LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.

The eukaryotic exon junction complex component Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. Using immunoprecipitation-RNA-seq, we identified a set of Y14-associated long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1 serves as a strong candidate that mediates the interaction between Y14 and the NHEJ complex. HOTAIRM1 localized to near ultraviolet laser-induced DNA damage sites. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and compromised the efficiency of NHEJ-mediated DSB repair. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and mRNA surveillance factors that act in concert to repair DSBs.

Klotho Null Mutation Involvement in Adenosine A2B Receptor-Related Skeletal Muscle Degeneration.

Klotho is known for its age-suppressing function and has been implicated in sarcopenia pathology. It has recently been proposed that the adenosine A2B receptor plays a crucial role in skeletal muscle energy expenditure. However, the association between Klotho and A2B remains elusive. In this study, Klotho knockout mice, aged 10 weeks, and wild-type mice, aged 10 and 64 weeks, were used for comparison in indicators of sarcopenia (n = 6 for each group). PCR was performed to confirm the mice genotypes. Skeletal muscle sections were analyzed using hematoxylin and eosin staining as well as immunohistochemistry staining. The skeletal muscle cross-sectional area was significantly reduced in Klotho knockout mice and wild-type mice, aged 64 weeks, when compared with wild-type mice, aged 10 weeks, with a decreased percentage of type IIa and IIb myofibers. Likely impaired regenerative capacity, as reflected by the reduction of paired box 7 (Pax7)- and myogenic differentiation protein 1 (MyoD)-positive cells, was also observed in Klotho knockout mice and aged wild-type mice. 8-Hydroxy-2-deoxyguanosine expression was enhanced with Klotho knockout and aging, indicating higher oxidative stress. Adenosine A2B signaling was impaired, with a lower expression of the A2B receptor and the cAMP-response element binding protein in Klotho knockout and aged mice. The present study provides the novel finding that sarcopenia involves adenosine signaling under the influence of Klotho knockout.

A meta-analysis of the association between RBP4 rs3758539 genotype and metabolic syndrome factors.

AIM: To explore the link between the RBP4 rs3758539 genotype and metabolic syndrome risk factors and whether the impact of this genetic variation displays any potential race discrepancy. MATERIALS AND METHODS: This meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (registration no. CRD42023407999). PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Airiti Library and CINAHL databases were used for the study search until October 2023. We evaluated the methodological quality using the Joanna Briggs Institute checklist and determined the correlation using a random-effects meta-analysis. RESULTS: The results indicated that individuals with the rs3758539 GA/AA genotype had a higher risk profile, including lower high-density lipoprotein levels [correlation: -0.045, 95% confidence interval (CI): -0.080 to -0.009, p = .015, I2 = 46.9%] and higher body mass index (correlation: 0.117, 95% CI: 0.036-0.197, p = .005, I2 = 82.0%), body fat (correlation: 0.098, 95% CI: 0.004-0.191, p = .041, I2 = 64.0%), and low-density lipoprotein levels (correlation: 0.074, 95% CI: 0.010-0.139, p = .024, I2 = 0%), of developing metabolic syndrome than those with the GG genotype. The subgroup analysis maintained a significantly positive correlation between the rs3758539 GA/AA genotype and body mass index (correlation: 0.163, 95% CI: 0.031-0.289, p = .016, I2 = 88.9%) but a negative correlation with high-density lipoprotein levels (correlation: -0.047, 95% CI: -0.087 to -0.006, p = .025, I2 = 65.7%) in the Asian group only. CONCLUSION: The current meta-analysis supports a significant link between the RBP4 rs3758539 GA/AA genotype and the metabolic syndrome.

Sex difference in the associations among risk factors with gastroesophageal reflux disease in a large Taiwanese population study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants. METHODS: We enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis. RESULTS: The overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD. CONCLUSIONS: Our results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.

Sex difference in the associations among secondhand smoke with metabolic syndrome in non-smokers in a large Taiwanese population follow-up study.

Close associations among secondhand smoke (SHS) and metabolic syndrome (MetS) and its components have been demonstrated, however sex differences in these associations remain unclear. We collected 121,364 participants from the Taiwan Biobank, and excluded those with smoking history, the remaining 88,297 participants (male: 18,595; female: 69,702; mean age 50.1 ± 11.0 years) were included. SHS exposure was evaluated based on self-reported questionnaires. SHS was associated with MetS (odds ratio [OR], 1.268, p < 0.001 for males vs. 1.180, p < 0.001 for females), abdominal obesity (OR, 1.234, p < 0.001 for males vs. 1.199, p < 0.001 for females), low high-density lipoprotein cholesterol (OR, 1.183, p = 0.008 for males vs. 1.094, p = 0.011 for females), hyperglycemia (OR, 1.286, p < 0.001 for males vs. 1.234, p < 0.001 for females), but not with hypertriglyceridemia. SHS was associated with high blood pressure (BP) (OR, 1.278, p < 0.001) only in males, but not in females. Furthermore, significant interactions were found between sex x SHS on MetS (p = 0.023), abdominal obesity (p = 0.032), and elevated BP (p < 0.001). Moreover, the participants who were exposed to SHS for ≥1 hour per week were associated with a higher risk (OR = 1.316, p = 0.001 in males vs. OR = 1.220, p < 0.001 in females) of MetS compared to those with no exposure. These results showed an association between SHS and a high OR for MetS in both the males and females. Furthermore, sex differences were identified in the associations between SHS and MetS and its components, and SHS was more closely related to MetS, abdominal obesity, and high BP in males than in females.

Prediction of Arteriovenous Access Dysfunction by Mel Spectrogram-based Deep Learning Model.

Background: The early detection of arteriovenous (AV) access dysfunction is crucial for maintaining the patency of vascular access. This study aimed to use deep learning to predict AV access malfunction necessitating further vascular management. Methods: This prospective cohort study enrolled prevalent hemodialysis (HD) patients with an AV fistula or AV graft from a single HD center. Their AV access bruit sounds were recorded weekly using an electronic stethoscope from three different sites (arterial needle site, venous needle site, and the midpoint between the arterial and venous needle sites) before HD sessions. The audio signals were converted to Mel spectrograms using Fourier transformation and utilized to develop deep learning models. Three deep learning models, (1) Convolutional Neural Network (CNN), (2) Convolutional Recurrent Neural Network (CRNN), and (3) Vision Transformers-Gate Recurrent Unit (ViT-GRU), were trained and compared to predict the likelihood of dysfunctional AV access. Results: Total 437 audio recordings were obtained from 84 patients. The CNN model outperformed the other models in the test set, with an F1 score of 0.7037 and area under the receiver operating characteristic curve (AUROC) of 0.7112. The Vit-GRU model had high performance in out-of-fold predictions, with an F1 score of 0.7131 and AUROC of 0.7745, but low generalization ability in the test set, with an F1 score of 0.5225 and AUROC of 0.5977. Conclusions: The CNN model based on Mel spectrograms could predict malfunctioning AV access requiring vascular intervention within 10 days. This approach could serve as a useful screening tool for high-risk AV access.

Components of the Complete Blood Count as a Risk Predictor for Incident Hypertension in a Large Taiwanese Population Follow-up Study.

BACKGROUND: Previous studies investigating the relationship between hypertension (HT) and hematological parameters report inconsistent results, and most them included a small number of participants or only conducted a cross-sectional analysis of 1 or 2 hematological factors. Moreover, no large cohort follow-up studies have investigated this topic. The aim of this longitudinal study was to explore associations between components of the complete blood count (CBC) and incident HT using data from a large Taiwanese biobankMethods and Results: Hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit (HCT), and platelet count were evaluated. We included 21,293 participants who did not have HT at baseline and followed them for a mean period of 3.9 years. During follow-up, 3,002 participants with new-onset HT (defined as incident HT) were identified. Univariable analysis revealed that high WBC count, high RBC count, high hemoglobin, high HCT, and low platelet count were associated with incident HT. Multivariable analysis after adjusting potential confounding factors found high WBC count (odds ratio [OR], 1.057; 95% confidence interval [CI], 1.028 to 1.087; P<0.001) and high HCT (OR, 1.023; 95% CI, 1.010 to 1.036; P<0.001) were still significantly associated with incident HT. CONCLUSIONS: High WBC count and high HCT were associated with incident HT.

Daily association between parent-adolescent relationship and life satisfaction: The moderating role of emotion dysregulation.

