Antioxidant, anti-tyrosinase, hepatoprotective, and anti-inflammatory potential in flowers and seeds of Ochna integerrima (Lour.) Merr.

This study explored, for the first time, the antioxidant (total antioxidant content, reducing power, ferric ion reducing antioxidant power, hydroxyl radical scavenging, ferrous ion-chelating assays), anti-tyrosinase, anti-inflammatory properties, and hepatoprotective effect in HepG2 cell lines of Ochna integerrima (Loureiro) Merrill flowers and seeds. All extracts except n-hexane exhibited significant antioxidant activity, with high levels of tannin and proanthocyanidins. Luteolin (1), 6-γ,γ-dimethylallylkaempferol7-O-ß-d-glucopyranoside (2), 6-γ,γ-dimethylallylquercetin7-O-ß-d-glucopyranoside (3), and 6-γ,γ-dimethylallyldihydrokaempferol 7-O-ß-d-glucopyranoside (4) were isolated using semi-preparative HPLC. Compounds 1-3 demonstrated good anti-tyrosinase activity. The most active hepatoprotective extracts were found to be aqueous extracts. The flower extracts exhibited greater anti-inflammatory properties by the decrease of NO in RAW 264.7 cells and bovine serum albumin protein. Among them, the n-hexane and EtOAc extracts from flowers displayed promising anti-inflammatory activity. This was predicted by in silico analysis of 1-4. In summary, O. integerrima appears to be a promising natural source for antioxidant, anti-tyrosinase, and anti-inflammatory applications.

Biochemical Changes in Adult Male Gamers During Prolonged Gaming: Pilot Study.

BACKGROUND: Gaming has become an integrated part of life for children and adults worldwide. Previous studies on the impact of gaming on biochemical parameters have primarily addressed the acute effects of gaming. The literature is limited, and the study designs are very diverse. The parameters that have been investigated most thoroughly are blood glucose and cortisol. OBJECTIVE: This exploratory study is the first to investigate the effects of long gaming sessions on the biochemical parameters of healthy male adults. The extensive testing allowed us to observe short-term changes (within 6 hours), long-term changes during the duration of the gaming sessions, and follow-up after 1 week to determine whether any changes were longer lasting. METHODS: In total, 9 experienced gamers completed 2 back-to-back 18-hour gaming sessions interspersed with a 6-hour rest period. All participants adhered to a structured sleep pattern due to daytime employment or attending university. Blood, saliva, and urine samples were collected from the participants every 6 hours. Linear mixed-effect models were used to analyze the repeated-measures data accumulated during the study. A total of 51 biochemical parameters were investigated. RESULTS: In total, 12 of the 51 biochemical parameters significantly changed during the study: alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, creatinine, glucose, hemoglobin, immature reticulocyte fraction, lactate, methemoglobin, sodium, and thrombocytes. All changes were within the normal range. The mean glucose level of the participants was 4.39 (SD 0.07) mmol/L at baseline, which increased significantly by 0.24 (SD 0.07) mmol/L per 6 hours during the first period and by 0.38 (SD 0.07) mmol/L per 6 hours in the second period (P<.001). The glucose levels during the second session increased even though the participants had little energy intake. Cortisol levels did not change significantly, although the cortisol pattern deviated from the typical circadian rhythm. During both gaming sessions, we observed increasing cortisol levels from 6 AM until noon. The participants were relatively dehydrated at the start of the study. The patients were asked to fast before the first blood sampling. Within the first 6 hours of the study, the participants rehydrated, followed by relative dehydration during the remainder of the study. This pattern was identified using the following parameters: albumin, creatinine, hemoglobin, erythrocytes, potassium, and platelets. CONCLUSIONS: This study is the first of its kind, and many of the analyses in the study yielded novel results. The study was designed to emulate the behavior of gamers during the weekend and other long gaming sessions. At this point, we are not able to determine the difference between the effects of gaming and behavior during gaming. Regardless, the results of this study suggest that healthy gamers can partake in long gaming sessions, with ample amounts of unhealthy foods and little rest, without acute impacts on health.

