Genomic adaptation to small population size and saltwater consumption in the critically endangered Cat Ba langur.

Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam's famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.

Four New Tirucallane Triterpenoids from the Leaves of Ailanthus triphysa with Anti-inflammatory Activities.

Ten tirucallane triterpenes (1-10) including four undescribed compounds, ailantriphysas A-D (1-4), were isolated from the leaves of Ailanthus triphysa (Dennst.) Alston. Their structures were elucidated by using IR, HR-ESI-MS, 1D- and 2D-NMR spectra. Compound 1 exhibited nitric oxide inhibitory activity with a IC50 value of 8.1 ± µM. Additionally, compound 1 also displayed significant inhibitory effects on the secretion of IL-6 and TNF-α at tested concentrations of 4, 8, and 16 µM.

Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms.

This study investigates the efficacy of deep-learning models in expediting the generation of disconnectomes for individualized prediction of neuropsychological outcomes one year after stroke. Utilising a 3D U-Net network, we trained a model on a dataset of N = 1333 synthetic lesions and corresponding disconnectomes, subsequently applying it to N = 1333 real stroke lesions. The model-generated disconnection patterns were then projected into a two-dimensional 'morphospace' via uniform manifold approximation and projection for dimension reduction dimensionality reduction. We correlated the positioning within this morphospace with one-year neuropsychological scores across 86 metrics in a novel cohort of 119 stroke patients, employing multiple regression models and validating the findings in an out-of-sample group of 20 patients. Our results demonstrate that the 3D U-Net model captures the critical information of conventional disconnectomes with a notable increase in efficiency, generating deep-disconnectomes 720 times faster than current state-of-the-art software. The predictive accuracy of neuropsychological outcomes by deep-disconnectomes averaged 85.2% (R 2 = 0.208), which significantly surpassed the conventional disconnectome approach (P = 0.009). These findings mark a substantial advancement in the production of disconnectome maps via deep learning, suggesting that this method could greatly enhance the prognostic assessment and clinical management of stroke survivors by incorporating disconnection patterns as a predictive tool.

Alpha-glucosidase inhibitory compounds from Vietnamese lichen Usnea baileyi: in vitro and in silico aspects.

Using a bio-guided isolation on the Vietnamese lichen Usnea baileyi based on alpha-glucosidase inhibition, eleven compounds were isolated and structurally elucidated, namely, protocetraric acid (1), 8'-methylstictic acid (2), stictic acid (3), 4,6-diformyl-8-hydroxy-3-methoxy-1,9-dimethyl-11-oxo-11H-dibenzo[b,e][1,4]dioxepine-7-carboxylic acid (4), vicanicin (5), norstictic acid (6), diffractaic acid (7), barbatic acid (8), atranol (9), 5-chlorohaematommic acid (10), and eumitrin A1 (11). Their chemical structures were identified by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy and compared with those reported in literature. Protocetraric acid (1) and norstictic acid (6) were selected for further modification to derive new compounds, namely, 1a-1e and 6a. Both isolated and synthesized compounds were assessed for their alpha-glucosidase inhibitory activity. Compounds 1-6, 1a-1e, 6a, and 11 showed significant alpha-glucosidase inhibition with IC50 values ranging from 10.4 to 130 µM. Molecular docking was applied to the most active compounds 1-3, 6, 1a-1e, and 6a to clarify the inhibitory mechanism. Compound 1e was determined to be a mixed inhibitor through a kinetic study.

Near Complete Reversal Of Large Diffusion-Weighted Imaging Lesion After Thrombectomy: A Case Report And Literature Review.

