Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis.

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.

Vietnamese version of the Hypertension Knowledge-Level Scale (HK-LS): Translation and validation.

Introduction: In Vietnam, the prevalence of hypertension is increasing rapidly. Patients need to be conscious of the disease for timely prevention and treatment. The Hypertension Knowledge Level Scale (HK-LS) is commonly used to assess knowledge about hypertension. Methods: Data collection was took place in a hospital in Binh Thuan province, Vietnam in February 2020 with a total of 184 paticipants. Translation and adaptation of the HK-LS, validate the questionnaire through in-person interviews with outpatients diagnosed with hypertension. The translation process followed WHO guidelines. The appraisal process evaluates through reliability (Cronbach's alpha coefficient) and validity (meaningful relationship between the response results of the scale and the patient's characteristics). Results: The Vietnamese version of the HK-LS was translated and proven to be reliable (Cronbach's alpha=0.72) and valid (statistically significant difference between age groups (P=0.021) and educational background (P=0.007). Conclusion: The HK-LS was translated from English into Vietnamese; the questions are clear, intelligible, and suitable for surveying patients in Vietnam.

A Noninvasive Clinical Method to Measure in Vivo Mechanical Strains of the Lamina Cribrosa by OCT.

Objective: To measure mechanical strain of the lamina cribrosa (LC) after intraocular pressure (IOP) change produced 1 week after a change in glaucoma medication. Design: Cohort study. Participants: Adult glaucoma patients (23 eyes, 15 patients) prescribed a change in IOP-lowering medication. Intervention: Noninvasive OCT imaging of the eye. Main Outcome Measures: Deformation calculated by digital volume correlation of OCT scans of the LC before and after IOP lowering by medication. Results: Among 23 eyes, 17 eyes of 12 persons had IOP lowering ≥ 3 mmHg (reduced IOP group) with tensile anterior-posterior Ezz strain = 1.0% ± 1.1% (P = 0.003) and compressive radial strain (Err) = -0.3% ± 0.5% (P = 0.012; random effects models accounting inclusion of both eyes in some persons). Maximum in-plane principal (tensile) strain and maximum shear strain in the reduced-IOP group were as follows: Emax = 1.7% ± 1.0% and Γmax = 1.4% ± 0.7%, respectively (both P < 0.0001 vs. zero). Reduced-IOP group strains Emax and Γmax were significantly larger with greater % IOP decrease (P < 0.0001 and P < 0.0001, respectively). The compliances of the Ezz, Emax, and Γmax strain responses, defined as strain normalized by the IOP decrease, were larger with more abnormal perimetric mean deviation or visual field index values (all P ≤ 0.02). Strains were unrelated to age (all P ≥ 0.088). In reduced-IOP eyes, mean LC anterior border posterior movement was only 2.05 µm posteriorly (P = 0.052) and not related to % IOP change (P = 0.94, random effects models). Only Err was significantly related to anterior lamina depth change, becoming more negative with greater posterior LC border change (P = 0.015). Conclusions: Lamina cribrosa mechanical strains can be effectively measured by changes in eye drop medication using OCT and are related to degree of visual function loss in glaucoma. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Microbiome Analysis Revealed Acholeplasma as a Possible Factor Influencing the Susceptibility to Bacterial Leaf Blight Disease of Two Domestic Rice Cultivars in Vietnam.

The microbiomes of two important rice cultivars in Vietnam which differ by their susceptibility to the bacterial leaf blight (BLB) disease were analyzed through 16S rRNA amplicon technology. A higher number of operational taxonomic units and alpha-diversity indices were shown in the BLB-resistant LA cultivar than in the BLB-susceptible TB cultivar. The BLB pathogen Xanthomonas was scantly found (0.003%) in the LA cultivar, whereas was in a significantly higher ratio in the TB cultivar (1.82%), reflecting the susceptibility to BLB of these cultivars. Of special interest was the genus Acholeplasma presented in the BLB-resistant LA cultivar at a high relative abundance (22.32%), however, was minor in the BLB-sensitive TB cultivar (0.09%), raising a question about its roles in controlling the Xanthomonas low in the LA cultivar. It is proposed that Acholeplasma once entered the host plant would hamper other phytopathogens, i.e. Xanthomonas, by yet unknown mechanisms, of which the triggering of the host plants to produce secondary metabolites against pathogens could be a testable hypothesis.