INTRODUCTION: In adolescence, life satisfaction is an early indicator of later psychological well-being. However, researchers know little about how daily family relationships shape adolescent life satisfaction. The current study examined the day-to-day associations between parent-adolescent relationships and life satisfaction, and whether adolescent emotion dysregulation moderated these associations. METHODS: A total of 191 adolescents (Mage = 12.93, SDage = 0.75, 53% female) recruited from junior high schools in Taiwan participated in a 10-day daily diary protocol. We conducted multilevel analyses to examine within-family and between-family processes. RESULTS: At the within-family level, adolescents reported higher life satisfaction on days when parent-adolescent closeness was higher, but lower life satisfaction on days when parent-adolescent conflict was higher. At the between-family level, higher parent-adolescent closeness was associated with greater life satisfaction on average, while parent-adolescent conflict was not related to adolescent life satisfaction. Cross-level interactions indicated that within-family changes in parent-adolescent closeness and conflict were only associated with life satisfaction for adolescents with higher levels of emotion dysregulation, indicating emotion dysregulation may intensify the role of daily parent-adolescent relationships in shaping adolescent life satisfaction. CONCLUSIONS: This study expands current literature and provides novel evidence that changes in day-to-day parent-adolescent relationships have important implications for adolescent life satisfaction, especially for youth higher in emotion dysregulation. The findings underscore the importance of evaluating family and individual characteristics to better support adolescent well-being.

Comparative Gut Microbiome Differences between High and Low Aortic Arch Calcification Score in Patients with Chronic Diseases.

Gut dysbiosis can induce chronic inflammation and contribute to atherosclerosis and vascular calcification. The aortic arch calcification (AoAC) score is a simple, noninvasive, and semiquantitative assessment tool to evaluate vascular calcification on chest radiographs. Few studies have discussed the relationship between gut microbiota and AoAC. Therefore, this study aimed to compare the microbiota composition between patients with chronic diseases and high or low AoAC scores. A total of 186 patients (118 males and 68 females) with chronic diseases, including diabetes mellitus (80.6%), hypertension (75.3%), and chronic kidney disease (48.9%), were enrolled. Gut microbiota in fecal samples were analyzed by sequencing of the 16S rRNA gene, and differences in microbial function were examined. The patients were divided into three groups according to AoAC score, including 103 patients in the low AoAC group (AoAC ≤ 3), 40 patients in the medium AoAC group (3 < AoAC ≤ 6), and 43 patients in the high AoAC group (AoAC > 6). Compared to the low AoAC group, the high AoAC group had a significantly lower microbial species diversity (Chao1 index and Shannon index) and increased microbial dysbiosis index. Beta diversity showed that the microbial community composition was significantly different among the three groups (p = 0.041, weighted UniFrac PCoA). A distinct microbial community structure was found in the patients with a low AoAC, with an increased abundance at the genus level of Agathobacter, Eubacterium coprostanoligenes group, Ruminococcaceae UCG-002, Barnesiella, Butyricimonas, Oscillibacter, Ruminococcaceae DTU089, and Oxalobacter. In addition, there was an increased relative abundance of class Bacilli in the high AoAC group. Our findings support the association between gut dysbiosis and the severity of AoAC in patients with chronic diseases.

Selenium supplementation for polycystic ovary syndrome: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of selenium supplementation was elusive for polycystic ovary syndrome. This meta-analysis aimed to explore the efficacy of selenium supplementation for polycystic ovary syndrome. Methods: PubMed, EMbase, Web of science, EBSCO, Cochrane library database, CNKI, Chongqing VIP database and Wanfang databases have been searched through July 2022 and we included randomized controlled trials (RCTs) reporting the effect of selenium supplementation versus placebo in patients with polycystic ovary syndrome. Results: Five RCTs were included in the meta-analysis. Compared with placebo group for polycystic ovary syndrome, selenium supplementation was associated with significantly reduced total testosterone (SMD=-0.42; 95% CI=-0.78 to -0.06; p = 0.02) and cholesterol (SMD=-0.71; 95% CI=-1.41 to -0.02; p = 0.04), but revealed no remarkable influence on SHBG (SMD=-0.52; 95% CI=-1.29 to 0.25; p = 0.19), triglyceride (SMD=-1.45; 95% CI=-3.62 to 0.73; p = 0.19), LDL (SMD=-0.17; 95% CI=-0.72 to 0.37; p = 0.53), FPG (SMD=-0.95; 95% CI=-3.72 to 1.82; p = 0.50) or HOMA-IR (SMD=-0.51; 95% CI=-3.79 to 2.77; p = 0.76). Conclusions: Selenium supplementation may be able to improve the metabolic response for polycystic ovary syndrome, and this finding should be interpreted with caution.

Multidisciplinary care program in pre-end-stage kidney disease from 2010 to 2018 in Taiwan.

BACKGROUND: The Taiwanese government launched a universal pay-for-performance (P4P) program in 2006 to promote multidisciplinary care for patients with stage 3b-5 chronic kidney disease (CKD). This study aimed to understand the enrollments, care processes, and outcomes of the P4P program between 2010 and 2018. METHODS: We conducted a population-based study using the Taiwan National Health Insurance Research Data. We divided the incident dialysis population into joining and not joining P4P groups based on whether patients had joined the pre-ESRD program before dialysis or not. Trends in the medications prescribed, anemia correction, vascular access preparation before dialysis initiation, and cumulative survival rate were compared. RESULTS: The program included more than 100,000 patients with late-stage CKD. Enrollment increased by almost 100% from 2010 to 2018, with increases seen in those over 75 years old (127.5%), male (96.7%), and earlier CKD stages (≥35% stage 3b in 2018). Females were more likely to stay being enrolled. The joining P4P group was prescribed more appropriate medications, such as erythropoietin-stimulating agents and statins. However, a high number of patients were still prescribed metformin (≥40%) and non-steroidal anti-inflammatory drugs (≥20%). Compared to the not joining P4P group, the patients in the P4P group had better anemia management, dialysis preparation, and post-dialysis survival. CONCLUSION: The patients in the joining P4P program group were delivered more appropriate CKD care and were associated with better survival outcomes. Polices and action plans are needed to extend the coverage of and enrollment in the P4P program.

Heterogeneity and neurovascular integration of intraportally transplanted islets revealed by 3-D mouse liver histology.

Intraportal islet transplantation has been clinically applied for treatment of unstable type 1 diabetes. However, in the liver, systematic assessment of the dispersed islet grafts and the graft-hepatic integration remains difficult, even in animal models. This is due to the lack of global and in-depth analyses of the transplanted islets and their microenvironment. Here, we apply three-dimensional (3-D) mouse liver histology to investigate the islet graft microstructure, vasculature, and innervation. Streptozotocin-induced diabetic mice were used in syngeneic intraportal islet transplantation to achieve euglycemia. Optically cleared livers were prepared to enable 3-D morphological and quantitative analyses of the engrafted islets. 3-D image data reveal the clot- and plaque-like islet grafts in the liver: the former are derived from islet emboli and associated with ischemia, whereas the latter (minority) resemble the plaques on the walls of portal vessels (e.g., at the bifurcation) with mild, if any, perigraft tissue damage. Three weeks after transplantation, both types of grafts are revascularized, yet significantly more lymphatics are associated with the plaque- than clot-like grafts. Regarding the islet reinnervation, both types of grafts connect to the periportal nerve plexus and develop peri- and intragraft innervation. Specifically, the sympathetic axons and varicosities contact the α-cells, highlighting the graft-host neural integration. We present the heterogeneity of the intraportally transplanted islets and the graft-host neurovascular integration in mice. Our work provides the technical and morphological foundation for future high-definitional 3-D tissue and cellular analyses of human islet grafts in the liver.NEW & NOTEWORTHY Modern 3-D histology identifies the clot- and plaque-like islet grafts in the mouse liver, which otherwise cannot be distinguished with the standard microtome-based histology. The two types of grafts are similar in blood microvessel density and sympathetic reinnervation. Their differences, however, are their locations, severity of associated liver injury, and access to lymphatic vessels. Our work provides the technical and morphological foundation for future high-definitional 3-D tissue/cellular analyses of human islet grafts in the liver.

Environmental Pollution and Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global public health problem associated with high rates of morbidity and mortality due to end-stage renal disease and cardiovascular disease. Safe and effective medications to reverse or stabilize renal function in patients with CKD are lacking, and hence it is important to identify modifiable risk factors associated with worsening kidney function. Environmental pollutants, including metals, air pollutant, phthalate and melamine can potentially increase the risk of CKD or accelerate its progression. In this review, we discuss the epidemiological evidence for the association between environmental pollution and kidney disease, including heavy metals, air pollution and other environmental nephrotoxicants in the general population.

A high triglyceride-glucose index is associated with left ventricular dysfunction and atherosclerosis.

Background: The triglyceride-glucose (TyG) index has been reported to be a simple and reliable surrogate marker of insulin resistance. The aim of this study was to investigate associations between the TyG index and echocardiographic parameters including left ventricular mass (LVM), left atrial diameter (LAD) and left ventricular ejection fraction (LVEF), and markers of peripheral artery disease, ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). Methods: A total of 823 (483 males and 340 females) patients were enrolled from 2007 to 2011 at a regional hospital in southern Taiwan. Multivariable stepwise linear regression analysis was performed to identify the factors related to echocardiographic parameters and peripheral artery disease. Results: The patients were stratified into four groups according to TyG index quartile. Multivariable stepwise linear regression analysis showed that a higher TyG index was associated with elevated observed/predicted LVM (p = 0.081), increased LAD (p = 0.004), decreased LVEF (p = 0.003) and lower ABI (p = 0.030), but not observed/predicted LVM and baPWV. Conclusions: A high TyG index was significantly associated with high LAD, low LVEF and low ABI. However, the TyG index was not significantly associated with inappropriate LVM or baPWV. The results suggest that the TyG index, as a simple indicator of insulin resistance, may reflect cardiac remodeling and dysfunction and atherosclerosis.

Usefulness of Ankle-Brachial Index Calculated Using Diastolic Blood Pressure and Mean Arterial Pressure in Predicting Overall and Cardiovascular Mortality in Hemodialysis Patients.

No study has investigated the predictive ability of ankle-brachial index (ABI) calculated using diastolic blood pressure (DBP) (ABIdbp) and mean arterial pressure (MAP) (ABImap) for overall and cardiovascular (CV) mortality in hemodialysis (HD) patients. Our study was aimed to investigate the issue. Two hundred and seven routine HD patients were enrolled. ABI values were measured by ABI-form device. During the follow-up period (122 months), 124 of the 207 patients (59.0%) died, and 59 deaths due to CV cause. Multivariate analysis showed that low ABIsbp, ABIdbp, and ABImap were all significantly associated with increased overall (p ≤ 0.015) and CV mortality (p ≤ 0.015) in whole study patients. A subgroup analysis after excluding 37 patients with ABIsbp < 0.9 or > 1.3 found ABIsbp and ABIsbp < 0.9 were not associated with overall and CV mortality. However, ABImap and ABIdbp < 0.87 were significantly associated with overall mortality (p ≤ 0.042). Furthermore, ABIdbp and ABIdbp < 0.87 were significantly associated with CV mortality (p ≤ 0.030). In conclusion, ABIsbp, ABIdbp, and ABImap were all useful in predicting overall and CV mortality in our HD patients. In the subgroup patients with normal ABIsbp, ABIsbp and ABIsbp < 0.9 were not useful to predict overall and CV mortality. Nevertheless, ABImap and ABIdbp < 0.87 could still predict overall mortality, and ABIdbp and ABIdbp < 0.87 could predict CV mortality. Hence, calculating ABI using DBP and MAP may provide benefit in survival prediction in HD patients, especially in the patients with normal ABIsbp.

The association of echocardiographic parameters on renal outcomes in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) often have structural abnormalities of the heart due to pressure and volume overload. The aim of this study was to evaluate associations between echocardiographic parameters and renal outcomes (estimated glomerular filtration rate [eGFR] slope and progression to dialysis) in patients with stage 3-5 CKD. METHODS: This longitudinal study enrolled 419 patients. Changes in renal function were assessed using the eGFR slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min/1.73 m2/year, and the renal endpoint was defined as commencing dialysis. RESULTS: Increased left atrial diameter (LAD), ratio of left ventricular mass to body surface area (LVM/BSA), ratio of LVM to height2.7 (LVM/ht2.7), and ratio of observed to predicted LVM (o/p LVM) were associated with eGFR slope in an adjusted model, but left ventricular ejection fraction (LVEF) was not. Furthermore, LAD ≥ 4.7 cm, LVM/BSA > 115 g/m2 in males and > 95 g/m2 in females, and LVM/ht2.7 > 48 g/ht2.7 in males and > 44 g/ht2.7 in females were correlated with progression to dialysis, but o/p LVM and LVEF were not. The maximum change in χ2 change to predict renal outcomes was observed for LAD, followed by LVM/BSA and LVM/ht2.7. CONCLUSIONS: A large LAD and increased LVM, regardless of how it was measured (LVM/BSA, LVM/ht2.7 and o/p LVM), were correlated with adverse renal outcomes in patients with CKD stage 3-5. LAD had superior prognostic value to LVM and LVEF.

Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling.

d-Glycero-d-manno-heptose-1ß,7-bisphosphate (HBP) and d-glycero-d-manno-heptose-1ß-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.

