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Real estate in the Guangdong-Hong Kong-Macao Greater Bay Area (also known as the Greater Bay Area, GBA) - a good representation of China's advanced and developed urban agglomeration - has received considerable attention from the international community in recent years. However, the real estate market has been under extraordinary stress due to the expansion of COVID-19 in China, the strain on people's livelihoods brought on by the coronavirus pandemic, and the Chinese government's series of epidemic preventive initiatives. This study used a combination of qualitative and quantitative techniques, making use of interviews and questionnaires as instruments. It examined China's GBA real estate market as the pandemic looms. The primary goals are to demonstrate the current state of the GBA's real estate industry, pinpoint the factors holding back its growth, and estimate when the market might finally experience a breakthrough. Our findings suggested that the impact of COVID-19 on the GBA real estate sector in China is evident, but that it still has a bright future despite the negative externalities. This is because the city has a large population, high purchasing power, and is close to some of the most developed areas in southern China. This study establishes a baseline for studying the impact of China's "One Belt, One Road" initiative on the GBA real estate market in the future. It also provides valuable resources for China's GBA's real estate industry. [ABSTRACT FROM AUTHOR]

Objective: To summarize the effect of adding Lactobacillus reuteri in the treatment plan for diarrheal disease in children, and analyze the potential of probiotics in preventing the occurrence of diarrheal disease. Methods: Search for randomized controlled trials of Lactobacillus reuteri for the treatment and prevention of diarrhea in the Pubmed, Web of science, Medline, and Cochrane databases. Data such as the number of diarrhea patients, time, length of stay, clinical symptoms and effect of diarrhea prevention were extracted for meta-analysis. Relative risk and confidence interval (RR and 95% CI) were used as outcome indicators. Results: 963 participants in the 9 RCTs came from multiple countries/regions. Compared with placebo/no intervention, the number of diarrhea patients in the Lactobacillus reuteri group was significantly reduced on the day 1 (RR = 0.87, 95%CI: 0.78–0.97) and day 2 (RR = 0.61, 95%CI: 0.44–0.83). Cumulative statistics analysis showed that the effect was stable and significant starting on the 4th day after treatment. A few studies have shown that Lactobacillus reuteri can reduce the time of diarrhea, the number of days with watery stools, and days of hospital stay. However, it has no effect on the occurrence of nosocomial diarrhea (RR = 1.11, 95%CI: 0.68–1.83), rotavirus diarrhea (RR = 1.46, 95%CI: 0.78–2.72), antibiotic-related diarrhea (RR = 1.76, 95%CI: 0.77–4.05), and diarrhea (RR = 1.35, 95%CI: 0.95–1.92). Conclusion: Addition of Lactobacillus reuteri in the treatment plan has a significant effect on reducing the number of diarrhea and reducing the symptoms of diarrhea, but has no obvious effect on the prevention of diarrhea. Combining probiotics and improving the ability of probiotics to respond is the focus of attention. [ABSTRACT FROM AUTHOR]

Microglia-involved neuroinflammation in the central nervous system (CNS) has been shown to aggravate brain damage and is associated with the pathogenesis of various neurodegenerative diseases. Thus, suppression of microglial activity has the potential to be a strategy for the treatment of neurodegenerative diseases. Pinitol, a methylated product of d-chiro-inositol, has been used as a treatment for blood-sugar metabolism and as an anti-tumor agent via its anti-inflammatory effects in cancer. However, whether or not pinitol can inhibit microglia-associated neuroinflammation is still unknown. This study aims to determine the effects of pinitol on inflammatory responses in BV2 microglia induced by LPS. Here, we found that the presence of pinitol ameliorates LPS-induced oxidative stress by reducing the production of ROS. Pinitol suppresses the expression and secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Notably, pinitol prevents the production of NO and PGE2 by inhibiting the expression of iNOS and COX-2. Mechanistically, our findings demonstrate that pinitol inhibits the phosphorylation and degradation of IκBα and subsequent activation of NF-κB. Furthermore, we show that pinitol increases the expression of TREM2 in BV2 microglia, and silencing of TREM2 abolished the anti-inflammatory effects of pinitol. These findings suggest that TREM2 mediates the protective effects of pinitol against LPS in microglia. In summary, our results display that pinitol possesses a robust and beneficial effect against the LPS-induced inflammatory response in microglia. [ABSTRACT FROM AUTHOR]

Abstract This paper aims to explore the influencing factors that facilitate sustainable energy transitions in China. For this purpose, this paper assumes that the impact of the energy transition is from three main factors, energy technology innovations, the energy market, and socio-technical regimes, which can be subdivided into 11 subfactors. To empirically test the proposed hypotheses, questionnaire survey data collected from Chinese energy enterprises are statistically analysed by structural equation models (SEMs). The results show that, first, energy technology innovations, the energy market, and socio-technical regimes are the major forces in the transition to sustainable energy in China. Second, the effects of the three main factors on the energy transition vary according to 11 different subfactors. Some subfactors, i.e., innovation strategy, innovation factors, innovation policy, innovation network, and new energy competitiveness, have very important positive effects on the energy transition. Some subfactors, i.e., competitiveness of the coal industry, customer habits and coal-based infrastructure, have negative effects on the transition to sustainable energy in China. Third, the influence of the subfactors on the transition performance is diminished as a result of the joint intermediate effects of transition behaviours. Highlights • The aim is to explore the influencing factors of China's sustainable energy transition. • Data was collected from Chinese energy enterprises through a questionnaire survey. • Results reveal energy technology innovation is the most important dynamic for transition. • Effects on energy transition vary according to 11 different subfactors. [ABSTRACT FROM AUTHOR]

Highly magnetic polymer submicrospheres with a hairy core–shell structure were facilely synthesized by combining distillation–precipitation polymerization (DPP) with subsequent surface-initiated atom transfer radical polymerization (SI-ATRP), and then investigated for protein adsorption. A robust polymer shell consisting of poly(divinylbenzene- co -chloromethylstyrene) (P(DVB- co -CMS)) was coated on superparamagnetic submicrometer-sized magnetite colloid nanocrystal clusters (MCNCs) via DPP. With the benzyl chloride groups on the shell as initiator, poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) hairs were grafted by SI-ATRP approach. The resulting hairy core–shell structured Fe 3 O 4 @ P(DVB- co -CMS)–PDMAEMA microspheres showed pH- and temperature-sensitivity, and high-magnetization. The composite microspheres were further investigated for adsorption of a typical acidic protein, i.e. bovine serum albumin (BSA). They exhibited a high binding capacity up to over 660 mg/g (corresponding to 158 DMAEMA monomer units cooperating for binding one BSA molecule) and could rapidly reach binding equilibrium within 5 min. Moreover, the adsorption of BSA was found to be remarkably dependent on the pH and salt concentration of the protein solutions, and the bound protein could be quantitatively desorbed by washing with a medium with lowered pH or raised salt concentration. [ABSTRACT FROM AUTHOR]

Objective: The aim of study was to construct a nomogram to effectively predict the overall survival (OS) and cancer‐specific survival (CSS) for patients with vulvar squamous cell carcinoma (VSCC). Methods: The training cohort consisted of 5405 patients with VSCC, extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Eighty‐four patients with VSCC were selected from the disease database of the Shengjing Hospital of China Medical University from 2014 to 2020, and enrolled as the external validation cohort. Significant independent prognostic factors were identified using Cox regression analysis and used to develop nomograms to predict 1‐, 3‐, and 5‐year OS and CSS in patients with VSCC. Results: The nomogram predicting OS was developed based on tumor size, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, regional lymph node involvement, distant metastases, surgery, chemotherapy, age, and race. The nomogram for CSS was constructed using the similar factors, excluding race but including marital status. The nomogram for 1‐, 3‐, and 5‐year OS demonstrated robust performance with receiver operating characteristic curves (AUCs) exceeding 80% (0.86, 0.84, and 0.82), outperforming the FIGO staging alone (0.77, 0.75, and 0.72). Similarly, for CSS, our nomograms achieved larger AUCs of 0.89, 0.88, and 0.86 compared with FIGO staging alone (0.81, 0.79, and 0.78). Conclusion: The nomograms more accurately predict prognosis than simple FIGO staging. Moreover, the nomograms developed in this study provide a convenient, operable, and reliable tool for individual assessment and clinical decision‐making for patients with VSCC. Synopsis: The VSCC nomograms established in this study showed a good prognostic prediction effect and could be used as a supplement to FIGO staging. [ABSTRACT FROM AUTHOR]

Abstract: Molecularly imprinted polymers against proteins are regarded as promising substitutes for natural antibodies, but have been frustrated with the problems including reduced interaction between functional monomers and protein template in the aqueous media required during their synthesis and restricted mass transfer across the resulting crosslinked polymer matrixes. For addressing these issues, herein we proposed a strategy for imprinting of a protein on the surface of nanoparticles using a metal chelating monomer. With lysozyme as a model protein template and Cu2+ chelating N-(4-vinyl)-benzyl iminodiacetic acid as the coordination monomer along with other monomers, protein imprinted polymer nanoshells were formed over vinyl-modified silica nanoparticles via surface polymerization in high-dilution monomer solution. The feed concentration of the crosslinking monomer was optimized toward achieving the best imprinting effect. Compared with the related imprinted materials reported previously, the resultant core–shell imprinted particles showed greatly faster binding kinetics, elevated rebinding capacity and selectivity. More importantly, noticeably high binding affinity was achieved with an estimated dissociation constant of 4.1×10−8 M which is comparable to that of conventional antibodies [Copyright &y& Elsevier]

Introduction. Vitamin D plays a key role in maintaining calcium homeostasis and skeletal health. The liver is critically involved in vitamin D metabolism, as 25-hydroxyvitamin D3 (25(OH)D3) is synthesized in the liver. Therefore liver dysfunction may lead to vitamin D deficiency and bone problems. The aim of this study was to examine vitamin D status and bone turnover markers in hepatitis B patients from northeastern China. Methods. We recruited 39 patients with hepatitis B (23 noncirrhotic and 16 cirrhotic) and 48 healthy controls in Shenyang, a metropolitan city in northeastern China, and measured serum 25(OH)D3 levels and serum and urinary bone turnover markers in these subjects. Results. Serum 25(OH)D3 levels in the patients with or without cirrhosis were markedly lower compared to the nonhepatitis controls (19.2 ± 1.2 and 18.5 ± 1.3 vs. 31.6 ± 1.3 nmol/L control), whereas serum and urinary bone turnover markers (alkaline phosphatase, C-terminal telopeptide of type I collagen, and pyridinoline) were significantly higher in these patients than in the controls. Moreover, serum levels of osteoprotegerin, a bone mass-regulating protein, were substantially reduced in the patients, with the lowest seen in patients with cirrhosis (2.7 ± 1.1 and 1.4 ± 0.4 vs. 3.4 ± 0.7 pg/mL control). Serum 25(OH)D3 levels below 30 nmol/L were positively correlated with serum osteoprotegerin levels in this cohort. Conclusions. Severe vitamin D deficiency is very common in hepatitis B patients in northeastern China, which negatively impacts their bone health. These data strongly suggest a need to treat these patients with vitamin D supplementation to protect their bone health. [ABSTRACT FROM AUTHOR]

Abstract: Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), but the molecular mechanism remains unknown. Here we show that exposure of mouse embryonic fibroblasts to TNFα or LPS led to a marked induction of PAI-1, which was blunted by 1,25(OH)2D3, NF-κB inhibitor or p65 siRNA, suggesting the involvement of NF-κB in 1,25(OH)2D3-induced repression. In mouse Pai-1 promoter a putative cis-κB element was identified at −299. EMSA and ChIP assays showed that TNF-α increased p50/p65 binding to this κB site, which was disrupted by 1,25(OH)2D3. Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNFα or LPS, and the induction was blocked by 1,25(OH)2D3. Mutation of the κB site blunted TNFα, LPS or 1,25(OH)2D3 effects. 1,25(OH)2D3 blocked IκBα degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated PAI-1 expression in the heart and macrophages, and the stimulation was blunted by pre-treatment with a vitamin D analog. Together these data demonstrate that 1,25(OH)2D3 down-regulates PAI-1 by blocking NF-κB activation. Inhibition of PAI-1 production may contribute to the reno- and cardio-protective effects of vitamin D. [Copyright &y& Elsevier]

Anelastic recovery during creep deformation of a whisker-reinforced Al2O3 matrix is examined in order to study the complex interactions of the reinforcement network with the matrix. In this paper, the finite-element method is used to model the elastic and creep properties of a representative volume element during creep deformation. Two types of unit cells are investigated. The first is a three-dimensional (3D) unit cell in which randomly oriented short fibers do not contact each other. The second case examined is a 2D cell within which fibers are aligned regularly so as to percolate through the unit cell. Simulation results from the 3D model verify the necessity of a percolating network for the anelastic recovery. Results from the 2D model show that anelastic recovery is attributed more to whisker bending, rather than to contact effects between fibers of the whisker network. Finally, FEM simulations of the maximum recoverable strain and characteristic relaxation time are found to be in good agreement with an analytical model recently developed by Wilkinson and Pompe, which is based on the application of Euler's beam theory in a 2D visco-elastic unit cell. [ABSTRACT FROM AUTHOR]

Previously, we showed that vitamin D receptor gene knockout leads to hyperreninemia independent of calcium metabolism; however, the contribution of parathyroid hormone to renin upregulation remained unclear. Here we separated the role of vitamin D and parathyroid hormone in the regulation of renin expression in vivo by generating transgenic mice that overexpressed the human vitamin D receptor in renin-producing cells using the 4.1 kb Ren-1c gene promoter. Targeting of human vitamin D receptor to the juxtaglomerular cells of the mice was confirmed by immunohistochemistry. Renal renin mRNA levels and plasma renin activity were decreased in these transgenic mice by about 50% and 30%, respectively, with no significant change in blood pressure, calcium, or parathyroid hormone levels. Moreover using vitamin D receptor knockout mice, we found that expression of the human receptor in their juxtaglomerular cells reduced renin expression in these mice without affecting calcium or parathyroid hormone status. Our study shows that suppression of renin expression by 1,25-dihydroxyvitamin D in vivo is independent of parathyroid hormone and calcium.Kidney International (2008) 74, 1577–1581; doi:10.1038/ki.2008.452; published online 1 October 2008 [ABSTRACT FROM AUTHOR]

Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR+/+ mice were mostly resistant to 2.5% DSS, VDR-/- mice developed severe diarrhea, rectal bleeding and marked body weight loss, leading to death in 2 weeks. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR-/- mice. Severe ulceration in VDR-/- mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared to VDR+/+ mice. Confocal and electron microscopy revealed severe disruption in epithelial junctions in VDR-/- mice after 3-day DSS treatment. Therefore, VDR-/- mice were much more susceptible to DSS-induced mucosal injury than VDR+/+ mice. In cell cultures, 1,25-dihaydroxy-vitamin D3 [1,25(OH)2D3] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)2D3 can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D-deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD. [ABSTRACT FROM AUTHOR]

1,25-Dihydroxyvitamin D [1,25(OH)2D3] is known to have anti-inflammatory activity; however, the molecular mechanism remains poorly defined. Here we show that the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-κB activation, a pathway essential for inflammatory response. In mouse embryonic fibroblasts (MEFs) derived from VDR-/- mice, the basal level of κB inhibitor (1κB) α protein was markedly decreased compared with VDR+/- MEFs; however, degradation of IκBα and its phosphorylation in response to TNF-α treatment or Salmonella infection were not altered in VDR-/- cells, neither were the levels of IκB kinase-α and IκB kinase-β proteins. Consistent with IκBα reduction, p65 accumulation in the nucleus was markedly increased in unstimulated VDR-/- cells. In addition, the physical interaction between VDR and p65 was absent in VDR-/- MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in nuclear p65 DNA binding and NF-κB transcriptional activity; consistently, induction of IL-6 by TNF-α or IL-1β was much more robust in VDR-/- than in VDR+/- cells, indicating that VDR-/- cells are more susceptible to inflammatory stimulation. Therefore, cells lacking VDR appear to be more proinflammatory due to the intrinsic high NF-κB activity. The reduction of IκBα in VDR-/- MEFs may be partially explained by the lack of VDR-mediated stabilization of IκBα by 1,25(OH)2D3. This is supported by the observation that IκBα degradation induced by TNF-α was inhibited by 1,25(OH)2D3 in VDR+/- cells, but not in VDR-/- cells. Taken together, these data suggest that VDR plays an inhibitory role in the regulation of NF-κB activation. [ABSTRACT FROM AUTHOR]

Abstract: The renin-angiotensin system (RAS) plays a central role in the pathogenesis of hypertension. Recently, we discovered that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] functions as a negative endocrine regulator of renin biosynthesis, which provides a molecular basis to explore the potential of Vitamin D analogs as renin inhibitors to control the RAS. To search for renin-inhibiting Vitamin D analogs, we screened 20 Vitamin D analog compounds using As4.1-hVDR cell (a juxtaglomerular cell line) culture by Northern blot and luciferase reporter assays. We found that the Gemini compounds, which have two side-chains at carbon-20 position, were particularly active in suppressing renin expression. Eight Gemini compounds were identified that were equally or 10- to 100-times more potent than 1,25(OH)2D3 in renin inhibition. These Gemini compounds also potently stimulate 25-hydroxyvitamin D 24-hydroxylase expression in As4.1-hVDR cells. Administration of compound RO-27-5646 [1,25-dihydroxy-21-(3-methyl-3-hydroxy-butyl)-19-nor-cholecalciferol] in mice caused a marked reduction in renal renin mRNA expression without invoking severe hypercalcemia as seen in 1,25(OH)2D3 treatment. These data establish in principle that Vitamin D analogs can indeed inhibit renin expression in vitro and in vivo, and support the notion that low calcemic Vitamin D analogs can potentially be used as therapeutic agents to control the RAS. [Copyright &y& Elsevier]

Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the rennin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angintensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D3 regulates cardiac functions, at least in part, through the RAS. [ABSTRACT FROM AUTHOR]

The high-temperature oxidation behavior of titanium-based alloys coated with Al–Cu–Fe–Cr quasicrystal using the low-pressure plasma spraying (LPPS) method was studied. The results showed that Al–Cu–Fe–Cr quasicrystal line coating improved the oxidation resistance of titanium-based alloys. The weight gains at 750 and 800 °C for Al–Cu–Fe–Cr quasicrystalline coating are very low and the oxidation kinetics follows a parabolic law. During the oxidation period there is no evident spallation of the coating from the substrate. Oxide formed on the surface of Al–Cu–Fe–Cr quasicrystalline coating after oxidation consisted of Al2O3. [Copyright &y& Elsevier]

Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. [ABSTRACT FROM AUTHOR]

Alopecia is a predominant feature of vitamin D receptor inactivation in mice and humans. To determine the role of vitamin D receptor in the regulation of hair growth directly, we used the human keratin 14 promoter to target human vitamin D receptor expression to the skin of transgenic mice, and generated vitamin D receptor null mice that express the human vitamin D receptor transgene. Parallel studies were carried out in littermates of wild-type, vitamin D receptor null, transgenic, and human vitamin D receptor-expressing null mice in two transgenic lines. The transgenic mice were grossly normal. The vitamin D receptor null and vitamin D receptor null/human vitamin D receptor mice were growth retarded and developed hypocalcemia, secondary hyperparathyroidism, and rickets. In contrast to the vitamin D receptor null mice that developed alopecia, however, the vitamin D receptor null/human vitamin D receptor mice displayed a normal hair coat, and their hair shaft and skin histology were indistinguishable from those of the wild-type mice. Immunohistochemical analyses revealed that the human vitamin D receptor was highly expressed in the basal layer of the epidermis and outer root sheath of the hair follicle. During follicular morphogenesis, no major histologic differences were seen in the skin of wild-type, vitamin D receptor null, transgenic, and vitamin D receptor null/human vitamin D receptor littermates. When anagen was induced by hair depilation at day 20 after birth, the vitamin D receptor null mice failed to initiate the hair cycle, whereas the vitamin D receptor null/human vitamin D receptor mice displayed the same pattern of anagen follicle formation as the wild-type mice. Interestingly, the transgenic mice initiated the follicular cycle earlier than the wild-type and vitamin D receptor null/human vitamin D receptor mice in a gene concentration-dependent manner. Taken together, these data provide direct evidence that vitamin D receptor is required for the... [ABSTRACT FROM AUTHOR]

Background: Limited evidence exists for the association between dietary patterns and later obesity phenotypes among Chinese adults. This longitudinal study aimed to evaluate associations of dietary patterns with general and central obesity in Chinese adults. Methods: Based on the China Health and Nutrition Survey (CHNS) waves 2004 and 2015, the study was conducted on 4207 adult men and women (age range: 18–65 years). Dietary intakes were assessed by three consecutive 24-h dietary recalls, and dietary patterns were identified using exploratory factor analysis. Longitudinal associations of dietary patterns with general and central obesity were evaluated using logistic regression analyses. Results: The prevalence rates of general and central obesity were 14.2% and 42.1%, respectively. Factor analysis extracted three major dietary patterns: "traditional southern," "modern," and "traditional northern." After adjustment for potential confounders, adults in the highest quartile of the traditional southern dietary group were less likely to develop over 10 years general (odds ratio [OR] = 0.50, 95% confidence interval [95%CI]: 0.39, 0.65) and central (OR = 0.52, 95%CI: 0.43, 0.63) obesity compared to those in the lowest quartile group. The modern dietary pattern was not significantly associated with general and central obesity. Adherence to the traditional northern dietary pattern increased the chance of both general and central obesity (OR = 1.61, 95%CI: 1.23, 2.10; OR = 1.64, 95%CI: 1.36, 1.98) after 10 years. Conclusions: Our study provides longitudinal evidence for associations between dietary patterns and later obesity phenotypes among Chinese adults. Our findings may guide the development of evidence-based preventive nutrition interventions to control the obesity epidemic. [ABSTRACT FROM AUTHOR]

