Oxidative cyclization reagents reveal tryptophan cation-π interactions.

Methods for selective covalent modification of amino acids on proteins can enable a diverse array of applications, spanning probes and modulators of protein function to proteomics1-3. Owing to their high nucleophilicity, cysteine and lysine residues are the most common points of attachment for protein bioconjugation chemistry through acid-base reactivity3,4. Here we report a redox-based strategy for bioconjugation of tryptophan, the rarest amino acid, using oxaziridine reagents that mimic oxidative cyclization reactions in indole-based alkaloid biosynthetic pathways to achieve highly efficient and specific tryptophan labelling. We establish the broad use of this method, termed tryptophan chemical ligation by cyclization (Trp-CLiC), for selectively appending payloads to tryptophan residues on peptides and proteins with reaction rates that rival traditional click reactions and enabling global profiling of hyper-reactive tryptophan sites across whole proteomes. Notably, these reagents reveal a systematic map of tryptophan residues that participate in cation-π interactions, including functional sites that can regulate protein-mediated phase-separation processes.

Hydrogenated Soy Phosphatidylcholine Liposomes Stimulate Differential Expression of Chemokines And Cytokines by Rat Alveolar Macrophages In Vitro.

Liposomes are being developed as inhalable drug delivery systems, but concerns remain about their impact on the lungs. To better understand the impact of liposomes and their physicochemical properties on alveolar macrophages, the cytokine and chemokine expression profile of rat alveolar Nr8383 macrophages exposed to 0.1 and 1 mg/ml hydrogenated soy phosphatidylcholine (HSPC) liposomes was examined. Expression patterns varied considerably between liposomes in a concentration-dependent manner, with both anti- and pro-inflammatory chemokines/cytokines produced. Uncharged liposomes induce the greatest production of cytokines and chemokines, followed by PEGylated liposomes. The most significant increase in cytokine/chemokine expression was seen for IL-2 (up to 24-fold), IL-4 (up to 5-fold), IL-18 and VEGF (up to 10-fold), while liposome exposure significantly reduced MIP1 expression (5-fold). In summary, we demonstrate that liposome surface properties promote variable patterns of cytokine and chemokine secretion by alveolar macrophages. This suggests that the type of liposome employed may influence the type of immune response generated in the lung and by extension, dictate how inhaled liposomal nanomedicines affect the lungs response to inhaled toxicants and local infections.

Impact of interventions on the quality of life of cancer patients: a systematic review and meta-analysis of longitudinal research.

The impact of cancer interventions has been conducted in several research due to the significant burden of this non-communicable disease. The interventions that played an important role in the improvement of the patient's quality of life (QoL) and health-related quality of life (HRQL) can be classified into two main groups: pharmaceutical and non-pharmacological methods. However, studies so far often analyze a specific group of interventions for specific types of cancer. Thus, in this systematic review and meta-analysis, we synthesized the overall impact of cancer interventions on patients' quality of life in several cancers.In this research, we followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) to search the longitudinal original research on the Web of Science (WOS) database. After that, the Newcastle-Ottawa Scale (NOS) and Jadad Scale were used to assess the quality of non-randomized control trials and randomized control trials, respectively. Then, the characteristics of the included studies were described in the six main fields table and the random effect model with robust estimation was applied to analyze the impact of interventions on the health utility of patients.From the database, 122 longitudinal original research were included in the meta-regression, with most of them having high or fair quality. The European Organization for the research and treatment of cancer scale for quality of life (EORTC-QLQ) was the most used health utility measurement at 65.15%. In the adjusted effect models, the Visual Analogue Scale (VAS) had significant statistics in all models when we compared it with the EQ-5D Scale (p < 0.05) and several types of cancer such as breast, lung, and prostate cancer had significant statistics when comparing with hematological cancer in the model types of cancer (p < 0.01). Moreover, radiotherapy, screening, and a combination of chemotherapy and best supportive care also had significant statistics (p < 0.01) in the model of interventions when compared with radiotherapy applied only. Our research can suggest a vital combination of both pharmaceutical and non-pharmacological interventions to improve the quality of life of some common types of cancer patients.

