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401 result(s) for "Pham, Thanh H."
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A Redox Regulatory System Critical for Mycobacterial Survival in Macrophages and Biofilm Development
Survival of M. tuberculosis in host macrophages requires the eukaryotic-type protein kinase G, PknG, but the underlying mechanism has remained unknown. Here, we show that PknG is an integral component of a novel redox homeostatic system, RHOCS, which includes the ribosomal protein L13 and RenU, a Nudix hydrolase encoded by a gene adjacent to pknG. Studies in M. smegmatis showed that PknG expression is uniquely induced by NADH, which plays a key role in metabolism and redox homeostasis. In vitro, RenU hydrolyses FAD, ADP-ribose and NADH, but not NAD+. Absence of RHOCS activities in vivo causes NADH and FAD accumulation, and increased susceptibility to oxidative stress. We show that PknG phosphorylates L13 and promotes its cytoplasmic association with RenU, and the phosphorylated L13 accelerates the RenU-catalyzed NADH hydrolysis. Importantly, interruption of RHOCS leads to impaired mycobacterial biofilms and reduced survival of M. tuberculosis in macrophages. Thus, RHOCS represents a checkpoint in the developmental program required for mycobacterial growth in these environments.
Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis. Genetic mutagenesis, chemical complementation, and metabolomic profiling revealed trap-mediated metabolic imbalances, which induced thymineless death, a phenomenon in which rapidly growing cells succumb to thymine starvation. Restriction of B12 bioavailability, required for preventing trap formation, using an \"antivitamin B12\" molecule, sensitized intracellular bacteria to sulfonamides. Since boosting the bactericidal activity of sulfonamides through methylfolate trap induction can be achieved in Gram-negative bacteria and mycobacteria, it represents a novel strategy to render these pathogens more susceptible to existing sulfonamides.
Enhanced Photocatalytic Activity of Spherical Nd3+ Substituted ZnFe2O4 Nanoparticles
In this study, nanocrystalline ZnNdxFe2−xO4 ferrites with x = 0.0, 0.01, 0.03 and 0.05 were fabricated and used as a catalyst for dye removal potential. The effect of Nd3+ ions substitution on the structural, optical and photo-Fenton activity of ZnNdxFe2−xO4 has been investigated. The addition of Nd3+ ions caused a decrease in the grain size of ferrites, the reduction of the optical bandgap energies and thus could be well exploited for the catalytic study. The photocatalytic activity of the ferrite samples was evaluated by the degradation of Rhodamine B (RhB) in the presence of H2O2 under visible light radiation. The results indicated that the ZnNdxFe2−xO4 samples exhibited higher removal efficiencies than the pure ZnFe2O4 ferrites. The highest degradation efficiency was 98.00%, attained after 210 min using the ZnNd0.03Fe1.97O4 sample. The enhanced photocatalytic activity of the ZnFe2O4 doped with Nd3+ is explained due to the efficient separation mechanism of photoinduced electron and holes. The effect of various factors (H2O2 oxidant concentration and catalyst loading) on the degradation of RhB dye was clarified.
Onset of the summer monsoon over the southern Vietnam and its predictability
The summer monsoon onset over southern Vietnam is determined through a new criterion based on both in situ daily rainfall at six selected stations provided by the Institute of Meteorology and Hydrology, Vietnam, and the zonal component of the wind at 1,000 hPa from the National Center for Environmental Prediction/Department of Energy Reanalysis 2. Over the period 1979–2004, the summer monsoon onset mean date is on 12 May, with a standard deviation of 11.6 days. The temporal and spatial structures of the atmospheric conditions prevailing during the onset period are detailed. Clear changes are seen in the zonal wind (strengthened over the Bay of Bengal and changed from negative to positive over South Vietnam) and in convection (deeper), in association with an intensification of the meridional gradients of sea level pressure at 1,000 hPa and of moist static energy at 2 m over Southeast Asia. The predictability of onset dates is then assessed. Cross-validated hindcasts based upon four predictors linked to robust signals in the atmospheric dynamics are then provided. They are highly significant when compared to observations (56% of common variance). Basically, late (early) onsets are preceded in March–April by higher (lower) sea level pressure over the East China Sea, stronger (weaker) southeasterly winds over southern Vietnam, decreasing (increasing) deep convection over the Bay of Bengal, and the reverse situation over Indonesia (120–140°E, 0–10°S).
A Redox Regulatory System Critical for Mycobacterial Survival in Macrophages and Biofilm Development
Survival of M. tuberculosis in host macrophages requires the eukaryotic-type protein kinase G, PknG, but the underlying mechanism has remained unknown. Here, we show that PknG is an integral component of a novel redox homeostatic system, RHOCS, which includes the ribosomal protein L13 and RenU, a Nudix hydrolase encoded by a gene adjacent to pknG. Studies in M. smegmatis showed that PknG expression is uniquely induced by NADH, which plays a key role in metabolism and redox homeostasis. In vitro, RenU hydrolyses FAD, ADP-ribose and NADH, but not NAD+. Absence of RHOCS activities in vivo causes NADH and FAD accumulation, and increased susceptibility to oxidative stress. We show that PknG phosphorylates L13 and promotes its cytoplasmic association with RenU, and the phosphorylated L13 accelerates the RenU-catalyzed NADH hydrolysis. Importantly, interruption of RHOCS leads to impaired mycobacterial biofilms and reduced survival of M. tuberculosis in macrophages. Thus, RHOCS represents a checkpoint in the developmental program required for mycobacterial growth in these environments.
Enhanced Photocatalytic Activity of Spherical Nd 3+ Substituted ZnFe 2 O 4 Nanoparticles
In this study, nanocrystalline ZnNd Fe O ferrites with x = 0.0, 0.01, 0.03 and 0.05 were fabricated and used as a catalyst for dye removal potential. The effect of Nd ions substitution on the structural, optical and photo-Fenton activity of ZnNd Fe O has been investigated. The addition of Nd ions caused a decrease in the grain size of ferrites, the reduction of the optical bandgap energies and thus could be well exploited for the catalytic study. The photocatalytic activity of the ferrite samples was evaluated by the degradation of Rhodamine B (RhB) in the presence of H O under visible light radiation. The results indicated that the ZnNd Fe O samples exhibited higher removal efficiencies than the pure ZnFe O ferrites. The highest degradation efficiency was 98.00%, attained after 210 min using the ZnNd Fe O sample. The enhanced photocatalytic activity of the ZnFe O doped with Nd is explained due to the efficient separation mechanism of photoinduced electron and holes. The effect of various factors (H O oxidant concentration and catalyst loading) on the degradation of RhB dye was clarified.
Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during Large Nationwide Outbreak of COVID-19, Vietnam, 2021
We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.
The bacterial etiology and antimicrobial susceptibility of lower respiratory tract infections in Vietnam
Background Lower respiratory tract infection (LRTI) remains the leading infectious cause of morbidity and mortality globally. Key bacterial pathogens include Acinetobacter baumannii , Pseudomonas aeruginosa , Klebsiella pneumoniae , Escherichia coli , Staphylococcus aureus and Streptococcus pneumoniae . This study examined the prevalence and antimicrobial resistance patterns of major bacterial pathogens from community- and hospital-acquired LRTIs across six major hospitals in Vietnam. Methods Between January 2022 and May 2023, 1000 bacterial isolates were collected through an isolate-based surveillance. Species identification and antimicrobial susceptibility testing were performed by VITEK-2/Phoenix M50, with MICs determined by E-test or broth microdilution. Multiplex PCRs were used to detect common AMR genes. Results A. baumannii (49.6%), P. aeruginosa (21%), K. pneumoniae (18.6%) were predominant, followed by S. aureus (6.7 %) , E. coli (3.9%) and S. pneumoniae (0.2%). Most isolates (94.4%) were identified from hospital-acquired cases. High prevalence of MDR and carbapenem resistance were identified in A. baumannii (96% and 95%), P. aeruginosa (56.7% and 57.1%), and K. pneumoniae (78% and 69.2%), respectively. Notably, resistance to ceftazidime-avibactam was detected in K. pneumoniae (34.3%), P. aeruginosa (29%), and E. coli (7.7%), while colistin resistance was found in K. pneumoniae (18.2%) and A. baumannii (2.8%). MRSA prevalence was 79.1%, though S. aureus remained susceptible to vancomycin, linezolid and ceftaroline. Most bla NDM -positive K. pneumoniae (62/71, 87.3%), E. coli (2/2, 100%), and P. aeruginosa (23/25, 85.2%) showed resistance to ceftazidime-avibactam. Whole genome sequencing revealed that the bla NDM -positive but ceftazidime-avibactam susceptible isolates (9 K. pneumoniae and 2 P. aeruginosa ) carried truncated bla NDM . Overall, ceftazidime-avibactam was effective against K. pneumoniae , E. coli , and P. aeruginosa isolates carrying ESBL, ESBL and bla OXA−48 , or ESBL and bla KPC . Alternatively, no detectable AMR genes were found in 35 ceftazidime-avibactam resistant P. aeruginosa isolates. Conclusions Carbapenem-resistant Gram-negative pathogens were predominant among hospital-acquired LRTIs in Vietnam, with notable resistance to ceftazidime-avibactam and colistin. The lack of effective treatment for A. baumannii remains a major concern. We found a strong correlation between AMR phenotype and genotype among K. pneumoniae and E. coli , supporting gene-based therapy to guide ceftazidime-avibactam use. However, the presence of disrupted bla NDM underscores the need to re-evaluate commercial PCR assays for carbapenemase detection.
Unmasking Viral Causes of Hospitalized Respiratory Infection: Five Years of Respiratory Virus Surveillance in Vietnam by Multiplex Real-Time PCR Assay
Aim of the study: To investigate the detection rate of respiratory viruses identified by multiplex real-time PCR (MPL real-time PCR) in respiratory specimens collected from hospitalized patients with acute lower respiratory tract infections (LRTI) over a five-year period (2020–2024), and to emphasize the importance of MPL real-time PCR testing in identifying respiratory viruses responsible for severe lower respiratory tract infections requiring hospitalization. Subjects and Methods: This cross-sectional retrospective study analyzed 15,936 respiratory specimens collected from hospitalized patients between 2020 and 2024. Seventeen respiratory viruses were detected using MPL real-time PCR. Statistical comparisons were performed using the chi-square test. Results and Discussion: The overall respiratory virus detection rate was 31.88% and was significantly higher in children than in adults (52.98% vs. 18.10%). The most frequently detected viruses were rhinovirus, influenza A, respiratory syncytial virus, and parainfluenza virus type 3, while influenza A and SARS-CoV-2 predominated in adults. During the peak of the COVID-19 pandemic in 2021, SARS-CoV-2 accounted for 78.92% of detected viruses, accompanied by marked suppression of other respiratory pathogens. Measles virus re-emerged in 2024, predominantly affecting children (17.65%). Most Respiratory virus-positive cases (82.8%) involved single-agent infections. Conclusions: Hospitalized acute LRTI cases often lack distinctive clinical signs to identify viral pathogens. MPL real-time PCR provides simultaneous multi-virus detection, enabling accurate etiological diagnosis and strengthening hospital-based viral surveillance, particularly in resource-limited settings.
Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults
In this randomized trial, HIV-positive adults with tuberculous meningitis were assigned to receive 6 to 8 weeks of dexamethasone or placebo in addition to tuberculosis treatment. No benefit of dexamethasone was observed.