Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Value Of Anteroposterior-To-Transverse Ratio in Ultrasonic Diagnosis of Thyroid Nodule in Different Locations.

PURPOSE: To investigate the value of anteroposterior-to-transverse ratio (ATR) and the effect on features of nodules in ultrasound (US) diagnosis of thyroid nodules in different locations.  Methods: The nodules were divided into three groups according to the different nodule location: isthmus group; upper and lower poles of bilobed thyroid group; and the middle of the bilobed thyroid group. The diameters of the nodules were recorded, and ATR of the nodule was calculated on the transverse and longitudinal sections. The transverse and the longitudinal sections of ATR of thyroid nodules in different groups were compared.  Result: The transverse section of ATR was significantly different among the three groups (p = 0.001). In addition, there are significant differences in many US features among three groups, including nodule composition, thyroid parenchyma, morphology, echogenicity, shape, calcifications, vascularity, nodule ACR TI-RADS and histopathologic (all p < 0.05). In the group of upper and lower poles of bilobed thyroid, significant difference was found between the transverse and the longitudinal section of ATR (p = 0.019). The cut-off values of transverse section and longitudinal section of ATR were 0.967 and 0.750, respectively.  Conclusion: The transverse section of ATR at different location of thyroid may be a predictor for malignancy with clinical diagnostic significance.

[Effects of bisphenol-A on blastocyst development and implantation].

OBJECTIVE: To determine the effects of bisphenol-A (BPA) on blastocyst development and implantation. METHODS: According to completely randomized grouping method, 90 pregnant mice were divided into 100, 300, and 600 mg/(kg·d)BPA groups and control group. BPA-treated pregnant mice were orally administered with BPA at concentrations of 100, 300 and 600 mg/(kg·d) from day 0.5 to day 3.5 of their pregnancy. Blastocyst implantation and development were studied. RESULTS: In the 300 mg/(kg·d) BPA group, the number of implantation sites and implantation rate were significantly decreased. In the 600 mg/(kg·d) group, no implantation sites were observed among pregnant mice and BPA inhibited embryo implantation. Blastocyst development on day 4 was examined, and findings showed that the development rate and total numbers of blastocysts in BPA treatment groups had no significant difference from the control group. However, BPA at 300 and 600 mg/(kg·d) significantly reduced blastocyst hatching rate and dramatically increased the number of blastocyst apoptotic cells when compared with those in the control group. CONCLUSION: BPA at a high concentration damages the blastocyst development before implantation and inhibits embryo implantation.

Metabolic dysfunction-associated steatotic liver disease-related hepatic fibrosis increases risk of insulin resistance, type 2 diabetes, and chronic kidney disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8-57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2-11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance ( ß â€…= 2.19; P  = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22-6.02], type 2 diabetes (OR 2.69; 95% CI 1.72-4.20), and CKD (OR 1.70; 95% CI 1.24-2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity.

[Effects of Biochar-loaded Ammonia Nitrogen on Soil Carbon Emissions, Enzyme Activity, and Microbial Communities].