INTRODUCTION: Diffusion-Weighted Imaging (DWI) plays a crucial role in acute ischemic stroke (AIS), as it is used to evaluate the ischemic lesions that are irreversibly damaged. The reversibility of DWI ischemic lesions has been noted in patients with AIS who undergo revascularization therapy. In addition, the occurrence of this phenomenon in large ischemic regions remains rare, particularly the near-complete reversal of large DWI lesion cases. CASE PRESENTATION: A 58-year-old male presented with a generalized tonic-clonic seizure. Emergent magnetic resonance imaging (MRI) revealed an extremely large infarction lesion in the right hemisphere with an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 2 and occlusion of the terminal right internal carotid artery. The patient was immediately transferred to the Digital Subtraction Angiography (DSA) Unit for endovascular treatment with a stent retriever. After a rapid successful reperfusion with expanded treatment in cerebral infarction (eTICI) score of 3, the patient promptly recovered 24 hours after the procedure. A brain MRI was repeated after 8 days of admission, and interestingly, the DWI lesion showed significant reversal. The modified Rankin scale (mRS) at discharge was 2 and 1 at 90-day follow-up, respectively. CONCLUSIONS: Our case shows that the reversibility of DWI ischemic lesions can occur during the acute stroke phase, even in patients with extremely large regions, if rapid and successful reperfusion is achieved. The clinical implications of this phenomenon indicate that using DWI to evaluate the infarct core should be interpreted with caution.

Spatiotemporal performance evaluation of high-resolution multiple satellite and reanalysis precipitation products over the semiarid region of India.

The present investigation evaluates three satellite precipitation products (SPPs), Multi-Source Weighted-Ensemble Precipitation (MSWEP), Global Precipitation Climatology Centre (GPCC), Climate Hazard Infrared Precipitation with Station Data (CHIRPS), and two reanalysis datasets, namely, the ERA5 atmosphere reanalysis dataset (ERA5) and Indian Monsoon Data Assimilation and Analysis (IMDAA), against the good quality gridded reference dataset (1991-2022) developed by the India Meteorological Department (IMD). The evaluation was carried out in terms of the rainfall detection ability and estimation accuracy of the products using metrics such as the false alarm ratio (FAR), probability of detection (POD), misses, root mean square error (RMSE), and percent bias (PBIAS). Among all the rainfall products, ERA5 had the best ability to capture rainfall events with a higher POD, followed by MSWEP. Both MSWEP and ERA5 had PODs of 70-100% in more than 90% of the grids and less than 35% of missing rainfall events in the entire Tamil Nadu. In the case of the rainfall estimation accuracy evaluation, the MSWEP exhibited superior performance, with lower RMSEs and biases ranging from - 25 to 25% at the annual and seasonal scales. In northeast monsoon (NEM), CHIRPS demonstrated a comparable performance to that of MSWEP in terms of the RMSE and PBIAS. These findings will help product users select the best reliable rainfall dataset for improved research, diversified applications in various sectors, and policy-making decisions.

Three New Spirostan Glycosides from Dracaena cochinchinensis with NO Production Inhibitory and Antimicrobial Activity.

Three new spirostan glycosides, dracochinosides A-C (1-3), and four known steroidal glycosides (4-7) were isolated from the aerial parts of Dracaena cochinchinensis (Lour.) S.C.Chen. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-3, 6 and 7 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 57.5 to 92.8 µM. In addition, all the isolated compounds exhibited at least one of seven tested microbial strains with the MIC values ranging from 0.016 to 0.128 mg/mL. This is the first report of compounds 5-7 from the genus Dracaena.

Patient With a Diffuse Large B-Cell Non-Hodgkin Lymphoma in the Right Heart Chamber That Caused Cardiogenic Shock Was Well-Responded to Corticosteroids and Chemotherapy.

Heart tumors are sporadic. Secondary heart tumors are 30 times more common than primary ones. Depending on the location and origin of the tumor, clinical pictures vary from asymptomatic to severe manifestations such as arrhythmia, heart failure, pericardial effusion, and cardiogenic shock. We report hereby a rare case who presented with faint clinical symptoms, rapidly progressing to right heart failure within a month. Echocardiography and computed tomography of the chest revealed a tumor in the right heart chamber of 72.0 × 43.0 mm, in addition to large mediastinal lymph and left supraclavicular lymph nodes, cardiogenic shock appeared 4 days after admission. Through examination, it was suspected that this was a cardiac lymphoma. The patient was treated with 2 mg methylprednisolone per kg body weight. Symptoms of cardiogenic shock improved significantly and disappeared after 6 hours of treatment. After supraclavicular lymph node biopsy and immunohistochemistry, the final result was diagnosed as diffuse large B-cell non-Hodgkin lymphoma with large lymphoma in the right heart. The patient received chemotherapy with the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone). Re-examination before the 5th chemotherapy cycle showed no signs of right heart failure, normal self-activity, and no dyspnea on exertion, and the tumor size in the heart on the echocardiogram was 23.8 × 19.1 mm. The report shows that a large right heart tumor with a clinical picture of cardiogenic shock in a patient with diffuse large B-cell non-Hodgkin's lymphoma was well-responded to initial treatment with methylprednisolone at a dose of 2 mg/kg body weight and R-CHOP chemotherapy.

Anticoagulation Patterns in Ischemic Stroke Patients with Atrial Fibrillation in Developing Country: Insights from the Stroke Registry in Vietnam.

(1) Background: Atrial fibrillation (AF) poses a growing cardiovascular challenge globally, with significant implications in Vietnam. This study aimed to investigate the impact of AF on ischemic stroke/transient ischemic attack (TIA) and clinical outcomes, as well as the utilization of oral anticoagulation (OAC) therapy in Vietnam. (2) Methods: Data from the Registry of Stroke Care Quality (RES-Q) across 66 hospitals in Vietnam between 2017 and 2023 were utilized. Patients diagnosed with ischemic stroke or TIA were included, and clinical characteristics, pre- and post-hospitalization medication, and hospitalized outcomes were examined. (3) Results: Of 94,144 patients, 15.1% had AF. Patients with AF were older and had a higher prevalence of heart failure and more severe strokes. AF was associated with increased mortality during hospitalization and a poorer prognosis. In AF patients, anticoagulation therapy utilization increased from 15.8% pre-hospitalization to 82.4% at discharge, with a preference for direct oral anticoagulants. (4) Conclusions: AF significantly impacts ischemic stroke/TIA outcomes in Vietnam. Pre-hospitalization and anticoagulation therapy utilization were low but improved at discharge. These findings emphasize the need for improved AF management and stroke prevention strategies in developing countries.

Sterol-lipids enable large-scale, liquid-liquid phase separation in bilayer membranes of only two components.

Despite longstanding excitement and progress toward understanding liquid-liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid-liquid phase separation in bilayers has stubbornly remained at three: a sterol, a phospholipid with ordered chains, and a phospholipid with disordered chains. This requirement of three components is puzzling because only two components are required for liquid-liquid phase separation in lipid monolayers, which resemble half of a bilayer. Inspired by reports that sterols interact closely with lipids with ordered chains, we tested whether phase separation would occur in bilayers in which a sterol and lipid were replaced by a single, joined sterol-lipid. By evaluating a panel of sterol-lipids, some of which are present in bacteria, we found a minimal bilayer of only two components (PChemsPC and diPhyPC) that robustly demixes into micron-scale, liquid phases. It suggests an additional role for sterol-lipids in nature, and it reveals a membrane in which tie-lines (and, therefore, the lipid composition of each phase) are straightforward to determine and will be consistent across multiple laboratories.

Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing.

In forensics, one-third of sudden deaths remain unexplained after a forensic autopsy. A majority of these sudden unexplained deaths (SUDs) are considered to be caused by inherited cardiovascular diseases. In this study, we investigated 40 young SUD cases (<40 years), with non-diagnostic structural cardiac abnormalities, using Targeted NGS (next-generation sequencing) for 167 genes previously associated with inherited cardiomyopathies and channelopathies. Fifteen cases identified 17 variants on related genes including the following: AKAP9, CSRP3, GSN, HTRA1, KCNA5, LAMA4, MYBPC3, MYH6, MYLK, RYR2, SCN5A, SCN10A, SLC4A3, TNNI3, TNNI3K, and TNNT2. Of these, eight variants were novel, and nine variants were reported in the ClinVar database. Five were determined to be pathogenic and four were not evaluated. The novel and unevaluated variants were predicted by using in silico tools, which revealed that four novel variants (c.5187_5188dup, p.Arg1730llefsTer4 in the AKAP9 gene; c.1454A>T, p.Lys485Met in the MYH6 gene; c.2535+1G>A in the SLC4A3 gene; and c.10498G>T, p.Asp3500Tyr in the RYR2 gene) were pathogenic and three variants (c.292C>G, p.Arg98Gly in the TNNI3 gene; c.683C>A, p.Pro228His in the KCN5A gene; and c.2275G>A, p.Glu759Lys in the MYBPC3 gene) still need to be further verified experimentally. The results of our study contributed to the general understanding of the causes of SUDs. They provided a scientific basis for screening the risk of sudden death in family members of victims. They also suggested that the Targeted NGS method may be used to identify the pathogenic variants in SUD victims.

