Cryo-EM structures of wild-type and E138K/M184I mutant HIV-1 RT/DNA complexed with inhibitors doravirine and rilpivirine.

Structures trapping a variety of functional and conformational states of HIV-1 reverse transcriptase (RT) have been determined by X-ray crystallography. These structures have played important roles in explaining the mechanisms of catalysis, inhibition, and drug resistance and in driving drug design. However, structures of several desired complexes of RT could not be obtained even after many crystallization or crystal soaking experiments. The ternary complexes of doravirine and rilpivirine with RT/DNA are such examples. Structural study of HIV-1 RT by single-particle cryo-electron microscopy (cryo-EM) has been challenging due to the enzyme's relatively smaller size and higher flexibility. We optimized a protocol for rapid structure determination of RT complexes by cryo-EM and determined six structures of wild-type and E138K/M184I mutant RT/DNA in complexes with the nonnucleoside inhibitors rilpivirine, doravirine, and nevirapine. RT/DNA/rilpivirine and RT/DNA/doravirine complexes have structural differences between them and differ from the typical conformation of nonnucleoside RT inhibitor (NNRTI)-bound RT/double-stranded DNA (dsDNA), RT/RNA-DNA, and RT/dsRNA complexes; the primer grip in RT/DNA/doravirine and the YMDD motif in RT/DNA/rilpivirine have large shifts. The DNA primer 3'-end in the doravirine-bound structure is positioned at the active site, but the complex is in a nonproductive state. In the mutant RT/DNA/rilpivirine structure, I184 is stacked with the DNA such that their relative positioning can influence rilpivirine in the pocket. Simultaneously, E138K mutation opens the NNRTI-binding pocket entrance, potentially contributing to a faster rate of rilpivirine dissociation by E138K/M184I mutant RT, as reported by an earlier kinetic study. These structural differences have implications for understanding molecular mechanisms of drug resistance and for drug design.

HISTONE DEACETYLASE 9 promotes hypocotyl-specific auxin response under shade.

Vegetative shade causes an array of morphological changes in plants called shade avoidance syndrome, which includes hypocotyl and petiole elongation, leaf hyponasty, reduced leaf growth, early flowering and rapid senescence. Here, we show that loss-of-function mutations in HISTONE DEACETYLASE 9 (HDA9) attenuated the shade-induced hypocotyl elongation in Arabidopsis. However, the hda9 cotyledons and petioles under shade were not significantly different from those in wild-type, suggesting a specific function of HDA9 in hypocotyl elongation in response to shade. HDA9 expression levels were stable under shade and its protein was ubiquitously detected in cotyledon, hypocotyl and root. Organ-specific transcriptome analysis unraveled that shade induced a set of auxin-responsive genes, such as SMALL AUXIN UPREGULATED RNAs (SAURs) and AUXIN/INDOLE-3-ACETIC ACIDs (AUX/IAAs) and their induction was impaired in hda9-1 hypocotyls. In addition, HDA9 binding to loci of SAUR15/65, IAA5/6/19 and ACS4 was increased under shade. The genetic and organ-specific gene expression analyses further revealed that HDA9 may cooperate with PHYTOCHROME-INTERACTING FACTOR 4/7 in the regulation of shade-induced hypocotyl elongation. Furthermore, HDA9 and PIF7 proteins were found to interact together and thus it is suggested that PIF7 may recruit HDA9 to regulate the shade/auxin responsive genes in response to shade. Overall, our study unravels that HDA9 can work as one component of a hypocotyl-specific transcriptional regulatory machinery that activates the auxin response at the hypocotyl leading to the elongation of this organ under shade.

epiTCR: a highly sensitive predictor for TCR-peptide binding.

MOTIVATION: Predicting the binding between T-cell receptor (TCR) and peptide presented by human leucocyte antigen molecule is a highly challenging task and a key bottleneck in the development of immunotherapy. Existing prediction tools, despite exhibiting good performance on the datasets they were built with, suffer from low true positive rates when used to predict epitopes capable of eliciting T-cell responses in patients. Therefore, an improved tool for TCR-peptide prediction built upon a large dataset combining existing publicly available data is still needed. RESULTS: We collected data from five public databases (IEDB, TBAdb, VDJdb, McPAS-TCR, and 10X) to form a dataset of >3 million TCR-peptide pairs, 3.27% of which were binding interactions. We proposed epiTCR, a Random Forest-based method dedicated to predicting the TCR-peptide interactions. epiTCR used simple input of TCR CDR3ß sequences and antigen sequences, which are encoded by flattened BLOSUM62. epiTCR performed with area under the curve (0.98) and higher sensitivity (0.94) than other existing tools (NetTCR, Imrex, ATM-TCR, and pMTnet), while maintaining comparable prediction specificity (0.9). We identified seven epitopes that contributed to 98.67% of false positives predicted by epiTCR and exerted similar effects on other tools. We also demonstrated a considerable influence of peptide sequences on prediction, highlighting the need for more diverse peptides in a more balanced dataset. In conclusion, epiTCR is among the most well-performing tools, thanks to the use of combined data from public sources and its use will contribute to the quest in identifying neoantigens for precision cancer immunotherapy. AVAILABILITY AND IMPLEMENTATION: epiTCR is available on GitHub (https://github.com/ddiem-ri-4D/epiTCR).

Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks.

BACKGROUND: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. METHODS: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. RESULTS: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. CONCLUSIONS: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.

Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos.

BACKGROUND: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs. METHODS: Human ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks. RESULTS: Our standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63+ (∼30%) and CD81+ -CD63+ (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%. CONCLUSIONS: This study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation.

Chemical Compositions, Molecular Docking, Anti-Inflammatory, and Anti-Cancer Effects of the Leaf Essential Oils Isolated from Three Species of the Rutaceae Family in Vietnam.

Three species of the Rutaceae family, including Acronychia pedunculata, Euodia lepta, and Severinia monophylla have been used in traditional medicine. However, the comparison of the chemical composition, anti-cancer, and anti-inflammatory effects of the leaf essential oils of these species have not been investigated yet. A total of 38 compounds were identified via gas chromatography-mass spectrometry, comprising 96.5-99.8% of the total composition.  Both A. pedunculata and E. lepta essential oils exhibited strong inhibitory effects against cancer cells (IC50: 59.04-97.52 µg/mL) while that of S. monophylla showed a lower anti-cancer effect (IC50>100 µg/mL). Among three essential oils, only the E. lepta leaf oil demonstrated a high anti-inflammatory effect on LPS-stimulated macrophages (IC50=6.47 ± 0.65 µg/mL), while the other showed a moderate anti-inflammatory effect (IC50>50 µg/mL). Molecular docking studies also suggested the binding potential of the key compounds from three essential oils against inducible nitric oxide synthase and cyclooxygenase-2, two proteins associated with inflammatory response, with the negative energies ranging from -41.0 to -71.9 kcal/mol. The present findings suggest the leaf essential oils from these species as potential medicines for treatment of cancer or inflammation associated diseases, especially the ones from A. pedunculata and E. lepta oils.

A pre-post evaluation of a digital intervention to improve psychosocial outcomes of caregivers of people living with cancer in Vietnam.

OBJECTIVES: To evaluate a co-designed intervention using digital resources "Vietnam Cancer Caring Coping" (V-CCC) on the health literacy, depression, and quality of life of caregivers supporting a cancer patient in oncology hospitals in Vietnam. METHODS: A pre-post quantitative evaluation with adult cancer caregivers across regional Oncology hospitals in Vietnam (Ho Chi Minh City, Da Nang, Can Tho, and Hue). Participants completed baseline and follow-up measures of health literacy (HLS-SF12) depression (PHQ-9) and Health-related Quality of Life (5Q-5D-5L). Participants accessed and reviewed V-CCC for a 2-week period. RESULTS: Two hundred and thirty-four caregivers completed pre and post-tests. Most participants were female (n = 143, 61%), married (n = 165, 70%), aged 18-44 (n = 155, 66%), lived rurally (n = 157, 67%). All health literacy scores of participants in post-intervention were significantly higher than that in pre-intervention across all domain's healthcare, disease prevention, and health promotion as well as the total score (p < 0.001). A significant reduction in the proportion of caregivers reporting PHQ-9 moderately severe/severe depression post-intervention was demonstrated (10.2 vs. 6.1%, respectively (p ≤ 0.001). No significant differences were observed pre and post-intervention across four 5Q-5D-5L health dimensions: mobility, self-care, usual activities, and pain/discomfort. Regarding anxiety/depression as measured by 5Q-5D-5L the proportion of participants who reported having moderate, severe, and extreme problems in pre- and post-intervention was statistically significant (32 vs. 24%), respectively (p = 0.0028). CONCLUSION: Co-designed digital resources can reduce health literacy inequities and improve psychological outcomes for cancer caregivers.

Essential Oil from Vietnamese Peperomia leptostachya Hook. & Arn. (Piperaceae): Chemical Composition, Antioxidant, Anti-Inflammatory, Cytotoxic Activities, and In Silico Analysis.

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and ß-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 µg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.

The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis.

BACKGROUND: Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients. METHODS: The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents. RESULTS: 12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851_854del (p.R284Rfs*3), c.70-63_133del (p.Y24_72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638_1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851_854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63_133del (p.Y24_72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]). CONCLUSION: The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries' reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis.

Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma.

BACKGROUND: Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. METHODS: Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. RESULTS: Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. CONCLUSIONS: Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Conarubins A-D: Four Monoterpene-Chalcone Conjugates from Conamomum rubidum and Their Anti-inflammatory and Cytotoxic Activities.

Four novel compounds, conarubins A-D (1-4), were isolated from the whole plants of Conamomum rubidum collected in Vietnam. Their structures were elucidated by extensive spectroscopic analyses and by quantum chemical calculations of NMR and ECD. Compounds 1 and 2 were the first examples of monoterpene-monoterpene-chalcone conjugates in nature, whereas compound 4 was an unprecedented monoterpene-substituted chalcone containing a 3,4,5-trioxygenated cyclohexa-2,5-diene-1-one ring. The anti-inflammatory and cytotoxic activities of all isolates were investigated.

Testosterone and aging male, a perspective from a developing country.

PURPOSE: Hypogonadism is associated with a wide range of physical and psychological symptoms that can affect the overall health of men. However, in a developing country, there are several imposing challenges in the diagnosis and treatment of hypogonadism, including a lack of awareness and understanding of the condition among healthcare providers and patients, limited resources and the high cost of treatment. This review aimed to examine the potential benefits and risks of testosterone replacement therapy (TRT) and provides a perspective of a developing country on the topic. MATERIALS AND METHODS: A comprehensive literature review was conducted to gather relevant information on the impact of testosterone deficiency on ageing males and the effectiveness of TRT for treating hypogonadism. Published peer-reviewed articles were analyzed to evaluate the benefits and risks of TRT. Additionally, the unique challenges faced in the diagnosis and treatment of hypogonadism in a developing country were considered. RESULTS: Testosterone replacement therapy has been shown to be an effective treatment for hypogonadism, particularly in symptomatic men with low testosterone levels. It offers potential benefits such as improvements in symptoms and overall quality of life. However, there are associated risks and side effects that need to be considered. In a developing country, challenges such as limited awareness and understanding of hypogonadism, resource constraints, and high treatment costs pose additional barriers to accessing TRT and comprehensive care. CONCLUSION: In conclusion, TRT holds promise as a treatment for hypogonadism, but its implementation and accessibility face significant challenges in a developing country. Addressing these challenges, including raising awareness, allocating resources, and finding cost-effective solutions, is crucial for ensuring that men with hypogonadism in such settings receive appropriate diagnosis and treatment. Further research and efforts are needed to improve the management of hypogonadism in developing countries and optimize the potential benefits of TRT for affected individuals.

Sex differences in quality of life of patients following percutaneous coronary intervention in Vietnam.

PURPOSE: Data regarding the health-related quality of life (HRQoL) in men and women after percutaneous coronary intervention (PCI) in low-and-middle incomes countries remains scarce. To investigate sex difference in the HRQoL at 30 days and 12 months post PCI in Vietnam. METHODS: We used data from a single percutaneous coronary registry established in the Vietnam National Heart Institute. The HRQoL was measured using the EQ-5D-3L instrument via telephone interviews, and information about demographics, clinical presentation and procedures was obtained through face-to-face interviews and medical records. The HRQoL between men and women were compared using independent samples t tests, the Mann-Whitney U test or univariate/multivariate logistic regression. RESULTS: There were 866 patients included in this cohort, with the proportion of women being nearly half of men (32.1 vs 67.9%). Women were 3.5 years older, had lower income and educational levels but greater prevalence of cardiovascular risk factors. At 30 days, women significantly had more problems in mobility, personal care and pain/discomfort compared to men. At 12 months, women had more problem than men in usual activity. The geometric means of HRQoL was lower in women at 30 days, but not in 12 months. From 30 days to 12 months after discharge, women showed better recovery in mobility compared to men, but not in other dimensions. CONCLUSIONS: In this first insight of sex differences in HRQoL following PCI in Vietnam, women appeared to have worse quality of life, especially at 30 days after discharge but they showed better recovery in mobility at 12 months compared to men.

Prevalence and risk factors of prehypertension/hypertension among freshman students from the Vietnam National University: a cross-sectional study.

BACKGROUND: Prehypertension (PHT) and hypertension (HTN) in young adults are essential risk factors for other cardiovascular diseases (CVD) in later years of life. However, there is a lack of knowledge about the burden and risk factors of PHT/HTN for Vietnamese youth. The aim of this study was to investigate the prevalence of PHT/HTN and risk factors among university students in Hanoi, Vietnam. METHODS: This study was designed as a cross-sectional investigation with 840 students (394 males and 446 females) randomly sampled from freshmen of Vietnam National University, Hanoi (VNU). Socio-demographic, anthropometric, and lifestyle data were collected using questionnaire forms and physical measurements. HTN was defined as blood pressure (BP) ≥ 140/90 mmHg and/or current treatment with antihypertensive medications. PHT was defined as a systolic BP from 120 to 139 mmHg and/or a diastolic BP from 80 to 89 mmHg. Body mass index (BMI) was classified according to the WHO diagnostic criteria for Asian adults: normal weight (BMI 18.5-22.9 kg/m2), underweight (BMI < 18.5 kg/m2), overweight (BMI 23-24.9 kg/m2), and obese (BMI ≥ 25 kg/m2). Bivariable and multivariable log-binomial regression analyses were conducted to explore the association of PHT/HTN with different risk factors. RESULTS: The overall prevalence of prehypertension and hypertension was 33.5% [95% CI: 30.3-36.8%] (54.1% in men and 15.3% in women) and 1.4% [95% CI: 0.7-2.5%] (2.5% in men and 0.5% in women), respectively. Regarding CVD major risk factors, 119 (14.2%) were identified as overweight/obese, 461 (54.9%) were physical inactivity, 29.4% of men and 8.1% of women reported consuming alcohol. The multivariable analysis indicated the male sex (adjusted prevalence ratio [aPR] = 3.07; 95% CI: 2.32-4.06), alcohol consumption (aPR = 1.28; 95% CI: 1.03-1.59) and obesity (aPR = 1.35; 95% CI: 1.08-1.68) as the independent risk factors for PHT/HTN. CONCLUSIONS: The results revealed the high burden of prehypertension and hypertension among university freshmen in VNU. Male sex, alcohol consumption, and obesity were identified as important risk factors for PHT/HTN. Our study suggests an early screening program for PHT/HTN and campaigns to promote a healthy lifestyle for young adults in Vietnam.

Impacts of COVID-19 crisis and some related factors on the mental health of 37150 Vietnamese students: a cross-sectional online study.

BACKGROUND: University students are vulnerable to changes due to COVID-19 pandemic. Although warning has been made about the impact of this crisis on students' mental health, there are barely any sufficient study. This work investigated how the pandemic affected the mental health of students at the Vietnam National University of Ho Chi Minh City (VNU-HCMC) and efficiency of available mental health supportive methods. METHODS: An online survey was conducted among students at Vietnam National University of Ho Chi Minh City (VNU-HCMC) from October 18, 2021, to October 25, 2021. Microsoft Excel 16.51 (Microsoft, USA) and R language, Epi packages 2.44 and 4.1.1 (rdrr.io) were used for data analysis. RESULTS: Thirty-seven thousand one hundred fifty students participated in the survey, including 48.4% female and 51.6% male. Online learning pressure was mainly recorded (65.1%). Many students suffered from sleeping disorders (56.2%). Some reported being victims of abuse (5.9%). Female students expressed a significantly higher level of distress than males, particularly the feeling of ambiguity about the purpose of life (p-value < 0.0001, OR: 0.94, 95% CI: [0.95-0.98]). Third-year students suffered higher stress levels than others, especially in online learning (68.8%, p-value < 0.05). Mental health statuses among students of different lockdown status regions were not significantly different. Therefore, lockdown status did not affect the stress levels of students which suggested that poor mental health outcomes seemed to root in the suspension of everyday university life rather than the prohibition of going out. CONCLUSIONS: During COVID-19, students experienced lots of stress and mental problems. These findings underscore the importance of academic and innovative activities, bringing attention to the needs of interactive study and extra-curricular activities.

Asterosaponins from the starfish Protoreaster nodosus.

Five asterosaponins (1-5), including one new compound named protonodososide (1), were isolated from the methanol extract of the starfish Protoreaster nodosus, after subjecting to various chromatographic separations. The structural elucidation was confirmed by careful analysis of the 1D, 2D NMR, and HR ESI QTOF mass spectra. The cytotoxicity of isolated compounds was evaluated on five human cancer cell lines including HepG2, KB, MCF7, LNCaP, and SK-Mel2.

Three new chromanes and one new flavone C-glycoside from Mallotus apelta.

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.

Harmonising Individual Patient Level Cardiac Registry Data Across the Asia Pacific Region-A Feasibility Study of In-Hospital Outcomes of STEMI Patients From the Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Network.

OBJECTIVE: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration was established to inform on percutaneous coronary intervention (PCI) in the Asia-Pacific Region. Our aims were to (i) determine the operational requirements to assemble an international individual patient dataset and validate the processes of governance, data quality and data security, and subsequently (ii) describe the characteristics and outcomes for ST-elevation myocardial infarction (STEMI) patients undergoing PCI in the ASPECT registry. METHODS: Seven (7) ASPECT members were approached to provide a harmonised anonymised dataset from their local registry. Patient characteristics were summarised and associations between the characteristics and in-hospital outcomes for STEMI patients were analysed. RESULTS: Six (6) participating sites (86%) provided governance approvals for the collation of individual anonymised patient data from 2015 to 2017. Five (5) sites (83%) provided >90% of agreed data elements and 68% of the collated elements had <10% missingness. From the registry (n=12,620), 84% were male. The mean age was 59.2±12.3 years. The Malaysian cohort had a high prevalence of previous myocardial infarction (34%), almost twice that of any other sites (p<0.001). Adverse in-hospital outcomes were the lowest in Hong Kong whilst in-hospital mortality varied from 2.7% in Vietnam to 7.9% in Singapore. CONCLUSIONS: Governance approvals for the collation of individual patient anonymised data was achieved with a high level of data alignment. Secure data transfer process and repository were established. Patient characteristics and presentation varied significantly across the Asia-Pacific region with this likely to be a major predictor of variations in the clinical outcomes observed across the region.

Development and Characterization of a Hydrogel Containing Curcumin-Loaded Nanoemulsion for Enhanced In Vitro Antibacteria and In Vivo Wound Healing.

Curcumin (CUR) is a natural compound extracted from turmeric (Curcuma longa L.) used to cure acne, wound healing, etc. Its disadvantages, such as poor solubility and permeability, limit its efficacy. Nanoemulsion (NE)-based drug delivery systems have gained popularity due to their advantages. This study aimed to optimize a CUR-NE-based gel and evaluate its physicochemical and biological properties. A NE was prepared using the catastrophic phase inversion method and optimized using the Design Expert 12.0 software. The CUR-NE gel was characterized in terms of visual appearance, pH, drug release, antibacterial and wound healing effects. The optimal formulation contained CUR, Capryol 90 (oil), Labrasol:Cremophor RH40 (1:1) (surfactants), propylene glycol (co-surfactant), and water. The NE had a droplet size of 22.87 nm and a polydispersity index of 0.348. The obtained CUR-NE gel had a soft, smooth texture and a pH of 5.34 ± 0.05. The in vitro release of CUR from the NE-based gel was higher than that from a commercial gel with nanosized CUR (21.68 ± 1.25 µg/cm2, 13.62 ± 1.63 µg/cm2 after 10 h, respectively). The CUR-NE gel accelerated in vitro antibacterial and in vivo wound healing activities as compared to other CUR-loaded gels. The CUR-NE gel has potential for transdermal applications.

In Vivo Assembly and Expression of DNA Containing Non-canonical Bases in the Yeast Saccharomyces cerevisiae.

Chemically modified nucleic acids are of utmost interest in synthetic biology for creating a regulable and sophisticated synthetic system with tailor-made properties. Implanting chemically modified nucleic acids in microorganisms might serve biotechnological applications, while using them in human cells might lead to new advanced medicines. Previously, we reported that a fully modified DNA sequence (called DZA) composed of the four base-modified nucleotides - 7-deaza-adenine, 5-chlorouracil, 7-deaza-guanine and 5-fluorocytosine - could function as a genetic template in prokaryotic cells, Escherichia coli. Here, we report the synthesis of long, partially, or fully modified DZA fragments that encode the yeast-enhanced red fluorescent protein (yEmRFP). The DZA sequences were directly introduced in the genome of the eukaryotic cells, Saccharomyces cerevisiae, via the yeast natural homologous recombination machinery. The simple and straightforward DZA cloning strategy reported here might be of interest to scientists working in the field of xenobiology in yeast.