Abstract Acute lung injury (ALI) is a type of diffuse lung inflammation with a high mortality rate. Studies show that miR-155 plays an important role in inflammation. Here, we investigated the role of miR-155 in lipopolysaccharide (LPS)-induced ALI. The mice with bone marrow transplantation between MiR-155 knockout and wild-type were used as animal models of LPS-induced sepsis. In response to LPS injection, ALI was less severe in miR-155 knockout mice than in wild-type mice, and mainly manifested as reduced pulmonary vascular leakage, pulmonary edema, and neutrophil infiltration. The expression levels of Ang-2 and apoptosis-associated caspases-3 and -9, as well as myosin light chain (MLC) phosphorylation in the lungs were also decreased. A bone marrow transplantation experiment showed that miR-155 expressed in bone marrow-derived lymphocytes rather than lung parenchymal lymphocytes promoted inflammation. Findings suggest that miR-155 expressed in bone marrow-derived lymphocytes promoted LPS-induced ALI through the modulation of the Ang-2-Tie-2 pathway. Highlights • Deletion of miR-155 inhibited the Ang2-Tie2 signaling pathway. • MiR-155 knockout inhibited phosphorylation of MLCK and MLC. • MiR-155 expressed in bone marrow-derived lymphocytes promoted inflammation. [ABSTRACT FROM AUTHOR]

As the prevalence of obesity and metabolic syndrome escalates, it has become increasingly important to understand the physiology of adipocytes. 1,25-dihydroxyvitamin D (1,25(OH)[sub 2]D[sub 3]) is a steroid hormone that is traditionally known to be a regulator of mineral homeostasis. 1,25(OH)[sub 2]D[sub 3] exerts its effects through the vitamin D receptor (VDR), a nuclear receptor that regulates gene transcription. Our recent studies suggest that VDR plays an integral role in adipocyte differentiation. VDR expression is tightly regulated during adipocyte differentiation and treatment of preadipocytic cells with 1,25(OH)[sub 2]D[sub 3] suppresses differentiation. However, the in vivo role of VDR in lipid metabolism has not been explored. We, therefore, evaluated the body fat composition and lipid parameters of VDR(-/-) mice. On a regular diet, VDR (-/-) mice weighed less and contained less body fat than wild type (WT) mice. On the high calcium-high lactose diet that rescues the hypocalcemia, the difference between VDR(-/-) and WT mice appeared sex dependent. In males, VDR(-/-) mice weighed less and had a lower body fat than WT mice; however no significant difference was observed in females. On a high fat diet, VDR (-/-) mice gained weight at a much lower rate than WT mice regardless of the sex. The gene profile of adipocytes from VDR(-/-) mice was also found to be altered. Levels of leptin and adiponectin were reduced in VDR(-/-) mice compared to WT mice, whereas resistin levels were increased in VDR(-/-) mice. Plasma cholesterol and triglyceride levels were significantly lower in VDR (-/-) mice than WT mice. These observations indicate that VDR plays a role in the regulation of adipose mass and lipid metabolism in vivo, which is independent of its role in calcium metabolism. [ABSTRACT FROM AUTHOR]

Photovoltaic power generation is greatly affected by weather factors. To improve the prediction accuracy of photovoltaic power generation, complete ensemble empirical mode decomposition with an adaptive noise algorithm (CEEMDAN) is proposed to preprocess the power sequence. Then, the full convolutional network (FCN) model optimized based on the sparrow search algorithm (SSA) is used to predict the short-term photovoltaic power. SSA can more reasonably determine the parameters of FCN and improve the prediction performance of FCN. Therefore, the FCN model optimized by the SSA algorithm is used to establish prediction models for subsequences and predict each subsequence, respectively. Finally, the predicted value of each subsequence is superimposed. Taking the actual data of a photovoltaic power station in Jiangsu province of China as an example, by comparing some different common prediction models, it is proved that the proposed method is reasonable and feasible. [ABSTRACT FROM AUTHOR]

[Display omitted] Some epidemiological studies have revealed that vitamin D (VD) deficiency is closely linked with the prevalence of obesity, however, the role of VD in energy homeostasis is yet to be investigated, especially in central nervous system. Given that VD negatively regulates renin in adipose tissue, we hypothesized that central VD might play a potential role in energy homeostasis. The present study aims to investigate the potential role of VD in energy homeostasis in the CNS and elaborate its underlying mechanisms. This study was conducted in Cyp27b1 −/− mice, VD-treated and wild-type mice. After the intraventricular injection of renin or its inhibitors, the changes of renin-angiotensin system (RAS) and its down-stream pathway as well as their effects on metabolic rate were examined. The RAS activity was enhanced in Cyp27b1 −/− mice, exhibiting a increased metabolic rate. Additionally, corticotropin-releasing hormone (CRH), a RAS-mediated protein regulating energy metabolism in the hypothalamus, increased significantly in Cyp27b1 −/− mice. While in VD-treated group, the RAS and sympathetic nerve activities were slightly inhibited, hence the reduced metabolic rate. Collectively, the present study demonstrates that the VD/vitamin D receptor (VDR) has a significant impact on energy homeostasis through the modulation of RAS activity in the hypothalamus, subsequently altering CRH expression and sympathetic nervous activity. [ABSTRACT FROM AUTHOR]

Abstract: Submicron-sized superparamagnetic magnetite colloid nanocrystal clusters (MCNCs) composed of many interconnected tiny Fe3O4 nanoparticles provide a new avenue for constructing highly magnetic polymer submicrospheres for biotechnological and medical applications. Herein, a facile and efficient method is described for the synthesis of Fe3O4@poly(methacrylic acid) (PMAA) core–shell submicrospheres using the MCNCs modified with polymerizable vinyl groups as the submicronic cores. The controlled encapsulation of the MCNCs with PMAA shells was achieved via precipitation polymerization mediated by a reversible addition–fragmentation chain transfer (RAFT) agent. A variety of factors influencing the formation of PMAA layers were examined, such as the loading amounts of the magnetic seeds and monomers, polymerization time, and the MCNCs’ surface chemistry. Compared with previous approaches, much higher seed dosage could be employed in the polymerization system without leading to significant particle conglutination. The shell thickness was readily tailored via varying two synthesis parameters, that is, monomer dosage and reaction time. The resulting hybrid particles showed high saturation magnetization and pH responsiveness. Also, this method was successfully extended to coating other hydrophilic polymer shells over the MCNCs and hence may be a general way for the synthesis of magnetic polymer submicrospheres. [Copyright &y& Elsevier]

The intrarenal renin-angiotensin system (RAS) plays a key role in the development of diabetic nephropathy. Recently, we showed that combination therapy with an AT1 receptor blocker (ARB) and an activated vitamin D analog produced excellent synergistic effects against diabetic nephropathy, as a result of blockade of the ARB-induced compensatory renin increase. Given the diversity of vitamin D analogs, here we used a pro-drug vitamin D analog, doxercalciferol (1α-hydroxyvitamin D2), to further test the efficacy of the combination strategy in long-term treatment. Streptozotocin-induced diabetic DBA/2J mice were treated with vehicle, losartan, doxercalciferol (0.4 and 0.6 μg/kg), or losartan and doxercalciferol combinations for 20 wk. Vehicle-treated diabetic mice developed progressive albuminuria and glomeruloscierosis. Losartan alone moderately ameliorated kidney injury, with renin being drastically upregulated. A similar therapeutic effect was seen with doxercalciferol alone, which markedly suppressed renin and angiotensinogen expression. The losartan and doxercalciferol combination most effectively prevented albuminuria, restored glomerular filtration bartier structure, and dramatically reduced glomerulosclerosis in a dose-dependent manner. These effects were accompanied by blockade of intrarenal renin upregulation and ANG II accumulation. These data demonstrate an excellent therapeutic potential for doxercalciferol in diabetic renal disease and confirm the concept that blockade of the compensatory renin increase enhances the efficacy of RAS inhibition and produces synergistic therapeutic effects in combination therapy. [ABSTRACT FROM AUTHOR]

A novel chemiluminescence method for the quantitative assay of the organophosphorus pesticide chlorpyrifos in vegetable samples is presented. The determination is based on the reaction of chlorpyrifos with luminol-H2O2 in alkaline medium with sodium chloride being enhancer. Under the optimum conditions, the increased CL intensity was proportional with the concentration of chlorpyrifos in the range of 1.0 × 10-8 g ∙ ml-1 - 1.0 × 10-6 g ∙ ml-1 and the detection limit was 3.5 × 10-9 g ∙ ml-1 (3σ). The relative standard is less than 3.9% for 5.0 × 10-7 g ∙ ml-1 chlorpyrifos (n = 7). This method has been successfully applied to the determination of chlorpyrifos residue in vegetable sample. Further study was focused on the mechanism of chlorpyrifos and the possible mechanism was proposed. [ABSTRACT FROM AUTHOR]

We have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) down-regulates renin expression. To explore the molecular mechanism, we analyzed the mouse Ren-1c gene promoter by luciferase reporter assays. Deletion analysis revealed two DNA fragments from -2725 to -2647 (distal fragment) and from -117 to +6 (proximal fragment) that are sufficient to mediate the repression. Mutation of the cAMP response element (CRE) in the distal fragment blunted forskolin stimulation as well as 1,25(OH)2D3 inhibition of the transcriptional activity, suggesting the involvement of CRE in 1,25(OH)2D3-induced suppression. EMSA revealed that 1,25(OH)2D3 markedly inhibited nuclear protein binding to the CRE in the promoter. ChIP and GST pull-down assays demonstrated that liganded VDR blocked the binding of CREB to the CRE by directly interacting with CREB with the ligand-binding domain, and the VDR-mediated repression can be rescued by CREB, CBP, or p300 overexpression. These data indicate that 1,25(OH)2D3 suppresses renin gene expression at least in part by blocking the formation of CRE-CREB-CBP complex. [ABSTRACT FROM AUTHOR]

Abstract: We have used mouse embryonic fibroblasts (MEFs) derived from VDR(+/−) and VDR(−/−) mice to determine whether the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-κB activation. We found that the basal IκBα protein level was markedly decreased in VDR(−/−) MEFs compared to VDR(+/−) MEFs; however, degradation of IκBα and its phosphorylation were not altered in VDR(−/−) cells, neither were the levels of IKKα and IKKβ proteins. Consistently, p65 nuclear translocation was increased in unstimulated VDR(−/−) cells. The physical interaction between VDR and p65 was absent in VDR(−/−) MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in NF-κB transcriptional activity. Consistently, induction of IL-6 by TNFα or IL-1β was much more robust in VDR(−/−) than in VDR(+/−) cells, indicating that VDR(−/−) cells are more susceptible to inflammatory stimulation. Therefore, fibroblasts lacking VDR appear to be more pro-inflammatory due to the intrinsic high NF-κB activity. The reduction of IκBα in VDR(−/−) MEFs may be partially explained by the lack of VDR-mediated stabilization of IκBα by 1,25(OH)2D3. These data suggest that VDR plays an inhibitory role in the regulation of NF-κB activation. [Copyright &y& Elsevier]

Abstract: Calbindin (CaBP), the vitamin D-dependent calcium-binding protein, is believed to play an important role in intracellular calcium transport. The aim of this study was to investigate the effect of high dietary calcium on the expression of CaBP-D9k and CaBP-D28k in the presence and absence of a functional vitamin D receptor (VDR). Treatment with the HCa¿Lac diet containing 2% calcium, 1.5% phosphorus and 20% lactose reversed the hypocalcemia seen in adult VDR-null mice in 3 weeks but did not significantly change the blood ionized calcium in wild-type mice. This dietary treatment dramatically suppressed both the duodenal and the renal CaBP-D9k expression in wild-type mice at both mRNA and protein levels but had little effect on the expression of the same gene in VDR-null mice. Removal of this diet gradually restored the expression of CaBP-D9k to the untreated level in wild-type mice. Only moderate or little change in CaBP-D28k expression was seen in wild-type and VDR-null mice fed with the HCa¿Lac diet. The VDR content in the duodenum or kidney of wild-type mice was not altered by the dietary treatment. These results suggest that calcium regulates CaBP-D9k expression by modulating the circulating 1,25-dihydrxyvitamin D3 level and that VDR is thus required for the dietary calcium-induced suppression of CaBP-D9k expression. Calcium regulation of the CaBP-D9k level may represent an important mechanism by which animals maintain their calcium balance. [Copyright &y& Elsevier]

A friction- and wear-resistant Al–Cu–Fe–Cr quasicrystalline coating was fabricated on substrate of titanium alloy by low-pressure plasma-spraying (LPPS) method. The LPPS Al–Cu–Fe–Cr quasicrystalline coating has a rapidly solidified lamellar microstructure consisting of mainly decagonal phase and small amount of cubic phase peaks. The results showed that Al–Cu–Fe–Cr quasicrystalline coating improved the friction and wear resistance of titanium-based alloys under dry sliding wear test conditions. The excellent wear resistance may be attributed to the high hardness of Al–Cu–Fe–Cr quasicrystal. [Copyright &y& Elsevier]

[Display omitted] Intrinsic vitamin D affects the proliferation, apoptosis, invasion, metastasis, and tumorigenesis of lung cancer by regulating tumor signaling pathways. Histidine-rich calcium-binding protein (HRC) maintains Ca2+ homeostasis, which plays crucial roles in the occurrence and development of cancer. Our study aims to investigate the ability of vitamin D in the regulation of HRC and the role of HRC playing in lung cancer. We investigated the effects of vitamin D on lung cancer and the underlying mechanisms, by measuring HRC and vitamin D receptor (VDR) expression in lung cancer, paracancer, and normal tissues from patients using immunohistochemistry, western blotting, and real time RT-PCR. We transfected H460 lung cancer cells (supplemented or not with vitamin D) with PX458-HRC and pcDNA3.1-HRC plasmids and injected mice with lung cancer cells harboring pcDNA3.1-vector or pcDNA3.1-HRC plasmids. Vitamin D inhibited HRC expression and H460 cell migration and proliferation, and promoted apoptosis compared with controls. The expression of HRC and VDR was significantly upregulated and downregulated, respectively, in lung cancer versus paracancer or normal tissues. Cell proliferation and migration were reduced, apoptotic cells were more and tumors were smaller in mice treated with vitamin D/cholecalciferol cholesterol emulsion (CCE) than in vitamin D/CCE+HRC+/+ mice. Vitamin D inhibited lung cancer tumor growth, migration, and proliferation by downregulating HRC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Vitamin D reduced homocysteine levels in serum and myocardial tissue of mice. • NFE2L2 was a direct target gene of vitamin D/VDR. • NFE2L2 promoted MTHFR transcription. • Vitamin D/VDR could improve Hcy-induced myocardial inflammation through activation of NFE2L2 mediated MTHFR. Myocardial inflammation underlies a broad spectrum of conditions that cause damage to the myocardium and lead to structural and functional defects. Homocysteine (Hcy) is closely related to the occurrence and development of cardiovascular diseases. We investigated the mechanism underlying the effects of vitamin D as a prophylactic treatment for Hcy-induced cardiac inflammation. The levels of 25(OH)D 3 and Hcy were assessed using ELISA kits. Expression levels of the vitamin D receptor (VDR), NFE2 like bZIP transcription factor 2 (NFE2L2), methylenetetrahydrofolate reductase (MTHFR) and inflammatory factors were examined by Western blotting, immunohistochemistry and real time polymerase chain reaction. NFE2L2/MTHFR-knockdown HL-1 cells and NFE2L2+/- mouse were used to test the effects of vitamin D. We found the levels of Hcy in the serum and myocardial tissue of mice in the Hcy + CCE group were lower than in the Hcy groups, which was opposed to the trend exhibited by the serum 25(OH)D 3 level of mice. The mRNA and protein expression levels of the inflammatory factors in cardiac tissues and cardiomyocytes were strongly decreased by the Hcy treatment, compared to the Hcy + CCE/Hcy + 1,25(OH) 2 D 3 groups. Moreover, the results revealed that the level of nuclear NFE2L2 in Hcy + CCE/Hcy + 1,25(OH) 2 D 3 group was increased compared to Hcy group with a reciprocal decrease in the level of cytosolic NFE2L2 in vivo and in vitro. Similarly, the MTHFR mRNA and protein expression in the Hcy + CCE group was higher than the Hcy group. We determined that NFE2L2 promoted the expression of MTHFR. However, based on Hcy treatment, the combination of 1,25(OH)2D3 and MTHFR-/- reversed the decline in IL-6 and TNFα expression caused by 1,25(OH)2D3 alone. Chromatin immunoprecipitation and luciferase reporter assays showed the up-regulation effect of VDR on NFE2L2 and NFE2L2 on MTHFR. Our findings indicate that vitamin D/VDR could improve Hcy-induced myocardial inflammation through activation of NFE2L2 mediated MTHFR. [ABSTRACT FROM AUTHOR]

Background: Our recent study identified that human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 2 (CMTM2) was deregulated in hepatocellular carcinoma (HCC) tissues and posed as a potential tumor suppressor. However, the mechanism of CMTM2 in HCC occurrence and development has not been well elaborated. Materials and Methods: The expression of CMTM2 was knocked-down by RNA interruption in Huh-7 and SMMC7721 cells. Cell proliferation ability was detected by CCK8 test and colony formation assay. The cell invasion and migration were measured by wound healing and Transwell assay. Results: We found that the cell proliferation was significantly increased by interruption of CMTM2 expression, both in Huh-7 and SMMC7721 cells. Moreover, down-regulated CMTM2 could promote the invasion and migration ability of HCC cells through inducing the epithelial-mesenchymal transition (EMT) process. We further discovered that both the expression of CMTM2 and the EMT-associated marker E-cadherin were decreased in the same thirty cases of HCC tissues compared with the corresponding adjacent non-tumor tissues. Pearson correlation test showed that there was a significantly positive correlation between CMTM2 and E-cadherin in HCC tissues (P< 0.05). Conclusion: Based on the results of cell model and HCC tissues, our study suggests that down-regulated CMTM2 promotes HCC metastasis through inducing the EMT process. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in China, with high metastasis and poor prognosis. Recently, as the core component of the polycomb repressive complexes 1 (PRC1), chromobox protein homolog 8 (CBX8) is considered as an oncogene and prognostic marker in HCC. Methods: A tissue microarray of 166 paired HCC and adjacent non-tumor samples were collected to identify the relationship between CBX8 and epithelial mesenchymal transition (EMT) associated proteins by Spearman correlation analysis. Knock-down of CBX8 in HCC cells was conducted to detect the biologic functions of CBX8 in HCC metastasis. Results: We found out that CBX8 was over-expressed in HCC and its expression was closely related to the metastasis of HCC patients. In addition, knock-down of CBX8 was found to inhibit the invasion and migration ability of HCC cells. Moreover, there was a significant relationship between expression of CBX8 and EMT associated proteins both in HCC cells and tumor tissues. Conclusions: Our results indicate that CBX8 promotes metastasis of HCC by inducing EMT process. [ABSTRACT FROM AUTHOR]

Hyperuricemia is a metabolic disease of the kidney that results in decreased uric acid excretion. Here, we aimed to investigate the effects of ginsenosides and anserine on hyperuricemia and the expression of aquaporin (AQP) 1–4, which are indicators of renal excretion. Ginsenosides and anserine were administered separately or together after the establishment of hyperuricemia with adenine in BALB/c mice. Renal function indexes such as serum uric acid, creatinine, and urea nitrogen were measured in each group of mice, and the expression of AQP1–4 in renal tissues was detected. Serum uric acid and urea nitrogen were decreased in the ginsenoside and the anserine +UA groups. Meanwhile, the uric acid excretion and clearance rate were clearly increased in the co-treatment +UA group (p < 0.05). Moreover, ginsenosides or anserine ginsenosides or anserine alone and treatment with both increased the expression of AQP1–4; however, the synergistic effects were more significantly enhanced (p < 0.01). We provide the first reported evidence that ginsenosides and anserine have synergistic effects on uric acid excretion. The improvement in renal function in hyperuricemic mice after treatment with ginsenosides and anserine may result from up-regulation of AQP1–4 expressions. [ABSTRACT FROM AUTHOR]

Vitamin D receptor (VDR) plays an important role in regulating energy metabolism. Adipose tissue is a vital metabolic organ in energy balance and glucose homeostasis. In this study, we investigated the role of VDR expressed on adipose tissue in the balance of energy metabolism. This study was conducted in VDR-KO mice, VDR-Tg mice and wild-type mice. Energy metabolism was determined based on the energy expenditure, oxygen consumption, respiratory exchange rate, food and water intake, and a cool room test. VDR expression in the tissues of VDR-Tg mice was assessed by western blotting. The levels of total cholesterol, triglycerides, free fatty acids, leptin, and glucose were assessed using the respective kits. Insulin resistance in the whole body was evaluated by an intraperitoneal glucose tolerance test and insulin tolerance test. mRNA associated with energy metabolism expression in adipose and skeletal muscle tissue was examined by RT-PCR. Our results show that overexpression of VDR in adipose tissue induced an increase in body weight, fat mass, and serum lipid levels, and a decline in energy metabolism; these changes were ameliorated by VDR-KO mice. Overexpression of VDR in the adipose tissue of VDR-Tg mice induced a state of insulin resistance, which corresponded with decreased expression of UCP1, UCP2, UCP3, CPT2 and HK in both white adipose tissue and brown adipose tissue; these changes were also reversed by VDR-KO mice. Our study confirms that expression levels of VDR in adipose tissue play pivotal roles in energy balance and glycolipid metabolism by regulating adipose tissue remodeling. • Shrimp shells as nitrogen source were directly used to prepare ORR catalysts. • Removing CaCO3 and in-situ pore in shrimp shells promoted the active sites. • Hydrothermal process with phosphoric acid facilitated similar spherical carbon. • N, P co-doped carbon exhibited good ORR property, stability and application in MFC. [ABSTRACT FROM AUTHOR]

