Impact of ectopic fat on brain structure and cognitive function: A systematic review and meta-analysis from observational studies.

Ectopic fat, defined as a specific organ or compartment with the accumulation of fat tissue surrounding organs, is highly associated with obesity which has been identified as a risk factor for cognitive impairment and dementia. However, the relationship between ectopic fat and changes in brain structure or cognition is yet to be elucidated. Here, we investigated the effects of ectopic fat on brain structure and cognitive function via systemic review and meta-analysis. A total of 21 studies were included from electronic databases up to July 9, 2022. We found ectopic fat was associated with decreased total brain volumeand increased lateral ventricle volume. In addition, ectopic was associated with decreased cognitive scores and negatively correlated with cognitive function. More specifically, dementia development were correlated with increased levels of visceral fat. Overall, our data suggested that increased ectopic fat was associated with prominent structural changes in the brain and cognitive decline, an effect driven mainly by increases in visceral fat, while subcutaneous fat may be protective. Our results suggest that patients with increased visceral fat are at risk of developing cognitive impairment and, therefore, represent a subset of population in whom appropriate and timely preventive measures could be implemented.

Deep unsupervised adversarial domain adaptation for underwater source range estimation.

In this study, an underwater source range estimation method based on unsupervised domain adaptation (UDA) is proposed. In contrast to traditional deep-learning frameworks using real-world data, UDA does not require labeling of the measured data, making it more practical. First, a classifier based on a deep neural network is trained with labeled simulated data generated using acoustic propagation models and, then, the adaptive procedure is applied, wherein unlabeled measured data are employed to adjust an adaptation module using the adversarial learning algorithm. Adversarial learning is employed to alleviate the marginal distribution divergence, which reflects the difference between the measured and theoretically computed sound field, in the latent space. This divergence, caused by environmental parameter mismatch or other unknown corruption, can be detrimental to accurate source localization. After the completion of the adaptive procedure, the measured and simulated data are projected to the same space, eliminating distribution discrepancy, which is beneficial for source localization tasks. Experimental results show that range estimation based on UDA outperforms the match-field-processing method under four scenarios of few snapshots, few array elements, low signal-to-noise ratio, and environmental parameter mismatch, verifying the robustness of the method.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

The relationship between uric acid and brain health from observational studies.

This study conducts a systematic literature review and meta-analysis regarding the potential influence of serum uric acid levels on cerebral small vessel diseases and the cognitive status in the prodromal stages of dementia. We identified four different cerebral small vessel diseases and three specific domains of cognitive performance to be considered in the literature search. The analysis contained 14 studies (13 cross-sectional design and one longitudinal design) with 11,502 participants measuring the relationship between uric acid and cerebral small vessel disease. In both continuous and categorical analyses, significant associations were found between hyperuricemia and cerebral small vessel diseases (continuous data: pooled OR: 1.00, 95%CI: 1.00-1.01 and categorical data: pooled OR: 1.42, 95%CI: 1.15-1.75). For the relationship between uric acid and cognitive performance, 19 studies with 49,901 participants were considered, including eight cohort studies, and 11 cross-sectional studies. The cross-sectional data showed that a marginal relationship existed between uric acid and global cognition (ß: 0.00, 95%CI: -0.01-0.00). The pooled analysis of cohort studies indicated that higher uric acid had a deleterious effect on attention and executive function (continuous data: ß: -0.02, 95%CI: -0.04-0.00 and categorical data: ß: -0.03, 95%CI: -0.07-0.00). Conclusion: Our study indicated that a higher level of uric acid had an adverse effect on brain health. Furthermore, a high level of uric acid is related to cognitive decline in attention and executive function, which may exist a long time before the diagnosis of dementia.

LncRNA LOXL1-AS1 Facilitates the Oncogenic Character in Cervical Cancer by the miR-526b-5p /LYPLA1 Axis.

