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A new ruthenium complex was synthesized, which can effectively prevent the development of S. aureus drug-resistance and with high antibacterial activity in vitro and in vivo.

Human β-thalassemia is closely associated with aberrant expression of β-like globin genes. Human β-like globin genes are organized in the order of 5'-ε-Gγ-Aγ-δ-β-3' within the β-globin locus. The expression of β-like globin genes is regulated by 3'HS1 and five DNase I hypersensitive sites (5'HS5~5'HS1) in a locus control region. The 5'HS2 enhancer transcribes enhancer RNA and regulates the expression of ε-globin, γ-globin and β-globin. To further study the function of 5'HS2, we detected the local 3D genomic architecture via chromatin conformation capture experiments and used CRISPR/ Cas9-based DNA fragment editing to delete 5'HS2 in human K562 leukaemia cells. In this study, we found that 5'HS2-mediated chromatin interactions were enriched in a topologically associated domain that was bordered by 3'HS1 and 5'HS5. Within this topologically associated domain, 5'HS2 is highly close to the promoter regions of HBE1, HBG2 and HBG1. Upon deletion of the 5'HS2 enhancer, 91 genes were significantly down-regulated with reduced abundance of H3K27ac at their promoter regions. These down-regulated genes are mainly associated with oxygen transport, immune response, cell adhesion, anti-oxidant and thrombosis. These data suggested that many genes associated with functions of erythrocytes were decreased at transcriptional levels upon deletion of the 5'HS2 enhancer.人类β-地中海贫血的发病机制与β-样珠蛋白基因异常表达息息相关。人类β-样珠蛋白基因以5′-ε-Gγ-Aγ-δ-β-3′的顺序排列于β-珠蛋白基因座,受5′LCR (locus control region)中5个超敏位点(hypersensitive site, HS)5′HS5~5′HS1和3′HS1调控。其中5′HS2是最重要的增强子,能产生增强子RNA (enhancer RNA)并调控ε-globin、γ-globin和β-globin的表达。为了进一步探究K562细胞中增强子5′HS2的功能,本研究首先通过染色质构象捕获技术在人慢性髓原白血病K562细胞中探测到5′HS2介导的染色质相互作用集中在以包含CTCF (CCCTC-binding factor)位点的3′HS1和5′HS5为边界的拓扑结构域中,5′HS2在三维空间上与HBE1、HBG2和HBG1启动子区域相互靠近。其次运用CRISPR DNA片段编辑技术在K562细胞系中删除了增强子5′HS2。最后通过RNA-seq和CUTTag (cleavage under targettagmentation)实验分析两个5′HS2删除的单克隆细胞系的转录组和染色质H3K27ac组蛋白修饰,发现91个基因表达显著下调而且其启动子区的H3K27ac修饰程度显著降低。这些基因主要聚类于氧气运输、免疫应答、细胞粘附、抗氧化和维持血栓形成等与红细胞功能相关的生物过程中,表明K562细胞系中增强子5′HS2对红细胞功能相关基因的转录产生了广泛影响。. more...

BackgroundSodium is a critically important component of bones, and hyponatremia has firmly been established as a risk factor associated with the incidence of fragility fractures. However, researches have also revealed that lower serum sodium are linked to reductions in muscle mass and a higher risk of cardiovascular disease even when these levels are within the normal range. Accordingly, this study was developed to examine the relationships between normal serum sodium concentrations and bone turnover in patients with type 2 diabetes (T2D).MethodsPatients with T2D were enrolled in the present study from January 2021 to April 2022. All patients underwent analyses of serum sodium levels, oral glucose tolerance testing (OGTT), bone turnover markers (BTMs), and dual-energy X-ray absorptiometry (DXA) scanning. BTMs included bone formation markers osteocalcin (OC) and N-terminal propeptide of type-I procollagen (PINP), and bone resorption marker C-terminal telopeptide (CTx). Patients were stratified into three subgroups based on the tertiles of their serum sodium concentrations.ResultsIn total, 372 patients with T2D and sodium levels in the normal range were enrolled in this study. Serum OC and PINP levels were increased from subgroup with the low sodium tertile to that with the high sodium tertile (p for trend < 0.05), whereas CTx level was comparable among the subgroups. A positive correlation was detected between serum sodium levels and both lnOC (r = 0.210, p < 0.001) and lnPINP (r = 0.196, p < 0.001), with these relationships remaining significant even following adjustment for age, sex, body mass index (BMI), and HbA1c. Only after adjusting for these four factors a positive correlation was detected between serum sodium levels and CTx levels (r = 0.108, p < 0.05). Linear regression analyses revealed that following adjustment for potential covariates, serum sodium level was and positively significantly associated with lnOC level (β = 0.134, t = 2.281, p < 0.05) and PINP level (β = 0.179, t = 3.023, p < 0.01).ConclusionThese results highlight a significant association between low-normal serum sodium levels and low bone turnover. more...

