Anxiety symptoms and risk factors in patients with SARS-cov-2 omicron variant in shanghai, China.

OBJECTIVES: The psychological effects of the COVID-19 pandemic may include anxiety. However, the association between demographic and physiological factors in COVID-19 associated anxiety symptoms is poorly understood. Therefore, the present cross-sectional study was conducted to examine anxiety symptoms and associated factors among patients with the SARS-CoV-2 omicron variant during quarantine in Shanghai. METHODS: The study was conducted between April 16, 2022, and May 21, 2022, at Fangcang Shelter Hospital in Shanghai, China. Data were collected using an anonymous online questionnaire. Demographic characteristics, respiratory symptoms, vaccine dose, comorbidities (such as hypertension and diabetes), type of work, and mental health symptoms were evaluated. Logistic regression was used to investigate the relationship between anxiety symptoms and risk factors. Stratification analysis was performed to investigate potential interactions. RESULTS: A total of 2132 patients with confirmed omicron variant SARS-CoV-2 infection were enrolled. The results showed that sex, age, type of work, respiratory symptoms, and comorbidities were positively associated with anxiety symptoms. Female gender (OR = 1.47, 95% CI = 1.11-1.94), nonmanual labor (OR = 1.62, 95% CI = 1.25-2.09), respiratory symptoms (OR = 3.19, 95% CI = 2.30-4.43), and other comorbidities (OR = 1.65, 95% = 1.09-2.50)were positively associated with anxiety symptoms. A significant interaction was observed between gender and nonmanual labor (OR = 1.54, 95% = 1.29-1.85), respiratory symptoms (OR = 2.06, 95% = 1.72-2.48), and comorbidities (OR = 1.57, 95% = 1.16-2.12), such that effects were stronger in women compared to men. There were also significant interactions between age group and nonmanual labor and respiratory symptoms in their association with anxiety symptoms. CONCLUSIONS: Alleviation of respiratory symptoms, addressing comorbidities, and both psychological and psychopharmacological treatments may help reduce anxiety symptoms following infection with the SARS-CoV-2 omicron variant in mainland China.

Unraveling the signaling pathways of phytohormones underlying salt tolerance in Elymus sibiricus: A transcriptomic and metabolomic approach.

Understanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding phytohormone-mediated tolerance pathways under salt stress in Elymus sibiricus, an important species for forage and ecological restoration, remains limited. In this study, transcriptomic and metabolomic approaches uncover the dynamics of phytohormonal signaling in Elymus sibiricus under salt stress. Notably, four hours after exposure to salt, significant activity was observed in the ABA, JA, IAA, and CTK pathways, with ABA, JA, JA-L-Ile, and IAA identified as key mediators in the response of Elymus sibiricus' to salinity. Moreover, SAPK3, Os04g0167900-like, CAT1, MKK2, and MPK12 were identified as potential central regulators within these pathways. The complex interactions between phytohormones and DEGs are crucial for facilitating the adaptation of Elymus sibiricus to saline environments. These findings enhance our understanding of the salt tolerance mechanisms in Elymus sibiricus and provide a foundation for breeding salt-resistant varieties.

The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis.

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase respiratory burst oxidase homolog D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in the rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N-terminus of RBOHD at 4 serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16-RBOHD module shapes the ROS production during hypoxia and reoxygenation in Arabidopsis.

7-Methoxy-13-dehydroxypaxilline: New indole diterpenoid from an endophytic fungus Penicillium sp. Nb 19.

ABSTACTA chemical investigation of the endophyte Penicillium sp. Nb 19, isolated from leaves of the traditionally medical plant Baphicacanthus cusia (Nees) Bremek., yielded one new indole diterpenoid, 7-methoxy-13-dehydroxypaxilline (1) together with seven known metabolites (2-8). The obtained structure of compound 1 was elucidated by its spectroscopic data. In addition, the absolute configuration of compound 6 was confirmed by ECD for the first time. Compounds 1-6 were evaluated for antitumor activity against MCF-7, HepG2, and HCCC-9810 cell lines.

The landscape of investigator-initiated oncology trials conducted in mainland China during the past decade (2010-2019).

The number of clinical trials conducted in mainland China, including investigator-initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer-related IITs. We performed a comprehensive analysis of the landscape of cancer-related IITs in mainland China in the past decade. All cancer-related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer-related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double-blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer-related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015-2019 vs. 40.2% in 2010-2014, p < 0.001) and data monitoring committee use (44.5% vs. 40.0%, p = 0.001) and a decrease in randomization (51.5% vs. 62.7%, p < 0.001) and funding (36.4% vs. 56.3%, p < 0.001) between these periods. We also observed changes in intervention type (decrease in cytotoxic drug therapy [34.8% vs. 48.9%, p < 0.001]; increase in targeted therapy [17.8% vs. 14.2%, p = 0.004], immune checkpoint inhibitor therapy [6.6% vs. 0.0%, p < 0.001], and immune cell therapy [9.6% vs. 4.5%, p < 0.001]). Details of cancer-related IITs conducted during the past decade illustrate the merits of oncology research in mainland China. Although the increased quantity of IITs is encouraging, limitations remain regarding the quality of clinical trials, regional imbalances, and funding allocation.

A recombinase polymerase amplification-SYBR Green I assay for the rapid and visual detection of Brucella.

Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Liraglutide Suppresses Myocardial Fibrosis Progression by Inhibiting the Smad Signaling Pathway.

OBJECTIVE: Liraglutide is a commonly used hypoglycemic agent in clinical practice, and has been demonstrated to have protective effects against the development of cardiovascular disease. However, its potential role in myocardial fibrosis remains unexplored. The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts. METHODS: Primary rat adult fibroblasts were isolated, cultured, and randomly allocated into 4 groups: control group, transforming growth factor beta1 (TGFß1) stimulation group, liraglutide group, and TGFß1+liraglutide group. Fibroblast activation was induced by TGFß1. Cell proliferation activity was assessed using the CKK-8 kit, and cellular activity was determined using the MTT kit. Reverse transcrition-quantitative polymerase chain reaction (RT-qPCR) was utilized to quantify the level of collagen transcription, immunofluorescence staining was performed to detect the expression level of type III collagen and α-smooth muscle protein (α-SMA), and immunoblotting was conducted to monitor alterations in signal pathways. RESULTS: The addition of 10, 25, 50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts (P>0.05). The rate of cellular proliferation was significantly higher in the TGFßl stimulation group than in the control group. However, the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFßl-induced cell proliferation (P<0.05). The RT-qPCR results revealed that the transcription levels of type I collagen, type III collagen, and α-SMA were significantly upregulated in the TGFßl stimulation group, when compared to the control group (P<0.05). However, the expression levels of these aforementioned factors significantly decreased in the TGFßl+liraglutide group (P<0.05). The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen and α-SMA in the TGFßl stimulation group, when compared to the control group (P<0.05). However, these expression levels significantly decreased in the TGFßl+liraglutide group, when compared to the TGFßl stimulation group (P<0.05). The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFßl stimulation group, when compared to the control group (P<0.05), while these decreased in the TGFßl+liraglutide group (P<0.05). CONCLUSION: Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway, reducing the activation and secretion of cardiac fibroblasts.

A rapid and sensitive triplex-recombinase polymerase amplification for simultaneous differentiation of Brucella abortus, Brucella melitensi s, and Brucella suis in sera and foods.

Brucella is the causative agent of brucellosis and can be transmitted to humans through aerosolized particles or contaminated food. Brucella abortus (B. abortus), Brucella melitensis (B. melitensis), and Brucella suis (B. suis) are the most virulent of the brucellae, but the traditional detection methods to distinguish them are time-consuming and require high instrumentation. To obtain epidemiological information on Brucella during livestock slaughter and food contamination, we developed a rapid and sensitive triplex recombinant polymerase amplification (triplex-RPA) assay that can simultaneously detect and differentiate between B. abortus, B. melitensis, and B. suis. Three pairs of primers (B1O7F/B1O7R, B192F/B192R, and B285F/B285R) were designed and screened for the establishment of the triplex-RPA assay. After optimization, the assay can be completed within 20 min at 39°C with good specificity and no cross-reactivity with five common pathogens. The triplex-RPA assay has a DNA sensitivity of 1-10 pg and a minimum detection limit of 2.14 × 104-2.14 × 105 CFU g-1 in B. suis spiked samples. It is a potential tool for the detection of Brucella and can effectively differentiate between B. abortus, B. melitensis, and B. suis S2, making it a useful tool for epidemiological investigations.

The Relationship Between Social Support and Suicide Resilience in Chinese Cancer Patients: A Serial Multiple Mediation Model Through Self-care Self-efficacy and Meaning in Life.

BACKGROUND: A growing body of literature has shown a higher risk of suicide in cancer patients compared with the general population. Early detection of factors related to suicide resilience in cancer patients could prevent loss of life. OBJECTIVE: The study aimed to investigate the serial-multiple mediation of self-care self-efficacy and meaning in life in the relationship between social support and suicide resilience among Chinese cancer patients. METHODS: A cross-sectional investigation of 287 cancer patients using a battery of self-reported questionnaires was performed. For preliminary analyses, descriptive, univariate, and Pearson correlation analyses were performed. Mediation analyses were tested using a serial-multiple mediation model (PROCESS model 6). RESULTS: Mediation analysis indicated the indirect effects of social support on suicide resilience mediated solely by either self-care self-efficacy (point estimate = 0.20; 95% confidence interval [CI], 0.12-0.30), or by meaning in life (point estimate = 0.06; 95% CI, 0.01-0.12), or by the multiple mediation of self-care self-efficacy to meaning in life (point estimate = 0.03; 95% CI, 0.01-0.06). CONCLUSIONS: The findings demonstrated the crucial direct or indirect effects of social support, self-care self-efficacy, and meaning in life on facilitating cancer patients' suicide resilience. IMPLICATIONS FOR PRACTICE: Oncology nurses, as 24-hour care providers for cancer patients, may interact with and be important sources for the psychosocial care of cancer patients at risk of suicide. Prevention and intervention efforts must be directed at assisting cancer patients, improving self-care self-efficacy, and finding meaning in life after a cancer diagnosis.

BsLPMO10A from Bacillus subtilis boosts the depolymerization of diverse polysaccharides linked via ß-1,4-glycosidic bonds.

Lytic polysaccharide monooxygenase (LPMO) is known as an oxidatively cleaving enzyme in recalcitrant polysaccharide deconstruction. Herein, we report a novel AA10 LPMO derived from Bacillus subtilis (BsLPMO10A). A substrate specificity study revealed that the enzyme exhibited an extensive active-substrate spectrum, particularly for polysaccharides linked via ß-1,4 glycosidic bonds, such as ß-(Man1 â†’ 4Man), ß-(Glc1 â†’ 4Glc) and ß-(Xyl1 â†’ 4Xyl). HPAEC-PAD and MALDI-TOF-MS analyses indicated that BsLPMO10A dominantly liberated native oligosaccharides with a degree of polymerization (DP) of 3-6 and C1-oxidized oligosaccharides ranging from DP3ox to DP6ox from mixed linkage glucans and beechwood xylan. Due to its synergistic action with a variety of glycoside hydrolases, including glucanase IDSGLUC5-38, xylanase TfXYN11-1, cellulase IDSGLUC5-11 and chitinase BtCHI18-1, BsLPMO10A dramatically accelerated glucan, xylan, cellulose and chitin saccharification. After co-reaction for 72 h, the reducing sugars in Icelandic moss lichenan, beechwood xylan, phosphoric acid swollen cellulose and chitin yielded 3176 ± 97, 7436 ± 165, 649 ± 44, and 2604 ± 130 µmol/L, which were 1.47-, 1.56-, 1.44- and 1.25-fold higher than those in the GHs alone groups, respectively (P < 0.001). In addition, the synergy of BsLPMO10A and GHs was further validated by the degradation of natural feedstuffs, the co-operation of BsLPMO10A and GHs released 3266 ± 182 and 1725 ± 107 µmol/L of reducing sugars from Oryza sativa L. and Arachis hypogaea L. straws, respectively, which were significantly higher than those produced by GHs alone (P < 0.001). Furthermore, BsLPMO10A also accelerated the liberation of reducing sugars from Celluclast® 1.5 L, a commercial cellulase cocktail, on filter paper, A. hypogaea L. and O. sativa L. straws by 49.58 % (P < 0.05), 72.19 % (P < 0.001) and 54.36 % (P < 0.05), respectively. This work has characterized BsLPMO10A with a broad active-substrate scope, providing a promising candidate for lignocellulosic biomass biorefinery.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Physiological pharmacokinetic model of children and its application of modeling software / 药学学报

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

Age-Related Clinical Characteristics, Inflammatory Features, Phenotypes, and Treatment Response in Asthma.

BACKGROUND: Emerging evidence suggests that aging affects asthma outcomes, but the mechanism remains largely unexplored. OBJECTIVE: To explore age-related clinical characteristics, inflammatory features, phenotypes, and treatment response in asthma. METHODS: This was a prospective cohort study of asthmatic patients with a 12-month follow-up in a real-world setting. Clinical inflammatory and phenotypic characteristics, future risk for exacerbations, and treatment response were assessed across different age groups (young was defined as age 18 to 39 years; middle-aged, 40 to 64 years; and elderly, 65 years or older). RESULTS: Compared with young (n = 106) and middle-aged (n = 179) asthmatic patients, elderly patients (n = 55) had worse airway obstruction, more comorbidities including chronic obstructive pulmonary disease and diabetes, less atopy, and lower levels of IgE and FeNO, and were more likely to have late-onset and fixed airflow obstruction asthma and a reduced risk for having type 2 profile asthma. Levels of IFN-gamma, IL-17A, and IL-8 in induced sputum were significantly increased in elderly asthmatic patients (all P < .05). Path analysis indicated that age directly and significantly led to future exacerbations in asthma, partially mediated by an upregulation of airway IFN-gamma. Moreover, elderly patients with asthma had a reduced treatment response (improvement in FEV1 of 12% or greater, or 200 mL, and a reduction in Borg scores of 1 or greater) (adjusted odds ratio = 0.11; 95% CI, 0.02-0.52; and adjusted odds ratio = 0.12; 95% CI, 0.03-0.49, respectively). CONCLUSIONS: This study confirms that asthma in the elderly population represents a specific phenotype and indicates that aging can influence asthma in terms of clinical characteristics, inflammatory features, exacerbations, and treatment response.

Cloning, expression, and characterization of two pectate lyases isolated from the sheep rumen microbiome.

Pectate lyases (Pels) have a vital function in degradation of the primary plant cell wall and the middle lamella and have been widely used in the industry. In this study, two pectate lyase genes, IDSPel16 and IDSPel17, were cloned from a sheep rumen microbiome. The recombinant enzymes were expressed in Escherichia coli and functionally characterized. Both IDSPel16 and IDSPel17 proteins had an optimal temperature of 60 ℃, and an optimal pH of 10.0. IDSPel16 was relatively stable below 60 °C, maintaining 77.51% residual activity after preincubation at 60 °C for 1 h, whereas IDSPel17 denatured rapidly at 60 °C. IDSPel16 was relatively stable between pH 6.0 and 12.0, after pretreatment for 1 h, retaining over 60% residual activity. IDSPel16 had high activity towards polygalacturonic acid, with a Vmax of 942.90 ± 68.11, whereas IDSPel17 had a Vmax of only 28.19 ± 2.23 µmol/min/mg. Reaction product analyses revealed that IDSPel17 liberated unsaturated digalacturonate (uG2) and unsaturated trigalacturonate (uG3) from the substrate, indicating a typical endo-acting pectate lyase (EC 4.2.2.2). In contrast, IDSPel16 initially generated unsaturated oligogalacturonic acids, then converted these intermediates into uG2 and unsaturated galacturonic acid (uG1) as end products, a unique depolymerization profile among Pels. To the best of our knowledge, the IDSPel16 discovered with both endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities. These two pectate lyases, particularly the relatively thermo- and pH-stable IDSPel16, will be of interest for potential application in the textile, food, and feed industries. KEY POINTS: • Two novel pectate lyase genes, IDSPel16 and IDSPel17, were isolated and characterized from the sheep rumen microbiome. • Both IDSPel16 and IDSPel17 are alkaline pectate lyases, releasing unsaturated digalacturonate and unsaturated trigalacturonate from polygalacturonic acid. • IDSPel16, a bifunctional pectate lyase with endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities, could be a potential candidate for industrial application.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

Heterologous expression and characterization of two novel glucanases derived from sheep rumen microbiota.

ß-Glucanases are a suite of glycoside hydrolases that depolymerize ß-glucan into cellooligosaccharides and/or monosaccharides and have been widely used as feed additives in livestock. In this study, two novel glucanase genes, IDSGluc5-26 and IDSGluc5-37, derived from sheep rumen microbiota, were expressed and functionally characterized. The optimal temperatures/pH of recombinant IDSGLUC5-26 and IDSGLUC5-37 were 50 °C/5.0 and 40 °C/6.0, respectively. Notably, IDSGLUC5-26 showed considerable stability under acidic conditions. Both IDSGLUC5-26 and IDSGLUC5-37 showed the highest activities toward barley ß-glucan, with Vmax values of 89.96 ± 9.19 µmol/min/mg and 459.50 ± 25.02 µmol/min/mg, respectively. Additionally, these two glucanases demonstrated hydrolysis of Icelandic moss lichenan and konjac gum, IDSGLUC5-26 releasing cellobiose (G2; occupying 17.37% of total reducing sugars), cellotriose (G3; 23.97%), and cellotetraose (G4; 30.93%) from barley ß-glucan and Icelandic moss lichenan after 10 min and suggestive of a typical endo-ß-1,4-glucanase (EC.3.2.1.4). In contrast, IDSGLUC5-37 was capable of liberating dominant G3 (64.11% or 67.55%) from barley ß-glucan or Icelandic moss lichenan, suggesting that the enzyme was likely an endo-ß-1,3 - 1,4-glucanases/lichenase (EC3.2.1.73). These findings describe the expression and characterization of two novel glucanase genes from sheep rumen microbiota. The two recombinant enzymes, particularly the acid-stable IDSGLUC5-26, will be of interest for potential application in food-/feed-additive development.

Circulating FAM19A5 level is associated with the presence and severity of coronary artery disease.

BACKGROUND: Family with sequence similarity 19 member A5 (FAM19A5) has been identified as a novel adipokine that plays an important role in inhibiting inflammation and vascular smooth muscle cell proliferation. However, the clinical associations between FAM19A5 levels and the presence and severity of coronary artery disease (CAD) remains uncertain. METHODS: We measured serum FAM19A5 levels in 186 CAD patients and 58 non-CAD patients who underwent coronary arteriography (CAG) recruited in Shanxi Medical University Affiliated Second Hospital. The severity of coronary artery stenosis was represented in the Gensini score. Logistic and linear regression analyses were used to analyze the relationship between serum FAM19A5 and CAD. RESULTS: Serum FAM19A5 levels in CAD group were significantly lower than those in the non-CAD group [1.53 (1.13-2.27) ng/mL vs 2.33 (1.69-3.51) ng/mL; P = 0.013]. Logistic regression analysis showed that decreased serum FAM19A5 level was a risk factor for CAD (OR: 0.563, 95% CI: 0.409-0.776, P < 0.001). Circulating FAM19A5 levels were negatively associated with the Gensini score. FAM19A5 had 87.9% sensitivity and 52.7% specificity for identifying CAD. CONCLUSIONS: Serum FAM19A5 levels were negatively associated with the presence and severity of CAD and may represent a novel biomarker for diagnosing and indication the severity of CAD.

Abiraterone, Orteronel, Enzalutamide and Docetaxel: Sequential or Combined Therapy?

Objective: To summarize the current therapeutic status using chemotherapeutic agent docetaxel and endocrine therapeutic agents (ARAT, abiraterone, orteronel or enzalutamide) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including sequential therapy and combined therapy, to promote the consensus on the optimal regimen for achieving superior treatment efficacy. Methods: Through literature search in PubMed, articles with the following relevant keywords were collected and anlyzed: CRPC, abiraterone, orteronel and enzalutamide, median survival, overall survival, prostate specific antigen (PSA), PSA response rate and median radiologic progression-free survival. Results: Fifty-eight articles were obtained and analyzed in this review. These articles included androgen axis-targeting agents after docetaxel, docetaxel after androgen axis-targeting agents, Triple sequential and combination therapy, covering four current drugs for mCRPC treatment: docetaxel, abiraterone, orteronel, and enzalutamide. It was found that there may be some cross-resistance between androgen axis-targeting agents, which will reduce the efficacy of subsequent drug treatment. Although neither of the studies of using combination therapy showed serious drug toxicity, the efficacy of sequential therapy was not as good as expected. Most adverse reactions after treatment were reported to be level 1-2. Conclusion: Based on the results of the current studies, abiraterone followed by enzalutamide treatment is the best sequential treatment for most docetaxel-naïve patients. This treatment achieves not only good OS, but also PFS and PSA response rates. In addition, for patients who have previously failed docetaxel treatment, enzalutamide is the best choice as the subsequent treatment.