Five pimarane diterpenoids from Kaempferia champasakensis and their cytotoxic activities.

A phytochemical investigation of Kaempferia champasakensis rhizomes led to the isolation of five new pimarane diterpenes, kaempferiols E-I (1-5). The structures of 1-5 were elucidated by extensive spectroscopic techniques, including HR-ESI-MS, UV, IR, and 1D and 2D NMR. The absolute configurations of 1-3 were determined by the modified Mosher method, and those of 4 and 5 were established by ECD calculations. Further cytotoxic assay for all isolated compounds against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) indicated that 5 showed moderate cytotoxic activities against the three tested cell lines, with IC50 values of 44.78, 25.97, and 41.39 Mµ for A549, HeLa, and MCF-7 cell lines, respectively.

Synthesis, crystal structure and photophysical properties of a dinuclear MnII complex with 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline.

A new quinoline derivative, namely, 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline, C24H23N3 (QP), and its MnII complex aqua-1κO-di-µ-chlorido-1:2κ4 Cl:Cl-di-chlorido-1κCl,2κCl-bis-[6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline]-1κ2 N 1,N 2;2κ2 N 1,N 2-dimanganese(II), [Mn2Cl4(C24H23N3)2(H2O)] (MnQP), were synthesized. Their compositions have been determined with ESI-MS, IR, and 1H NMR spectroscopy. The crystal-structure determination of MnQP revealed a dinuclear complex with a central four-membered Mn2Cl2 ring. Both MnII atoms bind to an additional Cl atom and to two N atoms of the QP ligand. One MnII atom expands its coordination sphere with an extra water mol-ecule, resulting in a distorted octa-hedral shape. The second MnII atom shows a distorted trigonal-bipyramidal shape. The UV-vis absorption and emission spectra of the examined compounds were studied. Furthermore, when investigating the aggregation-induced emission (AIE) properties, it was found that the fluorescent color changes from blue to green and eventually becomes yellow as the fraction of water in the THF/water mixture increases from 0% to 99%. In particular, these color and intensity changes are most pronounced at a water fraction of 60%. The crystal structure contains disordered solvent mol-ecules, which could not be modeled. The SQUEEZE procedure [Spek (2015 ▸). Acta Cryst. C71, 9-18] was used to obtain information on the type and qu-antity of solvent mol-ecules, which resulted in 44 electrons in a void volume of 274 Å3, corresponding to approximately 1.7 mol-ecules of ethanol in the unit cell. These ethanol mol-ecules are not considered in the given chemical formula and other crystal data.

Prognosticating global functional outcome in the recurrent ischemic stroke using baseline clinical and pre-clinical features: A machine learning study.

BACKGROUND AND PURPOSE: Recurrent ischemic stroke (RIS) induces additional functional limitations in patients. Prognosticating globally functional outcome (GFO) in RIS patients is thereby important to plan a suitable rehabilitation programme. This study sought to investigate the ability of baseline features for classifying the patients with and without improving GFO (task 1) and identifying patients with poor GFO (task 2) at the third month after discharging from RIS. METHODS: A total of 86 RIS patients were recruited and divided into the training set and testing set (50:50). The clinical and pre-clinical data were recorded. The outcome was the changes in Modified Rankin Scale (mRS) (task 1) and the mRS score at the third month (mRS 0-2: good GFO, mRS >2: poor GFO) (task 2). The permutation importance ranking method selected features. Four algorithms were trained on the training set with five-fold cross-validation. The best model was tested on the testing set. RESULTS: In task 1, the support vector machine (SVM) model outperformed the other models, with the high performance matrix on the training set (sensitivity = 0.80; specificity = 1.00) and the testing set (sensitivity = 0.80; specificity = 0.95). In task 2, the SVM model with selected features also performed well on both datasets (training set: sensitivity = 0.76; specificity = 0.92; testing set: sensitivity = 0.72; specificity = 0.88). CONCLUSION: A machine learning model could be used to classify GFO responses to treatment and identify the third-month poor GFO in RIS patients, supporting physicians in clinical practice.

Introducing a Novel Innovative Technique for the Recording and Interpretation of Dynamic Coronary Angiography.

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena-such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation-are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes.

Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.

Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

Combination of Anterior and Posterior Vaginal Mesh Implants and Delorme Procedure in a 94-year-old female with Pelvic Organ Prolapse.

Pelvic organ prolapse refers to the descent of pelvic floor organs resulting from the weakening of pelvic muscles, fascia and connective tissue. The overall prevalence of pelvic organ prolapse is approximately 41%, including bladder prolapse (25%-34%), uterine prolapse (4%-14%) and rectal prolapse (13%-19%). Various methods are currently employed to repair damaged structures and improve patient symptoms, consequently enhancing their quality of life. This report focuses on a 94-year-old female diagnosed with pelvic organ prolapse, specifically Grade 3 bladder prolapse, Grade 3 uterine prolapse and complete rectal prolapse. A comprehensive surgical treatment was carried out to repair the pelvic organs on all three levels (rectum, uterus and bladder) by combining the Delorme procedure with synthetic graft implants. The surgical outcomes were good, illustrating immediate improvement in symptoms without early complications. A multispeciality approach helps functionally repair pelvic organ prolapse while preserving structural integrity.

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.

Challenging Recurrence and Management of Squamous Cell Carcinoma in the Calcaneal Region: A Case Report.

Squamous cell carcinoma (SCC) is the second most common type of skin cancer. As ultraviolet exposure represents an important risk factor, SCC commonly occurs on the face, lips, scalp, hands, and heels. The foot is an unusual location to manifest SCC. In this report, we present a case of a 44-year-old woman with severe local recurrence of SCC in the right heel, four years after an initial excision of a primary, small lesion. For various reasons, the patient did not visit the clinic for follow-up assessment during this period. Considering the extent of the lesion and infection risk, the affected leg was amputated at one-third of the lower leg. This case report underlines the importance of educating patients about the risk of SCC and assisting them in attending follow-up visits. In addition, adequate attention should be given to foot lesions with suspicious appearance. Early detection would minimize systemic risks, including metastasis and infection, and maximize preserved function after surgical intervention.

Treatment duration by morphology and location of impacted maxillary canines: A cone-beam computed tomography investigation.

INTRODUCTION: This study aimed to identify whether patients with impacted maxillary canines take longer to treat than orthodontic patients without an impacted canine. We also sought to identify factors that are predictive of increased treatment duration in patients with impacted maxillary canines and treated by surgical exposure. METHODS: A retrospective investigation of 37 patients with an impacted maxillary canine, treated by surgical exposure and fixed appliance therapy, was undertaken. In addition, an age- and sex-matched control group of 39 patients (without impacted canines) was also collected. Patient age, sex, and total treatment duration were recorded. For patients with an impacted canine, patient records and pretreatment cone-beam computed tomography datasets were assessed. Point coordinates identifying relevant landmarks were recorded, and a geometric method was used to calculate variables describing canine location, orientation, and apical morphology. RESULTS: Controlling for age and sex, linear regression identified a statistically significant increase in treatment duration of 46.7 and 41.5 weeks for palatal and labial/midalveolar impacted canines, respectively, vs controls (P <0.002). Age and sex of patients with impacted canines collectively affected treatment duration (P = 0.04), with females of increased age being treated faster than younger males. Rotation of the impacted canine crown had a highly significant effect on treatment duration, with every degree of rotation increasing treatment duration by 0.32 weeks (P <0.001). There was a significant degree of multicollinearity between the other radiographic variables. Collectively, radiographic variables describing canine displacement significantly prolonged treatment duration (P <0.001) and explained 29.8% of the variability in total treatment time. The apical morphology of impacted maxillary canines was significantly associated with increased treatment duration (P = 0.01) and explained 11.3% of the overall treatment variability (P = 0.01). CONCLUSIONS: Increased total treatment duration of surgically exposed impacted maxillary canines is associated with increasing mesiopalatal canine crown rotation, worsening displacement, and hooked apical morphology.

Comprehensive assessment of chlorination disinfection on microplastic-associated biofilms.

Chlorination on microplastic (MP) biofilms was comprehensively investigated with respect to disinfection efficiency, morphology, and core microbiome. The experiments were performed under various conditions: i) MP particles; polypropylene (PP) and polystyrene (PS), ii) MP biofilms; Escherichia coli for single-species and river water microorganisms for multiple-species, iii) different chlorine concentrations, and iv) different chlorine exposure periods. As a result, chlorination effectively inactivated the MP biofilm microorganisms. The disinfection efficiency increased with increasing the free chlorination concentration and exposure periods for both single- and multiple-species MP biofilms. The multiple-species MP biofilms were inactivated 1.3-6.0 times less than single-species MP biofilms. In addition, the PP-MP biofilms were more vulnerable to chlorination than the PS-MP biofilms. Morphology analysis verified that chlorination detached most MP biofilms, while a small part still remained. Interestingly, chlorination strongly changed the biofilm microbiome on MPs; the relative abundance of some microbes increased after the chlorination, suggesting they could be regarded as chlorine-resistant bacteria. Some potential pathogens were also remained on the MP particles after the chlorination. Notably, chlorination was effective in inactivating the MP biofilms. Further research should be performed to evaluate the impacts of residual MP biofilms on the environment.

Association between quality of life and burden of cancer caregivers: An example in a low and middle income country.

OBJECTIVE: Limited knowledge on burden and quality of life (QoL) among cancer caregivers is available in low and middle income countries. This study aims to investigate the QoL, levels of burden, and their associations among Vietnamese cancer caregivers. METHODS: This study was conducted across three hospitals in Vietnam. 348 caregivers were recruited from January to June 2021. Data were collected by using socio-demographic questionnaires, the Zarit Burden Interview scale, and Caregiver Qol Cancer. The association between QoL and burden was analyzed by using multivariate linear regression. RESULTS: Older age (p = 0.03), employed (p = 0.01), and care more than 40 h (p = 0.007) were associated with a higher burden, respectively. QoL of financial concern had the lowest score (mean = 48.03, SD = 28.87), compared to the other subscale. Caregivers who had pre-existing health conditions, unstable work, spent more than 40 h per week, and took care dependent cancer patients were associated with a lower overall QoL score. Comparing to caregivers of no burden, those of mild burden had a lower QoL score by 10.70; while those of mild severe burden had the worse QoL (lower by 23.80 scores). CONCLUSIONS: Perceptional burden among caregivers is associated with QoL. Further policies are recommended to protect cancer caregivers, to alleviate the caregiving burden, and thus to improve the overall QoL.

Testusterol, a new sterol of the sponge species Xestospongia testudinaria from Phu Quoc island, Vietnam.

A new sterol, named testusterol (1), and five known compounds (2-6) were isolated from the n-hexane and dichloromethane extracts of the sponge species Xestospongia testudinaria. Their chemical structures were elucidated based on extensive spectroscopic analyses (1D, 2D NMR, ESIMS and HRESIMS) and comparison with published data. The results of in vitro test (utilizing brine shrimp Artemia salina LEACH) showed that three extracts ethanol, dichloromethane, and ethanol/water, significantly inhibited Artemia salina with LC50 values ranging from 6.09 to 16.83 µg/mL. Remarkably, the new compound 1 exhibited potent inhibition against both Gram-positive (Staphyloccocus aureus, Bacillus subtilis, Lactobacillus fermentum), and Gram-negative (Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa) bacteria species, with IC50 values of less than 12.0 nM and MIC ranging from 4.70 to 75.23 nM as determined by the broth-microdilution assay.

Are Gamers Prone to eThrombosis during Long Gaming Sessions?

During the last two decades, several cases of venous thrombosis (VTE) after a prolonged period at a computer have been described, denominated as "eThrombosis". Video gaming on a computer has become very popular and can be a social activity where several players gather to play against each other or in a virtual environment for several days ("LAN (i.e., Local Area Network) parties") where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate potential coagulation activation during a 42 h LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 h, and plasma was analyzed for thrombin generation, thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h of gaming with minimal physical activity. Although increased activity cannot be excluded, it does not directly indicate a risk of VTE in general.

Development and characterization of microsatellite markers for population genetics of the cocoa pod borer Conopomorpha cramerella (Snellen) (Lepidoptera: Gracillaridae).

The cocoa pod borer (CPB) Conopomorpha cramerella (Snellen) (Lepidoptera: Gracillaridae) is one of the major constraints for cocoa production in South East Asia. In addition to cultural and chemical control methods, autocidal control tactics such as the Sterile Insect Technique (SIT) could be an efficient addition to the currently control strategy, however SIT implementation will depend on the population genetics of the targeted pest. The aim of the present work was to search for suitable microsatellite loci in the genome of CPB that is partially sequenced. Twelve microsatellites were initially selected and used to analyze moths collected from Indonesia, Malaysia, and the Philippines. A quality control verification process was carried out and seven microsatellites found to be suitable and efficient to distinguish differences between CPB populations from different locations. The selected microsatellites were also tested against a closely related species, i.e. the lychee fruit borer Conopomorpha sinensis (LFB) from Vietnam and eight loci were found to be suitable. The availability of these novel microsatellite loci will provide useful tools for the analysis of the population genetics and gene flow of these pests, to select suitable CPB strains to implement the SIT.

Cellular data extraction from multiplexed brain imaging data using self-supervised Dual-loss Adaptive Masked Autoencoder.

Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations. In addition, to examine the generalizability of DAMA, we also experimented on TissueNet, a multiplexed imaging dataset comprised of two-channel fluorescence images from six distinct tissue types, captured using six different imaging platforms. Our code is publicly available at https://github.com/hula-ai/DAMA.

Possible vertical transmission of Chikungunya virus infection detected in the cord blood samples from a birth cohort in Vietnam.

BACKGROUND: Chikungunya virus (CHIKV) is an alphavirus (genus Alphavirus, family Togaviridae) that is primarily transmitted to humans by Aedes mosquitoes, and can be transmitted from mother to child. Little is known about CHIKV transmission in Vietnam, where dengue is endemic and Aedes mosquitoes are abundant. This study aimed to determine the prevalence and characteristics of vertical CHIKV infection in a birth cohort, and seroprevalence of anti-CHIKV antibodies with or without confirmation by neutralization tests among women bearing children in Vietnam. METHODS: We collected umbilical cord blood plasma samples from each newly delivered baby in Nha Trang, Central Vietnam, between July 2017 and September 2018. Samples were subjected to molecular assay (quantitative real-time RT-PCR) and serological tests (anti-CHIKV IgM capture and IgG indirect enzyme-linked immunosorbent assay, and neutralization tests). RESULTS: Of the 2012 tested cord blood samples from newly delivered babies, the CHIKV viral genome was detected in 6 (0.3%) samples by RT-PCR, whereas, 15 samples (0.7%) were anti-CHIKV-IgM positive. Overall, 18 (0.9%, 95% CI: 0.6-1.5) samples, including three positives for both CHIKV IgM and viral genome on RT-PCR, were regarded as vertical transmission of CHIKV infection. Of the 2012 cord blood samples, 10 (0.5%, 95% CI: 0.2-0.9) were positive for both anti-CHIKV IgM and IgG. Twenty-nine (1.4%, 95% CI: 1.0-2.1) were seropositive for anti-CHIKV IgG while 26 (1.3%, 95% CI: 0.8-1.9) of them were also positive for neutralizing antibodies, and regarded as seropositive with neutralization against CHIKV infection. CONCLUSION: This is the first report of a possible CHIKV maternal-neonatal infection in a birth cohort in Vietnam. The findings indicate that follow-up and a differential diagnosis of CHIKV infection in pregnant women are needed to clarify the potential for CHIKV vertical transmission and its impact in the newborn.

Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.

Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFß-signaling, and inhibition of TGFß-signaling suppressed EndMT in PDIA-4-silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions.