Transfer of natural radionuclides from soil to water spinach (Ipomoea aquatica Forssk) under flooded and unflooded conditions in Hanoi, Vietnam.

Transfer of natural radionuclides from soil to water spinach (Ipomoea aquatica Forssk) in Hanoi, Vietnam have been investigated using a low background gamma spectrometer with an HPGe detector (Model-GC5019). Twenty pairs of soil and water spinach samples in two environmental conditions, i.e., flooded and unflooded, were collected for measuring the activity concentrations and determining the soil-to-plant transfer factors (TFs) of natural radionuclides. For water spinach, stems and leaves were collected as the main parts for human consumption and livestock food. The TF of 40K is within the range of 0.32-2.49, which is greater than that of 228Ra (0.01-0.17) and 226Ra (0.01-0.13). The geometric means (geometric standard deviations) of the TFs are 1.17(1.89), 0.05(2.41) and 0.04(1.88) for flooded sites, and 0.89(1.73), 0.03(2.12) and 0.03(1.82) for unflooded sites, respectively. Comparing between the flooded and unflooded sites, the TFs are all greater at the flooded sites.

Surface-Displayed Mannanolytic and Chitinolytic Enzymes Using Peptidoglycan Binding LysM Domains.

Using Lactiplantibacillus plantarum as a food-grade carrier to create non-GMO whole-cell biocatalysts is gaining popularity. This work evaluates the immobilization yield of a chitosanase (CsnA, 30 kDa) from Bacillus subtilis and a mannanase (ManB, 40 kDa) from B. licheniformis on the surface of L. plantarum WCFS1 using either a single LysM domain derived from the extracellular transglycosylase Lp_3014 or a double LysM domain derived from the muropeptidase Lp_2162. ManB and CsnA were fused with the LysM domains of Lp_3014 or Lp_2162, produced in Escherichia coli and anchored to the cell surface of L. plantarum. The localization of the recombinant proteins on the bacterial cell surface was successfully confirmed by Western blot and flow cytometry analysis. The highest immobilization yields (44-48%) and activities of mannanase and chitosanase on the displaying cell surface (812 and 508 U/g of dry cell weight, respectively) were obtained when using the double LysM domain of Lp_2162 as an anchor. The presence of manno-oligosaccharides or chito-oligosaccharides in the reaction mixtures containing appropriate substrates and ManB or CsnA-displaying cells was determined by high-performance anion exchange chromatography. This study indicated that non-GMO Lactiplantibacillus chitosanase- and mannanase-displaying cells could be used to produce potentially prebiotic oligosaccharides.

Preimplantation Genetic Diagnosis of Androgen Resistance Syndrome Caused by Mutation on the AR Gene in Vietnam.

Background: Androgen resistance syndrome or androgen insensitivity syndrome (AIS - Androgen Insensitivity Syndrome, OMIM 300068) is an X-linked recessive genetic syndrome causing disorders of sexual development in males. This disease is caused by mutations in the AR gene located on the X chromosome, which encodes the protein that structures the androgen receptor, with the role of receiving androgens. Mutation of the AR gene causes complete or partial loss of androgen receptor function, thereby androgen not being obtained and exerting its effect on target organs, resulting in abnormalities of the male reproductive system due to this organ system, differentiating towards feminization under the influence of estrogen. Disease prevention can be achieved by using pre-implantation genetic diagnosis, which enables couples carrying the mutation to have healthy offspring. Aim: To carry out preimplantation genetic diagnosis of androgen resistance syndrome. Methods: Sanger sequencing was used to detect the mutation in the blood samples of the couple, their son, and 01 embryo that were biopsied on the fifth day based on the findings of next-generation sequencing (NGS) of the affected son. We combined Sanger sequencing and linkage analysis using short tandem repeats (STR) to provide diagnostic results. Results: We performed preimplantation genetic diagnosis for AIS on an embryo from a couple who had previously had an affected son. Consequently, one healthy embryo was diagnosed without the variant NM_000044: c.796del (p.Asp266IlefsTer30). Conclusion: We report on a novel variant (NM_000044: c.796del (p.Asp266IlefsTer30)) in the AR gene discovered in Vietnam. The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of AIS but wish to have healthy children.