Increasing reports demonstrate that long noncoding RNAs participate in the regulation of numerous malignancies, cervical cancer included. Although lncRNA LOXL1 antisense RNA 1 has been commonly accepted to be an oncogene in many cancers. Here, the role of LOXL1-AS1 in CC still need to be explored. In this study, LOXL1-AS1 was found elevated in CC tissues and cells. LOXL1-AS1 depletion restrained CC cell proliferation, migration, invasion, and angiogenesis in vivo. Furthermore, we found that LOXL1-AS1 upregulated Lysophospholipase 1 expression via sequestering miR-526b-5p. Rescue assays revealed that overexpression of LYPLA1 reversed the LOXL1-AS1 silencing-induced inhibitory effects on the malignant phenotypes of CC cells. To conclude, this study showed that LOXL1-AS1 facilitates cellular process in CC via functioning as a miR-526b-5p sponge.

Critical Quality Control Methods for a Novel Anticoagulant Candidate LFG-Na by HPSEC-MALLS-RID and Bioactivity Assays.

A low molecular weight fucosylated glycosaminoglycan sodium (LFG-Na) is a novel anticoagulant candidate from the sea cucumber Holothuria fuscopunctata that selectively inhibits intrinsic tenase (iXase). The molecular weight, molecular weight distribution and bioactivities are the critical quality attributes of LFG-Na. The determination of these quality attributes of such an oligosaccharides mixture drug is challenging but critical for the quality control process to ensure its safety and efficacy in clinical use. Herein, the molecular weight and molecular weight distribution of LFG-Na were successfully determined using high performance size exclusion chromatography coupled with multi angle laser light scattering and refractive index detector (HPSEC-MALLS-RID). Comparing to the conventional method, HPSEC-MALLS-RID based on the refractive index increment (dn/dc) did not require the reference substances to establish the calibration curve. The acceptance criteria of LFG-Na were established, the weight-average molecular weight (Mw) should be 4000 to 6000 Da, the polydispersity (Mw/Mn) < 1.40, and the fraction with molecular weights of 1500 to 8000 Da should be no less than 80% of the total. HPSEC-MALLS-RID was also utilized for the determination of the starting material native fucosylated glycosaminoglycan (NFG) to choose a better manufacturing process. Furthermore, APTT assay was selected and the potency of anti-iXase, referring to the parallel line assay (PLA) method, was established to clarify the consistency of its biological activities. The results suggest that HPSEC-MALLS-RID and bioactivity assays are critical quality control methods for multi-component glycosaminoglycan LFG-Na. The methods also provide a feasible strategy to control the quality of other polysaccharide medicines.

LncRNA NR2F1-AS1 Inhibits the Malignant Properties of Cervical Cancer Cells via Targeting miR-642a-3p/NR2F1 Axis.

Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objectives: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusions: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

Heterozygous PAX6 mutations may lead to hyper-proinsulinaemia and glucose intolerance: A case-control study in families with congenital aniridia.

AIM: PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA. METHODS: In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated. RESULTS: Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032). CONCLUSION: PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

The clinical significance of vitamin D levels and vitamin D receptor mRNA expression in colorectal neoplasms.

BACKGROUND/AIM: This study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development. METHODS: Plasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients. RESULTS: Vitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para-cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively. CONCLUSIONS: The 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.

Convex compressive beamforming with nonconvex sparse regularization.

The convex sparse penalty based compressive beamforming technique can achieve robust high resolution in direction-of-arrival (DOA) estimation tasks, but it often leads to an insufficient sparsity-inducing problem due to its convex loose approximation to ideal ℓ0 nonconvex penalty. On the contrary, the nonconvex sparse penalty can tightly approximate ℓ0 penalty to effectively enhance DOA estimation accuracy, but it incurs an initialization sensitivity problem due to its multiple local minimas. Leveraging their individual advantages, a minimax-concave penalty (MCP) regularized DOA estimation algorithm is proposed to achieve a maximally sparse level while maintaining the convex property of the overall objective function. Moreover, an accelerated block gradient descent-ascent algorithm with convergence guarantee is developed to rapidly achieve its one optimal point. Simulation results demonstrate that MCP penalty improves DOA estimation accuracy compared with popular sparse compressive beamforming techniques in strong noise scenarios and weak source confirmation. Ocean experimental results also validate that it retains more stable DOA estimation accuracy and incurs less artificial interferences.

Poor Oral Health in Patients with Schizophrenia: a Meta-Analysis of Case-Control Studies.

