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and kann obtained from numerical simulations of Ti:sapphire annealing experiments (left) and their applications during crystal growth (right).

Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39–2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48–0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.

Metabolic syndrome (MetS) is a health disorder characterized by metabolic abnormalities that predict an increased risk to develop cardiovascular disease (CVD) and type 2 diabetes. Biomarkers can provide an insight into the novel mechanism for MetS and can be potentially used for personalized response to therapies. We exploited a targeted HPLC-MS/MS method to characterize plasma amino acids and carnitine metabolic profile in MetS patients. A training set (40 cases and 40 controls) and validation set (80 MetS patients and 80 healthy controls) were carried out to find the metabolic profiles. We discovered two carnitine metabolites including hydroxydecanoyl carnitine and methylglutarylcarnitine. Our results indicated that the decreased level of hydroxydecanoyl carnitine and methylglutarylcarnitine may be associated with the risk of MetS. These biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.

Background and aims Akebia Saponin D (ASD) is a major bioactive triterpenoid saponin compound isolated from the Chinese herb Dipsacus asper wall (DSW). DSW has been long used as an anti-Alzheimer disease and anti-osteoporosis agent in clinics. However, anti-atherosclerotic effects of ASD have not been fully investigated. The objective of this study is to further investigate the anti-atherosclerotic activities and mechanisms of ASD in vivo and in vitro. Methods In in vitro experiments, ASD (50, 100, and 200 μM) was used to explore the effects of preventing H2O2-induced endothelial cell apoptosis and the possible mechanism involved. In in vivo experiments, ApoE−/− mice were fed a high fat diet (HFD) and treated with atorvastatin (10 mg/kg/d), ASD (50, 150, 450 mg/kg/d), or the combination therapy (atorvastatin 10 mg/kg/d and ASD 150 mg/kg/d) for 14 weeks. Results We found that ASD reduced the generation of reactive oxygen species, inhibited mitochondrial membrane potential (MMP) impairment, diminished the expression of Bax and Caspase-3, increased Bcl-2 expression, and inhibited apoptosis in endothelial cells. ASD significantly increased the expression of anti-oxidant enzymes (GSH, SOD, and CAT) in both liver and vascular tissue, reduced blood lipid levels (TG, TC, and LDL-C), and decreased lipid deposition in the liver and atherosclerotic lesion size in ApoE−/− mice. Conclusions Our study revealed that ASD inhibited atherosclerosis development in ApoE−/− mice by inhibiting oxidative stress-induced endothelial cell apoptosis signaling pathway, and suggested that ASD might be a potential therapeutic drug in the prevention of atherosclerosis.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. Glycosyltransferases (GTs) catalyze the synthesis of glycosidic linkages and are essential in the biosynthesis of glycans, glycoconjugates (glycolipids and glycoproteins), and glycosides. Plant genomes generally encode many more GTs than animal genomes due to the synthesis of a cell wall and a wide variety of glycosylated secondary metabolites. The Arabidopsis thaliana genome is predicted to encode over 573 GTs that are currently classified into 42 diverse families. The biochemical functions of most of these GTs are still unknown. In this study, we updated the JBEI Arabidopsis GT clone collection by cloning an additional 105 GT cDNAs, 508 in total (89%), into Gateway-com-patible vectors for downstream characterization. We further established a functional analysis pipeline using transient expression in tobacco (Nicotiana benthamiana) followed by enzymatic assays, fractionation of enzymatic products by reversed-phase HPLC (RP-HPLC) and characterization by mass spectrometry (MS). Using the GT14 family as an exemplar, we outline a strategy for identify-ing effective substrates of GT enzymes. By addition of UDP-GlcA as donor and the synthetic accep-tors galactose-nitrobenzodiazole (Gal-NBD), β-1,6-galactotetraose (β-1,6-Gal4) and β-1,3-galacto-pentose (β-1,3-Gal5) to microsomes expressing individual GT14 enzymes, we verified the β-glucu-ronosyltransferase (GlcAT) activity of three members of this family (AtGlcAT14A, B, and E). In ad-dition, a new family member (AT4G27480, 248) was shown to possess significantly higher activity than other GT14 enzymes. Our data indicate a likely role in arabinogalactan-protein (AGP) biosyn-thesis for these GT14 members. Together, the updated Arabidopsis GT clone collection and the biochemical analysis pipeline present an efficient means to identify and characterize novel GT catalytic activities.

Glycosyltransferases (GTs) catalyze the synthesis of glycosidic linkages and are essential in the biosynthesis of glycans, glycoconjugates (glycolipids and glycoproteins), and glycosides. Plant genomes generally encode many more GTs than animal genomes due to the synthesis of a cell wall and a wide variety of glycosylated secondary metabolites. The Arabidopsis thaliana genome is predicted to encode over 573 GTs that are currently classified into 42 diverse families. The biochemical functions of most of these GTs are still unknown. In this study, we updated the JBEI Arabidopsis GT clone collection by cloning an additional 105 GT cDNAs, 508 in total (89%), into Gateway-compatible vectors for downstream characterization. We further established a functional analysis pipeline using transient expression in tobacco (Nicotiana benthamiana) followed by enzymatic assays, fractionation of enzymatic products by reversed-phase HPLC (RP-HPLC) and characterization by mass spectrometry (MS). Using the GT14 family as an exemplar, we outline a strategy for identifying effective substrates of GT enzymes. By addition of UDP-GlcA as donor and the synthetic acceptors galactose-nitrobenzodiazole (Gal-NBD), β-1,6-galactotetraose (β-1,6-Gal4) and β-1,3-galactopentose (β-1,3-Gal5) to microsomes expressing individual GT14 enzymes, we verified the β-glucuronosyltransferase (GlcAT) activity of three members of this family (AtGlcAT14A, B, and E). In addition, a new family member (AT4G27480, 248) was shown to possess significantly higher activity than other GT14 enzymes. Our data indicate a likely role in arabinogalactan-protein (AGP) biosynthesis for these GT14 members. Together, the updated Arabidopsis GT clone collection and the biochemical analysis pipeline present an efficient means to identify and characterize novel GT catalytic activities.

Background Ceramide, a bioactive lipid, plays an essential role in the development of several pulmonary inflammatory diseases. Matrix metallopeptidase 9 (MMP-9) regulates the synthesis and degradation of extracellular matrix, and is associated with airway remodeling and tissue injury. This study was conducted to investigate the effects and underlying mechanisms of ceramide on MMP-9 expression in airway epithelium. Methods BEAS-2B cells, normal human bronchial epithelium cell lines, were pretreated with AG490, a selective janus tyrosine kinase 2 (JAK2) inhibitor, or Stattic, a selective signal transducer and activator of transcription 3 (STAT3) inhibitor. The cells were then stimulated with C6-ceramide. The levels of MMP-9 were determined by ELISA and real-time quantitative PCR (RT-qPCR). JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3) expression was examined by Western blotting. BALB/c mice were pretreated with AG490 or Stattic before intratracheally instillated with C6-ceramide. Pathological changes in lung tissues were examined by Hematoxylin and Eosin staining, Periodic-acid Schiff staining, and Masson’s trichrome staining. MMP-9, JAK2, p-JAK2, STAT3, and p-STAT3 expression in the lung tissues was examined by Western blotting. Results The expression of MMP-9, p-JAK2 and p-STAT3 in BEAS-2B cells was significantly increased after the treatment of C6-ceramide. Furthermore, the increased expression of MMP-9 induced by C6-ceramide was inhibited by AG490 and Stattic. Similar results were obtained in the lung tissues of C6-ceramide-exposed mice which were treated with AG490 or Stattic. Conclusions Ceramide could up-regulate MMP-9 expression through the activation of the JAK2/STAT3 pathway in airway epithelium. Targeted modulation of the ceramide signaling pathway may offer a potential therapeutic approach for inhibiting MMP-9 expression. This study points to a potentially novel approach to alleviating airway remodeling in inflammatory airway diseases.

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD. Keywords: BNip3, Mitophagy, NAFLD, Akebia saponin D

An original physico-chemical model is proposed that accounts for the conversion mechanism between Ti3+ and Ti4+ during Ti:sapphire crystal growth process. This model involves release of O2 from the crystal surface, which consumes aluminum vacancies. Consequently, these vacancies diffuse from the bulk crystal toward the surface, leading to the conversion of Ti4+ into Ti3+. A set of mass balance differential equations is established for these chemical species, taking into account diffusion and chemical reaction. The boundary condition for concentration of aluminum vacancies on crystal surface is given as the function of PO2 and temperature. A preliminary numerical simulation is performed to study the proposed model, using COMSOL Multiphysics® software. The obtained radial concentration distribution profiles of Ti3+ and Ti4+ are in qualitative agreement with the experimental results, showing that the proposed model has potential for further studying point defect reactions during crystal growth of ionic crystals.

Background: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. Summary: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.

Clusterin (CLU) is a stress-responding protein associated with cytoprotection in a broad range of pathological processes. However, clusterin's function in diabetes-induced endothelial dysfunction has not been defined. Herein, using two diabetes models, we investigated the role of clusterin in endothelial dysfunction triggered by diabetes and the molecular mechanisms involved. The results revealed that clusterin overexpression inhibited ICAM-1/VCAM-1 expression in aortas and improved endothelium-dependent vasodilatation in db/db diabetic mice and streptozotocin (STZ)-induced diabetes models. Consistently, in vitro, adenoviral clusterin overexpression reduced the expression of a range of pro-inflammatory cytokines and suppressed monocyte adhesion to endothelial cells subjected to high glucose and high palmitate. Further study indicated that clusterin overexpression mitigated mitochondrial excessive fission and reduced mitochondrial ROS production. Conversely, silencing clusterin aggravated mitochondrial fission and endothelial inflammatory activation in high glucose-exposed endothelial cells. Accumulating evidence indicates that impaired mitochondrial dynamics plays a considerable role in promoting endothelial dysfunction in diabetic subjects. Therefore, treatments targeting mitochondrial undue fission may be promising measures to prevent vascular complications of diabetes. Furthermore, AMP-activated protein kinase (AMPK) activation contributed to the modulation of mitochondrial dynamics executed by clusterin. Mechanistically, clusterin promoted the phosphorylation of AMPKα and its downstream target acetyl-CoA carboxylase (ACC), while the inhibition of AMPKα negated the improvement in mitochondrial dynamics provided by clusterin overexpression. Over all, these findings suggest that clusterin exerts beneficial effects in endothelial cells under diabetic conditions via inhibiting mitochondrial fragmentation mediated by AMPK.

Background Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. Aims This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. Materials and methods Cur (0.5, 1, and 2 μM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE−/− mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. Key findings As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. Significance This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function.

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

Bamboo shoots may become lignified after harvest and even deteriorate rapidly under low-temperature storage. Melatonin reportedly delays plant senescence. This study was designed to investigate the effect of melatonin on texture quality index, lignin formation, scavenging-enzyme activity, and transcription-factor expression in Moso bamboo ( Phyllostachys edulis ) shoots stored at 4 °C for 12 d. Application of melatonin effectively retarded shoot lignification, as indicated by a reduction in the rate of hardening and yellowing, as well as reduced lignin and cellulose contents. Furthermore, melatonin treatment inhibited phenylalanine ammonia-lyase and peroxidase activities significantly, while enhancing superoxide dismutase, catalase, and ascorbate peroxidase activities at different storage stages. Additionally, transcription factors of SND2 , KNAT7 , MYB20 and MYB85 from the NAC and MYB families were upregulated during postharvest storage of bamboo shoots, and melatonin treatment significantly inhibited their expression. These results suggest that the delaying effect of postharvest bamboo shoot lignification by melatonin treatment was mainly attributed to decreased activity of lignin biosynthesis-related enzymes and induced activation of antioxidant enzyme activity. Moreover, exogenous melatonin may be involved in the transcriptional regulation of the lignification process of bamboo shoots.

Graphitic C3N4 (g-C3N4), as an advanced metal free photocatalyst, is known to be poorly exfoliated and dispersed in water from its powder form which has a layered structure, the intrinsic plane structure is not destroyed, and this has largely limited its application. In this work, we report our progress on successful sonication exfoliation of g-C3N4 nanosheets in graphene oxide (GO) aqueous solution. By making use of the substrate character of GO, g-C3N4 nanosheets of unvaried intrinsic structure were exfoliated and anchored on the GO surface, resulting in a GO/g-C3N4 hybrid. Moreover, the photocurrent of the hybrid was largely reinforced at the optimal weight fraction of GO. As a result, the corresponding photocatalytic performance of the hybrid with optimized photocurrent character was largely improved.

BACKGROUND:Histone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear. METHODS:PBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-κB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA. RESULTS:HDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers. CONCLUSIONS:HDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function.

Graphitic C3N4 (g-C3N4), as an advanced metal free photocatalyst, is known to be poorly exfoliated and dispersed in water from its powder form which has a layered structure, the intrinsic plane structure is not destroyed, and this has largely limited its application. In this work, we report our progress on successful sonication exfoliation of g-C3N4 nanosheets in graphene oxide (GO) aqueous solution. By making use of the substrate character of GO, g-C3N4 nanosheets of unvaried intrinsic structure were exfoliated and anchored on the GO surface, resulting in a GO/g-C3N4 hybrid. Moreover, the photocurrent of the hybrid was largely reinforced at the optimal weight fraction of GO. As a result, the corresponding photocatalytic performance of the hybrid with optimized photocurrent character was largely improved.