The composition of chemicals and anti-osteogenic properties in the volatile extracts from Homalomena gigantea rhizome.

In this study, the anti-osteogenic properties of the volatile oil extracted from Homalomena gigantea rhizome using ethyl acetate (EtOAc) and methanol (MeOH) were examined. Gas chromatography-mass spectrometry (GC-MS) was employed for the identification of volatile components. Following this, bioassays were performed to evaluate their effects on osteogenesis, encompassing parameters like cell viability, osteoblast differentiation, collagen synthesis and mineralization. The GC-MS analysis revealed 19 compounds in the EtOAc extract and 36 compounds in the MeOH extract. In the MeOH extract, major constituents included bis(2-ethylhexyl) terephthalate (13.83%), linalool (9.58%), palmitic acid (6.55%) and stearic acid (4.29%). The EtOAc extract contained bis(2-ethylhexyl) terephthalate (16.64%), palmitic acid (5.60%) and stearic acid (3.11%) as the predominant components. Both the EtOAc and MeOH extracts of H. gigantea exhibited promising potential for further investigation in anti-osteoporosis research. These findings contribute to the exploration of natural compounds with potential anti-osteoporotic properties, expanding our understanding of their therapeutic potential.

Toxicity in Older Patients with Cancer Receiving Immunotherapy: An Observational Study.

BACKGROUND: Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. OBJECTIVE: This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. METHODS: Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3-5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. RESULTS: Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41-13.02); OR 1.33 (95% CI 0.45-4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61-8.31); OR 2.18 (95% CI 0.7-6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39-35.4); OR 1.31 (95% CI 0.35-4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1-2 toxicity as well. CONCLUSIONS: Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1-2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity.

Application of short tandem repeats (STRs) in the preimplantation genetic diagnosis (PGD) of α-thalassemia.

OBJECTIVES: α-thalassemia is an autosomal recessive monogenic blood disorder, affecting up to 5% of the world's population. The occurrence rate of the disease in Vietnam varies up to up to 51.5%, with high rate of mutation carriers, of couples consisting of two carriers at risk of bearing a child with fetal Hb Bart, which can develop into hydrops fetalis syndrome, threatening the well-being of the mother and the child. Our study aims to facilitate birth of healthy/asymptomatic children of α-thalassemia carrier couples who received reproductive service at our centre during the period of 2019-2022. MATERIALS AND METHODS: 89 couples at risks of having α-thalassemia offsprings requested IVF procedures and PGD at Post Hospital during 2019-2022 were recruited for investigation. Couple and additional family members' peripheral blood samples of couples and additional family members were subjected to haemoglobin electrophoresis, DNA extraction for α-thalassemia gene mutation detection and STRs linkage analysis. Data were observed and analysed on GeneMarker software. RESULTS: 91 cycles of PGD for α-thalassemia were carried out for 89 couples. α-thalassemia large deletion (--SEA/αα) was the most common mutation identified in 88 couples, in which 4 cases also carried ß-thalassemia point mutations. Combining results of PGS and PGD, 278/424 amplified embryos were transferable (HBA-mutation free or carriers of single heterozygous HBA mutation, without chromosomal abnormality). 64/89 couples have been transferred with the embryos (prioritizing mutation free ones over carriers), resulting in the birth of 36 α-thalassemia disease-free children, 17 ongoing pregnancies, and 11 with miscarriages. CONCLUSION: Successful application of microsatellite-based method in PGD facilitated the birth of 36 healthy children and 17 ongoing pregnancies for 53/64 couples with embryo-transferred. All resulted clinical births displayed confirmation results in line with the PGD results, thus demonstrating the feasibility and credibility of the use of STR markers in PGD.

Triple burden of malnutrition among Vietnamese 0·5-11-year-old children in 2020-2021: results of SEANUTS II Vietnam.

OBJECTIVE: SEANUTS II Vietnam aims to obtain an in-depth understanding of the nutritional status and nutrient intake of children between 0.5-11.9 years old. DESIGN: Cross-sectional survey. SETTING: A multistage cluster systematic random sampling method was implemented in different regions in Vietnam: North Mountainous, Central Highlands, Red River Delta, North Central and Coastal Area, Southeast and Mekong River Delta. PARTICIPANTS: 4001 children between 6 months and 11.9 years of age. RESULTS: Prevalence of stunting and underweight was higher in rural than in urban children, whereas overweight and obese rates were higher in urban areas. 12.0% of the children had anemia and especially children 0.5-1-year-old were affected (38.6%). Low serum retinol was found in 6.2% of children ≥ 4 years old. Prevalence of vitamin D insufficiency was 31.1% while 60.8% had low serum zinc. For nutrient intake, overall, 80.1% of the children did not meet the estimated energy requirements. For calcium intake, ∼60% of the younger children did not meet the RNI while it was 92.6% in children >7 years old. For vitamin D intake, 95.0% of the children did not meet RNI. CONCLUSIONS: SEANUTS II Vietnam indicated that overnutrition was more prevalent than undernutrition in urban areas, while undernutrition was found more in rural areas. The high prevalence of low serum zinc, vitamin D insufficiency and the inadequate intakes of calcium and vitamin D are of concern. Nutrition strategies for Vietnamese children should consider three sides of malnutrition and focus on approaches for the prevention malnutrition.

Human-aided dispersal and population bottlenecks facilitate parasitism escape in the most invasive mosquito species.

During biological invasion process, species encounter new environments and partially escape some ecological constraints they faced in their native range, while they face new ones. The Asian tiger mosquito Aedes albopictus is one of the most iconic invasive species introduced in every inhabited continent due to international trade. It has also been shown to be infected by a prevalent yet disregarded microbial entomoparasite Ascogregarina taiwanensis. In this study, we aimed at deciphering the factors that shape the global dynamics of A. taiwanensis infection in natural A. albopictus populations. We showed that A. albopictus populations are highly colonized by several parasite genotypes but recently introduced ones are escaping it. We further performed experiments based on the invasion process to explain such pattern. To that end, we hypothesized that (i) mosquito passive dispersal (i.e. human-aided egg transportation) may affect the parasite infectiveness, (ii) founder effects (i.e. population establishment by a small number of mosquitoes) may influence the parasite dynamics, and (iii) unparasitized mosquitoes are more prompt to found new populations through active flight dispersal. The two first hypotheses were supported as we showed that parasite infection decreases over time when dry eggs are stored and that experimental increase in mosquitoes' density improves the parasite horizontal transmission to larvae. Surprisingly, parasitized mosquitoes tend to be more active than their unparasitized relatives. Finally, this study highlights the importance of global trade as a driver of biological invasion of the most invasive arthropod vector species.

Workplace wellbeing in community pharmacy practice: A cross-sectional study in Can Tho, Vietnam.

Background: Among pharmacy workers, low workplace wellbeing can lead to reduced effectiveness. However, to date, studies on this issue are limited within the community pharmacy setting in Vietnam. Objectives: This study was conducted to identify the component aspects of workplace wellbeing and their associations with demographic characteristics. Methods: The cross-sectional descriptive study was conducted in Can Tho, Vietnam. Self-administered questionnaires were hand-delivered to all pharmacy workers working at selected community pharmacies. The workplace wellbeing scale comprised 18 items. Results: In total, 382 pharmacy workers participated in this study. Factor analysis revealed three fundamental aspects to workplace wellbeing: Factor 1 - perceived self-worth and job satisfaction, Factor 2 - positive emotions with work, and Factor 3 - negative emotions with work. Factor 1 showed a positive correlation with Factor 2, with a correlation coefficient (ρ) of 0.509, while both Factor 1 (ρ = -0.399) and Factor 2 (ρ = -0.416) demonstrated negative correlations with Factor 3. Higher income was associated with higher positive emotions with work (P = 0.008), higher perceived self-worth and job satisfaction (P = 0.013), and lower negative emotions with work (P < 0.001). Conclusion: Workplace wellbeing of pharmacy workers in their professional environments was associated with financial aspects. These findings suggest that policies aimed at improving income for pharmacy workers could bring benefits to enhancing job satisfaction and workplace wellbeing.

Pharmacological expansion of type 2 alveolar epithelial cells promotes regenerative lower airway repair.

Type 2 alveolar epithelial cells (AEC2s) are stem cells in the adult lung that contribute to lower airway repair. Agents that promote the selective expansion of these cells might stimulate regeneration of the compromised alveolar epithelium, an etiology-defining event in several pulmonary diseases. From a high-content imaging screen of the drug repurposing library ReFRAME, we identified that dipeptidyl peptidase 4 (DPP4) inhibitors, widely used type 2 diabetes medications, selectively expand AEC2s and are broadly efficacious in several mouse models of lung damage. Mechanism of action studies revealed that the protease DPP4, in addition to processing incretin hormones, degrades IGF-1 and IL-6, essential regulators of AEC2 expansion whose levels are increased in the luminal compartment of the lung in response to drug treatment. To selectively target DPP4 in the lung with sufficient drug exposure, we developed NZ-97, a locally delivered, lung persistent DPP4 inhibitor that broadly promotes efficacy in mouse lung damage models with minimal peripheral exposure and good tolerability. This work reveals DPP4 as a central regulator of AEC2 expansion and affords a promising therapeutic approach to broadly stimulate regenerative repair in pulmonary disease.

In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis.

Objective: Medicinal herbs with a phytonutrient background has been applied globally as major alternatives to ameliorate the continuous increase in rheumatoid arthritis cases worldwide. We herein aimed to critically examine the bioactive components of the medicinal herb Piper sarmentosum Roxb leaf fractionated extract for its potential to inhibit the influx of interleukin-6 (IL-6) in rheumatoid arthritis. Methods: The Schrödinger platform was employed as the main computational acumen for the screening of bioactive compounds identified and reference compounds subjected to molecular simulation (MDS) for analyzing the stability of docked complexes to assess fluctuations and conformational changes during protein-ligand interactions. Results: The values of the simulatory properties and principal component analysis (PCA) revealed the good stability of these phytochemicals in the active pocket of interleukin-6 (IL-6). Discussion: Our findings reveal new strategies in which these phytochemicals are potential inhibitory agents that can be modified and further evaluated to develop more effective agents for the management of rheumatoid arthritis, thereby providing a better understanding and useful model for the reproduction and/or discovery of new drugs for the management of rheumatoid arthritis and its complications.

Electric-Field-Assisted Synthesis of Cu/MoS2 Nanostructures for Efficient Hydrogen Evolution Reaction.

Molybdenum sulfide-oxide (MoS2, MS) emerges as the prime electrocatalyst candidate demonstrating hydrogen evolution reaction (HER) activity comparable to platinum (Pt). This study presents a facile electrochemical approach for fabricating a hybrid copper (Cu)/MoS2 (CMS) nanostructure thin-film electrocatalyst directly onto nickel foam (NF) without a binder or template. The synthesized CMS nanostructures were characterized utilizing energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and electrochemical methods. The XRD result revealed that the Cu metal coating on MS results in the creation of an extremely crystalline CMS nanostructure with a well-defined interface. The hybrid nanostructures demonstrated higher hydrogen production, attributed to the synergistic interplay of morphology and electron distribution at the interface. The nanostructures displayed a significantly low overpotential of -149 mV at 10 mA cm-2 and a Tafel slope of 117 mV dec-1, indicating enhanced catalytic activity compared to pristine MoS2.This research underscores the significant enhancement of the HER performance and conductivity achieved by CMS, showcasing its potential applications in renewable energy.

Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: a cross-sectional study in central Vietnam.

Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.

A Case Study: Electrically Assisted Stress Relief Annealing for Cold-Coiled Helical Automotive Springs.

This study experimentally investigated electrically assisted (EA) stress relief annealing for cold-coiled commercial automotive springs. In EA stress relief annealing, the temperature of a spring is rapidly increased to the annealing temperature (400 °C) and is held constant for a specified time using a pulsed electric current. Experimental findings show that the effectiveness of the EA stress relief annealing is superior to that of the conventional stress relief annealing, especially in terms of process time. The present study suggests that EA stress relief annealing, with properly selected process parameters, can effectively substitute for time-consuming conventional stress relief annealing using a furnace for cold-coiled automotive springs.

Stakeholder perspectives following implementation of Vietnam's first speech-language pathology degrees: recommendations for future curriculum development.

