Multiscale imaging and quantitative analysis of plasma membrane protein-cortical actin interplay.

The spatiotemporal organization of cell surface receptors is important for cell signaling. Cortical actin (CA), the subset of the actin cytoskeleton subjacent to the plasma membrane (PM), plays a large role in cell surface receptor organization. However, this has been shown largely through actin perturbation experiments, which raise concerns of nonspecific effects and preclude quantification of actin architecture and dynamics under unperturbed conditions. These limitations make it challenging to predict how changes in CA properties can affect receptor organization. To derive direct relationships between the architecture and dynamics of CA and the spatiotemporal organization of PM proteins, including cell surface receptors, we developed a multiscale imaging and computational analysis framework based on the integration of single-molecule imaging (SMI) of PM proteins and fluorescent speckle microscopy (FSM) of CA (combined: SMI-FSM) in the same live cell. SMI-FSM revealed differential relationships between PM proteins and CA based on the PM proteins' actin binding ability, diffusion type, and local CA density. Combining SMI-FSM with subcellular region analysis revealed differences in CA dynamics that were predictive of differences in PM protein mobility near ruffly cell edges versus closer to the cell center. SMI-FSM also highlighted the complexity of cell-wide actin perturbation, where we found that global changes in actin properties caused by perturbation were not necessarily reflected in the CA properties near PM proteins, and that the changes in PM protein properties upon perturbation varied based on the local CA environment. Given the widespread use of SMI as a method to study the spatiotemporal organization of PM proteins and the versatility of SMI-FSM, we expect it to be widely applicable to enable future investigation of the influence of CA architecture and dynamics on different PM proteins, especially in the context of actin-dependent cellular processes.

Trace element contamination in rice and its potential health risks to consumers in North-Central Vietnam.

Lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr), and nickel (Ni) are poisonous, widely distributed, persistent, and transferable to crops, posing potential health risks. This study aims to assess the potential health risks of those elements in rice collected from North-Central Vietnam: Thanh Hoa, Nghe An, and Ha Tinh provinces. Element analysis was performed on rice harvested in November 2020 by ICP-MS. The estimated daily intake (EDI), target hazard quotient (THQ), non-carcinogenic hazard index (HI), and target carcinogenic risk (TR) were used to assess potential health risks for different population groups. The highest element levels (mg kg-1 dry weight) were observed for Cr (0.30 ± 0.11), As (0.17 ± 0.025) and for Pb (0.24 ± 0.013) in Thanh Hoa, and for Cd (0.088 ± 0.015) in Ha Tinh. Strong links were observed between geological formations, mining activities and Cr in rice (Thanh Hoa), or industrial activities and Ni accumulation in rice (Hung Nguyen and Ky Anh districts). Children had greater EDIs than adults, with As having a higher EDI than RfD. Rice THQs indicated a risk trend: Thanh Hoa > Ha Tinh > Nghe An, with As being a significant contributor to HIs. Cr and Cd were significant risk factors and HIs in female children were 1.5 times higher than in other groups. Based on TR values for Ni and Pb, a potential carcinogenic risk to rice eaters was observed, particularly Ni. The data revealed a significant human health risk (both non-carcinogenic and carcinogenic) connected with rice consumption. Therefore, crops and foods from North-Central Vietnam should be strictly regulated.

Modulation of mitogen-activated protein kinase-activated protein kinase 3 by hepatitis C virus core protein.

Hepatitis C virus (HCV) is highly dependent on cellular proteins for its own propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assays using the HCV core protein as a probe. Of ~9,000 host proteins immobilized in a microarray, approximately 100 cellular proteins were identified as HCV core-interacting partners. Of these candidates, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) was selected for further characterization. MAPKAPK3 is a serine/threonine protein kinase that is activated by stress and growth inducers. Binding of HCV core to MAPKAPK3 was confirmed by in vitro pulldown assay and further verified by coimmunoprecipitation assay. HCV core protein interacted with MAPKAPK3 through amino acid residues 41 to 75 of core and the N-terminal half of kinase domain of MAPKAPK3. In addition, both RNA and protein levels of MAPKAPK3 were elevated in both HCV subgenomic replicon cells and cell culture-derived HCV (HCVcc)-infected cells. Silencing of MAPKAPK3 expression resulted in decreases in both protein and HCV infectivity levels but not in the intracellular HCV RNA level. We showed that MAPKAPK3 increased HCV IRES-mediated translation and MAPKAPK3-dependent HCV IRES activity was further increased by core protein. These data suggest that HCV core may modulate MAPKAPK3 to facilitate its own propagation.

Mercury distribution, mobilization and bioavailability in polluted sediments of Scheldt Estuary and Belgian Coastal Zone.

In this study, the vertical distribution of mercury (Hg) in estuarine and marine sediment porewaters and solid phases was assessed by conventional and passive sampling techniques in the historically polluted Scheldt Estuary and Belgian Coastal Zone (BCZ). The Diffusive Gradients in Thin-films (DGT) measured labile Hg concentrations (HgLA) were mostly lower than the porewater Hg concentrations (HgPW), and they also presented different vertical distribution patterns. Still high Hg concentrations in the sediment solid phases, comparable to the historical ones, were observed. Even though pH, redox potential and dissolved sulfide concentration could influence the Hg biogeochemical behaviour, organic matter (OM) played a key role in governing Hg mobilization from sediment solid phase to porewater and in its partitioning between porewater and solid phase over depth. In the marine sediments, where OM had a marine signature, higher labile Hg concentrations in the porewater and faster resupply from the solid phase were observed. The DGT technique showed significant potential not only for the measurement of bioavailable Hg fractions in porewater, but also for the assessment of kinetic parameters governing the release of labile Hg species from the solid phase with the assistance of the DGT Induced Fluxes in Sediments (DIFS) model.

Land-based plastic leakage into the aquatic environment from municipal solid waste - Waste flow diagram applied to Tuy Hoa City, Phu Yen, Vietnam.

Plastic mismanagement and its subsequent pollution by rapid economic development and urbanisation pose significant challenges for modern world society. Notwithstanding one of the main sources for macro plastic leakage into the ocean from land, precise assessment of plastic pollution origins from Southeast Asia is yet to be clearly examined. In order to make informed decisions and prioritise areas of improvement it is required to better understand the waste leakage dynamics at the local level. In this work, the Waste Flow Diagram (WFD) was applied to understand the sources and fates of plastics leaking from the solid waste management system for the case of Tuy Hoa City, Phu Yen, Vietnam. The study shows scenarios of leakage into the aquatic environment ranging from 0.8 to 2.7 kg/cap/year, which originates mainly from the collection system. Targeted improvements to this stage of the service could reduce leakages and the overall environmental impacts of mismanaged plastic waste. The results of this study show the necessity and importance of having up to date and reliable data to better inform stakeholders and service planning, facilitating efficient action against plastic pollution. As the first peer-reviewed scientific article critically applying the WFD, this work highlights the steps and challenges of the methodology and critically analyses different methodological pathways.

Detection of enteroviruses related to hand foot and mouth disease in wastewater of Asian communities.

Hand, foot, and mouth disease (HFMD) is contagious and predominantly affects children below the age of five. HFMD-associated serotypes of Enterovirus A (EVA) family include EVA71, Coxsackievirus A type 6 (CVA6), 10 (CVA10), and 16 (CVA16). Although prevalent in numerous Asian countries, studies on HFMD-causing agents in wastewater are scarce. This study aimed to conduct wastewater surveillance in various Asian communities to detect and quantify serotypes of EVA associated with HFMD. In total, 77 wastewater samples were collected from Indonesia, the Philippines, Thailand, and Vietnam from March 2022 to February 2023. The detection ratio for CVA6 RNA in samples from Vietnam was 40 % (8/20). The detection ratio for CVA6 and EVA71 RNA each was 25 % (5/20) for the Indonesian samples, indicating the need for clinical surveillance of CVA6, as clinical reports have been limited. For the Philippines, 12 % (2/17) of the samples were positive for CVA6 and EVA71 RNA each, with only one quantifiable sample each. Samples from Thailand had a lower detection ratio (1/20) for CVA6 RNA, and the concentration was unquantifiable. Conversely, CVA10 and CVA16 RNAs were not detected in any of the samples. The minimum and maximum concentrations of CVA6 RNA were 2.7 and 3.9 log10 copies/L and those for EVA71 RNA were 2.5 and 4.9 log10 copies/L, respectively. This study underscores the importance of wastewater surveillance in understanding the epidemiology of HFMD-associated EVA serotypes in Asian communities. Long-term wastewater surveillance is recommended to monitor changes in dominant serotypes, understand seasonality, and develop effective prevention and control strategies for HFMD.

Prevalence of hepatitis A and E viruses in wastewater in Asian countries.

Hepatitis A and E viruses (HAV and HEV, respectively) remain a significant global health concern despite advancements in healthcare and vaccination programs. Regular monitoring and vaccine efficacy of HAV are still lacking in different countries. This study aimed to investigate HAV and HEV prevalence in developed, developing, and least-developed Asian countries using wastewater as a surveillance tool. A total of 232 untreated wastewater samples were collected from six wastewater treatment plants, a sewage treatment plant, or an open drainage in six countries [Nepal (n = 51), Indonesia (n = 37), Thailand (n = 30), Vietnam (n = 27), the Philippines (n = 17), and Japan (n = 70)] between April and October 2022. Viruses in wastewater were concentrated by simple centrifugation or polyethylene glycol precipitation method, followed by viral RNA extraction and reverse transcription-quantitative polymerase chain reaction. HAV and HEV RNA were detected in the samples from Nepal (51 % for HAV and 2 % for HEV), Thailand (3 % for both viruses), and Japan (1 % for HAV and 24 % for HEV). Only HAV RNA was found in 11 % of the samples in Indonesia, whereas only HEV RNA was detected in Vietnam and the Philippines, with a positive ratio of 15 % and 12 %, respectively. These results highlighted the geographic variability in HAV and HEV prevalence, underscoring the need for localized public health strategies to address specific viral hepatitis challenges in each country.

Severity influences categorical likelihood communications: A case study with Southeast Asian weather forecasters.

Risk assessments are common in multiple domains, from finance to medicine. They require evaluating an event's potential severity and likelihood. We investigate the possible dependence of likelihood and severity within the domain of impact-based weather forecasting (IBF), following predictions derived from considering asymmetric loss functions. In a collaboration between UK psychologists and partners from four meteorological organisations in Southeast Asia, we conducted two studies (N = 363) eliciting weather warnings from forecasters. Forecasters provided warnings denoting higher likelihoods for high severity impacts than low severity impacts, despite these impacts being described as having the same explicit numerical likelihood of occurrence. This 'Severity effect' is pervasive, and we find it can have a continued influence even for an updated forecast. It is additionally observed when translating warnings made on a risk matrix to numerical probabilities.

Multiscale imaging and quantitative analysis of plasma membrane protein-cortical actin interplay.

The spatiotemporal organization of cell surface receptors is important for cell signaling. Cortical actin (CA), the subset of the actin cytoskeleton subjacent to the plasma membrane (PM), plays a large role in cell surface receptor organization. This was however shown largely through actin perturbation experiments, which raise concerns of nonspecific effects and preclude quantification of actin architecture and dynamics under unperturbed conditions. These limitations make it challenging to predict how changes in CA properties can affect receptor organization. To derive direct relationships between the architecture and dynamics of CA and the spatiotemporal organization of PM proteins, including cell surface receptors, we developed a multiscale imaging and computational analysis framework based on the integration of single-molecule imaging (SMI) of PM proteins and fluorescent speckle microscopy (FSM) of CA (combined: SMI-FSM) in the same live cell. SMI-FSM revealed differential relationships between PM proteins and CA based on the PM proteins’ actin binding ability, diffusion type and local CA density. It also highlighted the complexity of cell wide actin perturbation, where we found that global changes in actin properties caused by perturbation were not necessarily reflected in the CA properties near PM proteins, and the changes in PM protein properties upon perturbation varied based on the local CA environment. Given the widespread use of SMI as a method to study the spatiotemporal organization of PM proteins and the versatility of SMI-FSM, we expect it to be widely applicable to enable future investigation of the influence of CA architecture and dynamics on different PM proteins, especially in the context of actin-dependent cellular processes, such as cell migration. Significance: Plasma membrane protein organization, an important factor for shaping cellular behaviors, is influenced by cortical actin, the subset of the actin cytoskeleton near the plasma membrane. Yet it is challenging to directly and quantitatively probe this influence. Here, we developed an imaging and analysis approach that combines single-molecule imaging, fluorescent speckle microscopy and computational statistical analysis to characterize and correlate the spatiotemporal organization of plasma membrane proteins and cortical actin. Our approach revealed different relationships between different proteins and cortical actin, and highlighted the complexity of interpreting cell wide actin perturbation experiments. We expect this approach to be widely used to study the influence of cortical actin on different plasma membrane components, especially in actin-dependent processes.

Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis.

Patients with pulmonary graft-versus-host disease (pGVHD) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, pGVHD pathogenesis is not fully elucidated in humans, and currently available immunosuppressants are inadequately effective. We performed pathologic evaluation of lung specimens from 45 allo-HSCT recipients with pGVHD who underwent lung transplantation. Patient pathology was characterized by bronchiolitis and subpleural perivascular inflammation, with B-cell, monocyte, and T-cell accumulation around bronchioles. Bronchiolitis, perivascular inflammation, and peribronchial macrophage aggregation were also identified in a murine pGVHD model after transplant of bone marrow cells and splenocytes from C57BL/6 to B10.BR mice. Among mitogen-activated protein kinase kinase (MEK) inhibitors, cobimetinib, but not trametinib, improved survival rates. Cobimetinib attenuated bronchiolitis, improved airway resistance and lung compliance in the mice, and suppressed activation of B cells and tumor necrosis factor α production by monocytes in vitro; these features were not suppressed by trametinib or tacrolimus. Furthermore, cobimetinib suppressed activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling, resulting in B-cell and monocyte suppression. Dual inhibition of the MEK/extracellular signal-regulated kinase (ERK) and PI3K/AKT pathways using a combination of trametinib and the PI3K inhibitor taselisib strongly suppressed B-cell activation in vitro and improved mouse survival rates compared with vehicle or monotherapy with trametinib or taselisib. Imaging mass cytometry of human pGVHD revealed that T cells around bronchioles were positive for phosphorylated ERK, whereas B cells were positive for phosphorylated AKT. Thus, perivascular inflammation and bronchiolitis mediated by activation of the MEK/ERK and PI3K/AKT pathways are essential for pGVHD and represent a potential novel therapeutic target in humans.

Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation.

BACKGROUND & AIMS: Hepatitis C virus (HCV) requires host cellular proteins for its own propagation. To identify the cellular factors necessary for HCV propagation, we have recently screened the small interfering RNA (siRNA) library targeting cell cycle genes using cell culture grown HCV (HCVcc)-infected cells. In the current study, we have selected and characterized the gene encoding Cyclin A2 (CycA2). Deregulation of CycA2 has been implicated in many types of cancers, including hepatocellular carcinoma. METHODS: The effects of CycA2 on HCV propagation were investigated by siRNA-mediated knockdown assay, in vitro and in vivo protein binding assays, luciferase reporter gene assay, and immunoblot assay. RESULTS: We showed that siRNA-mediated depletion of CycA2 significantly inhibited HCV replication in both HCV subgenomic replicon cells and HCVcc-infected cells. Furthermore, HCV non-structural 5B (NS5B) specifically interacted with CycA2 in vitro and in vivo. Protein interaction was mediated through the cyclin box of CycA2 and the palm domain of NS5B. We further showed that R/HxL motif in the palm domain of HCV NS5B mediated protein interaction with CycA2 and this interaction was necessary for HCV replication. Moreover, we demonstrated that tylophorine, the natural plant product exerting a CycA2 inhibitory function, abrogated HCV replication. CONCLUSIONS: HCV regulates CycA2 via NS5B protein for its own propagation. In addition, tylophorine may be a potential therapeutic agent for HCV.

Marine fish parasites of Vietnam: a comprehensive review and updated list of species, hosts, and zoogeographical distribution.

With a long coastline stretching from tropical to subtropical climate zones, and an immense exclusive economic zone with over 4000 islands, the Vietnamese marine waters support a rich and biodiverse parasite fauna. Although the first parasitological record was in 1898, systematic studies of the parasite fauna have increased during the last 50 years. This comprehensive review covers the current state of knowledge of marine fish parasites in Vietnam and lists 498 species found in 225 fish species, and their geographical distribution. In addition, 251 marine parasite species have newly been added to the already known fauna of 247 species since 2006 (more than two-fold increase). The most speciose group was the Digenea, which accounted for 43% of the total parasite species biodiversity, followed by Monogenea (23.5%), Crustacea (11.6%), Nematoda, and Acanthocephala (8.0% each). The shallow and muddy Gulf of Tonkin showed a rich parasite fauna, accounting for 66.3% of the whole marine parasite fauna of Vietnam, with Digenea accounting for 51% of the regional total parasite richness, followed by Monogenea (27%), Acanthocephala (8.8%), and Nematoda (5.8%). Only a few species belonged to Hirudinea, Myxozoa, and Cestoda, suggesting that these taxa may be understudied. Despite significant progress in studies of marine fish parasites in Vietnam since 2006, only about 12% and 13% of the total fish species have been examined for parasites in the whole country and the Gulf of Tonkin, respectively.

Title: Parasites des poissons marins du Vietnam : synthèse complète et mise à jour des listes d'espèces, des hôtes et de la distribution zoogéographique. Abstract: Avec un long littoral s'étendant des zones climatiques tropicales à subtropicales et une immense zone économique exclusive incluant plus de 4 000 îles, les eaux marines vietnamiennes abritent une faune parasitaire abondante et riche en biodiversité. Le premier signalement parasitologique remonte à 1898 et les études systématiques de la faune parasitaire se sont multipliées au cours des 50 dernières années. Cette synthèse complète couvre l'état actuel des connaissances sur les parasites des poissons marins au Vietnam et répertorie 498 espèces trouvées dans 225 espèces de poissons et leur répartition géographique. De plus, 251 espèces de parasites marins ont été nouvellement ajoutées à la faune déjà connue de 247 espèces depuis 2006 (soit une augmentation de plus du double). Le groupe le plus riche en espèces était les Digenea, qui représentaient 43% de la biodiversité totale des espèces de parasites, suivis des Monogenea (23,5 %), des Crustacea (11,6 %), des Nematoda et des Acanthocephala (8,0 % chacun). Le golfe peu profond et boueux du Tonkin a montré une riche faune parasitaire, représentant 66,3 % de l'ensemble de la faune parasitaire marine du Vietnam, avec les Digenea représentant 51 % de la richesse parasitaire totale régionale, suivi des Monogenea (27 %), Acanthocephala (8,8 %) et Nematoda (5,8 %). Seules quelques espèces appartenaient aux Hirudinea, Myxozoa et Cestoda, ce qui suggère que ces taxons pourraient être sous-étudiés. Malgré des progrès significatifs dans les études sur les parasites des poissons marins au Vietnam depuis 2006, seulement 12 % et 13 % des espèces de poissons ont été examinées, respectivement pour les parasites de l'ensemble du pays et du golfe du Tonkin.

Adverse Effects of Toxic Metal Pollution in Rivers on the Physiological Health of Fish.

Toxic metal pollution influences the lives of diverse aquatic organisms and humans who consume contaminated aquatic products. However, its potential impacts on aquatic organism health and, thus, ecological health, have been neglected in many regions. This research was carried out to contribute to filling that knowledge gap. Three freshwater fish species in the Nhue−Day River basin, Vietnam, have been chosen to study the bioaccumulation of metals (Zn, Cu, Pb, and Cd) in the tissues (livers, kidneys, gills) and their effects on fish physiological health (changes in the oxidative-GST activity, and physiological biomarkers-energy reserves, respectively) from 2013 to 2017. The extensive results revealed significant spatial and temporal variations in metal concentrations in tissues of common carp (Cyprinus carpio), silver carp (Hypothalmic molitrix), and tilapia (Oreochromis niloticus), and well correlated to their concentration in the water (p < 0.05). Fish bioaccumulated metals in the following order: Zn > Cu > Pb > Cd, with more in the kidneys and livers (spring and summer) than in other tissues. Metal accumulation in O. niloticus and C. carpio was higher than in H. molitrix. Biomarker responses (except for glycogen variation) were also higher during warm seasons. Changes in metal levels in water and fish tissues caused variations in biomarkers in the respective fish tissues, particularly in the livers, as demonstrated by significant correlations of metal concentrations in water and fish tissues to biochemical and physiological responses (p < 0.05). The findings suggest that metal pollution in the river basin adversely impacts the physiological health of both wild and cultured fish. Seasonal shifts in the levels of metal accumulation and biomarkers could be connected to species-specific differences in physiology and the levels of metals in environments. This biomarker set is simple but effective in assessing the impact of metal pollution on fish health and, hence, the aquatic ecosystem. This is one of the first biomonitoring studies to assist in designing better water management strategies for the Nhue−Day River basin.

Movement restrictions, vaccine coverage, and reduction of the COVID-19 incidence rate in the fourth wave of the pandemic: Analysis results from 63 provinces in Vietnam.

On April 27, 2021, the fourth wave of the coronavirus disease 2019 (COVID-19) pandemic originating from the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Vietnam. The adoption of travel restrictions, coupled with rapid vaccination and mask-wearing, is a global strategy to prevent the spread of COVID-19. Although trade-off between health and economic development are unavoidable in this situation, little evidence that is specific to Vietnam in terms of movement restrictions, vaccine coverage, and real-time COVID-19 cases is available. Our research question is whether travel restrictions and vaccine coverage are related to changes in the incidence of COVID-19 in each province in Vietnam. We used Google's Global Mobility Data Source, which reports different mobility types, along with reports of vaccine coverage and COVID-19 cases retrieved from publicly and freely available datasets, for this research. Starting from the 50th case per province and incorporating a 14-day period to account for exposure and illness, we examined the association between changes in mobility (from day 27 to 04-03/11/2021) and the ratio of the number of new confirmed cases on a given day to the total number of cases in the past 14 days of indexing (the potentially contagious group in the population) per million population by making use of LOESS regression and logit regression. In two-thirds of the surveyed provinces, a reduction of up to 40% in commuting movement (to the workplace, transit stations, grocery stores, and entertainment venues) was related to a reduction in the number of cases, especially in the early stages of the pandemic. Once both movement and disease prevalence had been mitigated, further restrictions offered little additional benefit. These results indicate the importance of early and decisive actions during the pandemic.

Metal Pollution and Bioaccumulation in the Nhue-Day River Basin, Vietnam: Potential Ecological and Human Health Risks.

(1) Background: Metal pollution in the Nhue-Day River basin has impacted approximately 12 million people. However, none of the previous studies considered the entire basin's environmental and health risks. Thus, this research aims to fill knowledge gaps and reduce risks. (2) Methods: Sediment and fish samples from the basin were analyzed to determine the levels of Zn, Cu, Pb, and Cd pollution and their potential ecological (EF, modified Pollution Index-mPI, and expanded, modified potential ecological risk index-emRI) and human health risks (THQ, HI, and TR indices). (3) Results: Metal levels in sediment exceeded Canadian aquatic life protection guidelines, indicating moderate to severe contamination (EFs: 1.3-58.5 and mPIs: 4-39). Compared to the new proposed ecological risk threshold, all river sites and Site 1 for ponds had elevated metal levels; and these posed a very high ecological risk in spring (emRI > 4.5), with Cd being the most hazardous. Lead levels in all fish tissues surpassed Vietnamese and EU food regulations. In agreement with THQ, EWI (Zn, Cu) and EMI (Cd) were both less than 2.5% of the PTWI and PTMI, respectively. However, HI values of 0.67-1.26 suggested a moderate health risk. Carcinogenic risk (TR > 10-6; estimated for Pb) was detected in several localities for Common carp and Tilapia during the warm season. (4) Conclusions: Metals had a negative impact on the basin's ecosystem, with Cd being the most dangerous. Because of lead, consumption of Common carp and Tilapia from the basin may pose both non-carcinogenic and carcinogenic health concerns.

KIR3DL1 Allotype-Dependent Modulation of NK Cell Immunity against Chronic Myeloid Leukemia.

Tyrosine kinase inhibitor (TKI)-treated chronic myeloid leukemia (CML) patients with increased NK cell number have a better prognosis, and thus, NK cells may suppress CML. However, the efficacy of TKIs varies for reasons yet to be fully elucidated. As NK cell activity is modulated by interactions between their killer cell Ig-like receptors (KIRs) and HLAs of target cells, the combination of their polymorphisms may have functional significance. We previously showed that allelic polymorphisms of KIR3DL1 and HLAs were associated with the prognosis of TKI-treated CML patients. In this study, we focus on differential NK cell activity modulation through KIR3DL1 allotypes. KIR3DL1 expression levels varied according to their alleles. The combination of KIR3DL1 expression level and HLA-Bw4 motifs defined NK cell activity in response to the CML-derived K562 cell line, and Ab-mediated KIR3DL1 blocking reversed this activity. The TKI dasatinib enhanced NK cell activation and cytotoxicity in a KIR3DL1 allotype-dependent manner but did not significantly decrease effector regulatory T cells, suggesting that it directly activated NK cells. Dasatinib also enhanced NK cell cytotoxicity against K562 bearing the BCR-ABL1 T315I TKI resistance-conferring mutation, depending on KIR3DL1/HLA-Bw4 allotypes. Transduction of KIR3DL1*01502 into the NK cell line NK-92 resulted in KIR3DL1 expression and suppression of NK-92 activity by HLA-B ligation, which was reversed by anti-KIR3DL1 Ab. Finally, KIR3DL1 expression levels also defined activation patterns in CML patient-derived NK cells. Our findings raise the possibility of a novel strategy to enhance antitumor NK cell immunity against CML in a KIR3DL1 allotype-dependent manner.

Negative Impact of Fear of COVID-19 on Health-Related Quality of Life Was Modified by Health Literacy, eHealth Literacy, and Digital Healthy Diet Literacy: A Multi-Hospital Survey.

BACKGROUND: The COVID-19 pandemic has been disseminating fear in the community, which has affected people's quality of life, especially those with health problems. Health literacy (HL), eHealth literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. METHODS: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. RESULTS: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = -0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = -0.93, p < 0.001; to the mean, B = -0.85, p < 0.001; and one SD above the mean, B = -0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = -0.92, p < 0.001; to the mean, B = -0.82, p < 0.001; and one SD above the mean, B = -0.72, p < 0.001). CONCLUSIONS: eHealth literacy and digital healthy diet literacy could help to protect patients' health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors.

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.

A Mixed-Metal Porphyrinic Framework Promoting Gas-Phase CO2 Photoreduction without Organic Sacrificial Agents.

A photoactive porphyrinic metal-organic framework (MOF) has been prepared by exchanging Ti into a Zr-based MOF precursor. The resultant mixed-metal Ti/Zr porphyrinic MOF demonstrates much-improved efficiency for gas-phase CO2 photoreduction into CH4 and CO under visible-light irradiation using water vapor compared to the parent Zr-MOF. Insightful studies have been conducted to probe the photocatalysis processes. This work provides the first example of gas-phase CO2 photoreduction into methane without organic sacrificial agents on a MOF platform, thereby paving an avenue for developing MOF-based photocatalysts for application in CO2 photoreduction and other types of photoreactions.

Healthy Dietary Intake Behavior Potentially Modifies the Negative Effect of COVID-19 Lockdown on Depression: A Hospital and Health Center Survey.

Background: The COVID-19 pandemic causes a huge burden for affected countries. Several public health interventions were applied to contain the infection. However, the pandemic itself and the lockdown measure negatively influence people's lifestyles and psychological health. Purpose: To explore determinants of healthy dietary intake and depression, and examine the interaction between healthy dietary intake and COVID-19 lockdown on depression. Methods: A cross-sectional study was conducted at 18 hospitals and health centers from February 14 to May 31, 2020. Data of 8,291 outpatients were collected including patients' characteristics, clinical parameters, health literacy, healthy dietary intake (using the healthy eating score, HES), other health-related behaviors, and depression (using the patient health questionnaire, PHQ). Depression was defined as PHQ score ≥ 10. Results: Protective factors of healthy dietary intake and depression were higher education, better medication payment ability, higher social status, more physical activity, and higher health literacy, whereas older age, ever married, own business or other types of occupation, lockdown, suspected COVID-19 symptoms, and comorbidity were associated with lower HES scores and a higher depression likelihood. Besides, overweight/obesity and alcohol drinking were associated with lower HES scores. As compared with patients not under lockdown and with lowest HES score, those who were under lockdown and with lowest HES score had 10.6 times higher depression likelihood (odds ratio, OR, 10.60; 95% CI 6.88, 16.32; p < 0.001), whereas people with higher HES score had 15% lower depression likelihood (OR 0.85; 95% CI 0.82, 0.89; p < 0.001). Conclusions: Healthy dietary intake and depression were determined by several sociodemographic, clinical, and behavioral factors. Lockdown measure affects people's dietary intake behavior and depression. Importantly, healthy dietary intake potentially modifies the negative effect of lockdown on depression.