Patients with schizophrenia have high rates of comorbid physical illness, but there has been less attention to dental diseases in these patients. This meta-analysis of case-control studies systematically examined the oral health in patients with schizophrenia. Case-control studies comparing the oral health in patients with schizophrenia and healthy controls were screened and identified. Standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated using RevMan version 5.3. Three case-control studies comprising 306 patients with schizophrenia and 306 healthy controls were included in this meta-analysis. All studies were rated as "high quality". Patients with schizophrenia had significantly higher scores of decayed, missing and filled teeth (SMD = 0.83, 95%CI: 0.57, 1.09, p < 0.001; I2 = 51%), missing teeth (SMD = 0.79, 95%CI: 0.59, 0.98, p < 0.001; I2 = 19%), and decayed teeth (SMD = 0.89, 95%CI: 0.24, 1.54, p = 0.008; I2 = 92%) when compared to healthy controls. Similarly, patients with schizophrenia had significantly lower filled teeth scores (SMD = -0.76, 95%CI: -1.44, -0.09, p = 0.03; I2 = 93%) when compared to healthy controls. This meta-analysis found that patients with schizophrenia were likely to have worse oral health when compared to healthy controls.

3D Underwater Uncooperative Target Tracking for a Time-Varying Non-Gaussian Environment by Distributed Passive Underwater Buoys.

Accurate 3D passive tracking of an underwater uncooperative target is of great significance to make use of the sea resources as well as to ensure the safety of our maritime areas. In this paper, a 3D passive underwater uncooperative target tracking problem for a time-varying non-Gaussian environment is studied. Aiming to overcome the low observability drawback inherent in the passive target tracking problem, a distributed passive underwater buoys observing system is considered and the optimal topology of the distributed measurement system is designed based on the nonlinear system observability analysis theory and the Cramer-Rao lower bound (CRLB) analysis method. Then, considering the unknown underwater environment will lead to time-varying non-Gaussian disturbances for both the target's dynamics and the measurements, the robust optimal nonlinear estimator, namely the adaptive particle filter (APF), is proposed. Based on the Bayesian posterior probability and Monte Carlo techniques, the proposed algorithm utilizes the real-time optimal estimation technique to calculate the complex noise online and tackle the underwater uncooperative target tracking problem. Finally, the proposed algorithm is tested by simulated data and comprehensive comparisons along with detailed discussions that are made to demonstrate the effectiveness of the proposed APF.

Adaptive Two-Step Bearing-Only Underwater Uncooperative Target Tracking with Uncertain Underwater Disturbances.

The bearing-only tracking of an underwater uncooperative target can protect maritime territories and allows for the utilization of sea resources. Considering the influences of an unknown underwater environment, this work aimed to estimate 2-D locations and velocities of an underwater target with uncertain underwater disturbances. In this paper, an adaptive two-step bearing-only underwater uncooperative target tracking filter (ATSF) for uncertain underwater disturbances is proposed. Considering the nonlinearities of the target's kinematics and the bearing-only measurements, in addition to the uncertain noise caused by an unknown underwater environment, the proposed ATSF consists of two major components, namely, an online noise estimator and a robust extended two-step filter. First, using a modified Sage-Husa online noise estimator, the uncertain process and measurement noise are estimated at each tracking step. Then, by adopting an extended state and by using a robust negative matrix-correcting method in conjunction with a regularized Newton-Gauss iteration scheme, the current state of the underwater uncooperative target is estimated. Finally, the proposed ATSF was tested via simulations of a 2-D underwater uncooperative target tracking scenario. The Monte Carlo simulation results demonstrated the reliability and accuracy of the proposed ATSF in bearing-only underwater uncooperative tracking missions.

Non-linear association between diabetes mellitus and pulmonary function: a population-based study.

