from the fiscal pressure (FP) perspective. Importantly, the bidirectional interaction mechanism is easily ignored. This study measured local government FP, EGC, ER, and environmental governance efficiency (EGE) in China's Yangtze River Delta (YRD) region from 2000 to 2020. Moran's I index was used to identify the change characteristics of local government behavioral preferences. The interaction mechanism was analyzed by a panel vector autoregression (PVAR) model. The results show that (1) from 2000 to 2020, FP was generally strengthened. EGE generally showed fluctuating and rising change characteristics, with more obvious fluctuating and rising characteristics before 2012 and after 2012, respectively. Local governments shifted from a strong alternative preference to a weak synergistic preference. (2) FP had a self-reinforcing effect. EGC and ER had a self-weakening effect. EGE had not only a self-weakening effect but also a weak self-dependence. (3) There is a double negative interaction mechanism between FP and local government behavioral preferences. FP made local governments prefer to reduce EGC and relax ER, but in fact, EGC and ER were conducive to alleviating FP. (4) There is a negative transitive influence mechanism between FP, local government behavioral preferences and EGE. The negative effect of FP on EGE can be transmitted by reducing EGC and ER. This paper provides a scientific basis for improving EGE in the YRD region and understanding the behavioral logic of local governments' environmental governance and a reference for other rapidly industrializing and urbanizing regions.

OTX1 promotes tumorigenesis and progression of cervical cancer by regulating the Wnt signaling pathway.

Cervical cancer is a common malignant tumor in females. Orthodenticle homolog 1 (OTX1) serves a key role in the occurrence and progression of tumors. The present study aimed to investigate the role and potential mechanism of OTX1 in cervical cancer. OTX1 expression was analyzed by western blotting, reverse transcription­quantitative PCR and immunohistochemistry. MTT assay was performed to assess cell viability. EdU and colony formation assay were used to measure cell proliferation. Wound healing and Transwell assays were performed to measure cell migration and invasion. Western blot assay was performed for the assessment of protein expression. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways regulated by OTX1. Co­Immunoprecipitation assay was performed to confirm the interaction between OTX1 and Wnt9b. In cervical cancer tissue and cells, OTX1 was significantly upregulated. OTX1 overexpression promoted proliferation, migration and invasion of cervical cancer cells. OTX1 silencing significantly decreased cell proliferation, migration and invasion of cervical cancer. GSEA showed that OTX1 activated the Wnt signaling pathway. OTX1 silencing inhibited the increased levels of adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)­3ß and axis inhibition protein (AXIN)2 and decreased levels of Wnt9b and ß­catenin. OTX1 overexpression decreased the levels of APC, GSK­3ß and AXIN2 and increased levels of Wnt9b and ß­catenin. However, XAV939 (a Wnt signaling inhibitor) and ß­catenin silencing partly eliminated the effect of OTX1 overexpression on cervical cancer cells. OTX1 promoted the progression of cervical cancer by activating the Wnt signaling pathway.

Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study.

Purpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients. Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped. Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC. Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.

Associations Between microRNA-related Genetic Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients.

BACKGROUND: Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response. OBJECTIVE: To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients. METHODS: One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology. RESULTS: Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis. CONCLUSION: Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.

sMRT: Multi-Resident Tracking in Smart Homes With Sensor Vectorization.

Smart homes equipped with anonymous binary sensors offer a low-cost, unobtrusive solution that powers activity-aware applications, such as building automation, health monitoring, behavioral intervention, and home security. However, when multiple residents are living in a smart home, associating sensor events with the corresponding residents can pose a major challenge. Previous approaches to multi-resident tracking in smart homes rely on extra information, such as sensor layouts, floor plans, and annotated data, which may not be available or inconvenient to obtain in practice. To address those challenges in real-life deployment, we introduce the sMRT algorithm that simultaneously tracks the location of each resident and estimates the number of residents in the smart home, without relying on ground-truth annotated sensor data or other additional information. We evaluate the performance of our approach using two smart home datasets recorded in real-life settings and compare sMRT with two other methods that rely on sensor layout and ground truth-labeled sensor data.