In order to implement 3D point cloud scanning of small hole structure, which could not be contacted or damaged, we propose a noncontact 3D measuring method. The system contains a laser triangulation displacement sensor, a Michelson interferometer system and a coordinate measuring machine, with the advantages of non-invasive scanning, fast measurement speed and high precision. Focusing on reconstructing 3D point cloud data, random sample consensus is used to separate surface data and hole data respectively from the raw dataset. Least square optimization determines the function of the cylinder, as well as hole diameter and inclined angle between the hole and the surface. In the experiment scanning a round hole, the estimated result has diameter error and angle error within 30 µm and 0.2°, respectively. Results manifest the effectiveness and feasibility of this system and express practicality in manufacturing industry. more...

While 8-oxo-7,8-dihydro-2′-deoxyguanosine (dOG) on DNA G-quadruplex (G4) has been studied, the influence of 8-oxo-7,8-dihydro-guanosine (rOG) lesions on telomeric repeat-containing RNA (TERRA) G4 d... more...

This study aimed to evaluate the efficiency of the powdered formulation with the nematophagous fungi Duddingtonia flagrans against gastrointestinal nematodes of sheep under three feeding systems in... more...

BackgroundDyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterol/apoprotein B (LDL-C/Apo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-C/Apo B ratio and bone turnover in patients with T2D.MethodsThis study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip.ResultsA total of 335 patients with T2D were enrolled in the study, and the LDL-C/Apo B ratio ranged from 0.78 to 4.00. Along with the LDL-C/Apo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all p < 0.05). There were no differences in lumbar spine and hip T-score, proportion of osteoporosis (all p > 0.05) among the three subgroups. The LDL-C/Apo B ratio was positively correlated with lnOC (r = 0.244, p < 0.001), lnCTx (r = 0.226, p < 0.01) and lnPINP (r = 0.211, p < 0.001). These significant positive correlations persisted even when divided into male and female subgroups. Furthermore, three multiple linear regression analyses were constructed to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. After adjusting for other clinical parameters, the LDL-C/Apo B ratio was still significantly associated with OC level (β = 0.199, t = 3.348, p < 0.01), CTx level (β = 0.238, t = 4.084, p < 0.001) and PINP level (β = 0.162, t = 2.741, p < 0.01).ConclusionThe LDL-C/Apo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-C/Apo B ratio is relatively low for the purpose of maintaining bone health. more...

Background Plasma 1,5-anhydro-d-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia. Methods We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c Z-score of latency, amplitude and NCV were calculated. DPN was identified as both at least a neurologic symptom/sign and an abnormality of peripheral nerve function. Results Among the recruited patients, 23.9% (n = 137) were identified to be with DPN, and the prevalence of DPN decreased from 36.6%, 24.5%, 21.2%, 13.3% from first (Q1), second (Q2), and third (Q3) to fourth quartile (Q4) of 1,5-AG. Moreover, multivariable linear regression analysis showed 1,5-AG was associated with composite Z-score of nerve latency (β = − 0.18, t = − 3.84, p β = 0.26, t = 5.35, p β = 0.24, t = 5.61, p Conclusions Low plasma 1,5-AG is closely associated with impaired peripheral nerve function and DPN in T2D patients under mild-to-moderate hyperglycemia. more...

The incidence of gestational diabetes mellitus (GDM) has increased recently worldwide with a subsequent occurrence of the associated adverse pregnancy outcomes. The objective of this study was to estimate the association between women with GDM and adverse pregnancy outcomes based on a cohort study and an integrated meta-analysis. A retrospective cohort of 15,097 pregnant women (1718 GDM with 13,379 non-GDM controls) who delivered at two affiliated medical centers of Nantong University from Jan. 1, 2014 to Sep. 30, 2015, was conducted. Then, a meta-analysis was performed to explore and compare adverse pregnancy outcomes between GDM and non-GDM women. In our cohort study, women with GDM were at significantly greater risk for cesarean section [crude relative risk (RR): 2.20, 95% confidence interval (CI): 1.97–2.44], macrosomia (crude RR: 2.36, 95% CI: 2.04–2.74) and large for gestational age (LGA) (crude RR: 2.03, 95% CI: 1.81–2.27), and a lower risk of low birth weight (LBW) (crude RR: 0.64, 95% CI: 0.47–0.86) and small for gestational age (SGA) (crude RR: 0.60, 95% CI: 0.45–0.80) than GDM-free women. However, the preterm birth incidence was not associated with GDM [crude RR: 1.08, 95% CI: 0.91–1.29]. Similarly, the meta-analysis including our cohort study also showed a significant association between GDM and preterm birth (pooled RR: 1.36, 95% CI: 1.26–1.48). Women with GDM still have an increased incidence of adverse pregnancy outcomes, which indicated that early prevention and clinical treatment of disease should be enhanced. more...

The objective of this study was to identify proteins that are differentially expressed in the cystic wall tissues of ovarian endometriotic cysts, simple ovarian cysts, and in normal ovarian tissues. Specimens of ovarian endometriotic cyst wall tissue, simple ovarian cyst wall tissue, and normal ovarian tissue (six specimens per group) were collected from patients who received gynecologic surgery, respectively. Differentially expressed proteins related to the ovarian endometriotic cysts were screened by use of isobaric tags for relative and absolute quantitation (iTRAQ) combined with functional annotation and bioinformatics analyses. All differentially expressed proteins related to cysts were validated using immunohistochemistry methods in recurrent and non-recurrent ovarian endometriotic cyst. A total of 359 proteins were identified as up-regulated in ovarian endometriotic cyst groups when compared with both the normal ovary and simple ovarian cyst groups. The levels of 27 proteins were >two-fold higher in the ovarian endometriotic cyst group than that in the other two groups. Of note, the five most significantly upregulated proteins were Charcot-Leyden Crystal Galectin (CLC), Defensin, alpha 1 (DEFA1), S100 calcium-binding protein A9 (S100A9), S100 calcium-binding protein A8 (S100A8), and Ferritin Light Chain (FTL). Immunohistochemistry results showed that the changes of S100A9 and S100A8 were consistent with the results shown by iTRAQ. However, no similarity of CLC, DEFA1, and FTL proteins was found between iTRAQ and immunohistochemistry. The ratio of patients with abnormally high S100A9 and S100A8 expression in the recurrent ovarian endometriotic cyst group was significantly higher than that in the non-recurrent group (P < 0.05). Our data identify differentially expressed proteins S100A9 and S100A8, and suggest they may serve as novel molecular markers to predict postoperative recurrence of an ovarian endometriotic cysts.Abbreviations: iTRAQ: isobaric tags for relative and absolute quantitation; HPRD: Human Protein Reference Database; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; EM: Endometriosis; COX-2: cyclooxyenase-2; NF-kB: nuclear factor kappa-B; PR-B: progesterone receptor type B. more...

The genome architectural protein CTCF (CCCTC-binding factor) not only mediates long-distance chromatin interactions between distal enhancers and target promoters, but also functions as an important insulator-binding factor to block improper enhancer activation of non-target promoters, and is thus of great significance to transcriptional regulation of developmental genes. The三维基因组染色质架构蛋白CTCF (CCCTC-binding factor)能够介导增强子与基因启动子的远距离染色质相互作用,也可以结合调控区域的绝缘子发挥增强子绝缘功能,对发育中的基因表达调控具有重要作用。同源框基因家族(Homeobox gene family more...

Ovarian cancer is a fatal gynecologic tumor, and conventional treatment is mainly limited by chemoresistance. The mechanism contributing to chemoresistance in ovarian cancer has yet to be established. This study aimed to investigate the specific role of circ_C20orf11 in regulating chemoresistance to cisplatin (DDP)in ovarian cancer. We first established two DDP-resistant ovarian cancer cell lines. Then, we identified the effect of circ_C20orf11 on specific cellular characteristics (proliferation, apoptosis, DDP resistance) via a series of experiments. The binding sites between circ_C20orf11 and miR-527 and between miR-527 and YWHAZ were predicted using a bioinformatics tool and confirmed with a dual-luciferase reporter assay. Furthermore, extracellular vesicles (EVs) derived from DDP-resistant cell lines were identified, and the effect of EVs on macrophage polarization was examined. circ_C20orf11 was upregulated in ovarian cancer. Increased circ_C20orf11 expression enhanced DDP resistance and cell proliferation and reduced cell apoptosis in DDP-resistant cell lines after DDP treatment by sponging miR-527 and promoting YWHAZ expression. In addition, we found that DDP-resistant cell-derived EVs can induce macrophage M2 polarization, whereas silencing of circ_C20orf11 inhibited EV-induced macrophage M2 polarization. Consistent with these results, silencing of circ_C20orf11 enhanced sensitivity to DDP in vivo. Importantly, we proved that circ_C20orf11 expression was upregulated in EVs extracted from the serum of DDP-resistant patients. Our study demonstrated that silencing circ_C20orf11 sensitizes ovarian cancer to DDP by promoting miR-527/YWHAZ signaling and EV-mediated macrophage M2 polarization. more...

The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning. more...

Cell patterning holds significant implications for cell-based analysis and high-throughput screening. The challenge and key factor for formation of cell patterns is to precisely modulate the interaction between cells and substrate surfaces. Many nanosubstrates have been developed to control cell adhesion and patterning, however, requirements of complicated fabrication procedures, harsh reaction conditions, and delicate manipulation are not routinely feasible. Here, we developed a hierarchical polydimethylsiloxane nanosubstrate (HPNS) coated with mussel-inspired polydopamine (PDA) micropatterns for effective cell patterning, depending on both surface topography and chemistry. HPNSs obtained by facile template-assisted replication brought enhanced topographic interaction between cells and substrates, but they were innately hydrophobic and cell-repellent. The hydrophobic nanosubstrates were converted to be hydrophilic after PDA coatings formed via spontaneous self-polymerization, which greatly facilitated cell adhesion. As such, without resorting to any external forces or physical constraints, cells selectively adhered and spread on spatially defined PDA regions with high efficiency, and well-defined cell microarrays could be formed within 20 min. Therefore, this easy-to-fabricate nanosubstrate with no complex chemical modification will afford a facile yet effective platform for rapid cell patterning. more...

Type 2 diabetes (T2D) is characterized by islet β-cell dysfunction and impaired suppression of glucagon secretion of α-cells in response to oral hyperglycaemia. Bile acid (BA) metabolism plays a dominant role in maintaining glucose homeostasis. So we evaluated the association of fasting serum total bile acids (S-TBAs) with insulin sensitivity, islet β-cell function and glucagon levels in T2D. Total 2,952 T2D patients with fasting S-TBAs in the normal range were recruited and received oral glucose tolerance tests for determination of fasting and postchallenge glucose, C-peptide and glucagon. Fasting and systemic insulin sensitivity were assessed by homeostasis model assessment (HOMA) and Matsuda index using C-peptide, i.e., ISHOMA-cp and ISIM-cp, respectively. Islet β-cell function was assessed by the insulin-secretion-sensitivity-index-2 using C-peptide (ISSI2cp). The area under the glucagon curve (AUCgla) was used to assess postchallenge glucagon. The results showed ISHOMA-cp, ISIM-cp and ISSI2cp decreased, while AUCgla notably increased, across ascending quartiles of S-TBAs but not fasting glucagon. Moreover, S-TBAs were inversely correlated with ISHOMA-cp, ISIM-cp and ISSI2cp (r = -0.21, -0.15 and -‍0.25, respectively, p < 0.001) and positively correlated with AUCgla (r = 0.32, p < 0.001) but not with fasting glucagon (r = 0.033, p = 0.070). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the S-TBAs were independently associated with ISHOMA-cp (β = -0.04, t = -2.82, p = 0.005), ISIM-cp (β = -0.11, t = -7.05, p < 0.001), ISSI2cp (β = -0.15, t = -10.26, p < 0.001) and AUCgla (β = 0.29, t = 19.08, p < 0.001). Increased fasting S-TBAs are associated with blunted fasting and systemic insulin sensitivity, impaired islet β-cell function and increased glucagon levels in response to glucose challenge in T2D. more...

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The detection and analysis of circulating tumor cells (CTCs) from patients´ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients´ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization. more...

High-normal thyrotropin (TSH) is related to reduced insulin sensitivity and may contribute to glycemic disorders in diabetes. We investigated the relationship between normal serum TSH levels and glycemic variability in euthyroid type 2 diabetic patients. A total of 432 newly diagnosed type 2 diabetic patients with euthyroid function and normal serum TSH levels were recruited between March 2013 and February 2017. Insulin sensitivity was evaluated by the Matsuda index (ISIMatsuda) following a 75-g oral glucose tolerance test. Multiple glycemic variability indices, including the mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and standard deviation of glucose (SD), were calculated from glucose data obtained with a continuous glucose monitoring system. Average glucose accessed by 24-h mean glucose (24-h MG) was also calculated. A normal serum TSH level was positively correlated with MAGE, MODD, SD, and 24-h MG (r = 0.206, 0.178, 0.186, and 0.132, respectively, p more...

The aim of this study is to compare the efficacy of bromocriptine (BRC) versus cabergoline (CAB) in patients with giant prolactinomas. We searched MEDLINE, EMBASE, CENTRAL and Clinical Trials.gov for studies dated before March 1st, 2016, that used BRC or CAB for the treatment of patients with giant prolactinomas. Specific eligibility criteria were set to identify articles and cases. The selected articles were reviewed, and the data were extracted for analysis. The compared outcomes included tumor shrinkage, tumor response, normalization of prolactin (PRL) level, and visual field defect (VFD) improvement. Gender differences were also considered. Differences between the groups were assessed using Student's t test and the chi-square test. Two hundred and forty-five records were identified, and 10 articles and 104 cases met the inclusion criteria. Based on our analysis, CAB is significantly better than BRC in normalizing PRL levels in patients, especially males, with giant prolactinomas (69.4% versus 31.7%, p = 0.01). However, there was no significant difference between the two drugs in terms of tumor shrinkage, tumor response and VFD improvement (p > 0.05) in male or female patients. CAB exhibits significantly better efficacy than BRC in the normalization of PRL levels in male patients with giant prolactinomas. Regarding tumor reduction and VFD improvement, both drugs are comparably effective for patients of both genders. This quantitative and systematic review provides preliminary evidence in favor of CAB as a medical therapy for treating giant prolactinomas in male patients, especially those with extremely high PRL levels. more...

Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p more...

Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. more...

To screen the differentially expressed proteins (DEPs) in human bronchial epithelial cells (HBE) treated with atmospheric fine particulate matter (PMHBE cells were treated with PMOverall, 67 DEPs were screened in the Shenzhen sample-treated group, of which 46 were upregulated and 21 were downregulated. In total, 252 DEPs were screened in the Taiyuan sample-treated group, of which 134 were upregulated and 118 were downregulated. KEGG analysis demonstrated that DEPs were mainly enriched in ubiquitin-mediated proteolysis and HIF-1 signal pathways in Shenzhen PMOur findings provide a valuable basis for further evaluation of PM more...

Prokaryotes use repetitive genomic elements termed CRISPR (clustered regularly interspaced short palindromic repeats) to destroy invading genetic molecules. Although CRISPR systems have been widely used in DNA and RNA technology, certain adverse effects do occur. For example, constitutively active CRISPR systems may lead to a certain risk of off-target effects. Here, we introduce post-synthetic masking and chemical activation of guide RNA (gRNA) to controlling CRISPR systems. An RNA structure profiling probe (2-azidomethylnicotinic acid imidazolide) is used. Moreover, we accomplish conditional control of gene editing in live cells. This proof-of-concept study demonstrates promising potential of chemical activation of gRNAs as a versatile tool for chemical biology., Constituitively active CRISPR systems have the risk of adverse off-target effects. Here the authors use chemical masking and activation of gRNA to control activity. more...

Benefiting from the simple DNAzyme and a duplex-specific nuclease, a series of microRNA-stimulated DNAzyme logic gates were rationally assembled for the highly accurate detection of multiple low-abundant microRNA biomarkers that correspond to the specific aberrant microRNA expression patterns of cancer tissues, thus showing a great potential in early diagnosis. more...

Serum complement C3 has been shown to contribute to the incidence of type 2 diabetes (T2D), but how serum complement C3 affects islet β-cell function throughout the course of T2D is unclear. This study explored whether serum complement C3 is independently associated with changes in islet β-cell function over time in patients with T2D. Serum complement C3 was measured, and endogenous β-cell function was evaluated by area under the C-peptide curve (AUCcp) during an oral glucose tolerance test (OGTT) in 411 patients with T2D at baseline from 2011 to 2015. Next, 347 of those patients with available data were pooled for a final follow-up analysis from 2014 to 2018. Changes in islet β-cell function at follow-up were evaluated by AUCcp percentage changes (ΔAUCcp%). In addition, other possible clinical risks for diabetes were also examined. The 347 patients included in the analysis had a diabetes duration of 4.84 ± 3.63 years at baseline. Baseline serum complement C3 (baseline C3) levels were positively correlated with baseline natural logarithm of AUCcp (lnAUCcp) (n = 347, r = 0.288, p more...

UDP-glucuronosyltransferases (UGTs) are an important family of phase 2 drug-metabolizing enzymes that catalyze the glucuronidation of numerous endogenous or exogenous small compounds. The aberrant expression of UGT isoforms causes many diseases, such as hyperbilirubinemia and affect drug efficacy or toxicity. Understanding mechanisms of UGT gene regulation will provide scientific foundations for disease prevention and personalized or precision medicine. Vertebrate UGT family genes can be divided into UGT1 and UGT2 subfamilies. Similar to the protocadherin, immunoglobulin, and T-cell receptor gene clusters and different from the UGT2 gene cluster, the UGT1 gene cluster is organized into variable and constant regions. The UGT1 variable region contains a tandem array of variable exons, each of which can be alternatively spliced to a single set of 4 downstream constant exons, generating at least nine UGT1 mRNAs that could be translated into different UGT1 glucuronyltransferase isoforms. Our previous work reveals that the relative orientations and locations of CTCF binding sites play a key role in the three-dimensional organization of the mammalian genomes in cell nuclei. Thus in order to study the transcriptional mechanisms of UGT1 gene cluster, the distributions and orientations of CTCF binding sites (CBSs) are analyzed and compared between human and mouse UGT1 gene clusters. We find that the CBSs in the UGT1 gene cluster are not conserved between human and mouse species. We show that CTCF and cohesin regulate the transcription of the UGT1 gene cluster by knocking down the CTCF or the cohesin subunit SMC3 in the human A549 cell line. By using CRISPR DNA-fragment editing, we deleted and inverted hCBS1. By RNA-seq experiments, we find that hCBS1 deletion results in a significant decrease of levels of the UGT1A6, UGT1A7, and UGT1A9 gene expression and that hCBS1 inversion results in a significant decrease of levels of the UGT1A7 gene expression. Our data suggest that the CTCF binding site hCBS1 plays an important regulatory role in the regulation of UGT1 gene expression, providing an experimental basis for further mechanistic studies of the 3D genome regulation of the UGT1 gene cluster. more...

To study the pollution characteristics, sources, and transportation process of PM

In order to explore the characteristics of PM

To investigate the correlation between the expression of lncRNA PCAT-1 and clinicopathological features of oral squamous cell carcinoma.In this study, 112 oral tissue specimens, including 60 oral squamous cell carcinoma, and 52 non-cancer oral tissues were collected from Department of Stomatology in Anhui Provincial Hospital during 2013 to 2016. Reverse transcription quantitative PCR (RT-PCR) was performed to detect the expression of PCAT-1 and c-Myc. The correlation between the levels of PCAT-1 and clinical features (age, gender, high risk habit, histological stage, cervical lymphatic metastasis, differentiation) were analyzed. Graphpad Prism 7.0 software package was used for statistical analysis.Significant different levels of PCAT-1 were found between the high risk habit (alcohol and tobacco) group and low risk habit group, between patients with cervical lymphnode metastasis and patients without cervical lymphnode metastasis. The expression of PCAT-1 and c-Myc were up-regulated in OSCC, and there were positive correlation between the expression of PCAT-1 and c-Myc; up-regulated expression of PCAT-1 may be associated with higher morbidity of OSCC.PCAT-1 is overexpressed in oral squamous cell carcinoma and is associated with higher morbidity of OSCC. more...

The extracellular matrix (ECM) maintenance is crucial to the structural integrity of adipocytes and whole adipose tissue formation. However, the potential impact of the ECM on adipocyte lineage commitment is unclear. Herein, we demonstrate that forced expression of matrix-associated metalloproteinase Adamts1 (a disintegrin and metalloproteinase with thrombospondin motifs 1), which we show is targeted by microRNA-181d (miR-181d) during BMP4-induced adipocytic lineage commitment, markedly impairs adipocyte commitment. Conversely, siRNA-induced inhibition of Adamts1 promotes adipocyte commitment. Adamst1 metalloprotease activity is required for this inhibition and is determined to function via remodeling ECM components followed by activating FAK-ERK signaling pathway during the commitment process. Furthermore, ablation of Adamts1 in adipose tissue increases adipose tissue mass, reduces insulin sensitivity, and disrupts lipid homeostasis. This finding is consistent with Adamts1 decreased expression in the adipose tissue of obese mice and an inverse correlation of Adamts1 expression with body mass index in humans. Collectively, our results indicate that Adamts1 acts as an ECM 'modifier', with miR-181d-induced downregulation, that regulates adipocyte lineage commitment and obesity. more...

Five new unusual C17/C15 sesquiterpene lactone dimers, carabrodilactones A–E (1–5), along with four known common C15/C15 SLDs, carpedilactones A and B (6 and 7), faberidilactone A (8), and faberidilactone C (9), were isolated from the whole plants of Carpesium abrotanoides. The structures of 1–5 featured a flexible C-11/C-13′ linked single bond between two sesquiterpene units and a tailed acetyl connected to the C-13 position. The preferential conformation of 1–5 was elucidated by the diagnostic NMR data of geminal proton of H-13. The biogenetic pathway of 1–5 was proposed to involve Stetter and Michael addition reactions. In addition, compound 1 exhibited significant cytotoxicities against the four cell lines (A549, HCT116, MDA-MB, and BEL7404 cells) with IC50 value in the range of 3.08–8.05 μM, while compounds 2–5 showed weak cytotoxicities. more...

CRISPR (clustered regularly interspaced short palindromic repeats) systems have been established as valuable genome‐editing tools. Controlling CRISPR systems has high biological significance and this field has garnered intense interest. There is a considerable need for simple approaches with no need for protein engineering. The CRISPR systems usually require a guide RNA (gRNA) moiety to recruit and direct the nuclease complexes. In this respect, the ninhydrin (1,2,3‐indantrione monohydrate) seems to have considerable potential, as yet unexploited, for modifying gRNA. In this study, ninhydrin chemistry is explored for reversible postsynthetic modification of gRNA molecules. It is further shown that ninhydrin chemistry is efficient in modulating two important CRISPR systems. Thus, ninhydrin chemistry exhibits potential applications in future chemical biology studies., In this study, ninhydrin chemistry is explored for reversible modification of guide RNA molecules. It is further shown that ninhydrin chemistry is useful in modulating two important clustered regularly interspaced short palindromic repeats systems. Thus, ninhydrin chemistry exhibits potential applications in future chemical biology studies. more...

Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies. more...

Few studies have specifically focused on the effect of cabergoline on invasive giant prolactinomas (IGPs) resistant to bromocriptine. This study aims to evaluate whether cabergoline could be used as an effective therapy for patients with bromocriptine-resistant IGPs. This retrospective study included 15 patients with bromocriptine-resistant IGPs who received treatment at our department during 2007–2015. Cabergoline was administered in all 15 patients, with the dose adjusted depending on the prolactin response of each patient. Parameters for outcome assessment included prolactin level, pituitary function, tumor size, improvement of the clinical symptoms, visual field defects, drug tolerance, and disease recurrence. Cabergoline was effective for the treatment of the patients with bromocriptine -resistant IGPs as represented by normalization of the prolactin level in 12/15 patients; improvement or normalization of the pituitary function in 4/5 patients with hypopituitarism; significant reduction in tumor size in 14/15 patients; and relief of the clinical symptoms in 11/15 patients. All 15 patients showed good tolerance to cabergoline. In addition, no recurrence was observed during the mean follow-up period of 63.47 (range 30–145) months. Data of this retrospective study demonstrate that cabergoline is an excellent option for the treatment of patients with bromocriptine-resistant IGPs. more...

To assess treatment outcomes and associated factors of extremely preterm infants (EPIs) in GuangXi, China.This was a retrospective study consisting of 131 eligible cases with gestational age (GA) between 22 and 28 weeks, and infants were followed until 18-24 months. Data including clinical characteristics, perinatal factors and after-birth conditions were collected from the neonatal intensive care unit in 10 hospitals in Guangxi from January 1st 2010 until May 31st 2016.During that period, 307 EPIs were born in the hospitals. 137 infants died in hospital after their parents decided to withdraw clinical treatment, and 11 infants died despite full resuscitation was provided. Of the 159 surviving infants, 28 infants were lost to follow-up. In total, 131 infants who survived and were presented to follow-up at 18-24 months of age were enrolled into this study. Of the 131 infants evaluated at 18-24 months follow-up, 47 (35.9%) were diagnosed with neurodevelopmental disability (ND), and 84 (64%) demonstrated on tract motor and language skills. The incidence of chorioamnionitis, early onset sepsis (EOS), bronchopulmonary dysplasia (BPD) were all higher in the group of infants who were diagnosed with ND compared to those with normal motor language development (NML), the duration of mechanical ventilation (MV) was longer in ND group, and the higher incidence of ND was seen in the smaller GA babies (p 0.05). Adjusted the BPD severity, GA was a protective factor of neurodevelopmental outcome (combined OR = 0.338, 95% CI: 0.145-0.791). In EPIs with moderate BPD and severe BPD, chorioamnionitis was a risk factor of ND (OR = 10.313 and 5.778，respectively, 95% CI: 1.389-6.486 and 1.444-23.119, respectively). The Logistic regression analysis showed that GA (OR = 0.207, 95%CI = 0.047-0.917) was a protective factor for ND, and chorioamnionitis (OR = 6.010, 95%CI: 1.331-27.138), moderate-to-severe BPD (OR = 4.285, 95%CI: 1.495-12.287), the duration of MV (OR = 3.508, 95%CI: 2.077-5.926) were independent risk factors for ND in EPIs.Chorioamnionitis, moderate-to-severe BPD, and the duration of MV were associated with neurodevelopmental disability in EPIs. The smaller the GA, the higher incidence of neurodevelopmental disability. more...

Objective The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished. Methods Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis. Results A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3′ UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment. Conclusions Taken together, these results suggest a novel role for miR-27 in repressing adipogenic lineage commitment by targeting Lox. more...

A finite element model of tailiings dam was used to analyze the dynamic responses of the stress field, displacement and acceleration of the dam with the dynamic time-history response analysis method in this paper. The time-history curves of different responses were obtained. And an evaluation for dynamic stability of the tailings dam was also discussed. The analysis result shows that this case can provide a certain reference value for the dynamic calculation and the dynamic stability analysis of tailings dam under seismic load. more...

Obesity is associated with chronic low-level inflammation, especially in fat tissues, which contributes to insulin resistance and type 2 diabetes mellitus (T2DM). Protein inhibitor of activated STAT 1 (PIAS1) modulates a variety of cellular processes such as cell proliferation and DNA damage responses. Particularly, PIAS1 functions in the innate immune system and is a key regulator of the inflammation cascade. However, whether PIAS1 is involved in the regulation of insulin sensitivity remains unknown. Here, we demonstrated that PIAS1 expression in white adipose tissue (WAT) was downregulated by c-Jun N-terminal kinase in prediabetic mice models. Overexpression of PIAS1 in inguinal WAT of prediabetic mice significantly improved systemic insulin sensitivity, whereas knockdown of PIAS1 in wild-type mice led to insulin resistance. Mechanistically, PIAS1 inhibited the activation of stress-induced kinases and the expression of nuclear factor-κB target genes in adipocytes, mainly including proinflammatory and chemotactic factors. In doing so, PIAS1 inhibited macrophage infiltration in adipose tissue, thus suppressing amplification of the inflammation cascade, which in turn improved insulin sensitivity. These results were further verified in a fat transplantation model. Our findings shed light on the critical role of PIAS1 in controlling insulin sensitivity and suggest a therapeutic potential of PIAS1 in T2DM. more...

Commercial serological tests for the diagnosis of tuberculosis (TB) show poor sensitivity and specificity, and a new approach to antigen screening is required to improve the accuracy of serodiagnosis.Using an indirect enzyme-linked immunosorbent assay (ELISA), we evaluated the responses of IgG and IgM antibodies to the recombinant PstS1-LEP protein expressed in Escherichia coli, a polyprotein of PstS1 and line multi-epitopes polypeptide (LEP).The mixture of anti-human IgG and IgM added to a well [Ig(G + M)], which was different from the combination of IgG and IgM (IgG + IgM), had a stronger immunoreactivity to PstS1-LEP than the single antibody. IgG and Ig(G + M), but not IgM against the PstS1-LEP protein effectively distinguished TB patients from patients with nontuberculous pulmonary disease (NTBPD) and healthy controls (HCs). Compared with IgG, the sensitivities of Ig(G + M) and IgG + IgM varied from 71.4% to 77.6% and 72.7% in pulmonary TB (PTB) patients and from 42.1% to 64.0% and 55.8% in extrapulmonary TB (EPTB) patients, respectively. The specificity of Ig(G + M) did not decrease, and was higher than that provided by IgG + IgM in HCs with positive tuberculin skin test.These findings suggest that PstS1-LEP can act as a candidate for detecting Ig(G + M) in serum from PTB and EPTB patients. more...

To investigate the ability of carbon nanoparticles (CNs) to identify lymph nodes and protect parathyroid glands during thyroid cancer surgery.English and Chinese literature in PubMed, ClinicalTrials.gov, EMBASE, the Cochrane Database of Systematic Reviews, the China Biology Medicine Database, the China Master's and Doctoral Theses Full-Text Database, the China National Knowledge Infrastructure, the WANFANG database, and the Cqvip database (from January 2009 to July 2014).Studies were included if they were randomized controlled trials or nonrandomized controlled trials for thyroidectomy and central neck dissections that compared the use of CNs with methylene blue or a blank control in patients undergoing initial thyroid cancer surgery. The primary outcomes were the number of retrieved central lymph nodes and the accidental parathyroid removal rate.This meta-analysis identified 11 randomized controlled trials and 4 nonrandomized controlled trials comprising 1055 patients. Compared with the outcomes of the blank controls, the use of CNs resulted in an average of 2.71 more lymph nodes removed per patient (weighted mean difference = 2.71, 95% confidence interval [CI] = 1.68-3.74, P.001), a 23% lower rate of accidental parathyroid removal (odds ratio = 0.23, 95% CI = 0.10-0.54, P = .0008), and similarly reduced rates of transient hypoparathyroidism and hypocalcemia. Compared with methylene blue, the use of CNs resulted in an average of 1.50 more lymph nodes removed per patient (weighted mean difference = 1.50, 95% CI = 0.11-2.89, P = .03) and a 5% reduction in the rate of accidental parathyroid removal (odds ratio = 0.05, 95% CI = 0.01-0.29, P = .0007).CNs partially improve the extent and accuracy of neck dissection and preserve the normal anatomic structure and physiologic function of the parathyroid glands during thyroid cancer surgery. more...

Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4‐induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up‐regulates BMP4‐induced expression of CCAAT/enhancer binding protein (C/EBP) homologous protein 10 (CHOP‐10), which then promotes BMP4‐induced osteogenesis of MSCs both in vitro and in vivo. Specifically, Lox inhibition or CHOP‐10 up‐regulation activated Wnt/β‐catenin signalling to enhance BMP4‐induced osteogenesis, with pro‐adipogenic p38 MAPK and Smad signalling suppressed. Together, we demonstrate that Lox/CHOP‐10 crosstalk regulates BMP4‐induced osteogenic and adipogenic fate determination of MSCs, presenting a promising therapeutic target for osteoporosis and other bone diseases. more...

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development. more...