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Description of the subject. Alkaline phosphatases (APases) are commonly used as nonradioactive markers for detecting specific proteins or DNA targets in clinical medicine and molecular biology. However, their applications in the biotechnology industry require thermostability and storage stability. Our preliminary study revealed that APase from Thermus sp. NTU-237 (TsAPase) is thermostable and exhibits high activity. Therefore, it is desirable to establish the optimal conditions for its application. Objectives. To characterize APase from thermophile Thermus sp. NTU-237 and to evaluate its potential applications. Method. The APase gene of Thermus sp. NTU-237 was cloned and expressed in Escherichia coli. Subsequently, the effects of buffer, glycerol, sodium dodecyl sulfate (SDS), NaCl, and temperature on enzyme activity were studied to establish the optimal conditions for TsAPase assays. In addition, the potential for application of TsAPase was evaluated using the 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium (BCIP/NBT) active staining method. Results. Recombinant TsAPase was identified as having a dimeric structure and a molecular mass of 109 kDa. Sequence alignment analysis of known thermophilic APases with TsAPase and E. coli APase revealed that catalytic and binding residues were highly conserved. This finding suggested that the catalytic mechanism of TsAPase is the same as that of other APases. TsAPase activity was inhibited by glycerol and SDS but enhanced by NaCl and Tris-HCl buffer. The kinetic parameters Km, kcat, and Vmax were determined to be 81 µM, 6.08 s-1, and 6.76 U·mg-1, respectively. The optimum temperature of TsAPase was 80 °C, and TsAPase was stable at room temperature for more than 10 days. Moreover, TsAPase could catalyze the dephosphorylation of BCIP and could elicit blue color development by the BCIP/NBT reaction kit at room temperature. Conclusions. These results illustrate that TsAPase has potential for application in medical or basic research.

Objective: To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes.Research Design and Methods: In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day).Results: The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1-26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 +/- 320.0 daily steps) compared with the half-shoe (1,461.8 +/- 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 +/- 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15).Conclusions: The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe. [ABSTRACT FROM AUTHOR]

Objective: In this study the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (LT) (grade and stage) wound classification systems.Research Design and Methods: Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded, and patients were followed up until healing or for 6 months.Results: Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5 (3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade (P < 0.0001), and UT grade (P < 0.0001) and stage (P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P < 0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001), but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner (P = 0.1) or the UT system (P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system (P < 0.05), and stage predicted healing (P < 0.05).Conclusions: Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system's inclusion of stage makes it a better predictor of outcome. [ABSTRACT FROM AUTHOR]

Symptomatic Zenker's diverticula are usually treated with diverticulectomy and myotomy. Other, more conservative open procedures consist of diverticulopexy, imbrication, and myotomy alone. These more conservative procedures do not result in a breach of esophageal mucosa and should have more rapid postoperative recovery. We performed a retrospective chart review of all open surgical procedures performed at the Marshfield Clinic and St. Joseph's Hospital between 1975 and 1996. Using Wilcoxon's rank sum test, the conservative procedures were compared with the standard diverticulectomy for duration of hospitalization and length of time to resumption of oral intake. Fifty-nine patients are reported. Statistically significant differences between the surgery groups were found for hospitalization (P < 0.001) and days to resumption of oral intake (P < 0.001). Conservative open surgical procedures for repair of Zenker's diverticula result in decreased hospitalization and earlier resumption of oral diet compared with diverticulectomy. [ABSTRACT FROM AUTHOR]