The Changes in the Inner-Structure and Mechanical Strength of the Composite Cement Materials and Silica-Carbon Nanotube-Nylon 66 Electrospun Nanofibers.

This study presents the feasibility of improving some selected mechanical strengths and the inner-structural analyses of cement matrix by electrospun nanofibers containing nylon 66, nanosilica, and carbon nanotube. The hybrid electrospun nanofibers were fabricated and mixed into ordinary Portland cement. From the mechanical strength test results, the hybrid nanofibers have shown their role in improving the tensile, compressive, and toughness behavior of the mixed cement material. The improvements of 62%, 38%, and 69%, respectively, were observed compared to those of the control paste. The novelty of the surface and inner structure of the hybrid fibers, as well as the modified cement matrix, were observed by the scanned images from electron microscopes. Besides, the additional pozzolanic reaction between the generated calcium hydroxide and the attached silica was clarified thanks to the results of energy dispersive spectroscopy, X-ray diffraction, and thermal gravimetric analysis. Finally, the consistency between mechanical strength results and inner-structure analyses showed the potential of the proposed fiber to improve cement-based materials.

Improper disposal of cigarette butts in a southeast Asian megacity (Hanoi, Vietnam): Pollution indexes, distribution profiles, and preliminary physicochemical characterization.

Although Southeast Asia is among the largest producers and consumers of cigarettes in the world, information about environmental contamination with littered cigarette butts (CBs) in this region is very limited, especially in urban areas. In this study, we collected CBs in 58 locations of 6 categories (i.e., parks, apartments, streets, shopping malls, universities, and relic sites) in Hanoi, a megacity of Vietnam, to elucidate the occurrence, pollution levels, and physicochemical properties of this specific waste type. A total of 25,943 CBs with 86 brands from 16 origin countries was obtained, showing a density range of 0.0056 to 1.16 (mean 0.125) CB/m2 and cigarette butt pollution index (CBPI) range of 0.23 to 86.9 (mean 6.14). CB contamination levels were higher in parks, apartments, streets, and shopping malls than in universities and relic sites, but CB density and CBPI values varied greatly between locations of the same category. Generally, CB contamination levels measured in Hanoi were within a moderate range compared to other countries worldwide. Several physicochemical properties of CBs were preliminarily determined, which partly confirmed the formation of smoking-derived chemicals captured in CBs and their release potentials into surrounding environments. Further investigations are required to evaluate detailed chemical profiles, leaching behavior, and toxic effects of hazardous substances in CBs.

CDK5-cyclin B1 regulates mitotic fidelity.

CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression1. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p392. Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity.

Biodegradation of DDT using multi-species mixtures: From genome-mining prediction to practical assessment.

DDT (dichlorodiphenyltrichloroethane) is a commonly used insecticide that is recalcitrant and highly stable in the environment. Currently, DDT residue contamination, especially in agricultural soil, is still a concern in many countries, threatening human health and the environment. Among the approaches to resolve such an issue, novel biodegradation-based methods are now preferred to physicochemical methods, due to the sustainability and the effectiveness of the former. In this study, we explored the possibility of building mixed microbial cultures that can offer improved DDT-degrading efficiencies and be more environmentally transilient, based on genome annotation using the KEGG database and prediction of interactions between single strains using the obtained metabolic maps. We then proposed 10 potential DDT-degrading mixed cultures of different strain combinations and evaluated their DDT degradation performances in liquid, semi-solid and solid media. The results demonstrated the superiority of the mixtures over the single strains in terms of degrading DDT, particularly in a semi-solid medium, with up to 40-50% more efficiency. Not only did the mixed cultures degrade DDT more efficiently, but they also adapted to broader spectra of environmental conditions. The three best DDT-degrading and transilient mixtures were selected, and it turned out that their component strains seemed to have more metabolic interactions than those in the other mixtures. Thus, our study demonstrates the effectiveness of exploiting genome-mining techniques and the use of constructed mixed cultures in improving biodegradation.