BACKGROUND: There is increasing evidence that the lung is a target organ of diabetes. This study aimed to examine in detail the association between diabetes mellitus and pulmonary function using a national cohort. We also aimed to explore the non-linear association between pulmonary function and blood glucose, insulin resistance, and C-reactive protein (CRP). METHODS: A total of 30,442 participants from the National Health and Nutrition Examination Survey from the period between 2007 and 2012 were included. The cross-sectional association between diabetes mellitus and pulmonary function was assessed using multiple linear regression. Where there was evidence of non-linearity, we applied a restricted cubic spline with three knots to explore the non-linear association. Partial mediation analysis was performed to evaluate the underlying mechanism. All analyses were weighted to represent the US population and to account for the intricate survey design. RESULTS: A total of 8584 people were included in the final study population. We found that diabetes was significantly associated with reduced forced expiratory volume in one second (FEV1) and forced vital capacity. We further found L-shaped associations between hemoglobin A1c (HbA1c) and pulmonary function. There was a negative association between HbA1c and FEV1 in diabetes participants with good glucose control (HbA1c < 7.0%), but not in patients with poor glucose control. A non-linear association was also found with fasting plasma glucose, 2 h-plasma glucose after oral glucose tolerance test, insulin resistance, and CRP. Finally, we found that diabetes duration did not affect pulmonary function, and the deleterious effect of diabetes on pulmonary function was mediated by hyperglycemia, insulin resistance, low-grade chronic inflammation (CRP), and obesity. CONCLUSIONS: Diabetes mellitus is non-linearly associated with pulmonary function. Our finding of a negative association between HbA1c and FEV1 in diabetes patients with good glucose control but not in patients with poor glucose control indicates that a stricter glycemic target should be applied to diabetic patients to improve pulmonary function. Given, the cross-sectional nature of this research, a longitudinal study is still needed to validate our findings.

Prediabetes and structural brain abnormalities: Evidence from observational studies.

Type 2 diabetes mellitus has been linked to structural brain abnormalities, but evidence of the association among prediabetes and structural brain abnormalities has not been systematically evaluated. Comprehensive searching strategies and relevant studies were systematically retrieved from PubMed, Embase, Medline and web of science. Twelve articles were included overall. Stratified analyses and regression analyses were performed. A total of 104 468 individuals were included. The risk of infarct was associated with continuous glycosylated haemoglobin (HbA1c ) [adjusted odds ratio (OR) 1.19 (95% confidence interval [CI]: 1.05-1.34)], or prediabetes [adjusted OR 1.13 (95% CI: 1.00-1.27)]. The corresponding ORs associated with white matter hyperintensities were 1.08 (95%CI: 1.04-1.13) for prediabetes, and 1.10 (95%CI: 1.08-1.12) for HbA1c . The association was significant between the decreased risk of brain volume with continuous HbA1c (the combined OR 0.92, 95% CI: 0.87-0.98). Grey matter volume and white matter volume were inversely associated with prediabetes [weighted mean deviation (WMD), -9.65 (95%CI: -15.25 to -4.04) vs WMD, -9.25 (95%CI: -15.03 to -3.47)]. There were no significant association among cerebral microbleeds, hippocampal volume, continuous total brain volume, and prediabetes. Our findings demonstrated that (a) both prediabetes and continuous HbA1c were significantly associated with increasing risk of infarct or white matter hyperintensities; (b) continuous HbA1c was associated with a decreased risk of brain volume; (c) prediabetes was inversely associated with grey matter volume and white matter volume. To confirm these findings, further studies on early diabetes onset and structural brain abnormalities are needed.

Obstructive sleep apnea is associated with coronary microvascular dysfunction: A systematic review from a clinical perspective.

There is now increasing evidence demonstrating that obstructive sleep apnea (OSA) contributes to microvascular disorder. However, whether OSA is associated with impaired coronary flow reserve is still unclear. Therefore, we conducted this systematic review and meta-analysis to summarize current evidence. In a systematic review, PubMed, Embase, the Cochrane Library and Web of Science were searched; five observational studies fulfilled the selection criteria and were included in this study. Data were extracted from selected studies and meta-analysis was performed using random-effects modelling. In all, 829 OSA patients and 507 non-OSA subjects were included and assessed for coronary flow reserve (CFR), the clinical indicator of coronary microvascular dysfunction (CMD). For all studies, OSA was significantly associated with reduced CFR. The pooled weighted mean difference (WMD) of CFR was -0.78 (95% confidence interval [CI] -1.25 to -0.32, p ï¼œ 0.001, I2  = 84.4%). The difference in the apnea-hypopnea index (AHI) between studies can explain 89% of heterogeneity (coef = -0.05, 95% CI -0.12 to 0.02, p = .078) in a meta-regression, indicating the CFR tended to negatively correlate with severity of OSA. The Egger regression test did not show statistical significance (p = .49). In conclusion, there are plausible biological mechanisms linking OSA and CMD, and the preponderance of evidence from this systematic review suggests that OSA, especially severe OSA, is associated with reduced CFR. Future studies are warranted to further delineate the exact role of OSA in CMD occurrence and development in a prospective setting.

Identification, Pathogenicity, and Fungicide Sensitivity of Ascochyta caulina (Teleomorph: Neocamarosporium calvescens) Associated with Black Stem on Quinoa in China.

Quinoa black stem is a new disease that affects the stems of quinoa plants and is more likely to develop under cool conditions (15 to 25°C, RH = 55 ± 2%). The typical symptoms include the formation of black necrotic lesions on the stem, which can completely wrap around the stem, causing lodging and blanking (development of 'empty' and sterile grain on the panicle). Furthermore, the pycnidia form small round protrusions on the surface of the lesions. Phylogenetic analysis revealed that representative isolates LMHS-3 and LMHS-5 were closely related to Ascochyta caulina (teleomorph: Neocamarosporium calvescens). Comprehensive morphological and molecular characterizations confirmed A. caulina as the pathogen that caused quinoa black stem. A. caulina mainly infected quinoa stems and could produce many pycnidia, but it rarely infected quinoa leaves. Pathogenicity testing showed that the most suitable temperature for the onset of quinoa black stem was from 15 to 25°C. When the temperature was increased above 30°C, the conidial germination of A. caulina became malformed, and when the temperature was decreased below 5°C, mycelium growth of A. caulina became extremely slow; thus, both extreme high and low temperatures affected the pathogenicity of A. caulina. Mancozeb and azoxystrobin fungicides were revealed to have had the strongest inhibitory effects on the conidial germination of A. caulina, and in some cases caused malformations in conidial germination. Tebuconazole and difenoconazole had the strongest inhibitory effects on A. caulina mycelial growth and less on the effects on the conidial germination. The results of the present study provide a basis for the recognition and management of quinoa black stem.

Identification of Rfx6 target genes involved in pancreas development and insulin translation by ChIP-seq.

Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6. We captured 4146 unique peaks in the genome region of the adult murine pancreas. Among all these binding peaks, a majority were located in intron or intergenic regions. We further annotated all peaks to their nearest gene, and over 1000 genes were captured as Rfx6-binding genes in the pancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that Rfx6-binding genes to be associated with the pancreas developmental process. A portion of selected ChIP-seq targets related with pancreas differentiation including Pdx1, Neurod1, Hnf1a, Nkx6-1, St18 and Shox2 were selected and validated as true targets by independent qPCR experiments. In addition, Rfx6 can directly bind to upstream of MiR-145, MiR-195, and possibly other non-protein-coding functional RNAs to control adult mouse pancreatic differentiation. Interestingly, our study revealed that Rfx6 played an important role in insulin translation by binding to the Eif2ak1, Upf1, and Eif5. Our data provide direct target genes of Rfx6 during pancreas development and point to Rfx6 as a potential therapeutic target for improving insulin protein content.

Could Vitamin D be Associated with Proliferative Diabetic Retinopathy? Evidence from Pooling Studies.

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

Do the toll-like receptors and complement systems play equally important roles in freshwater adapted Dolly Varden char (Salvelinus malma)?

Unlike the normal anadromous lifestyle, Chinese native Dolly Varden char (Salvelinus malma) is locked in land and lives in fresh water lifetime. To explore the effect of freshwater adaption on its immune system, we constructed a pooled cDNA library of hepatopancreas and spleen of Chinese freshwater Dolly Varden char (S. malma). A total of 27,829 unigenes were generated from 31,233 high-quality transcripts and 17,670 complete open reading frames (ORF) were identified. Totally 25,809 unigenes were successfully annotated and it classified more native than adaptive immunity-associated genes, and more genes involved in toll-like receptor signal pathway than those in complement and coagulation cascades (51 vs 3), implying the relative more important role of toll-like receptors than the complement system under bacterial injection for the freshwater Dolly Varden char. These huge different numbers of TLR and complement system identified in freshwater Dolly Varden char probably caused by distinct evolution pressure patterns between fish TLR and complement system, representative by TLR3 and TLR5 as well as C4 and C6, respectively, which were under purifying and positively selecting pressure, respectively. Further seawater adaptation experiment and the comparison study with our library will no doubt be helpful to elucidate the effect of freshwater adaption of Chinese native Dolly Varden char on its immune system.