Background: As an essential member of the Polycomb group (PcG) proteins, chromobox homolog 7 (CBX7) is found deregulated in some human cancers, and is thought to be a contributing factor in carcinogenesis. However, the expression and role of CBX7 in hepatocellular carcinoma (HCC) is still not well characterized. Materials and Methods: The levels of the CBX7 protein were quantified in 75 paired HCC and adjacent nontumor tissues by immunohistochemistry; comparisons were made using McNemar's chi-square test. The Kaplan–Meier estimate was used for survival analysis. Results: We found that the expression of CBX7 in HCC tissues was significantly lower than that of adjacent nontumor tissues. In addition, decreased CBX7 expression levels were correlated with liver cirrhosis in HCC patients. Furthermore, the survival times of HCC patients who were CBX7-expression-negative were shorter than HCC patients who were CBX7-expression-positive. Conclusion: Our results show that downregulation of CBX7 is related to HCC progression and a poor prognosis in HCC patients. [ABSTRACT FROM AUTHOR]

Abstract Vitamin D plays an important role in maintaining skeletal development and bone homeostasis. Although vitamin D has been extensively researched, the direct effect of 1,25(OH) 2 D 3 on osteoblasts is unclear. To explore the 1,25(OH) 2 D 3 action on murine osteoblasts, we performed tandem mass tag experiments on MC3T3-E1 cells treated with and without 1,25(OH) 2 D 3. Three up-regulated proteins (MRC2, WWTR1 and RASSF2) related to bone metabolism were confirmed in this study. 1,25(OH) 2 D 3 up-regulated the expression of MRC2 through vitamin D receptor. MRC2 affects collagen metabolism in osteoblasts. Combined with bioinformatics and parallel reaction monitoring analysis, we inhibited the expression of MRC2 to explore the relationship between MRC2 and collagens. Then we found MRC2 down-regulated COL5A2 and up-regulated MMP13. This study provides a protein profile of 1,25(OH) 2 D 3 -treated murine osteoblasts, reveals a newly discovered signaling axis (1,25(OH) 2 D 3 /VDR/MRC2/COL5A2 and MMP13), and explains the effect of 1,25(OH) 2 D 3 on bone metabolism from a new perspective. Graphical abstract Image 1 Highlights • This study provides a protein profile of 1,25(OH) 2 D 3 -treated murine osteoblasts. • 1,25(OH) 2 D 3 regulates some proteins related to collagen metabolism. • Vitamin D may play a role in negative regulation of bone ECM. [ABSTRACT FROM AUTHOR]

This study aimed to examine the expression level and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in paired hepatocellular carcinoma (HCC) and adjacent nontumor tissues. The expression of CMTM6 was detected in 75 paired HCC and adjacent nontumor tissues by immunohistochemistry. Chi-square test was used to compare the difference of CMTM6 expression between HCC tissues and adjacent nontumor tissues. The clinic-pathological features and prognosis of HCC patients were collected to analyze the relationship with CMTM6 expression. The positive expression of CMTM6 in HCC tissues was significantly lower than that of adjacent nontumor tissues. The difference of CMTM6 expression between HCC tissues and paired adjacent nontumor tissues was statistically significant (p < 0.05). Furthermore, CMTM6 expression was correlated with HCC metastasis and alpha-fetoprotein (AFP) (p < 0.05). Multivariate logistic regression analysis showed tumor staging, metastasis, and AFP had a significant relationship with CMTM6 expression. In addition, the survival time of HCC patients was different between CMTM6 positive group and CMTM6 negative group by Kaplan–Meier survival analysis (p < 0.05). Downregulation of CMTM6 is related to HCC metastasis and the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Aim. Vitamin D plays an important role in water and salt homeostasis. The aim of our study was to investigate the underlying relationship of Vitamin D and Aquaporins (AQP). Methods. The behaviors of 1α (OH)-ase knockout mice and wild type mice were observed before analysis. The ICR mice were treated with vehicle or paricalcitol, a vitamin D analogue, followed by animals receiving a standard diet and free access to drinking water either with aliskiren (renin blocker; 37.5 mg aliskiren in 100 ml water), or telmisartan (a angiotensin II type I receptor blocker; 40 mg telmisartan in 100 ml water) a week before study. The expressions of AQP-1, AQP-4, and renin in mice kidneys were detected by western bolting, immunohistochemistry, and immunofluorescence. Results. Diuresis and polydipsia were observed in 1α (OH)-ase knockout mice, and a decreased water intake and urine output in ICR mice was observed after paricalcitol treatment. Compared with wild type, the AQP-1 expressions were increased in renal papilla and AQP-4 expressions were decreased in renal proximal tubule of 1α(OH) ase knockout mice. In addition, AQP-1 was decreased in renal papilla and AQP-4 expressions were increased in proximal tubule by suppressing renin activity or supplement of Vitamin D analogue. After injecting renin into the lateral ventricle of the 1α(OH)ase knockout mice, the renin expression level was decreased in the kidney, followed by the decrease of AQP-1 in renal papilla and increase of AQP-4 in proximal tubule. Conclusions. Overall, Vitamin D and renin inhibitors have synergistic effects in regulating water channels in mice kidneys. [ABSTRACT FROM AUTHOR]

• TDCIPP could selectively inhibited the growth of female zebrafish. • TDCIPP altered the microbial communities in the intestine of zebrafish. • TDCIPP induced an increase in α-diversity of the gut microbiome in male zebrafish. • TDCIPP induced histological injury and inflammation responses in female intestine. • Abundances of pathogenic bacteria were negatively correlated with female growth. Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is ubiquitous in aquatic environment, but its effect on intestinal health of fish has yet not been investigated. In the present study, the AB strain zebrafish embryos were exposed to environmentally realistic concentrations (0, 30, 300, and 3000 ng·L−1) of TDCIPP for 90 days, after which the fish growth and physiological activities were evaluated, and the intestinal microbes were analyzed by 16S rRNA gene high-throughput sequencing. Our results manifested that the body length and body weight were significantly reduced in the female zebrafish but not in males. Further analyses revealed that TDCIPP resulted in notable histological injury of intestine, which was accompanied by impairment of epithelial barrier integrity (decreased tight junction protein 2), inflammation responses (increased interleukin 1β) , and disruption of neurotransmission (increased serotonin) in female intestine. Male intestines maintained intact intestinal structure, and the remarkably increased activity of glutathione peroxidase (GPx) might protect the male zebrafish from inflammation and intestinal damage. Furthermore, 16S rRNA sequencing analysis showed that TDCIPP significantly altered the microbial communities in the intestine in a gender-specific manner, with a remarkable increase in alpha diversity of the gut microbiome in male zebrafish, which might be another mechanism for male fish to protect their intestines from damage by TDCIPP. Correlation analysis revealed that abnormal abundances of pathogenic bacteria (Chryseobacterium, Enterococcus, and Legionella) might be partially responsible for the impaired epithelial barrier integrity and inhibition in female zebrafish growth. Taken together, our study for the first time demonstrates the high susceptibility of intestinal health and gut microbiota of zebrafish to TDCIPP, especially for female zebrafish, which could be partially responsible for the female-biased growth inhibition. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is a synthetic amino acid containing sulfhydryl group, which is an intermediate product of the deep metabolic pathway of methionine and cysteine. The abnormal increase in fasting plasma total Hcy concentration caused by various factors is called hyperhomocysteine (HHcy). HHcy is closely relevant to the occurrence and progression of diverse cardiovascular and cerebrovascular diseases, such as coronary heart disease, hypertension and diabetes, etc. Vitamin D/vitamin D receptor (VDR) pathway is pointed out that prevent cardiovascular disease by reducing serum homocysteine levels. Our research is designed to explore the potential mechanism of vitamin D in the prevention and treatment of HHcy. The Hcy and 25(OH)D 3 levels in mouse myocardial tissue, serum or myocardial cells were detected using ELISA kits. The expression levels of VDR, Nrf2 and methionine synthase (MTR) were observed using Western blotting, immunohistochemistry and real time polymerase chain reaction (PCR). General information of the mice, including diet, water intake and body weight, was recorded. Vitamin D up-regulated the mRNA and protein expression of Nrf2 and MTR in mouse myocardial tissue and cells. CHIP assay determined that the combination of Nrf2 binding to the S1 site of the MTR promoter in cardiomyocytes using traditional PCR and real time PCR. Dual Luciferase Assay was applied to detect the transcriptional control of Nrf2 on MTR. The up-regulation effect of Nrf2 on MTR was verified by Nrf2 knockout and overexpression in cardiomyocytes. The role of Nrf2 in vitamin D inhibition of Hcy was revealed using Nrf2-knockdown HL-1 cells and Nrf2 heterozygous mice. Western blotting, real time PCR, IHC staining and ELISA showed that Nrf2 deficiency could restrain the increase in MTR expression and the decrease in Hcy level induced by vitamin D. The transcriptional activities of Nrf2/MTR were activated by vitamin D/VDR with a decrease in Hcy. Vitamin D/VDR upregulates MTR in an Nrf2-dependent manner, thereby reducing the risk of HHcy. [Display omitted] • Vitamin D relieved hyperhomocysteinemia. • Vitamin D could up-regulate Nrf2 and MTR. • MTR was a direct target gene of Nrf2. • Vitamin D/VDR could reduce myocardial homocysteine levels through activation of Nrf2 mediated MTR. [ABSTRACT FROM AUTHOR]

There was evidence that 1,25(OH) 2 D 3 regulated aquaporin (AQP) 2 and 4 expression while ameliorating renal fibrosis. This study investigated whether cholecalciferol cholesterol emulsion (CCE), a precursor of 1,25(OH) 2 D 3 , has similar effects. The impact of CCE on renal fibrosis and AQP2 and AQP4 expression were studied in a unilateralureteral obstruction (UUO) mouse nephropathy model. CCE reduced both the extent of fibrosis and transforming growth factor (TGF)-β signaling compared with vehicle-treated UUO model controls. AQP2 protein expression was higher and AQP4 expression was lower in UUO-model mice treated with CCE than in vehicle-treated control mice. The results showed that CCE attenuated renal fibrosis by inhibiting TGF-β signaling, and regulated AQP2 and AQP4 expression in this UUO mouse model. [ABSTRACT FROM AUTHOR]

1,25-dihydroxyvitamin D 3 and its analog (paricalcitol) have beneficial effects on multiple systems and diseases, including myocarditis. However, the therapeutic effect of cholecalciterol cholesterol emulsion (CCE) on myocarditis and the role of pyroptosis in the progress of myocarditis have not been determined. The objective of this study was to investigate the effect of CCE on experimental autoimmune myocarditis and its underlying mechanisms. The ratio of heart weight to body weight was decreased after CCE treatment compared with vehicle-treated controls. In addition, CCE improved the general status of mice, suppressed myocardial apoptosis, and inhibited the pyroptosis signaling pathway. Therefore, CCE can ameliorate experimental autoimmune myocarditis by downregulating the pyroptosis signaling pathway. [ABSTRACT FROM AUTHOR]

The therapeutic effect of 1,25(OH) 2 vitamin D 3 and its analog (paricalcitol) on experimental colitis in animals has been heavily demonstrated. However, the response to Cholecalciterol Cholesterol Emulsion (CCE), a precursor of 1,25(OH) 2 vitamin D 3 , has not yet been reported. Whether pyroptosis is involved in colitic deterioration also remains unclear. Therefore, we adopted molecular biology and histology approaches to examine mechanisms by which CCE was able to regulate experimental colitis in the animal model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Our data revealed that mice displayed a remarkable reduction in colonic histological scores, colonic inflammation and colonic histological damage. In addition, there was an overall improvement in general status (change in body weight, food and water intake, mental status, activity) and a 30% increase in survival rate due to the downregulation of pyroptosis following treatment with CCE. In conclusion, our data have provided evidence that CCE can attenuate the damage of experimental colitis by suppressing pyroptosis signaling. [ABSTRACT FROM AUTHOR]

There have been several studies suggesting that cancer stem cells (CSCs) contribute to the high rates of recurrence and resistance to therapies observed in hepatocellular carcinoma (HCC). Epithelial cell adhesion molecule (EpCAM) has been demonstrated to be a biomarker of CSCs and a potential therapeutic target in HCC. Here, we prepared two anti-EpCAM monoclonal antibodies (1H8 and 2F2) and an anti-EpCAM bispecific T cell engager (BiTE) 1H8/CD3, which was derived from 1H8, and used them to treat HCC in vitro and in vivo. The results demonstrated that all of the developed anti-EpCAM antibodies specifically bound to EpCAM. Neither anti-EpCAM monoclonal antibody had obvious anti-HCC activities in vitro or in vivo. However, anti-EpCAM BiTE 1H8/CD3 induced strong peripheral blood mononuclear cell-dependent cellular cytotoxicity in Huh-7 and Hep3B cells but not EpCAM-negative SK-Hep-1 cells. Notably, 1H8/CD3 completely inhibited the growth of Huh-7 and Hep3B xenografts in vivo. Treatment of the Huh-7 HCC xenografts with 1H8/CD3 significantly suppressed tumor proliferation and reduced the expression of most CSC biomarkers. Intriguingly, galectin-1 (Gal-1) overexpression inhibited 1H8/CD3-induced lymphocytotoxicity in HCCs while knockdown of Gal-1 increased the lymphocytotoxicity. Collectively, these results indicate that anti-EpCAM BiTE 1H8/CD3 is a promising therapeutic agent for HCC treatment. Gal-1 may contribute to the resistance of HCC cells to 1H8/CD3-induced lysis. [ABSTRACT FROM AUTHOR]

Highlights: [•] EGFRvIII downregulates miR-520-3p which upregulates E2F-1 and ensuing TS in HCC. [•] 5-FU plus mAb CH12 has an additive antitumor effect on EGFRvIII-positive HCC. [•] CH12-elicited TS suppression contributes to increased sensitivity to 5-FU in HCC. [•] CH12 is a promising agent to circumvent EGFRvIII-mediated 5-FU-resistance in HCC. [Copyright &y& Elsevier]

The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4(+)CD45RB(hi) T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions. [ABSTRACT FROM AUTHOR]

The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4+CD45RBhi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-KB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent o nonepithelial immune VDR actions. [ABSTRACT FROM AUTHOR]