PURPOSE: To investigate perspectives of multiple stakeholders involved in development and delivery of Vietnam's first speech-language pathology degrees and derive recommendations for future degrees in Vietnam and other Majority World countries. METHODS: An exploratory-descriptive qualitative research design using focus groups and individual semi-structured interviews in the preferred language (English or Vietnamese) was used, with 70 participants from five stakeholder groups: project managers, students, academic educators, placement supervisors and interpreters. Transcriptions were analysed using thematic network analysis. RESULTS: Analysis identified five organising themes: (1) People enjoyed working with/learning from others; (2) Benefits from/to stakeholders; (3) The pandemic impacted program delivery and learning; (4) Practical challenges; (5) Preparation with flexibility required for success and sustainability. From the five organising themes, one synthesising global theme was developed, conveying that satisfying international collaborations require preparation, support, high quality interpreting, and management of challenges. CONCLUSIONS: Recommendations highlight the need for preparation, collaboration, support to manage challenges, flexibility, recognition for placement supervisors and high-quality interpreting. The recommendations are of relevance to other organisations engaged in development of professional degrees in Majority World countries. Future research would benefit from a critical investigation of the diverse perspectives of stakeholders involved in the development and implementation of international curricula.

Many Majority World countries are seeking to develop university degrees to build a workforce of speech-language pathologists to provide services to people with communication and swallowing disabilitiesCollaborative relationships, flexibility, and delineation of roles and commitments are vital to partnership successConceptualisation of rehabilitation services in cross-cultural contexts must privilege the knowledge, experiences and preferences of local partnersLocal capacity building will support training programs and rehabilitation services that are sustainable and culturally relevant.

Construction of a New Agrobacterium tumefaciens-Mediated Transformation System based on a Dual Auxotrophic Approach in Cordyceps militaris.

Cordyceps militaris is a significant edible fungus that produces a variety of bioactive compounds. We have previously established a uridine/uracil auxotrophic mutant and a corresponding Agrobacterium tumefaciens-mediated transformation (ATMT) system for genetic characterization in C. militaris using pyrG as a screening marker. In this study, we constructed an ATMT system based on a dual pyrG and hisB auxotrophic mutant of C. militaris. Using the uridine/uracil auxotrophic mutant as the background and pyrG as a selection marker, the hisB gene encoding imidazole glycerophosphate dehydratase, required for histidine biosynthesis, was knocked out by homologous recombination to construct a histidine auxotrophic C. militaris mutant. Then, pyrG in the histidine auxotrophic mutant was deleted to construct a ΔpyrG ΔhisB dual auxotrophic mutant. Further, we established an ATMT transformation system based on the dual auxotrophic C. militaris by using GFP and DsRed as reporter genes. Finally, to demonstrate the application of this dual transformation system for studies of gene function, knock out and complementation of the photoreceptor gene CmWC-1 in the dual auxotrophic C. militaris were performed. The newly constructed ATMT system with histidine and uridine/uracil auxotrophic markers provides a promising tool for genetic modifications in the medicinal fungus C. militaris.

Mimosa pudica L. extract ameliorates pulmonary fibrosis via modulation of MAPK signaling pathways and FOXO3 stabilization.