Involvement of BCR::ABL1 in laminin adhesion of Philadelphia chromosome-positive acute lymphoblastic leukemia through upregulation of integrin α6.

BACKGROUND: Adhesion of cancer cells to extracellular matrix laminin through the integrin superfamily reportedly induces drug resistance. Heterodimers of integrin α6 (CD49f) with integrin ß1 (CD29) or ß4 (CD104) are major functional receptors for laminin. Higher CD49f expression is reportedly associated with a poorer response to induction therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Moreover, a xenograft mouse model transplanted with primary BCP-ALL cells revealed that neutralized antibody against CD49f improved survival after chemotherapy. AIMS: Considering the poor outcomes in Philadelphia chromosome (Ph)-positive ALL treated with conventional chemotherapy without tyrosine kinase inhibitors, we sought to investigate an involvement of the laminin adhesion. METHODS AND RESULTS: Ph-positive ALL cell lines expressed the highest levels of CD49f among the BCP-ALL cell lines with representative translocations, while CD29 and CD104 were ubiquitously expressed in BCP-ALL cell lines. The association of Ph-positive ALL with high levels of CD49f gene expression was also confirmed in two databases of childhood ALL cohorts. Ph-positive ALL cell lines attached to laminin and their laminin-binding properties were disrupted by blocking antibodies against CD49f and CD29 but not CD104. The cell surface expression of CD49f, but not CD29 and CD104, was downregulated by imatinib treatment in Ph-positive ALL cell lines, but not in their T315I-acquired sublines. Consistently, the laminin-binding properties were disrupted by the imatinib pre-treatment in the Ph-positive ALL cell line, but not in its T315I-acquired subline. CONCLUSION: BCR::ABL1 plays an essential role in the laminin adhesion of Ph-positive ALL cells through upregulation of CD49f.

Understanding PFAS toxicity through cell culture metabolomics: Current applications and future perspectives.

Per- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health.

Subjective well-being population norms and inequalities in Hungary: a large cross-sectional, internet-based survey.

OBJECTIVES: This study aims to provide subjective well-being (SWB) population norms in Hungary and explore the contribution of explanatory factors of SWB inequality among the Hungarian adult general population. METHODS: The data originated from a large representative internet-based cross-sectional survey in Hungary, which was conducted in 2020. We applied validated multi-item instruments for measuring SWB, namely SWLS and WHO-5. Multiple linear regressions were employed to examine the relationship between demographic-socioeconomic-health status and both well-being instruments. The concentration index (CI) was used to measure the degree of income-related inequality in well-being. RESULTS: A total of 2,001 respondents were enrolled with the means ± SD WHO-5 scores and SWLS scores of 0.51 ± 0.21 and 0.51 ± 0.23, respectively. Higher household income, higher educational level, better general health status, and absence of chronic morbidity were significant positive predictors for both WHO-5 and SWLS scores. The CI of WHO-5 scores was lower than that of SWLS scores in the total sample (0.0480 vs. 0.0861) and in subgroups by gender (male: 0.0584 vs. 0.1035, female: 0.0302 vs. 0.0726). The positive CI values implied a slight pro-rich SWB inequality in this population. The regression analyses showed a positive association of SWB with having a higher household income and a better general health status. CONCLUSIONS: This is the first representative study in Hungary to compare population norm of two well-being instruments and analyze well-being inequality. Slight pro-rich inequality was found consistently with both SWB measures. Our findings support the need for health and social policies that effectively tackle inequalities in Hungary.

Longitudinal relationship between screen-based sedentary behavior and nutrient intake in Japanese children: an observational epidemiological cohort study.

BACKGROUND: Concerns regarding the impact of screen-based sedentary behavior on health have been increasing. Therefore, the present study investigated the longitudinal relationship between multiple screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted utilizing 3 years longitudinal data. Study subjects were 740 Japanese children aged between 6 and 12 years at baseline and between 9 and 15 years in the follow-up. Screen-based sedentary behavior was assessed using screen time, including television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use. The main outcomes were the intakes of nutrients. Mixed effect multivariate linear regression analyses were used to examine the longitudinal relationship between screen-based sedentary time and nutrient intake. Covariates included in the multivariable analysis consisted of sex, age, solitary eating, skipping breakfast, staying up late, and body weight status, as confounders, and physical inactivity, as mediator. RESULTS: In boys, a longer total screen time longitudinally correlated with higher intake of energy and lower intakes of protein, dietary fiber, minerals, and vitamins. In girls, longer total screen time longitudinally associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In boys, a longer TV viewing time was associated with higher intake of sucrose and lower intakes of protein, minerals, and vitamins. In girls, a longer TV viewing time was associated with higher intake of carbohydrates and lower intakes of protein, fat, minerals, and vitamins. In boys, relationships were observed between a longer PC use time and higher intakes of energy as well as lower intakes of protein, minerals, and vitamins. Relationship was observed between longer PC use time and lower intakes of minerals in girls. An increased MP use time was associated with higher intakes of energy, and lower intakes of protein, sucrose, dietary fiber, minerals, and vitamins in boys. A longer MP use time was associated with higher intakes of fat, and salt as well as lower intakes of carbohydrates, protein, minerals, and vitamins in girls. CONCLUSIONS: The present results revealed that longer screen-based sedentary behaviors were longitudinally associated with nutrient intake in children and adolescents. Future study is needed to elucidate these relationships.

Effects of Nanoparticle Wettability on the Meniscus Stability of Oil-Water Systems: A Coarse-Grained Modeling Approach.

A coarse-grained modeling approach is employed to probe the effect of nanoparticles and their wettability on the stability of the interface between two immiscible fluids. In this study, pure oil (dodecane) and water are placed side by side in a nanochannel, forming a meniscus. Homogeneous hydrophilic nanoparticles, Janus particles, and homogeneous hydrophobic nanoparticles are placed at the oil-water interface, and their dynamics are studied as they rearrange at the oil-water interface. The results show that when the water is set in motion, two instabilities occur: the formation of fingers and the detachment of water from the channel wall. It is observed that the formation of fingers is affected by the wettability of the nanoparticles. The second instability may lead to the formation of a drop that propagates through the channel. However, it is found that the wetting properties of the nanoparticles do not affect the critical flow rate for the detachment of the water from the wall. Therefore, detachment occurs at the same three-phase contact angle regardless of the nanoparticle wetting properties. These findings can be important for industrial applications such as enhanced oil recovery, separation technologies, and microfluidic and nanofluidic technologies.

Application of prime editing system to introduce TP53 R248Q hotspot mutation in acute lymphoblastic leukemia cell line.

In childhood acute lymphoblastic leukemia (ALL), TP53 gene mutation is associated with chemoresistance in a certain population of relapsed cases. To directly verify the association of TP53 gene mutation with chemoresistance of relapsed childhood ALL cases and improve their prognosis, the development of appropriate human leukemia models having TP53 mutation in the intrinsic gene is required. Here, we sought to introduce R248Q hotspot mutation into the intrinsic TP53 gene in an ALL cell line, 697, by applying a prime editing (PE) system, which is a versatile genome editing technology. The PE2 system uses an artificial fusion of nickase Cas9 and reverse-transcriptase to directly place new genetic information into a target site through a reverse transcriptase template in the prime editing guide RNA (pegRNA). Moreover, in the advanced PE3b system, single guide RNA (sgRNA) matching the edited sequence is also introduced to improve editing efficiency. The initially obtained MDM2 inhibitor-resistant PE3b-transfected subline revealed disrupted p53 transactivation activity, reduced p53 target gene expression, and acquired resistance to chemotherapeutic agents and irradiation. Although the majority of the subline acquired the designed R248Q and adjacent silent mutations, the insertion of the palindromic sequence in the scaffold hairpin structure of pegRNA and the overlap of the original genomic DNA sequence were frequently observed. Targeted next-generation sequencing reconfirmed frequent edit errors in both PE2 and PE3b-transfected 697 cells, and it revealed frequent successful edits in HEK293T cells. These observations suggest a requirement for further modification of the PE2 and PE3b systems for accurate editing in leukemic cells.

The Chronic Effects of a Single Low-Intensity Blast Exposure on Phosphoproteome Networks and Cognitive Function Influenced by Mutant Tau Overexpression.

Blast-induced neurotrauma (BINT) is a pressing concern for veterans and civilians exposed to explosive devices. Affected personnel may have increased risk for long-term cognitive decline and developing tauopathies including Alzheimer's disease-related disorders (ADRD) or frontal-temporal dementia (FTD). The goal of this study was to identify the effect of BINT on molecular networks and their modulation by mutant tau in transgenic (Tg) mice overexpressing the human tau P301L mutation (rTg4510) linked to FTD or non-carriers. The primary focus was on the phosphoproteome because of the prominent role of hyperphosphorylation in neurological disorders. Discrimination learning was assessed following injury in the subsequent 6 weeks, using the automated home-cage monitoring CognitionWall platform. At 40 days post injury, label-free phosphoproteomics was used to evaluate molecular networks in the frontal cortex of mice. Utilizing a weighted peptide co-expression network analysis (WpCNA) approach, we identified phosphopeptide networks tied to associative learning and mossy-fiber pathways and those which predicted learning outcomes. Phosphorylation levels in these networks were inversely related to learning and linked to synaptic dysfunction, cognitive decline, and dementia including Atp6v1a and Itsn1. Low-intensity blast (LIB) selectively increased pSer262tau in rTg4510, a site implicated in initiating tauopathy. Additionally, individual and group level analyses identified the Arhgap33 phosphopeptide as an indicator of BINT-induced cognitive impairment predominantly in rTg4510 mice. This study unveils novel interactions between ADRD genetic susceptibility, BINT, and cognitive decline, thus identifying dysregulated pathways as targets in potential precision-medicine focused therapeutics to alleviate the disease burden among those affected by BINT.

Impact of long COVID-19 on posttraumatic stress disorder as modified by health literacy: an observational study in Vietnam.

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.

Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers.

Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab-restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFNγ ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.

Metabolic disruptions and impaired reproductive fitness in wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated per- and polyfluoroalkyl substances (PFAS).

Per- and poly-fluoroalkyl substances (PFAS) pose a threat to organisms and ecosystems due to their persistent nature. Ecotoxicology endpoints used in regulatory guidelines may not reflect multiple, low-level but persistent stressors. This study examines the biological effects of PFAS on Eastern short-necked turtles in Queensland, Australia. In this study, blood samples were collected and analysed for PFAS, hormone levels, and functional omics endpoints. High levels of PFAS were found in turtles at the impacted site, with PFOS being the dominant constituent. The PFAS profiles of males and females differed, with males having higher PFAS concentrations. Hormone concentrations differed between impacted and reference sites in male turtles, with elevated testosterone and corticosterone indicative of stress. Further, energy utilisation, nucleotide synthesis, nitrogen metabolism, and amino acid synthesis were altered in both male and female turtles from PFAS-impacted sites. Both sexes show similar metabolic responses to environmental stressors from the PFAS-contaminated site, which may adversely affect their reproductive fitness. Purine metabolism, caffeine metabolism, and ferroptosis pathway changes in turtles can cause gout, cell death, and overall health problems. Further, the study showed that prolonged exposure to elevated PFAS levels in the wild could compromise turtle reproductive fitness by disrupting reproductive steroids and metabolic pathways.

Evidence for widespread cytoplasmic structuring into mesoscale condensates.

Compartmentalization is an essential feature of eukaryotic life and is achieved both via membrane-bound organelles, such as mitochondria, and membrane-less biomolecular condensates, such as the nucleolus. Known biomolecular condensates typically exhibit liquid-like properties and are visualized by microscopy on the scale of ~1 µm (refs. 1,2). They have been studied mostly by microscopy, examining select individual proteins. So far, several dozen biomolecular condensates are known, serving a multitude of functions, for example, in the regulation of transcription3, RNA processing4 or signalling5,6, and their malfunction can cause diseases7,8. However, it remains unclear to what extent biomolecular condensates are utilized in cellular organization and at what length scale they typically form. Here we examine native cytoplasm from Xenopus egg extract on a global scale with quantitative proteomics, filtration, size exclusion and dilution experiments. These assays reveal that at least 18% of the proteome is organized into mesoscale biomolecular condensates at the scale of ~100 nm and appear to be stabilized by RNA or gelation. We confirmed mesoscale sizes via imaging below the diffraction limit by investigating protein permeation into porous substrates with defined pore sizes. Our results show that eukaryotic cytoplasm organizes extensively via biomolecular condensates, but at surprisingly short length scales.

Combating Acute Myeloid Leukemia via Sphingosine Kinase 1 Inhibitor-Nanomedicine Combination Therapy with Cytarabine or Venetoclax.

MP-A08 is a novel sphingosine kinase 1 (SPHK1) inhibitor with activity against acute myeloid leukemia (AML). A rationally designed liposome-based encapsulation and delivery system has been shown to overcome the physicochemical challenges of MP-A08 and enable its effective delivery for improved efficacy and survival of mice engrafted with human AML in preclinical models. To establish therapies that overcome AML's heterogeneous nature, here we explored the combination of MP-A08-loaded liposomes with both the standard chemotherapy, cytarabine, and the targeted therapy, venetoclax, against human AML cell lines. Cytarabine (over the dose range of 0.1-0.5 µM) in combination with MP-A08 liposomes showed significant synergistic effects (as confirmed by the Chou-Talalay Combination Index) against the chemosensitised human AML cell lines MV4-11 and OCI-AML3. Venetoclax (over the dose range of 0.5-250 nM) in combination with MP-A08 liposomes showed significant synergistic effects against the chemosensitised human AML cell lines, particularly in venetoclax-resistant human AML cells. This strong synergistic effect is due to multiple mechanisms of action, i.e., inhibiting MCL-1 through SPHK1 inhibition, leading to ceramide accumulation, activation of protein kinase R, ATF4 upregulation, and NOXA activation, ultimately resulting in MCL-1 degradation. These combination therapies warrant further consideration and investigation in the search for a more comprehensive treatment strategy for AML.

PFAS removal from landfill leachate by ozone foam fractionation: System optimization and adsorption quantification.

Landfills are the primary endpoint for the disposal of PFAS-laden waste, which subsequently releases PFAS to the surrounding environments through landfill leachate. Ozone foam fractionation emerges as a promising technology for PFAS removal to address the issue. This study aims to (i) assess the effectiveness of the ozone foam fractionation system to remove PFAS from landfill leachate, and (ii) quantify equilibrium PFAS adsorption onto the gas-water interface of ozone bubbles, followed by a comparison with air foam fractionation. The results show that ozone foam fractionation is effective for PFAS removal from landfill leachate, with more than 90 % long-chain PFAS removed. The identified operating conditions provide valuable insights for industrial applications, guiding the optimization of ozone flow rates (1 L/min), dosing (43 mg/L) and minimizing foamate production (4 % wettability). The equilibrium modelling reveals that the surface excess of air bubbles exceeds that of ozone bubbles by 20-40 % at a corresponding PFAS concentration. However, the overall removal of PFAS from landfill leachate by ozone foam fractionation remains substantial. Notably, ozone foam fractionation generates foamate volumes 2 - 4 times less, resulting in significant cost savings for the final disposal of waste products and reduced site storage requirements.

Assessing the Impact of Genratest on Women With Recurrent Implantation Failure: A Single-Center Study.

Objective Recurrent implantation failure (RIF) is a significant challenge in assisted reproduction. Genratest has emerged as a potential tool to identify the displaced window of implantation (WOI). This study aimed to evaluate the impact of this test on the pregnancy outcomes of RIF patients. Methods A retrospective analysis was conducted on 143 RIF patients who were categorized into two groups: the personalized embryo transfer (pET, n=69) group and standard embryo transfer (sET, n=74) group. The main measured outcomes were clinical pregnancy, ongoing pregnancy, miscarriage, and live birth rates. Results Genratest effectively diagnoses the displaced WOI in 90% of RIF patients. The pET group exhibited a higher rate of clinical pregnancy (n=36/69, 52.2%) compared to the sET group (n=35/74, 47.3%), but this difference was not statistically significant (p=0.679). Ongoing pregnancy rates were comparable between the pET (n=28/69, 40.6%) and the sET (n=30/74, 40.5%) groups (p=0.996). Live birth rates showed no statistically significant difference between the two groups (n=26/69, 37.7% versus n=22/74, 29.7%, p=0.407). Miscarriage rates were similar in both groups (n=9/69, 13% versus n=11/74, 14.9%, p=0.942). Conclusions pET based on the results of the Genratest did not show a significant improvement in pregnancy outcomes, including clinical pregnancy, ongoing pregnancy, live birth, or miscarriage rates. Further research is needed to identify the role of Genratest in RIF patients.

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.