Background: Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program., Methods: We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019., Results: Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates., Conclusion: Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to evaluate the feasibility and initial outcomes of totally endoscopic aortic valve replacement (TEAVR) performed via a single working port at the fourth intercostal space (ICS) utilizing a 3D endoscopic system., Methods: A retrospective observational study was conducted on 35 consecutive patients who underwent TEAVR over a six-month period from December 2023 to June 2024. Patient selection was based on the presence of isolated aortic valve disease without the need for ascending aorta replacement or aortic root enlargement. A 4 cm single working port was created at the 4th ICS, extending from the right mid-axillary to the anterior axillary line. A 10-mm trocar for a 3D endoscope was placed at the right anterior-axillary line. Peripheral cardiopulmonary bypass (CPB) was established. The primary outcomes investigated included the success rate of the procedure, in-hospital mortality, and perioperative complications., Results: The mean age of the patients was 58.7 ± 12.8 years, with 22.9% being female. The majority of patients (77.1%) presented with aortic stenosis, often accompanied by severe calcification. The medianCPB time was 210 ± 43 min, and the median aortic cross-clamp time was 132 ± 41 min. The procedure was successfully completed in all patients using the endoscopic approach, with no conversions to full sternotomy. Two mortalities were recorded, attributed to postoperative complications including bleeding and cerebral infarctions. The early (30-day) mortality rate was 5.7%. Prolonged mechanical ventilation (>48 h) was required in 17.1% of patients, and reoperation for bleeding was necessary in 2.9% of patients., Conclusions: TEAVR is a feasible procedure with the potential to replace the traditional sternotomy approach for aortic valve replacement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Nguyen and Pham.)

Adenosquamous carcinoma (ASC) with the presence of a sarcomatous component is exceptionally uncommon in intrahepatic cholangiocarcinoma (iCCA). We report a case of hepatic ASC with rhabdoid transformation, one variation of sarcomatous change. A 72-year-old man was admitted to our hospital after being diagnosed with a 45 mm-diameter neoplastic lesion in the right hepatic duct on abdominal computed tomography. Laboratory findings showed increases in AST, ALT, ALP, gamma-GT, CA19-9 and DUPAN-II. The patient then underwent an extended right hepatectomy. Histopathologically, the tumor was composed of an ASC component within an abundant fibrous stroma and a sarcomatoid carcinoma component. By immunohistochemistry, keratin 7 and keratin 19 were expressed by all tumor cells. Expression of keratin 5/6, p40 and p63 was restricted to the squamous component. The sarcomatoid component was immunoreactive for vimentin with no loss of INI1 expression. This component also showed a loss of membranous E-cadherin expression and a reduction of membranous β-catenin expression. Staining for desmin, myoglobin and HepPar1 was negative in any tumor cells. The patient died of liver failure 3 months after surgery. This report aims to provide a better understanding of the clinicopathological characteristics and disease progression of the rare variants of iCCA to aid diagnosis and treatment., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Background: COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity., Methods: In this cross-sectional study, we evaluated the adaptive immune responses in US active duty personnel who completed a COVID-19 primary vaccine series and had heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were based on the most recent exposure in terms of timing (within or beyond 12 months) and type (vaccine or infection)., Results: Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants when compared with previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was >12 months from enrollment. In contrast, the CD4+ T-cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses., Conclusions: Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Challenges in classifying recurrent Plasmodium vivax infections constrain surveillance of antimalarial efficacy and transmission. Recurrent infections may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or reinfection. Molecular inference of familial relatedness (identity-by-descent or IBD) can help resolve the probable origin of recurrences. As whole genome sequencing of P. vivax remains challenging, targeted genotyping methods are needed for scalability. We describe a P. vivax marker discovery framework to identify and select panels of microhaplotypes (multi-allelic markers within small, amplifiable segments of the genome) that can accurately capture IBD. We evaluate panels of 50-250 microhaplotypes discovered in a global set of 615 P. vivax genomes. A candidate global 100-microhaplotype panel exhibits high marker diversity in the Asia-Pacific, Latin America and horn of Africa (median H E  = 0.70-0.81) and identifies 89% of the polyclonal infections detected with genome-wide datasets. Data simulations reveal lower error in estimating pairwise IBD using microhaplotypes relative to traditional biallelic SNP barcodes. The candidate global panel also exhibits high accuracy in predicting geographic origin and captures local infection outbreak and bottlenecking events. Our framework is open-source enabling customised microhaplotype discovery and selection, with potential for porting to other species or data resources., (© 2024. The Author(s).)

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association., Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL., Results: Higher HL scores B = 0.13 (95% CI = 0.06-0.21, p  = 0.001) and HDK scores B = 0.58 (95% CI = 0.31-0.85, p  = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = -6.12 (95% CI = -7.66 to - 4.58, p  = 0.001) and FCoV-19 B = -0.91 (95% CI = -1.03 to - 0.80, p  = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary., Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: In recent years, Vietnam has suffered multiple epizootics of influenza in poultry., Methods: From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs)., Results: Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus., Conclusions: This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In recent years, there has been growing interest in the prediction of financial market trends, due to its potential applications in the real world. Unlike traditional investment avenues such as the stock market, the foreign exchange (Forex) market revolves around two primary types of orders that correspond with the market's direction: upward and downward. Consequently, forecasting the behaviour of the Forex behaviour market can be simplified into a binary classification problem to streamline its complexity. Despite the significant enhancements and improvements in performance seen in recent proposed predictive models for the forex market, driven by the advancement of deep learning in various domains, it remains imperative to approach these models with careful consideration of best practices and real-world applications. Currently, only a limited number of papers have been dedicated to this area. This article aims to bridge this gap by proposing a practical implementation of deep learning-based predictive models that perform well for real-world trading activities. These predictive mechanisms can help traders in minimising budget losses and anticipate future risks. Furthermore, the paper emphasises the importance of focussing on return profit as the evaluation metric, rather than accuracy. Extensive experimental studies conducted on realistic Yahoo Finance data sets validate the effectiveness of our implemented prediction mechanisms. Furthermore, empirical evidence suggests that employing the use of three-value labels yields superior accuracy performance compared to traditional two-value labels, as it helps reduce the number of orders placed., Competing Interests: Data availability and accessData available within the article or its supplementary materials. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells in primates. In mice, an AB248 surrogate demonstrated superior antitumor activity and enhanced tolerability as compared with an untargeted IL2Rβγ agonist. Efficacy was associated with the expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a "better effector" population. These data support the potential utility of AB248 in clinical settings. Significance: The full potential of IL2 therapy remains to be unlocked. We demonstrate that toxicity can be decoupled from antitumor activity in preclinical models by limiting IL2 signaling to CD8+ T cells, supporting the development of CD8+ T cell-selective IL2 for the treatment of cancer. See related article by Kaptein et al. p. 1226., (©2024 The Authors; Published by the American Association for Cancer Research.)

Cleistocalyx operculatus flower buds have been widely used in traditional medicine because of their rich content of bioactive constituents. In this study, we obtained seven solvent extracts from the flower buds and evaluated their total phenolic (TPC), flavonoid (TFC), tannin (TTC), triterpenoid saponin (TSC), and alkaloid (TAC) contents. We assessed antioxidant activities using the DPPH assay and also looked at antimicrobial and enzyme inhibitory effects. The water extract possessed the highest TPC (328.9 mg GAE/g extract), followed by ethanol, methanol, and hexane extracts (85.4-101.5 mg GAE/g extract). Chloroform, butanol, ethyl acetate, and ethanol extracts had high TSCs (245.4-287.2 mg OAE/g extract). The hexane extract was richest in TTC and TFC (32.7 mg CE/g extract and 81.1 mg QE/g extract, respectively). Ethanol and methanol extracts exhibited the strongest antioxidant activities (IC 50 values of 25.2 and 30.3 μg/ml, respectively), followed by the water extract (IC 50 of 40.2 μg/ml). The hexane extract displayed the most growth-inhibitory activity against Helicobacter pylori ATCC51932 and ATCC43504 strains and Salmonella enterica serovar Typhimurium ATCC13311 (MIC values of 0.06, 0.13, and 0.4 mg/ml, respectively). Moreover, the hexane extract revealed the strongest inhibition of H. pylori urease activity (IC 50 of 4.51 μg/ml), whereas the water and methanol extracts had potent inhibitory effects on α-glucosidase activity (IC 50 values of 9.9 and 15.1 μg/ml, respectively). These flower bud extracts could be used for health protection, especially in preventing bacterial infections and inhibiting enzymes associated with various human diseases. Further investigation into the application of C. operculatus flower buds in the food and pharmaceutical industries is necessary., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 Institute of Bioorganic Chemistry, Polish Academy of Sciences.)

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.

Noni fruit (Morinda citrifolia L.) has many health-supporting compounds, but its biological extracts need protection against environmental impacts for stability and efficiency. To address this, microencapsulation is an advanced technology in food applications that require optimization of coating component and temperature regime. Gum arabic (GA) and maltodextrin (MD) were suitably combined at 2:1 ratio, which showed good and stable structure as well as successful microencapsulation efficiency of the enzymatic-ultrasonic assisted noni extract. A coating density of 20 % for the GA:MD formula was with highest performance. The heat setting of spray drying was optimized at 175 and 82 °C for inlet and outlet, respectively using response surface methodology with experimental validation of maximized TFC and TSC at 88.3 and 90.3 %, respectively. Noni microencapsulated powder was assessed via a series of reliably advanced techniques such as microscopy, spectrophotometry, diffraction, and calorimetry for structural properties. Noni powder was additionally tested for storage stability, heat exposure stability, and release efficiency in pH condition and in vitro digestive tract. Promising results were obtained with at least one year storage stability, better microcapsule stability at 60 and 100 °C, quite good release at pH 7.4, and suitable release efficiency in digestive tract simulation. These properties of microencapsulated noni powder open further scalability potential and various industrial applications., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The loss of ecosystem functions and services caused by rapidly declining coastal marine ecosystems, including corals and bivalve reefs and wetlands, around the world has sparked significant interest in interdisciplinary methods to restore these ecologically and socially important ecosystems. In recent years, 3D-printed artificial biodegradable structures that mimic natural life stages or habitat have emerged as a promising method for coastal marine restoration. The effectiveness of this method relies on the availability of low-cost biodegradable printing polymers and the development of 3D-printed biomimetic structures that efficiently support the growth of plant and sessile animal species without harming the surrounding ecosystem. In this context, we present the potential and pathway for utilizing low-cost biodegradable biopolymers from waste biomass as printing materials to fabricate 3D-printed biodegradable artificial structures for restoring coastal marine ecosystems. Various waste biomass sources can be used to produce inexpensive biopolymers, particularly those with the higher mechanical rigidity required for 3D-printed artificial structures intended to restore marine ecosystems. Advancements in 3D printing methods, as well as biopolymer modifications and blending to address challenges like biopolymer solubility, rheology, chemical composition, crystallinity, plasticity, and heat stability, have enabled the fabrication of robust structures. The ability of 3D-printed structures to support species colonization and protection was found to be greatly influenced by their biopolymer type, surface topography, structure design, and complexity. Considering limited studies on biodegradability and the effect of biodegradation products on marine ecosystems, we highlight the need for investigating the biodegradability of biopolymers in marine conditions as well as the ecotoxicity of the degraded products. Finally, we present the challenges, considerations, and future perspectives for designing tunable biomimetic 3D-printed artificial biodegradable structures from waste biomass biopolymers for large-scale coastal marine restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Light-Dependent Protochlorophyllide Oxidoreductase (LPOR) catalyzes a crucial step in chlorophyll biosynthesis: the rare biological photocatalytic reduction of the double C[double bond, length as m-dash]C bond in the precursor, protochlorophyllide (Pchlide). Despite its fundamental significance, limited structural insights into the active complex have hindered understanding of its reaction mechanism. Recently, a high-resolution cryo-EM structure of LPOR in its active conformation challenged our view of pigment binding, residue interactions, and the catalytic process. Surprisingly, this structure contrasts markedly with previous assumptions, particularly regarding the orientation of the bound Pchlide. To gain insights into the substrate binding puzzle, we conducted molecular dynamics simulations, quantum-mechanics/molecular-mechanics (QM/MM) calculations, and site-directed mutagenesis. Two Pchlide binding modes were considered, one aligning with historical proposals (mode A) and another consistent with the recent experimental data (mode B). Binding energy calculations revealed that in contrast to the non-specific interactions found for mode A, mode B exhibits distinct stabilizing interactions that support more thermodynamically favorable binding. A comprehensive analysis incorporating QM/MM-based local energy decomposition unraveled a complex interaction network involving Y177, H319, and the C13 1 carboxy group, influencing the pigment's excited state energy and potentially contributing to substrate specificity. Importantly, our results uniformly favor mode B, challenging established interpretations and emphasizing the need for a comprehensive re-evaluation of the LPOR reaction mechanism in a way that incorporates accurate structural information on pigment interactions and substrate-cofactor positioning in the binding pocket. The results shed light on the intricacies of LPOR's catalytic mechanism and provide a solid foundation for further elucidating the secrets of chlorophyll biosynthesis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane ( 1 ); along with two known compounds of betulinic acid ( 2 ) and ursolic acid ( 3 ). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α -glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane ( 1 ), betulinic acid ( 2 ), and ursolic acid ( 3 ) demonstrate the strong inhibitory with the IC 50 values of 106.1, 11.12, and 7.20 μM, respectively. All of these compounds interacted well with the allosteric site enzyme α -glucosidase MAL32 through H-bonds and hydrophobic interaction.

Background: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences., Objective: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences., Methods: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group., Results: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group., Conclusions: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being., (©Lan T H Le, Thi Ngoc Anh Hoang, Tan T Nguyen, Tien D Dao, Binh N Do, Khue M Pham, Vinh H Vu, Linh V Pham, Lien T H Nguyen, Hoang C Nguyen, Tuan V Tran, Trung H Nguyen, Anh T Nguyen, Hoan V Nguyen, Phuoc B Nguyen, Hoai T T Nguyen, Thu T M Pham, Thuy T Le, Thao T P Nguyen, Cuong Q Tran, Ha-Linh Quach, Kien T Nguyen, Tuyen Van Duong. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 02.04.2024.)

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 TGFβ-signaling, and inhibition of TGFβ-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.

Entanglement in bipartite systems has been applied to generate secure random numbers, which are playing an important role in cryptography or scientific numerical simulations. Here, we propose to use multipartite entanglement distributed between trusted and untrusted parties for generating randomness of arbitrary dimensional systems. We show that the distributed structure of several parties leads to additional protection against possible attacks by an eavesdropper, resulting in more secure randomness generated than in the corresponding bipartite scenario. Especially, randomness can be certified in the group of untrusted parties, even when there is no randomness in either of them individually. We prove that the necessary and sufficient resource for quantum randomness in this scenario is multipartite quantum steering when each untrusted party has a choice between only two measurements. However, the sufficiency no longer holds with more measurement settings. Finally, we apply our analysis to some experimentally realized states and show that more randomness can be extracted compared with the existing analysis.

Bound states in the continuum have recently been utilized in photonic crystal gratings to achieve strong coupling and ultralow threshold condensation of exciton-polariton quasiparticles with atypical Dirac-like features in their dispersion relation. Here, we develop the single- and many-body theory of these new effective relativistic polaritonic modes and describe their mean-field condensation dynamics facilitated by the interplay between protection from the radiative continuum and negative-mass optical trapping. Our theory accounts for tunable grating parameters giving full control over the diffractive coupling properties between guided polaritons and the radiative continuum, unexplored for polariton condensates. In particular, we discover stable cyclical condensate solutions mimicking a driven-dissipative analog of the zitterbewegung effect characterized by coherent superposition of ballistic and trapped polariton waves. We clarify important distinctions between the polariton nearfield and farfield explaining recent experiments on the emission characteristics of these long lived nonlinear Dirac polaritons., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Typhoniumobtusum is described as a new species endemic to Vietnam. It is unique in the genus in having an oblong-elliptic spathe limb with an obtuse apex and yellowish-greenish filiform staminodes with a down-curved acumen. The ecology, distribution and assessment of the conservation status of the new taxon, as well as a key to all known Typhonium species in Vietnam, are provided., Competing Interests: The authors have declared that no competing interests exist., (Hong Truong Luu, Nga Nguyen-Phi, Quoc Dat Nguyen, Hieu Cuong Nguyen, Hong Thien Van, Xuan Bach Nguyen-Le.)

Background: The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a "social vaccine" that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association., Methods: A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions., Results: Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63-2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97-0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96-0.99; p=0.001)., Conclusion: Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.

Brown seaweed is a promising source of polysaccharides and phenolics with industrial utility. This work reports the development of a green enzyme-assisted extraction method for simultaneously extracting polysaccharides and phenolics from the brown seaweed Padina gymnospora . Different enzymes (Cellulast, Pectinex, and Alcalase), individually and in combination, were investigated, with Alcalase alone showing the highest efficiency for the simultaneous extraction of polysaccharides and phenolics. Yields from Alcalase-assisted aqueous extraction were higher than those obtained using either water alone or conventional ethanol extraction. Alcalase-assisted extraction was subsequently optimized using a response surface methodology to maximize compound recovery. Maximal polysaccharide and phenolic recovery was obtained under the following extraction conditions: a water-to-sample ratio of 61.31 mL/g, enzyme loading of 0.32%, temperature of 60.5 °C, and extraction time of 1.95 h. The extract was then fractionated to obtain alginate-, fucoidan-, and phenolic-rich fractions. Fractions exhibited potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity with IC 50 values of 140.55 µg/mL, 126.21 µg/mL, and 48.17 µg/mL, respectively, which were higher than those obtained from conventional extraction methods. The current work shows that bioactive polysaccharides and phenolics can be obtained together in high yield through a single aqueous-only green and efficient Alcalase-assisted extraction.

CD8 + T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8 + T cell dysfunction showed that interleukin-2 (IL-2)-based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2's effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T reg ) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively. To address this, we developed a cis-targeted CD8-IL2 fusion protein, aiming to selectively stimulate dysfunctional CD8 + T cells in chronic HBV. In a mouse model, CD8-IL2 boosted the number of HBV-reactive CD8 + T cells in the liver without substantially altering T reg or NK cell counts. These expanded CD8 + T cells exhibited increased interferon-γ and granzyme B production, demonstrating enhanced functionality. CD8-IL2 treatment resulted in substantial antiviral effects, evidenced by marked reductions in viremia and antigenemia and HBV core antigen-positive hepatocytes. In contrast, an untargeted CTRL-IL2 led to predominant NK cell expansion, minimal CD8 + T cell expansion, negligible changes in effector molecules, and minimal antiviral activity. Human CD8-IL2 trials in cynomolgus monkeys mirrored these results, achieving a roughly 20-fold increase in peripheral blood CD8 + T cells without affecting NK or T reg cell numbers. These data support the development of CD8-IL2 as a therapy for chronic HBV infection.

Objective: Herewith, we report the development of Orthopedic Digital Image Analysis (ODIA) software that is developed to obtain quantitative measurements of knee osteoarthritis (OA) radiographs automatically. Manual segmentation and measurement of OA parameters currently hamper large-cohort analyses, and therefore, automated and reproducible methods are a valuable addition in OA research. This study aims to test the automated ODIA measurements and compare them with available manual Knee Imaging Digital Analysis (KIDA) measurements as comparison., Design: This study included data from the CHECK (Cohort Hip and Cohort Knee) initiative, a prospective multicentre cohort study in the Netherlands with 1,002 participants. Knee radiographs obtained at baseline of the CHECK cohort were included and mean medial/lateral joint space width (JSW), minimal JSW, joint line convergence angle (JLCA), eminence heights, and subchondral bone intensities were compared between ODIA and KIDA., Results: Of the potential 2,004 radiographs, 1,743 were included for analyses. Poor intraclass correlation coefficients (ICCs) were reported for the JLCA (0.422) and minimal JSW (0.299). The mean medial and lateral JSW, eminence height, and subchondral bone intensities reported a moderate to good ICC (0.7 or higher). Discrepancies in JLCA and minimal JSW between the 2 methods were mostly a problem in the lateral tibia plateau., Conclusions: The current ODIA tool provides important measurements of OA parameters in an automated manner from standard radiographs of the knee. Given the automated and computerized methodology that has very high reproducibility, ODIA is suitable for large epidemiological cohorts with various follow-up time points to investigate structural progression, such as CHECK or the Osteoarthritis Initiative (OAI)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the safety and efficacy of the Hanoi ASD procedure, which is totally endoscopic surgery for atrial septal defect (ASD) repair on beating heart. In addition, the present study also aimed to analyze the learning curve for this procedure., Methods: From May 2016 to February 2023, 198 consecutive ASD patients weighing ≥20 kg were enrolled in the retrospective study. The Hanoi ASD procedure includes (1) unilateral or bilateral femoral arterial cannulation; (2) two or three 5 mm trocars and a 15 mm port; (3) ASD repair on beating heart, preventing air embolism with CO 2 insufflation and keeping the left atrium full of blood; and (4) not snaring the inferior vena cava. Cumulative sum (CUSUM) analysis was used to evaluate the cardiopulmonary bypass (CPB) and operation time learning curves. Variables among the learning curve phases were compared., Results: The CPB and operation times were 90 (72 to 115) min and 180 (150 to 220) min, respectively. Total drainage volume was 190 (120 to 290) mL. No endoscopic failure or major complications were complications were excluding factors causing bias, the CUSUM CPBtime analysis for the remaining 131 patients included 3 phases. Phase 1 was the initial learning period (cases 1 to 34), phase 2 represented the technical competence period (cases 35 to 54), and phase 3 was the challenging period (cases 55 to 131)., Conclusions: The Hanoi ASD procedure is safe and feasible for repairing ASD in patients weighing ≥20 kg. According to the learning curve analysis, 34 cases were required to achieve technical efficiency, and 54 cases were required to address highly challenging cases., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

(1) Background: Complex proximal humerus fractures often result in complications following surgical treatment. A better understanding of the full 3D displacement would provide insight into the fracture morphology. Repositioning of fracture elements is often conducted by using the contralateral side as a reconstruction template. However, this requires healthy contralateral anatomy. The purpose of this study was to create a Statistical Shape Model (SSM) and compare its effectiveness to the contralateral registration method for the prediction of the humeral proximal segment; (2) Methods: An SSM was created from 137 healthy humeri. A prediction for the proximal segment of the left humeri from eight healthy patients was made by combining the SSM with parameters. The predicted proximal segment was compared to the left proximal segment of the patients. Their left humerus was also compared to the contralateral (right) humerus; (3) Results: Eight modes explained 95% of the variation. Most deviations of the SSM prediction and the contralateral registration method were below the clinically relevant 2 mm distance threshold.; (4) Conclusions: An SSM combined with parameters is a suitable method to predict the proximal humeral segment when the contralateral CT scan is unavailable or the contralateral humerus is unhealthy, provided that the fracture pattern allows measurements of these parameters.

The current study aimed to identify the chemical constituents and bioactivities of the crude ethanolic extract (CEE) and its fractions (ethyl acetate (EAF), hexane (HEF), and aqueous (AEF)) from leaves of cashew ( Anacardium occidentale L.) grown in Vietnam. A total of 31 compounds which belong to alkanes, hydrocarbons, iodine, terpenoids, phenolics, and flavonoids were determined by a gas chromatography-mass spectrometry (GC-MS) analysis, with bis(2-ethylhexyl) phthalate being the most prevailing compound. The highest total phenolic and flavonoid contents were obtained in the EAF, followed by HEF, CEE, and AQF. All samples showed promising in vitro antibacterial activity, enzyme inhibition, and anticancer activity. Among the samples tested, the EAF exhibited the highest enzyme inhibition activity against α-amylase and α-glucosidase (IC 50 values of 51.24 μg/mL and 99.29 μg/mL, respectively), cytotoxicity activity against HeLa cells (IC 50 value of 79.49 μg/mL), and antibacterial activity against Bacillus subtilis and Escherichia coli with MIC values of 5 mg/mL and 2.5 mg/mL, respectively. These findings suggest that the leaves of A. occidentale cultivated in Vietnam are a promising source of bioactive components and that EAF is a promising bioactive material warranting further pharmaceutical investigation., Competing Interests: The authors have declared no conflicts of interest for this article., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objectives: We assess the impact of the COVID-19 pandemic on health, treatment adherence and expectations of patients with chronic diseases in Vietnam., Methods: We conducted a national cross-sectional study using a questionnaire survey, distributed through social networks and presented on Google Forms. The survey was performed during two months of the most stringent social distancing in Vietnam (between 21 July and 21 September 2021)., Results: Most of the participants said that the COVID-19 epidemic had affected their daily activities (91.9%), health (53.6%), sleep behavior (52.3%), and mental health (79.8%). During social distancing in Vietnam, three-quarter could not go to hospitals for periodic health examination; nearly half of respondents did not do daily physical activity; a quarter of respondents did not adhere to recommended diet plan. Factors associated with the effect of the COVID-19 epidemic on patient's health included those living in Ho Chi Minh City ( p  = 0.015), lived alone ( p  = 0.027), uncontrolled chronic conditions ( p  < 0.001), treatment dissatisfaction or experienced anxiety/stress ( p  < 0.001). Factors associated with medication adherence included the elderly ( p  = 0.015), having periodic health examination ( p  = 0.012), direct consultation ( p  = 0.003), and telemedicine ( p  = 0.007)., Conclusion: This study highlights the urgent need for better chronic management strategies for the new post-COVID era in the future.

Adenosma bracteosum and Vitex negundo are natural sources of methoxylated flavonoids. Little is known about the α-glucosidase inhibition of multi-methoxylated flavonoid derivatives. Eighteen natural flavonoids were isolated from A. bracteosum and V. negundo. Seven halogenated derivatives were synthesized. Their chemical structures were elucidated by extensive NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. All compounds were evaluated for their α-glucosidase inhibition. Most compounds showed good activity with IC 50 values ranging from 16.7 to 421.8 μM. 6,8-Dibromocatechin was the most active compound with an IC 50 value of 16.7 μM. A molecular docking study was conducted, indicating that those compounds are potent α-glucosidase inhibitors., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Wetlands are one of the most important ecosystems as habitats for many animal and plant species and are crucial for disaster mitigation, improving environmental quality, storing carbon, and responding to climate change. However, these sensitive ecosystems have been heavily affected by anthropogenic activities, including aquaculture. In this study, we used multitemporal satellite imagery integrated with a verified field survey method to map the coverage of the wetland ecosystem in the Dong Rui commune, Tien Yen district, Quang Ninh Province, Vietnam, five times for four periods from 1975 to 2022, with high accuracy (overall accuracy = 92.3%, Kappa = 0.91). The results showed that from 1975 to 2000, the area of mangrove forests declined sharply (by nearly 2,000 ha), mainly due to policies of development and conversion of land use. From 2000 to 2022, the mangrove forest area was gradually restored, while the area under aquaculture shrank. Anthropogenic impacts, especially the effects of local economic development, and conservation and developmental policies, are the main causes of continuous change in each short period. Our study demonstrates satellite imagery as an effective tool for assessing wetland ecosystem area fluctuations and assessing the extent of human impacts on this natural ecosystem. Our findings can serve as a basis for planning, conservation strategies, and sustainable development of wetland ecosystems and for improving the associated livelihoods of the communities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)