ETHNOPHARMACOLOGICAL RELEVANCE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing pulmonary disorder that has a poor prognosis and high mortality. Although there has been extensive effort to introduce several new anti-fibrotic agents in the past decade, IPF remains an incurable disease. Mimosa pudica L., an indigenous Vietnamese plant, has been empirically used to treat respiratory disorders. Nevertheless, the therapeutic effects of M. pudica (MP) on lung fibrosis and the mechanisms underlying those effects remain unclear. AIM OF THE STUDY: This study investigated the protective effect of a crude ethanol extract of the above-ground parts of MP against pulmonary fibrogenesis. MATERIALS AND METHODS: Inflammatory responses triggered by TNFα in structural lung cells were examined in normal human lung fibroblasts and A549 alveolar epithelial cells using Western blot analysis, reverse transcription-quantitative polymerase chain reaction assays, and immunocytochemistry. The epithelial-to-mesenchymal transition (EMT) was examined via cell morphology observations, F-actin fluorescent staining, gene and protein expression measurements, and a wound-healing assay. Anti-fibrotic assays including collagen release, differentiation, and measurements of fibrosis-related gene and protein expression levels were performed on TGFß-stimulated human lung fibroblasts and lung fibroblasts derived from mice with fibrotic lungs. Finally, in vitro anti-fibrotic activities were validated using a mouse model of bleomycin-induced pulmonary fibrosis. RESULTS: MP alleviated the inflammatory responses of A549 alveolar epithelial cells and lung fibroblasts, as revealed by inhibition of TNFα-induced chemotactic cytokine and chemokine expression, along with inactivation of the MAPK and NFκB signalling pathways. MP also partially reversed the TGFß-promoted EMT via downregulation of mesenchymal markers in A549 cells. Importantly, MP decreased the expression levels of fibrosis-related genes/proteins including collagen I, fibronectin, and αSMA; moreover, it suppressed collagen secretion and prevented myofibroblast differentiation in lung fibroblasts. These effects were mediated by FOXO3 stabilization through suppression of TGFß-induced ERK1/2 phosphorylation. MP consistently protected mice from the onset and progression of bleomycin-induced pulmonary fibrosis. CONCLUSION: This study explored the multifaceted roles of MP in counteracting the pathobiological processes of lung fibrosis. The results suggest that further evaluation of MP could yield candidate therapies for IPF.

Reference the seabed topographic depth observations based on the national mean dynamic topography model.

The mean sea surface in different regions is non-equipotential, rendering Vietnam's traditional approach, which relies on the Hon-Dau tide gauge station as a reference, not yet scientifically invalid. To overcome this, our study utilized the Vietnam national mean dynamic topography model (MDTVN22) for depth observations, particularly in the Gulf of Tonkin. Covering 3430 monitoring sites in Hai Phong and 813 sites in Quang Ninh, our experiments highlighted a 5 to 6 mm difference between the mean sea surface and MDTVN22 references. •Our research establishes a resilient methodology, integrating shore tide gauge station data and the MDTVN22 model, aimed at enhancing precision in depth observations.•Validation experiments in Hai Phong demonstrate a minimal discrepancy of ±0.006 m between measurements obtained from the traditional mean sea surface and the MDTVN22 model.•These findings underscore the significance of adopting the MDTVN22 model for improved accuracy in assessing Vietnam's seabed topography.

Evaluation and estimation of compressive strength of concrete masonry prism using gradient boosting algorithm.

The compressive strength (CS) of the hollow concrete masonry prism is known as an important parameter for designing masonry structures. In general, the CS is determined using laboratory tests, however, laboratory tests are time-consuming and high-cost. Thus, it is necessary to evaluate and estimate the CS using different methods, for example, machine learning techniques. This study employed Gradient Boosting (GB) to evaluate and predict the CS of hollow masonry prism. The database consists of 102 hollow concrete specimens taken from different previous published literature used for modeling. The output is the CS of the hollow masonry prism, while the inputs include the compressive strength of mortar (fm), the compressive strength of blocks (fb), height-to-thickness ratio (h/t), the ratio of fm/fb. To reduce the overfitting problem, this study used K-Fold cross-validation, then particle swarm optimization (PSO) was employed to obtain the optimum hyperparameter. The GB model then was modeled using the optimum hyperparameters. The results showed that the GB model performed very well in evaluating and predicting the CS of the hollow masonry prims with a high prediction accuracy, the values of R2, RMSE, MAE, and MAPE are 0.977, 0.803 MPa, 0.612 MPa, and 0.036%, respectively. The performance of the GB model in this study outperformed in comparison to six different machine learning models (decision tree, linear regression, random forest regression, ridge regression, Artificial Neural network, and Extreme Gradient Boosting) used in previous studies. The results of sensitivity analysis using SHAP and PDP-2D indicate that the CS is strongly dependent on the fb (with a mean SHAP value of 3.2), h/t (with a mean SHAP value of 1.63), while the fm/fb (with a mean SHAP value of 0.57) had a small effect on the CS. Thus, it can be stated that this research provides a good method to evaluate and predict the CS of the hollow masonry prism, which can bring good knowledge for practical application in this field.

A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis.

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH.