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Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Abstract Background Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. Methods A tumour necrosis factor (TNF)‐α‐induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)‐treated 8‐week‐old model mice and 23‐month‐old (aged) mice were used to examine the therapeutic effects of handelin on cachexia‐ and aging‐induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. Results Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P

Continuous dynamic recrystallization (CDRX) is widely acknowledged to occur during hot forming and plays a significant role in microstructure development in alloys with moderate to high stacking fault energy. In this work, the flow stress and CDRX behaviors of the TC18 alloy subjected to hot deformation across a wide range of processing conditions are studied. It is observed that deformation leads to the formation of new low-angle grain boundaries (LAGBs). Subgrains rotate by absorbing dislocations, resulting in an increase in LAGB misorientation and the transition of some LAGBs into high-angle grain boundaries (HAGBs). The HAGBs migrate within the material, assimilating the (sub)grain boundaries. Subsequently, an internal state variable (ISV)-based CDRX model is developed, incorporating parameters such as the dislocation density, adiabatic temperature rise, subgrain rotation, LAGB area, HAGB area, and LAGB misorientation angle distribution. The values of the correlation coefficient (R), relative average absolute error (RAAE), and root-mean-square error (RMSE) between the anticipated true stress and measured stress are 0.989, 6.69%, and 4.78 MPa, respectively. The predicted outcomes demonstrate good agreement with experimental findings. The evolving trends of the subgrain boundary area under various conditions are quantitatively analyzed by assessing the changes in dynamic recovery (DRV)-eliminated dislocations and misorientation angles. Moreover, the ISV-based model accurately predicts the decreases in grain and crystallite sizes with higher strain rates and lower temperatures. The projected outcomes also indicate a transition from a stable and coarse-grained microstructure to a continuously recrystallized substructure.

Metabolic intermediates serve as precursors for bioactive molecule synthesis, the energy source for life activities, and signals for environmental adaptation. Ketone bodies are important metabolic intermediates produced in the liver by the degradation of fatty acids, acting as an alternative energy source for extrahepatic tissues when glucose is short in supply (especially during starvation). β-hydroxybutyric acid, with its conjugate base β-hydroxybutyrate, constitutes approximately 70% of ketone bodies. A growing number of studies have demonstrated the beneficial effects of β-hydroxybutyrate, especially in delaying aging, intervening in aging-related disease, and promoting longevity. This review systematically reviews the role of β-hydroxybutyrate in aging hallmarks, shedding light on the possible molecular mechanism by which β-hydroxybutyrate supports healthy aging. Higher circulating β-hydroxybutyrate can be achieved by lifestyle modification (ketogenic diet or caloric restriction) or exogenous β-hydroxybutyrate (or β-hydroxybutyrate precursors, derivates and agonists) supplementation. We will also discuss the pros and cons of different ways to upregulate β-hydroxybutyrate, emphasizing the promising future clinical use of poly-β-hydroxybutyrate, the polymers of β-hydroxybutyrate, which can be easily produced via a microbial platform and synthetic biology.

Whether promoting cash crop production can increase household welfare has long been the focus of the food policy debate. This study first investigated the determinants of household behavior in commercial pulse farming. It then examined how households’ commercial pulse production improves their economic welfare. We used a dataset of 848 households collected from 2018 to 2019 to estimate the determinants of household behavior in commercial pulse farming by the Heckman two-step model. The endogenous treatment regression (ETR) method was employed to examine the impact of commercial pulse farming on household economic welfare. The results showed that factors such as market purchase prices, agricultural technology services, farmers’ access to loans, and government subsidies promoted smallholders’ commercial pulse farming; production costs and perceptions of climate change risks constrained smallholders’ commercial pulse production. Overall, commercial pulse production has increased household farm income but there was a limited impact on household off-farm income. Our findings suggest that policies aiming to increase households’ cash crop production and market access could significantly improve the economic welfare of pulse farmers.

Two oxidovanadium(V) complexes, [VOLLa] (1) and [VOLLb] (2), where L is the dianionic form of the Schiff base ligand 2-(((2-hydroxyethyl)imino)methyl)-6-methylphenol (H2L), La and Lb are the deprotonated forms of 3-hydroxy-2-methyl-4H-pyran-4-one (HLa) and 2-ethyl-3-hydroxy-4H-pyran-4-one (HLb), respectively, have been prepared and characterized by elemental analyses, IR, UV−Vis, 1H NMR and single−crystal X−ray crystallographic determination. The V atoms in the complexes are in octahedral coordination, with the Schiff base ligand mer-coordinated to the metal atoms through the phenolate O, imino N and hydroxyl O atoms, and with the pyrone ligands coordinated to the metal atoms through the two O atoms. The effect of the compounds on the antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans was studied.

A new mononuclear dioxomolybdenum(VI) complex, [MoO2L1], and a new linear trinuclear nickel(II) complex, [Ni{NiL2(μ1-η1:η0-OAc)(μ2-η1:η1-OAc)}2]·H2O, where L1 is the dianionic form of N,N’-bis(5-fluorosalicylidene)-1,3-propanediamine (H2L1), L2 is the dianionic form of N,N’-bis(5-fluoro-2-hydroxybenzylidene)-2-hydroxy-1,3-propanediamine (H2L2), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray determination. The Mo atom in the molybdenum complex is coordinated by four donor atoms of the Schiff base ligand, and two oxo groups, forming an octahedral coordination. In the nickel complex, there are three bridges across the Ni-Ni atom pairs, involving two phenolate O atoms of a Schiff base ligand, and an O–C–O moiety of a μ2-η1:η1-OAc group. The central Ni atom is located on an inversion center and has octahedral coordination involving four bridging O atoms from two Schiff base ligands in the equatorial plane and two O atoms from two μ2-η1:η1-OAc ligands in the axial positions. The coordination around the terminal Ni atoms is also octahedral, with two imino N and two phenolate O atoms from a Schiff base ligand defining the equatorial plane, and with two O atoms respectively from a μ1-η1:η0-OAc and a μ2-η1:η1-OAc ligands occupying the axial positions. The molybdenum complex has excellent catalytic property for sulfoxidation reactions.

Two mononuclear zinc(II) and manganese(II) compounds, [ZnL2] (1) and [MnL(HL)]ClO4 (2), where L is the monoanionic form of N’-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL), and HL is the zwitterionic form of HL, have been prepared and characterized by elemental analyses, IR and UV-Vis spectroscopy, and single-crystal X-ray crystallographic determination. Compound 1 contains a neutral [ZnL2] complex molecule. Compound 2 contains a [MnL(HL)]+ complex cation and one perchlorate anion. The metal atoms in the complexes are in octahedral coordination. The hydrazone ligands coordinate to the metal atoms through the pyridine N, imine N, and enolate O atoms. The compounds were investigated for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans.

Objective(s): Tanshinone IIA (T. IIA), one of the most pharmacologically active components extracted from Salviae miltiorrhiza, has anti-inflammatory and antioxidant features. The aim of the present study is to investigate the benefit of T. IIA on asthma using a murine model of asthma induced by ovalbumin (OVA). Materials and Methods: Male BALB/c mice were used in the present study. The mice were sensitized by OVA intraperitoneal injection on days 0 and 14, and received aerosolized OVA challenge for 30 min daily on days 21-23Results: T. T. IIA (10 mg/kg twice daily) intraperitoneal injection was performed on days 18-23. Results: Treatment of T. IIA reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF) (PConclusion: T. IIA inhibits OVA-induced airway inflammation and hyperresponsiveness. T. IIA is a potential therapeutic agent for asthma.

In clinical practice, the important hygienic prevention of bacterial pathogen spread is disinfection of potentially contaminated area. Benzalkonium bromide and chlorhexidine acetate are commonly used disinfectants with a broad spectrum of anti-microbial effect. It is vital to inhibit the spread of pathogen in hospital. However, a large number of pathogens with the decreased antiseptic susceptibility have been isolated from clinical samples which showed an increased minimal inhibitory concentration (MIC) against those antiseptics. These resistant pathogens are the major causes for nosocomial cross-infections in hospital. The present study demonstrated the utility of Oxford plate assay system in determining the potential disinfectant resistance of bacteria. The microbiological assay is based on the inhibitory effect of tested disinfectants upon the strains of Staphylococcus aureus and Escherichia coli. Statistical analysis of the bioassay results indicated the linear correlation (r = 0.87–0.99, P

Abstract Based on the Padé approximation method, in this paper we determine the coefficients a j $a_{j}$ and b j $b_{j}$ ( 1 ≤ j ≤ k $1\leq j \leq k$ ) such that 1 e ( 1 + 1 x ) x = x k + a 1 x k − 1 + ⋯ + a k x k + b 1 x k − 1 + ⋯ + b k + O ( 1 x 2 k + 1 ) , x → ∞ , $$ \frac{1}{e} \biggl( 1+\frac{1}{x} \biggr) ^{x}= \frac{x^{k}+a_{1}x^{k-1}+ \cdots +a_{k}}{x^{k}+b_{1}x^{k-1}+\cdots +b_{k}}+O \biggl( \frac{1}{x ^{2k+1}} \biggr) , \quad x\to \infty , $$ where k ≥ 1 $k\geq 1$ is any given integer. Based on the obtained result, we establish new upper bounds for ( 1 + 1 / x ) x $( 1+1/x ) ^{x}$ . As an application, we give a generalized Carleman-type inequality.

Abstract Although many pharmaceutical proteins are produced in mammalian cells, there remains a challenge to select cell lines that express recombinant proteins with high productivity. Since most biopharmaceutical proteins are secreted by cells into the medium, it is difficult to select cell lines that produce large amounts of the target protein. To address this issue, a new protein expression system using the glycosylphosphatidylinositol (GPI)-anchor was developed. PGAP2 is involved in processing GPI-anchored proteins (GPI-APs) during transport. In PGAP2 mutant cells, most GPI-APs are secreted into the medium. Here, we established a HEK293 cell line where endogenous PGAP2 was knocked out and exogenous PGAP2 was inserted with a piggyBac transposon in the genome. Using these cells, human lysosomal acid lipase (LIPA) and α-galactosidase A (GLA) were expressed as GPI-anchored forms (LIPA-GPI and GLA-GPI) and cells expressing high levels of LIPA-GPI or GLA-GPI on the cell surface were enriched. Removal of the PGAP2 gene by piggyBac transposase or FLP recombinase converted LIPA-GPI and GLA-GPI from membrane-bound to the secreted forms. Thus, cells expressing LIPA or GLA in large amounts could be enriched using this approach. The GPI-based molecular switching system is an efficient approach to isolate cells expressing recombinant proteins with high productivity.

Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol.

Metabolic intermediates serve as precursors for bioactive molecule synthesis, the energy source for life activities, and signals for environmental adaptation. Ketone bodies are important metabolic intermediates produced in the liver by the degradation of fatty acids, acting as an alternative energy source for extrahepatic tissues when glucose is short in supply (especially during starvation). ß-hydroxybutyric acid, with its conjugate base ß-hydroxybutyrate, constitutes approximately 70% of ketone bodies. A growing number of studies have demonstrated the beneficial effects of ß-hydroxybutyrate, especially in delaying aging, intervening in aging-related disease, and promoting longevity. This review systematically reviews the role of ß-hydroxybutyrate in aging hallmarks, shedding light on the possible molecular mechanism by which ß-hydroxybutyrate supports healthy aging. Higher circulating ß-hydroxybutyrate can be achieved by lifestyle modification (ketogenic diet or caloric restriction) or exogenous ß-hydroxybutyrate (or ß-hydroxybutyrate precursors, derivates and agonists) supplementation. We will also discuss the pros and cons of different ways to upregulate ß-hydroxybutyrate, emphasizing the promising future clinical use of poly-ß-hydroxybutyrate, the polymers of ß-hydroxybutyrate, which can be easily produced via a microbial platform and synthetic biology. [ABSTRACT FROM AUTHOR]

The aim of this study is to reveal the potential value of dynamin3 (DNM3) in colorectal cancer (CRC) evaluation of clinical diagnosis and prognosis. A total of 100 tissue samples were collected from 50 patients with stages I–IV, CRC tissues (n = 50) paired with non-cancerous adjacent colorectal tissues (n = 50). The expression levels of DNM3 were detected in 50 cases of CRC tissues and 50 cases of non-cancerous adjacent colorectal tissues by real-time fluorescent quantitative reverse transcriptionpolymerase chain reaction (RT-PCR). Immunohistochemical method (IHC) was conducted to semi-quantify the expression of DNM3 protein. Results showed that the relative expression of DNM3 mRNA in CRC tissues was 0.634-fold of that in non-cancerous adjacent colorectal tissues. The positive rate of DNM3 protein in CRC tissues (42.0%) was much lower than that in non-cancerous adjacent colorectal tissues (66.0%; P < 0.05). The expression level of DNM3 protein in CRC tissues was dependent on tumor size, degree of histological differentiation, and clinical stage (P < 0.05). The expression level of DNM3 mRNA in CRC tissues was significantly correlated with tumor size and pathology classification (P < 0.05). The research shows that detecting the expression of DNM3 helps in analyzing the tumor size, degree of histological differentiation, and clinical stage. Expression of DNM3 may be associated with good outcome in CRC. [ABSTRACT FROM AUTHOR]

This study aimed to reveal the differences in intestinal microbes in osteoporotic rats. The rats were divided into two groups: the control and OP (osteoporosis) groups (n=6). Days 0 and 70 were set as the time points. The rats in the OP group underwent bilateral ovariectomy (OVX). Differences between the control and OP groups were determined by 16S rDNA analysis. The relative abundances of OTUs and alpha/beta diversities were determined at days 0 days and 70. The abundances of Verrucomicrobia at the phylum level and Aerococcus, Coprobacillus, Veillonella, Anaerobiospirillum, Flavobacterium, Comamonadaceae, Ohtaekwangia, etc., at the genus level were found to be different between the control_70d and OP_70d groups. KEGG ontology analysis showed that the function of lipid metabolism could be related to OP. The 16S rDNA analysis in the OP rats revealed that intestinal microbes take part in the processes of OP and could affect lipid metabolism. Further study of the relationship between OP and intestinal microbes is necessary, and the prospect for intestinal microbes is a potential treatment for OP. [ABSTRACT FROM AUTHOR]

The hematopoietic microenvironment regulates self-renewal and differentiation of hematopoietic stem cells. Mesenchymal stromal cells (MSCs) contribute to the niche and participate in supporting dendritic cell (DC) commitment in vitro and in vivo. However, due to MSCs being heterogenic, it is necessary to understand the function of the MSC subpopulation in modulating the DC commitment. The current study showed that one of the bone-related Sca1+ MSCs enhanced bone marrow cell differentiation into DCs by direct cell-to-cell contact. Furthermore, the expression of STAT3 and STAT5 genes decreased in supernatant cells after Sca1+ MSCs were cocultured with bone marrow cells. In contrast, the expression level of caspase-3 in cells increased. At the same time, the presentation of costimulatory molecules CD80/CD86 and the migration of activated DCs towards lymph nodes were augmented by Sca1+ MSCs. The results demonstrated that the Sca1+ MSC subpopulation promotes the differentiation of bone marrow cells into DCs by direct cell-to-cell contact via STAT3/STAT5 and caspase-3 signaling. Meanwhile, Sca1+ MSCs also mediate the activation and migration capabilities of DCs. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) have been characterized as an important component of the hematopoietic niche that plays a role in regulating hematopoietic stem cell (HSC) quiescence, self-renewal, and lineage commitment. Macrophages, one kind of innate immune cells, are mainly developed from HSCs in niche. However, how MSCs and their subpopulations regulate macrophage commitment is still unknown. The current study compared the contribution of MSCs and Sca-1+MSCs to macrophage commitment and further modulation on the function of macrophages. We found that Sca-1+MSCs could promote macrophage commitment through the M-CSFR gene, and Sca-1+MSCs led macrophage polarization towards the M2 phenotype. Further functional studies indicated that Sca- 1+MSCs could remarkably promote the phagocytosis capability of macrophages instead of their antigen-presentation ability. These data demonstrated that Sca-1+MSCs could regulate the commitment and function of macrophages from hematopoietic progenitors, which provided new evidence for elucidating the role of MSC subpopulations in hematopoiesis. [ABSTRACT FROM AUTHOR]

The pathogenesis of atherosclerosis is multi factorial. The proliferation and migration of vascular smooth muscle cells (VSMCs) are significant in the genesis and development of atherosclerosis plaques, and the degradation of VSMCs plays a crucial role in the process. Mimecan is a member of the Keratan sulfate family of proteoglycans, which are leucine-rich proteoglycans. It has been demonstrated that mimecan is associated with arteriogenesis and atherosclerosis. In the present study, the effect of mimecan on the characteristics of cultured human aortic smooth muscle cells (HASMCs) was investigated. In vitro, human mimecan was stably overexpressed in HASMCs using a lentiviral system. It was observed that the proliferation rate of HASMCs transduced with mimecan was lower compared with that of control cells; overexpression of mimecan induced HASMC apoptosis. To determine the effect of mimecan on HASMC migration, a Transwell cell culture chamber and sterile cloning cylinder assays were used, and it was noted that mimecan enhanced the migration of HASMCs horizontally and vertically. These data indicated that mimecan may be involved in the pathogenesis of atherosclerosis by regulating the proliferation, apoptosis and migration of VSMCs. [ABSTRACT FROM AUTHOR]

Obesity is related to hyperlipidemia and risk of cardiovascular disease. Health benefits of vegetarian diets have well-documented in the Western countries where both obesity and hyperlipidemia were prevalent. We studied the association between BMI and various lipid/lipoprotein measures, as well as between BMI and predicted coronary heart disease probability in lean, low risk populations in Southern China. The study included 170 Buddhist monks (vegetarians) and 126 omnivore men. Interaction between BMI and vegetarian status was tested in the multivariable regression analysis adjusting for age, education, smoking, alcohol drinking, and physical activity. Compared with omnivores, vegetarians had significantly lower mean BMI, blood pressures, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol to high density lipoprotein ratio, triglycerides, apolipoprotein B and A-I, as well as lower predicted probability of coronary heart disease. Higher BMI was associated with unfavorable lipid!lipoprotein profile and predicted probability of coronary heart disease in both vegetarians and onmivores. However, the associations were significantly diminished in Buddhist vegetarians. Conclusions: Vegetarian diets not only lower BMI, but also attenuate the BMI-related increases of atherogenic lipid/lipoprotein and the probability of coronary heart disease. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM) on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs) from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice) obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time. [ABSTRACT FROM AUTHOR]

Classical congenital adrenal hyperplasia (CAH) is characterized by the defects in cortisol and aldosterone secretion, and accompanied with adrenal hyperandrogenism. It is likely that the impaired adrenocortical function and intermittent treatment-related hypercortisolism may predispose patients to the development of metabolic syndrome in adulthood. Our aim was to assess the impact of hyperandrogenism on metabolic profiles in CAH women without glucocorticosteroid treatment. We evaluated the clinical characteristics and metabolic profiles in 30 untreated Chinese female adults with simple virilizing congenital adrenal hyperplasia (SV-CAH). Mutation analysis was performed by sequencing the entire 21-hydroxylase gene ( CYP21A2). As compared with the controls, CAH patients had higher BMI (BMI, 21.5 ± 2.1 vs. 20.0 ± 1.8 kg/m, P < 0.05), higher 2 h post-load plasma glucose levels (6. 35 ± 1.74 vs. 5. 35 ± 1.17 mmol/l, P < 0.05), higher serum triglycerides (TG) (1.12 ± 0.64 vs. 0.63 ± 0.15 mmol/l, P < 0.01), and lower high-density lipoprotein cholesterol (HDL-c) (1.30 ± 0.39 vs. 1.67 ± 0.29 mmol/l, P < 0.01). Moreover, CAH patients had higher fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (1.81 ± 0.99 vs. 1.24 ± 0.50, P < 0.05), while ΔIns30/ΔGlu30 showed no statistically significant difference in two groups. In addition, a marked reduction of serum adiponectin levels were observed in CAH patients (7.0 ± 3.3 vs. 13.2 ± 4.8 μg/ml, P < 0.001), however, serum CRP levels were not different between patients and the controls. Further regression analysis showed that higher serum testosterone concentrations were associated with metabolic disorder indexes and reduction of serum adiponectin. Our study demonstrates that untreated CAH patients are prone to have metabolic disorders in association with elevated serum testosterone levels and reduced insulin insensitivity. [ABSTRACT FROM AUTHOR]

The epididymis and efferent ducts play major roles in sperm maturation, transport, concentration and storage by reabsorbing water, ions and proteins produced from seminiferous tubules. Gpr48-null male mice demonstrate reproductive tract defects and infertility. In the present study, we found that estrogen receptor α (ERα) was dramatically reduced in the epididymis and efferent ducts in Gpr48-null male mice. We further revealed that ER? could be upregulated by Gpr48 activation via the cAMP/PKA signaling pathway. Moreover, we identified a cAMP responsive element (Cre) motif located at -1307 to -1300 bp in the ERα promoter that is able to interact with Cre binding protein (Creb). In conclusion, Gpr48 participates in the development of the male epididymis and efferent ducts through regulation of ERα expression via the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract  Wolfram syndrome (WFS), also known as DIDMOAD, is an infrequent cause of diabetes mellitus. WFS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders, and gonadal disorders. The majority of patients with WFS carry the loss of function mutations in the WFS1 gene. The exons 2–8 of the WFS1 gene from one Chinese WFS patient were amplified by the polymerase chain reaction (PCR), subcloning techniques and direct sequence determination was applied to the amplified fragments. The compound heterozygous mutation of a 3-bp (GAC) deletion (V434del) and another compound heterozygous mutation (G→N)(W666X) in exon 8 of WFS1 gene was identified in the patient. Other seventeen members of her family were investigated. Four cases with heterozygotes had been found through screening for the mutation V434del and five cases for the mutation W666X in the whole family. This is the first report of WFS with the mutation V434del and W666X in the WFS1 gene. [ABSTRACT FROM AUTHOR]

Objective The variations in the transcriptional regulatory regions of CYP21A2 were rarely investigated in patients with 21-hydroxylase deficiency (21-OHD). The present study aims to verify that the variations in the promoter of CYP21A2 relate to the classical form of 21OHD. Patients and methods CYP21A2 was screened for mutations in 20 patients with the simple virilizing form of 21OHD, including the promoter region. The transcriptional activities of the variants in the promoter were investigated using a dual-reporter luciferase assay system and electromobility gel shift assays. Results The heterozygous variants –447 A > G, –443InsA, –306G > C, –295T > C, –294 A > C, –283 A > G, –281T > G, –210T > C, –199C > T, –196 A > T, –126C > T, –113G > A, –110T > C, –103 A > G and –4C > T in the promoter of CYP21A2 gene were identified in a patient with simple virilizing form of 21OHD. The transcriptional activities of the promoter with the variants were reduced to 50% of the wild type. Conclusion We speculated that the 15 variants in the promoter of CYP21A2 combined with a compound heterozygous mutation Q318X lead to a simple virilizing form of 21OHD. [ABSTRACT FROM AUTHOR]

Background: Chemosensory systems play key roles in the survival and reproductive success of insects. Insect chemoreception is mediated by two large and diverse gene superfamilies, chemoreceptors and odorant binding proteins (OBPs). OBPs are believed to transport hydrophobic odorants from the environment to the olfactory receptors. Results: We identified a family of OBP-like genes in the silkworm genome and characterized their expression using oligonucleotide microarrays. A total of forty-four OBP genes were annotated, a number comparable to the 57 OBPs known from Anopheles gambiae and 51 from Drosophila melanogaster. As seen in other fully sequenced insect genomes, most silkworm OBP genes are present in large clusters. We defined six subfamilies of OBPs, each of which shows lineage-specific expansion and diversification. EST data and OBP expression profiles from multiple larvae tissues of day three fifth instars demonstrated that many OBPs are expressed in chemosensory-specific tissues although some OBPs are expressed ubiquitously and others exclusively in non-chemosensory tissues. Some atypical OBPs are expressed throughout development. These results reveal that, although many OBPs are chemosensory-specific, others may have more general physiological roles. Conclusion: Silkworms possess a number of OBPs genes similar to other insects. Their expression profiles suggest that many OBPs may be involved in olfaction and gustation as well as general carriers of hydrophobic molecules. The expansion of OBP gene subfamilies and sequence divergence indicate that the silkworm OBP family acquired functional diversity concurrently with functional constraints. Further investigation of the OBPs of the silkworm could give insights in the roles of OBPs in chemoreception. [ABSTRACT FROM AUTHOR]

Abstract  Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats. In parallel, Western blotting and RT-PCR showed a similar reduction of GSTM2 in left ventricles and aortas of 4-, 8-, and 16-week-old SHR, which is before the onset of hypertension. This suggests that differential expression is not attributable to long-term changes in blood pressure. Meanwhile, the activities of GSTM2 were significantly decreased in different ages old SHR. Conversely, there was an enhanced generation of superoxide anion and activation of NADPH oxidase in SHR, which was accompanied by an increase in the protein expression of p47phox, a subunit of NADPH oxidase. These data suggest that it maybe a reduction in antioxidant defenses, evident by a reduced expression and activity of GSTM2, in the left ventricles and aortas of SHR that leads to increased levels of superoxide anion and activation of NADPH oxidase. [ABSTRACT FROM AUTHOR]

Abstract  Hereditary fructose intolerance (HFI) is an inheritable disorder of fructose metabolism, inherited as an autosomal recessive disorder and caused by catalytic deficiency of aldolase B, which is critical for gluconeogenesis and fructose metabolism. The affected individuals develop severe hypoglycemia after taking foods containing fructose and cognate sugars. The exons 2–9 of the aldolase B (gene symbol ALDOB) gene from one Chinese HFI patient were amplified by the polymerase chain reaction (PCR), and direct sequence determination was applied to the amplified fragments. The mutation of a 4-bp (AACA) deletion (479_482 del) in exon 4 of ALDOB gene was identified in the patient, which had been reported to cause a frameshift at codon 118 and a truncated protein of 132 amino acids in the previous study. Then, the second case with the same homozygote deletion and eight cases with heterozygotes had been found through screening for the mutation c.479_482 del AACA in the whole family. This is the first report of HFI with the mutation c.479_482 del AACA in the ALDOB gene in a Chinese family. [ABSTRACT FROM AUTHOR]

In a test of the weak equivalence principle (WEP) with a rotating torsion pendulum, it is important to estimate the amplitude of the modulation signal with high precision. We use a torsional filter to remove the free oscillation signal and employ the correlation method to estimate the amplitude of the modulation signal. The data analysis of an experiment shows that the uncertainties of amplitude components of the modulation signal obtained by the correlation method are in agreement with those due to white noise. The power spectral density of the modulation signal obtained by the correlation method is about one order higher than the thermal noise limit. It indicates that the correlation method is an effective way to estimate the amplitude of the modulation signal and it is instructive to conduct a high-accuracy WEP test. [ABSTRACT FROM AUTHOR]

The first-principles methods have been employed to calculate the structural, electronic, and mechanical properties of the α, β, and γ phases of uranium under pressure up to 100 GPa. The electronic structure has been viewed in forms of density of states and band structure. The mechanical stability of metal U in the α, β, and γ phases have been examined. The independent elastic constants, polycrystalline elastic moduli, as well as Poisson’s ratio have been obtained. Upon compression, the elastic constants, elastic moduli, elastic wave velocities, and Debye temperature of α phase are enhanced pronouncedly. The value of B/G illustrates that α and γ phases are brittle in ground state. [ABSTRACT FROM AUTHOR]

Hydrogels as semi-solid materials with highly tunable mechanical properties are promising materials in numerous fields. The emergence of self-healing hydrogels, with the ability to recover their original structure post-fracture, has further expanded their applications in flexible devices, wound healing, and implant materials. Biopolymers have the advantages of biocompatibility, biodegradability, and environmental sustainability, making the self-healing hydrogels from biopolymers more promising materials in biomedical applications. In this paper, we started from the dynamic bonds that used to realize the self-healing properties of biopolymer-based hydrogels, and discussed their advantages and disadvantages. The construction mechanisms, self-healing properties of the hydrogels from different biopolymers were then introduced separately. We also reviewed the their potential applications, and discussed their challenges and prospects.

Polygoni Multiflori Radix (PMR) is increasingly being used not just as a traditional herbal medicine but also as a popular functional food. In this study, multivariate chemometric methods and mass spectrometry were combined to analyze the ultra-high-performance liquid chromatograph (UPLC) fingerprints of PMR from six different geographical origins. A chemometric strategy based on multivariate curve resolution-alternating least squares (MCR-ALS) and three classification methods is proposed to analyze the UPLC fingerprints obtained. Common chromatographic problems, including the background contribution, baseline contribution, and peak overlap, were handled by the established MCR-ALS model. A total of 22 components were resolved. Moreover, relative species concentrations were obtained from the MCR-ALS model, which was used for multivariate classification analysis. Principal component analysis (PCA) and Ward's method have been applied to classify 72 PMR samples from six different geographical regions. The PCA score plot showed that the PMR samples fell into four clusters, which related to the geographical location and climate of the source areas. The results were then corroborated by Ward's method. In addition, according to the variance-weighted distance between cluster centers obtained from Ward's method, five components were identified as the most significant variables (chemical markers) for cluster discrimination. A counter-propagation artificial neural network has been applied to confirm and predict the effects of chemical markers on different samples. Finally, the five chemical markers were identified by UPLC-quadrupole time-of-flight mass spectrometer. Components 3, 12, 16, 18, and 19 were identified as 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside, emodin-8-O-β-D-glucopyranoside, emodin-8-O-(6'-O-acetyl)-β-D-glucopyranoside, emodin, and physcion, respectively. In conclusion, the proposed method can be applied for the comprehensive analysis of natural samples. [ABSTRACT FROM AUTHOR]

Abstract Hydrogels for electronic applications require stretchability, high electrical conductivity, and high mechanical strength. A mechanically robust ionic conductive gelatin hydrogel is constructed by a simple soaking–heating process in an ammonium sulfate solution. Due to the combined effect of the salt‐out effect and heating, a gelatin hydrogel with large chain‐dense and ion‐rich regions is successfully constructed. This gel exhibits high ionic conductivity and high mechanical strength.