The form of soil nitrogen input significantly affects soil CO2 emission. As a new form of nitrogen input, biochar-loaded ammonia nitrogen not only reduces the input of chemical nitrogen fertilizer in farmland but also reduces the cost of environmental treatment. It is of great significance to promote the zero growth of national chemical fertilizer, the prevention and control of farmland non-point source pollution, and the realization of the national goal of "carbon peak" and "carbon neutralization." Through an indoor culture experiment, the effects of different nitrogen input forms on soil carbon emission, enzyme activity, and microbial community were studied through four treatments:no fertilization (CK), single application of chemical nitrogen fertilizer (CF), biochar combined application of chemical nitrogen fertilizer (BF), and biochar-loaded ammonia nitrogen (BN). The results showed that compared with that in CF, BF significantly increased cumulative carbon emissions (66.24 %), whereas BN had no significant difference. It is worth noting that the cumulative carbon emissions were significantly reduced by 35.28 % compared with that in BF and BN. Compared with those in CF and BF, the activities of ß-glucosidase, peroxidase, and polyphenol oxidase treated with BN significantly increased by 20.25 % and 5.20 %, respectively. Compared with that in CF, the BF treatment increased microbial community richness and community diversity, whereas the BN treatment decreased microbial community richness. Compared with that in BF, the relative abundance of Proteobacteria decreased by 11.16 %, and the relative abundance of Actinobacteria and Bacteroidota increased by 8.12 % and 5.83 %, respectively, in which xylosidase activity was the most important soil factor affecting microbial community structure. The relative abundance of Chloroflexi was significantly correlated with cellobiose hydrolase activity, and the relative abundance of Gemmatimonadetes was significantly correlated with ß-glucosidase activity. There was a very significant correlation between the relative abundance of Proteobacteria and cumulative carbon emissions. To summarize, compared with those under biochar combined with chemical nitrogen fertilizer, biochar loaded with ammonia nitrogen significantly reduced cumulative carbon emissions, and its emission reduction effect was better. The results of this study will be beneficial to the landing of the national "double carbon strategy," the healthy development of the biological natural gas industry, the construction of the national green cultivation circular agriculture system, and the realization of the national zero growth strategy of chemical fertilizer.

A case of endobronchial metastasis of colon cancer mimics sarcoidosis, and a review of related literature.

PURPOSE: Endobronchial metastases (EBM) are defined as bronchoscopically visible lesions histopathologically identical to extrapulmonary tumors. We summarized the literature on endobronchial metastasis of colorectal cancer and give a brief review. METHOD: We present a rare case with an episode mistaken for sarcoidosis and unexpectedly identified as colon cancer by bronchoscopic biopsy. A 53-year-old man with dry cough and dyspnea had diffuse micro lung nodules and lymphadenopathy on CT and PET/CT. He was diagnosed with sarcoidosis and took steroid therapy, but the symptoms could not be alleviated. Bronchoscopy was suggested. He was finally identified with colon cancer by bronchoscopic biopsy, which was confirmed by endoscopic biopsy. We summarise the clinical manifestations, imaging, prognosis of EMB of colorectal cancer. RESULT: EBM are rare. Colorectal cancer is common in EBM and the frequency is increasing. CONCLUSION: EBM should be distinguished from primary lung cancer, sarcoidosis.

Pyroptosis and its role in cancer.

Programmed cell death (PCD) is mediated by specific genes that encode signals. It can balance cell survival and death. Pyroptosis is a type of inflammatory, caspase-dependent PCD mediated by gasdermin proteins, which function in pore formation, cell expansion, and plasma membrane rupture, followed by the release of intracellular contents. Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway, which is dependent on caspase-1, and the non-classical pathway, which is dependent on caspase-4/5/11. Inflammasomes play a vital role in these processes. The various components of the pyroptosis pathway are related to the occurrence, invasion, and metastasis of tumors. Research on pyroptosis has revealed new options for tumor treatment. This article summarizes the recent research progress on the molecular mechanism of pyroptosis, the relationship between the various components of the pyroptosis pathway and cancer, and the applications and prospects of pyroptosis in anticancer therapy.

Global hotspots and trends in research on preschool children's motor development from 2012 to 2022: a bibliometric analysis.

Background: Motor development plays an important role in human development throughout the lifespans, from conception to death, and has received increasing scholarly attention in recent years. However, valuable comprehensive reviews and literature analysis on this topic are still lacking. Here, this bibliometric study aimed to identify global motor development research hotspots and trends on preschool children's motor development from 2012 to 2022. Methods: CiteSpace 6.1.R4 was used to visualize and analyze general bibliometric characteristics, research hotspots, and trends through a review of 2,583 articles on the motor development of preschool children, which were published from 2012 to 2022 and included in the Web of Science Core Collection. Results: Research on motor development in preschool children has been carried out into a phase of rapid development. The top five frequently occurring keywords were physical activity (n = 489), performance (n = 319), intervention (n = 222), health (n = 196), and executive function (n = 165); The top five keywords in terms of centrality are academic achievement (0.22), low birth weight (0.16), association (0.14), brain (0.13), and cerebral palsy (0.13). Thirteen keyword clusters were produced from the log-likelihood ratio (Q = 0.74, S = 0.88), and five research topics has been received focused attention in recent years. The keywords with the strongest citation bursts in the last 5 years are developing country (S = 5.92), school-aged children (S = 5.86), middle-income country (S = 3.46), efficacy (S = 5.41), readiness (S = 3.21), motor proficiency (S = 3.6), and screen time (S = 3.3), indicating newly emerging research trends. Conclusion: The results indicated that interventions involving fundamental movement skills, cognitive function, 24-h movement behaviors, neurodevelopmental disorders, and health-related fitness were hot topics in the field of motor development over the last decade. Emerging research trends generally center on school readiness, socioeconomic status, motor proficiency, and screen time.

[Progesterone receptor-mediated molecular mechanisms on mammalian female reproduction].

The steroid hormone, progesterone, plays a critical role in regulation of mammalian female reproductive activities. Besides the non-genomic activity of progesterone on target cells, its main physiological effect is caused through genomic action by the ligand-dependent nuclear progesterone receptor. The genomic and non-genomic effects of progesterone collectively mediate various female reproductive functions, including ovulation, embryo implantation, maintenance of pregnancy, initiation of parturition, and development of mammary gland. Although a large number of candidate genes regulated by progesterone have been identified by gene chip technology, the traditional progesterone response elements located in the promoter region of downstream target genes havenot been detected. Accordingly, it was suggested thatthe mechanism of nuclear progesterone receptors regulating transcription may be different from other nuclear steroid receptors. In this review, we summarized the mechanisms of progesterone receptors mediating the physiological effects in various female re-productive activities.

Association Between Water Intake and Mortality Risk-Evidence From a National Prospective Study.

Background: Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent. Objective: This study aimed to explore the water intake-mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics. Methods: We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999-2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose-response relationships among them. Results: With a median of 88 months (interquartile range: 49-136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose-response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033-1,524 and 1,612-3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose-response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose-response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found. Conclusion: Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.

Multiple vitamin co-exposure and mortality risk: A prospective study.

BACKGROUND & AIMS: Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks. METHODS: We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis. RESULTS: A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively. CONCLUSIONS: The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.

Targeted delivery of antisense inhibitor of miRNA for antiangiogenesis therapy using cRGD-functionalized nanoparticles.

MiRNAs are viable therapeutic targets for cancer therapy, but the targeted delivery of miRNA or its anti-miRNA antisense oligonucleotides (AMOs) remains a challenge. We report here a PEGylated LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with cyclic RGD peptide (cRGD) for specific and efficient delivery of AMO into endothelial cells, targeting α(v)ß3 integrin present on the tumor neovasculature. The nanoparticles effectively delivered anti-miR-296 AMO to the cytoplasm and downregulated the target miRNA in human umbilical vein endothelial cells (HUVECs), which further efficiently suppressed blood tube formulation and endothelial cell migration, owing to significant upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), whereas nanoparticles without cRGD modification showed only little AMO uptake and miRNA silencing activity. In vivo assessment of angiogenesis using Matrigel plug assay also demonstrated that cRGD modified LPH nanoparticles have potential for antiangiogenesis in miRNA therapeutics. With the delivery of anti-miR-296 AMO by targeted nanoparticles, significant decrease in microvessel formulation within Matrigel was achieved through suppressing the invasion of CD31-positive cells into Matrigel and prompting HGS expression in angiogenic endothelial cells.

Controllable synthesis of two adenosine 5'-monophosphate nucleotide coordination polymers via pH regulation: crystal structure and chirality.

Two types of Cu(ii)-AMP-4,4'-bipy coordination polymers, {[Cu(AMP)(4,4'-bipy)(H2O)3]·5H2O}n (1) and {[Cu2(HAMP)2(4,4'-bipy)2(H2O)4]·2NO3·11H2O}n (2) (Na2AMP = adenosine 5'-monophosphate disodium salt), were synthesised through pH control. X-ray single-crystal diffraction analysis revealed that 1 and 2 are one-dimensional (1D) coordinating coordination polymers. The nucleotide in 1 was not protonated whereas that in 2 was protonated. With the protonated NO3- in 2 entering the crystal lattice, it plays a role in balancing the charge. The chirality was studied using solid-state circular dichroism (CD) spectroscopy based on the analysis of crystal structures.

The Relationship Between ß-cell Function Indices and Sudomotor Function in Chinese Patients with Type 2 Diabetes.

PURPOSE: SUDOSCAN, a new non-invasive, quick, sensitive and quantitative technique, has been developed to detect diabetic peripheral neuropathy, and the latter is believed to be correlated with impaired ß-cell function. The purpose of the present study was to investigate the associations between ß-cell function indices and sudomotor function in Chinese type 2 diabetes. METHODS: A total of 266 Chinese patients with type 2 diabetes were enrolled. Sudomotor function was assessed using electrochemical skin conductance of hands and feet. Pancreatic ß-cell function was determined by homeostasis model assessment of ß-cell function index, early-phase ß-cell function indices and total ß-cell function indices. Pearson correlation analysis and multiple linear stepwise regression analysis were carried out to explore the associations between ß-cell function indices and sudomotor function. RESULTS: Patients with lower early-phase ß-cell function had lower electrochemical skin conductance levels of hands and feet and higher asymmetry ratio of hands and feet. Both Pearson correlation analysis and multiple linear stepwise regression analysis showed significantly positive relationships between early-phase ß-cell function and electrochemical skin conductance levels of hands and feet, after controlling for potential confounders (P<0.05). CONCLUSIONS: Impaired early-phase ß-cell function was positively associated with sudomotor dysfunction in Chinese patients with type 2 diabetes. We speculated that impaired early-phase ß-cell function may be associated with the incidence of sudomotor dysfunction in patients with T2DM.

GMFG Has Potential to Be a Novel Prognostic Marker and Related to Immune Infiltrates in Breast Cancer.

A growing amount of evidence has indicated immune genes perform a crucial position in the development and progression of breast cancer microenvironment. The purpose of our study was to identify immunogenic prognostic marker and explore potential regulatory mechanisms for breast cancer. We identified the genes related to ImmuneScore using ESTIMATE algorithm and WGCNA analysis, and we identified the differentially expressed gene (DEGs). Then, Glia maturation factor γ (GMFG) was determined as a predictive factor by intersecting immune-related genes with DEGs and survival analysis. We found the expression of GMFG was lower in breast cancer tissues compared with normal breast tissues, which was further verified by immunohistochemical (IHC). Moreover, the decreased expression of GMFG was significantly related to the poor prognosis. Besides, the expression of GMFG was related to the age, ER status, PR status, HER2 status and tumor size, which further suggested that the expression of GMFG was correlated with the subtype and the growth of tumor. The univariate and multivariate Cox regression analyses revealed that age, stage, the expression level of GMFG and radiotherapy were independent factors for predicting the prognosis of breast cancer patients. Subsequently, a prognostic model to predict the 3-year, 5-year and 10-year overall survival rate was developed based on the above four variables, and visualized as a nomogram. The values of area under the curve of the nomogram at 3-year, 5-year and 10-year were 0.897, 0.873 and 0.922, respectively, which was higher than stage in prognostic accuracy. In addition, we also found that GMFG expression level was correlated with sensitivity of some breast cancer chemotherapy drugs. Furthermore, the results of GSEA indicated immune-related pathways were mainly enriched in GMFG-high-expression group. CIBERSORT analysis for the proportion of tumor-infiltrating immune cells (TIICs) suggested that expression of GMFG was positively association with multiple kinds T-cell in BC. Among them, CD8+ T cells had the strongest correlation with GMFG expression, which revealed that GMFG might has an antitumor effect by increasing the infiltration of CD8+ T cells in breast cancer. Accordingly, GMFG has the potential to become a novel immune biomarker for the diagnosis and treatment of breast cancer.

Associations of multiple metals with bone mineral density: A population-based study in US adults.

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011-2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (ß = -0.022, 95% CI: -0.036, -0.008) and total BMD (ß = -0.015, 95% CI: -0.024, -0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose-response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.

Integrative Analysis of LGR5/6 Gene Variants, Gut Microbiota Composition and Osteoporosis Risk in Elderly Population.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population. Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10-6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10-4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (ß = -1.32, P < 0.001), Bifidobacteriaceae (ß = -1.70, P < 0.001), and Bifidobacterium (ß = -1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery.

An efficient and safe delivery system for small interfering RNA (siRNA) is required for clinical application of RNA interfering therapeutics. Polyethyleneimine (PEI)-capped gold nanoparticles (AuNPs) are successfully manufactured using PEI as the reductant and stabilizer, which bind siRNA at an appropriate weight ratio by electrostatic interaction and result in well-dispersed nanoparticles with uniform structure and narrow size distribution. With siRNA binding, PEI-capped AuNPs induce more significant and enhanced reduction in targeted green fluorescent protein expression in MDA-MB-435s cells, though more internalized PEI/siRNA complexes in cells are evidenced by confocal laser scanning microscopy observation and fluorescence-activated cell sorting analyses. PEI-capped AuNPs/siRNA targeting endogenous cell-cycle kinase, an oncogene polo-like kinase 1 (PLK1), display significant gene expression knockdown and induce enhanced cell apoptosis, whereas it is not obvious when the cells are treated with PLK1 siRNA using PEI as the carrier. Without exhibiting cellular toxicity, PEI-capped AuNPs appear to be suitable as a potential carrier for intracellular siRNA delivery.

[Analysis of mitochondrial DNA D-loop region mutation and its significance in human oncocytoma].

OBJECTIVE: To investigate the mutation in mitochondrial DNA displacement-loop (mtDNA D-loop) region in oncocytoma and its relationship with tumorigenesis and tumor development. METHODS: The mtDNA D-Loop region of 20 thyroid or renal oncocytomas and the adjacent normal tissues were amplified by PCR, and then sequenced. Five human fetal renal tissues were collected as matched controls. RESULTS: Among the 20 oncocytomas, 21 mutations which focused on hypervariable region I (HVI) were found in 7 tumor tissues and 1 normal tissue with the mutation rates of 35% and 5%, respectively. At the same time, 191 polymorphisms were found in the 20 cases. CONCLUSION: mtDNA D-loop region, especially HV I, is the mutational hotspot of oncocytomas, which may be closely related with mtDNA duplicating rate and the function of mitochondria.

Mediation analysis for the relationship between dyslipidemia and coronary artery disease via hypersensitive C-reactive protein in a case-control study.

BACKGROUND: The pathological basis of coronary artery disease (CAD) is atherosclerosis which is associated with inflammation and dyslipidemia. However, the involvement of hypersensitive C-reactive protein (hs-CRP) in lipid metabolism and how it affects the pathogenesis of CAD is uncertain. OBJECTIVE: To explore whether the relationship between dyslipidemia and CAD is partly mediated by hs-CRP levels. METHODS: Three hundred fifteen pairs of randomly sexand age-matched CAD and non-CAD subjects collected from Zhongda Hospital Affiliated to Southeast University were involved in the final analysis. We gathered information about each subjects clinical history as well as their results of detected hs-CRP and lipid levels. Linear regression analysis was used to determine the association between dyslipidemia and hs-CRP levels in which univariate and multivariate logistic regression analyzes were performed to determine the relationship between hs-CRP levels and CAD as well as dyslipidemia and CAD. Mediation analysis was used to evaluate whether hs-CRP levels act as a mediator of the relationship between dyslipidemia and CAD. RESULTS: Dyslipidemia and hs-CRP levels were significantly associated with an increased risk of CAD, with ß = 0.594 (P = 0.001) and ß = 0.016 (P = 0.024), respectively, and there was a correlation between dyslipidemia and hs-CRP levels (ß = 3.273, P = 0.004). Mediation analysis results revealed that the correlation between dyslipidemia and CAD was 8.27% mediated by hs-CRP levels with a direct effect of 0.621 and an indirect effect of 0.056. CONCLUSION: Hs-CRP levels played a partial mediation role in the association between dyslipidemia and CAD.