A general chemical principle for creating closure-stabilizing integrin inhibitors.

Integrins are validated drug targets with six approved therapeutics. However, small-molecule inhibitors to three integrins failed in late-stage clinical trials for chronic indications. Such unfavorable outcomes may in part be caused by partial agonism, i.e., the stabilization of the high-affinity, extended-open integrin conformation. Here, we show that the failed, small-molecule inhibitors of integrins αIIbß3 and α4ß1 stabilize the high-affinity conformation. Furthermore, we discovered a simple chemical feature present in multiple αIIbß3 antagonists that stabilizes integrins in their bent-closed conformation. Closing inhibitors contain a polar nitrogen atom that stabilizes, via hydrogen bonds, a water molecule that intervenes between a serine residue and the metal in the metal-ion-dependent adhesion site (MIDAS). Expulsion of this water is a requisite for transition to the open conformation. This change in metal coordination is general to integrins, suggesting broad applicability of the drug-design principle to the integrin family, as validated with a distantly related integrin, α4ß1.

Serum total iron-binding capacity and iron status in patients with non-dialysis-dependent chronic kidney disease: A cross-sectional study in Vietnam.

BACKGROUND AND OBJECTIVES: We performed this study to evaluate serum iron and ferritin concentrations, serum total iron-binding capacity (TIBC), and proportion of overall iron deficiency among patients with non-dialysisdependent chronic kidney disease (ND-CKD). METHODS AND STUDY DESIGN: A hospital-based cross-sectional observational study was conducted on 175 adult patients with stage 3-5 chronic kidney disease (CKD) by using 51 healthy age-sex-matched Vietnamese adults as the control group. We next examined the prevalence of anemia and determined the serum iron and ferritin concentrations and TIBC. Anemia in CKD was defined as hemoglobin levels <13 g/dL in men and <12 g/dL in women. Transferrin saturation (TSAT, %) was calculated as (serum iron x 100)/TIBC. Functional iron deficiency was defined as serum ferritin >100 ng/mL and TSAT <20%, and absolute iron deficiency was defined as serum ferritin <100 ng/mL and TSAT <20%. Overall iron deficiency was defined as the presence of either absolute or functional iron deficiency. RESULTS: Anemia prevalence in our study was approximately 88.6% with a mean hemoglobin concentration of 9.71±2.26 g/dL. The median serum TIBC was lower in the CKD group (50.4 µmol/L) than in the control group (66.0 µmol/L; p<0.001). The proportion of overall iron deficiency was 44.0%. TIBC had a diagnostic value for overall iron deficiency (area under the ROC curve=0.81; p<0.001). CONCLUSIONS: Anemia and iron deficiency are common in Vietnamese patients with NDCKD. TIBC had diagnostic value for overall iron deficiency.

Anti-cholinesterase activity of lycopodium alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis.

A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC50 value of 54.3 µg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC50 value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors.

University brand: A systematic literature review.

Despite its significant role, brand management is an oft-overlooked and challenging aspect in the development of academic institutions, especially in higher education context. Based on a systematic review of journal articles from various sources including ScienceDirect, Emerald Insight and SpringerLink during the 2000-2021 period, the authors of this paper seek to identify, evaluate, and analyze university brand. After careful consideration of academic publications based on their relevance for the research objectives, 43 articles have been included in this comprehensive and integrative review. Special attention is paid to the theories underlying brand management, brand positioning, brand identity of a higher education institution, marketing strategies, as well as implications for management, students, and staff. Moreover, some valuable lessons which a university can learn from a company in marketing are identified. Thereby, the competitive advantages of a university would be firmly enhanced. It is our hope that this paper will explore a new path for further research and provide another perspective for administrators, authors and practitioners in the area of university brand.

Identification of Five Serotypes of Enteropathogenic Escherichia coli from Diarrheic Calves and Healthy Cattle in Belgium and Comparative Genomics with Shigatoxigenic E. coli.

Enteropathogenic Escherichia coli (EPEC) produce attaching/effacing (AE) lesions and cause non-bloody diarrhea in mammals. A minority of bovine EPEC belong to one of the ten classical serotypes of human and bovine AE-STEC. The purpose of this study was to identify five non-classical O serotypes (O123/186, O156, O177, O182, and O183) among bovine EPEC and to characterize their virulence repertoires by whole genome sequencing. Around 40% of the 307 EPEC from 307 diarrheic calves, 368 EPEC from 47 healthy cattle, and 131 EPEC from 36 healthy calves in dairy farms were analyzed. Serotype O177 was the most frequent among EPEC from diarrheic and healthy calves, while the O156 was the most frequent in healthy cattle. The genomic analysis identified different H serotypes, MLSTypes, and/or eae gene subtypes among the O156 and O177 EPEC, while the O182 was homogeneous. The virulence gene profiles of bovine EPEC were closely related to each other and to the profiles of ten bovine and human AE-STEC. These results emphasize the need for additional studies to identify more O:H serotypes of bovine EPEC and to elucidate their origin and evolution of EPEC with regard to AE-STEC belonging to the same O:H serotypes.

Facile Synthesis of Carboxymethyl Cellulose Coated Core/Shell SiO2@Cu Nanoparticles and Their Antifungal Activity against Phytophthora capsici.

Cu nanoparticles are a potential material for creating novel alternative antimicrobial products due to their unique antibacterial/antifungal properties, stability, dispersion, low cost and abundance as well as being economical and ecofriendly. In this work, carboxymethyl cellulose coated core/shell SiO2@Cu nanoparticles (NPs) were synthesized by a simple and effective chemical reduction process. The initial SiO2 NPs, which were prepared from rice husk ash, were coated by a copper ultrathin film using hydrazine and carboxymethyl cellulose (CMC) as reducing agent and stable agent, respectively. The core/shell SiO2@Cu nanoparticles with an average size of ~19 nm were surrounded by CMC. The results indicated that the SiO2@Cu@CMC suspension was a homogenous morphology with a spherical shape, regular dispersion and good stability. Furthermore, the multicomponent SiO2@Cu@CMC NPs showed good antifungal activity against Phytophthora capsici (P. capsici). The novel Cu NPs-based multicomponent suspension is a key compound in the development of new fungicides for the control of the Phytophthora disease.

COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance.

While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow-COVseq-which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We benchmark COVseq against a standard library preparation method (NEBNext) on 29 SARS-CoV-2 positive samples, reaching 95.4% of concordance between single-nucleotide variants detected by both methods. Application of COVseq to 245 additional SARS-CoV-2 positive samples demonstrates the ability of the method to reliably detect emergent VOC as well as its compatibility with downstream phylogenetic analyses. A cost analysis shows that COVseq could be used to sequence thousands of samples at less than 15 USD per sample, including library preparation and sequencing costs. We conclude that COVseq is a versatile and scalable method that is immediately applicable for SARS-CoV-2 genomic surveillance and easily adaptable to other pathogens such as influenza viruses.

Measuring serum beta2-microglobulin to predict long-term mortality in hemodialysis patients using low-flux dialyzer reuse.

PURPOSE: Beta2-microglobulin (ß2-M) is recognized as a surrogate marker relating to the mechanisms of dialysis-associated amyloidosis. Few studies have evaluated the association of serum ß2-M with clinical outcome in hemodialysis patients using high-flux type. However, study on patients using low-flux dialyzer reuse has not been done yet. PATIENTS AND METHODS: Using serum ß2-M level on predicting long-term mortality of hemodialysis patients was examined in 326 prevalent hemodialysis patients (45.59±14.46 years, hemodialysis duration of 47.5 (26-79) months, 186 males and 140 females). The patients were divided into 3 groups with equal number of patients, according to their serum ß2-M levels: group A (n=109, serum ß2-M concentration ≤55.7 mg/L), group B (n=109, serum ß2-M level from 55.8 mg/L to 75.4 mg/L) and group C (n=108, serum ß2-M concentration >75.4 mg/L). RESULTS: During the follow-up period of 5 years, there were 75 all-cause deaths (23.0%). Kaplan-Meier analysis revealed that all-cause mortality in the higher ß2-M group was significantly higher compared to that in the lower ß2-M groups (p<0.001). Serum ß2-M level was a significant predictor for all-cause mortality (AUC =0.898; p<0.001; Cut-off value: 74.9 mg/L, Se=93.3%, Sp=92.9%). CONCLUSION: Serum ß2-M levels were a significant predictor of long-term mortality in hemodialysis patients, who use only low-flux dialyzers and reuse 6 times.

Prenatal diagnostic services in three regional centers in Vietnam.

OBJECTIVES: This study aims to give information on the prenatal diagnostic (PND) services provided in three major regional PND centers in Vietnam. METHODS: This cross-sectional study was conducted in early 2014. An inventory of services, human resources, facilities, and equipment and in-depth interviews were carried out. RESULTS: Three regional PND centers were set up between 2007 and 2014, and technical guidelines on PND tests were released by the Ministry of Health in 2010. There were a variety of services among centers, and the number of services provided by the three PND centers was far below the target set by the Ministry of Health. There is still limited capacity of human resources, facilities, and equipment in PND centers. Different measures were implemented by hospitals to improve capacity, including counseling. CONCLUSIONS: Despite a late start, with government support, PND services in Vietnam have developed quickly. However, to reach the objectives of 15 % of women receiving PND services by 2015 and 50 % by 2020, several actions should be taken to expand the service coverage and capacity of centers.

Precursors of 2-acetyl-1-pyrroline, a potent flavor compound of an aromatic rice variety.

The biological formation of a potent flavor compound, 2-acetyl-1-pyrroline, in the aromatic rice variety (Khao Dawk Mali 105) was studied in seedlings and callus of the rice. Concentrations of 2-acetyl-1-pyrroline were determined by GC-MS-SIM using an isotope dilution method. Increases in concentration occurred when proline, ornithine, and glutamate were present in solution, with proline increasing the concentration by more than 3-fold compared to that of the control. Results of tracer experiments using (15)N-proline, (15)N-glycine, and proline-1-(13)C indicated that the nitrogen source of 2-acetyl-1-pyrroline was proline, whereas the carbon source of the acetyl group was not the carboxyl group of proline. 2-acetyl-1-pyrroline was formed in the aromatic rice at temperatures below that of thermal generation in bread baking, and formed in the aerial part of aromatic rice from proline as the nitrogen precursor.

Standardization of the methylation­specific PCR method for analyzing BRCA1 and ER methylation.

The significant differences in DNA methylation that are considered to be a biomarker for the diagnosis of cancer are a barrier to the application of biomarkers in the clinical field. In the present study, new primers were designed and further standard controls were set up to validate the accuracy of the methylation­specific PCR (MSP), a method widely used to analyze DNA methylation. By analyzing the methylation pattern of breast cancer 1 (BRCA1) and estrogen receptor (ER) in 60 patients with breast cancer, the number of cases of methylated BRCA1 and ER detected by the primer was 7/60 and 21/60, respectively, whereas that detected by the previous widely used primers was 25/60 and 47/60, respectively. Sequencing of the MSP products indicated that the 18 and 26 false-positive methylations of BRCA1 and ER, respectively, were due to insufficient validation of the previously used primers. Thus, the present study proposes that all studies based on the MSP approach should incorporate more controls to validate the precision of the MSP primers.

Synthesis of spiroannulated oligopyrrole macrocycles derived from lithocholic acid.

Two new steroidal spiroannulated calix[4]pyrroles 5 and 10, derived from bile acids (lithocholate), were prepared by the acid catalyzed condensation of methyl-3,3-bis(pyrrol-2-yl)-5beta-cholan-24-oate 3 with carbonyl compounds and with 2,2'-propane-2,2-diylbis(1H-pyrrole), respectively. The new compounds were fully characterized by physicochemical methods.

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.