Alternate healthy eating index and risk of depression: A meta-analysis and systemematic review.

Objective: The alternate healthy eating index has been associated with depression. However, results reported in the literature are inconsistent. The present meta-analysis determined the association between the AHEI or AHEI-2010 and depression in adults without chronic disease.Methods: Nine electronic databases and the reference lists of identified studies were systematically searched for studies published up to December 2016. Articles examining the association between depression and the AHEI or AHEI-2010 in adults were included.Results: We identified eight observational studies with 10 effect sizes involving a total of 38,360 participants. When both the AHEI and AHEI-2010 were considered, the dietary index score was associated with a significant reduction in depression risk (odds ratio OR=0.70, 95% confidence interval CI=0.57-0.87). However, the subgroup analysis indicated that the AHEI-2010 (OR=0.69, 95% CI=0.56-0.89), but not the AHEI (OR=0.60, 95% CI=0.30-1.17), was significantly associated with reduced odds of depression. The heterogeneity among the included studies was significantly high (Q=48.9, P<0.01, I2=81.60%).Discussion: Our findings suggest that the AHEI-2010 is associated with a reduction in depression risk. However, well-designed randomized controlled trials must be conducted to confirm the causal relationship between the AHEI-2010 and depression.

Increased Proteinuria is Associated with Increased Aortic Arch Calcification, Cardio-Thoracic Ratio, Rapid Renal Progression and Increased Overall and Cardiovascular Mortality in Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) are associated with high prevalence rates of proteinuria, vascular calcification and cardiomegaly. In this study, we investigated relationships among proteinuria, aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) in patients with CKD stage 3A-5. In addition, we investigated correlations among proteinuria and decline in renal function, overall and cardiovascular (CV) mortality. Methods: We enrolled 482 pre-dialysis patients with CKD stage 3A-5, and determined AoAC and CTR using chest radiography at enrollment. The patients were stratified into four groups according to quartiles of urine protein-to-creatinine ratio (UPCR). Results: The patients in quartile 4 had a lower estimated glomerular filtration rate (eGFR) slope, and higher prevalence rates of rapid renal progression, progression to commencement of dialysis, overall and CV mortality. Multivariable analysis showed that a high UPCR was associated with high AoAC (unstandardized coefficient ß: 0.315; p = 0.002), high CTR (unstandardized coefficient ß: 1.186; p = 0.028) and larger negative eGFR slope (unstandardized coefficient ß: -2.398; p < 0.001). With regards to clinical outcomes, a high UPCR was significantly correlated with progression to dialysis (log per 1 mg/g; hazard ratio [HR], 2.538; p = 0.003), increased overall mortality (log per 1 mg/g; HR, 2.292; p = 0.003) and increased CV mortality (log per 1 mg/g; HR, 3.195; p = 0.006). Conclusions: Assessing proteinuria may allow for the early identification of high-risk patients and initiate interventions to prevent vascular calcification, cardiomegaly, and poor clinical outcomes.

Detection of membrane protein-protein interaction in planta based on dual-intein-coupled tripartite split-GFP association.

Despite the great interest in identifying protein-protein interactions (PPIs) in biological systems, only a few attempts have been made at large-scale PPI screening in planta. Unlike biochemical assays, bimolecular fluorescence complementation allows visualization of transient and weak PPIs in vivo at subcellular resolution. However, when the non-fluorescent fragments are highly expressed, spontaneous and irreversible self-assembly of the split halves can easily generate false positives. The recently developed tripartite split-GFP system was shown to be a reliable PPI reporter in mammalian and yeast cells. In this study, we adapted this methodology, in combination with the ß-estradiol-inducible expression cassette, for the detection of membrane PPIs in planta. Using a transient expression assay by agroinfiltration of Nicotiana benthamiana leaves, we demonstrate the utility of the tripartite split-GFP association in plant cells and affirm that the tripartite split-GFP system yields no spurious background signal even with abundant fusion proteins readily accessible to the compartments of interaction. By validating a few of the Arabidopsis PPIs, including the membrane PPIs implicated in phosphate homeostasis, we proved the fidelity of this assay for detection of PPIs in various cellular compartments in planta. Moreover, the technique combining the tripartite split-GFP association and dual-intein-mediated cleavage of polyprotein precursor is feasible in stably transformed Arabidopsis plants. Our results provide a proof-of-concept implementation of the tripartite split-GFP system as a potential tool for membrane PPI screens in planta.