Emerging Monkeypox Virus Sublineage C.1 Causing Community Transmission, Vietnam, 2023.

We studied a community cluster of 25 mpox cases in Vietnam caused by emerging monkeypox virus sublineage C.1 and imported into Vietnam through 2 independent events; 1 major cluster carried a novel APOBEC3-like mutation. Three patients died; all had advanced HIV co-infection. Viral evolution and its potential consequences should be closely monitored.

Essential Oils of The Leaves of Syzygium hemilamprum (F. Muell.) Craven & Biffin.: Chemical Analysis, Antimicrobial, Mosquito Larvicidal, ADMET, and Molecular Docking Studies.

Chemical constituents from essential oil and n-hexane extract of S hemilamprum leaves were first identified. The obtained essential oil was dominated by monoterpene hydrocarbons (71.55%), and their oxygenated derivatives (20.2%), in which ß-pinene (31.5%), limonene (19.4%), α-pinene (12.3%), and α-terpineol (7.4%) were the principal agents. The n-hexane extract was characterized by monoterpene hydrocarbons (42.2%) and non-terpenic compounds (34.0%) with ß-pinene (32.8%), and n-hexadecane (10.2%) being the major compounds. Both two samples showed antimicrobial activity against the Gram (+) bacterium Staphylococcus aureus ATCC 6538, the Gram (-) bacterium Pseudomonas aeruginosa ATCC 9027, and the yeast Saccharomyces cerevisiae ATCC 2601 with the same MIC value of 128 µg/mL. Remarkably, they strongly inhibited mosquito larvicidal activity against Aedes aegypti and Culex quinquefasciatus larvae with the LC50 and L90 values of less than 20 µg/mL for 24 and 48 h treatments. A molecular docking study suggested limonene and α-terpineol as potent inhibitors of the mosquito odorant binding protein. In silico study on the physicochemical and ADMET properties of the main components of essential oils was also conducted.

Identification of a novel BAAT frameshift mutation in a female child diagnosed with skeletal dysplasia: A case report.

RATIONALE: Skeletal dysplasias are a complex series of rare genetic disorders that cause irregular development of bones, joints, and cartilages in children. A total of 770 disorders associated with 41 groups of skeletal dysplasia have been documented, demonstrating a wide range of clinical manifestations and varying levels of severity. In addition to conventional methods, whole genome sequencing has emerged as a useful approach to pinpointing the underlying etiology of skeletal dysplasias. PATIENT CONCERNS: A 13-month-old female was admitted to the hospital due to the symptoms of jaundice and failure to thrive. DIAGNOSES: The child was subjected to blood tests and a radiographic assessment. The blood chemistries revealed elevated levels of total bilirubin (178 µmol/L), bile acids (198 µmol/L), and low levels of serum calcium (1.69 mmol/L) and phosphate (0.8 mmol/L), along with irregular skeletal development in the forearms and legs, considering rickets and cholestasis. INTERVENTIONS: Whole exome sequencing data of the proband revealed a homozygous mutation of c.388dupA in the BAAT (bile acid-CoA: amino acid N-acyltransferase) gene sequence. This mutation caused a frameshift in the amino acid of the BAAT protein, resulting in the pR130Kfs*12 variant. This mutation has been identified as the underlying cause of skeletal dysplasia in the proband. OUTCOMES: A novel frameshift mutation in the BAAT gene of a Vietnamese female child diagnosed with skeletal dysplasia has been studied by whole exome sequencing analysis. LESSONS: This research reported a case of skeletal dysplasia caused by a frameshift mutation in the BAAT gene. The results of this study contribute to our understanding of the diverse factors that influence irregular skeletal development in children and provide genetic data to support clinical practice.