Quality of life and mental health of adolescents: Relationships with social media addiction, Fear of Missing out, and stress associated with neglect and negative reactions by online peers.

Social networking is proliferating globally and in Vietnam, but this led to several negative aspects of adolescents' health, including physical activity, sleep quality, and depressive and anxiety symptoms. This study aimed to identify the relationship between social media usage and examine risk factors (Fear of Missing out and Risk of Neglect) on social media usage, and the overall quality of life and mental health among individuals actively using social media networks. An online cross-sectional study was conducted in three cities in Vietnam (Hanoi, Tuyen Quang, and Can Tho) from September through to October 2021. A structured questionnaire assessed for characteristics of social media use and other associated factors. 1891 participants were recruited, with 98.4% having access to social media. s. Factors like "PHQ-9 score", "Problematic Internet use", and "Time average used social media per day", were negatively associated with the EQ5D5L Index. By contrast, "Gender", and "Using smartphone" were positive factors of the EQ5D5L Index. "FOMO score" and "self-harm and suicide" were positive factors of the PHQ-9 score while "Using smartphone" was negative. In terms of self-harm and suicide, "FOMO score" and "Problematic Internet use" were positive factors, by contrast, "Using smartphone" was a negative factor. This is the first study to examine social media addiction among Vietnamese adolescents, its relationship with FOMO score, stresses associated with rejection and neglect, and the overall quality of life. Our results highlighted there is a relationship between FOMO score and impaired overall quality of life, increased depressive symptoms, and an association between stresses relating to negative rejection and FOMO score.

Investigation of thermodynamic and kinetic parameters of Albizia lebbeck seed pods using thermogravimetric analysis.

Thermodynamic and kinetic studies are very necessary to evaluate the conversion efficiency of biomass to energy. Therefore, this current work reported the thermodynamic and kinetic parameters of Albizia lebbeck seed pods through thermogravimetric analysis, which was carried out at temperatures from 25 °C to 700 °C, and heating rates of 5, 10, 15, and 20 °C/min. Apparent activation energies were determined by applying three iso-conversional model-free methods including Kissinger-Akahira-Sunose (KAS), Ozawa-Flynn-Wall (OFW), and Starink. Resultantly, average apparent activation energy values for the three models of KAS, OFW, and Starink were found to be 155.29, 156.14, and 155.53 kJ/mol, respectively. In addition, thermodynamic triplets such as enthalpy, Gibbs free energy, and entropy were obtained as 151.16 kJ/mol, 150.64 kJ/mol, and -7.57 J/mol·K, respectively. The above results suggest Albizia lebbeck seed pods could become a potential source for bioenergy production aiming to achieve the sustainable goal and waste-to-energy strategy.

Classifying of VN-Index Bullishness by Bayesian Inference.

Decision making in stock market is a movement in which investors gather information and carry out complex analysis to select options, based on market variations and investor's preferences. This involves the facts of risk of return, appreciating or depreciating of stock markets in value and dynamic circumstances. We present a design to study and discover bear and bull markets from macroeconomic variables in a probabilistic manner to assist the decision-making process. Features such as return, risk, simple, and exponential moving average are represented as flexible time series. The learning method that involves conditional dependence of stock variables and inference is described by the base of Bayesian theorem. We highlight our learning method using an actual case study with a consistent stock portfolio optimization. The case study addresses a set of selected stock symbols of VN-index and the logical method is illustrated by significant rates of accuracy over a variation of types of stock symbols.

Synthesis of Thermoresponsive, Catechol-Rich Poly(ethylene glycol) Brush Polymers for Attenuating Cellular Oxidative Stress.

Herein, we report a platform to integrate customizable quantities of catechol units into polymers by reacting caffeic acid carbonic anhydride with polymers having pendant amine groups. Brush poly(ethylene glycol)-caffeamide (PEG-CAF) copolymers based on oligo(ethylene glycol)methyl ether methacrylate (OEGMA500) were obtained with a catechol content of approximately 30, 40, and 50 mol % (vs OEGMA content). Owing to the hydrophobicity of the introduced CAF groups, the catechol copolymers exhibited cloud points in the range of 23-46 °C and were used to fabricate thermoresponsive FeIII metal-phenolic network capsules. Polymers with the highest CAF content (50 mol %) proved most effective for attenuating reactive oxygen species levels in vitro, in co-cultured fibroblasts, and breast cancer cells, even in the presence of an exogenous oxidant source. The reported approach to synthesize customizable catechol materials could be generalized to other amine-functional polymers, with potential biomedical applications such as adhesives or stimuli-responsive drug delivery systems.

Case Report: Successful Treatment of a Child With COVID-19 Reinfection-Induced Fulminant Myocarditis by Cytokine-Adsorbing oXiris® Hemofilter Continuous Veno-Venous Hemofiltration and Extracorporeal Membrane Oxygenation.

Background: Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities. Case Presentation: We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of oXiris ® hemofilter continuous venovenous hemofiltration (CVVH) and VA-ECMO. The patient made a full recovery without any sequelae. Conclusion: We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation.

Successful treatment of two extremely premature infants with perinatal tuberculosis and severe sepsis.

Perinatal tuberculosis (TB) is a rare disease with severe clinical conditions that may spread to several organs. Early diagnosis to initiate an anti-TB regimen is key to saving patients. We report the successful treatment of two preterm babies with perinatal TB and sepsis at the National Children's Hospital (NCH), Vietnam.

Lung function trajectory in progressive fibrosing interstitial lung disease.

BACKGROUND: Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design. METHODS: A retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups. RESULTS: 1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype. CONCLUSIONS: These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.

Nitroxide-functional PEGylated nanostars arrest cellular oxidative stress and exhibit preferential accumulation in co-cultured breast cancer cells.

The limited application of traditional antioxidants to reducing elevated levels of reactive oxygen species (ROS) is potentially due to their lack of stability and biocompatibility when tested in a biological milieu. For instance, the poor biological antioxidant performance of small molecular nitroxides arises from their limited diffusion across cell membranes and their significant side effects when applied at high doses. Herein, we describe the use of nanostructured carriers to improve the antioxidant activity of a typical nitroxide derivative, (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO). Polymers with star-shaped structures were synthesised and were further conjugated to TEMPO moieties via amide linkages. The TEMPO-loaded stars have small hydrodynamic sizes (<20 nm), and are better tolerated by cells than free TEMPO in a breast cancer-fibroblast co-culture, a system exhibiting elevated ROS levels. At a well-tolerated concentration, the polymer with the highest TEMPO-loading capacity successfully downregulated ROS production in co-cultured cells (a significant decrease of up to 50% vs. basal ROS levels), which was accompanied by a specific reduction in superoxide anion generation in the mitochondria. In contrast, the equivalent concentration of free TEMPO did not achieve the same outcome. Further investigation showed that the TEMPO-conjugated star polymers can be recycled inside the cells, thus providing longer term scavenging activity. Cell association studies demonstrated that the polymers can be taken up by both cell types in the co-culture, and are found to co-locate with the mitochondria. Interestingly the stars exhibited preferential mitochodria targeting in the co-cultured cancer cells compared to accompanying fibroblasts. The data suggest the potential of TEMPO-conjugated star polymers to arrest oxidative stress for various applications in cancer therapy.

Family History of Pulmonary Fibrosis Predicts Worse Survival in Patients With Interstitial Lung Disease.

BACKGROUND: A number of genetic markers linked to familial pulmonary fibrosis predict differential survival in interstitial lung disease (ILD) patients. Although genetic testing is not performed routinely for ILD, family history commonly is obtained and may inform outcome risk. RESEARCH QUESTION: Does survival vary between patients with and without self-reported familial pulmonary fibrosis? METHODS: Family history was acquired systematically for consecutive ILD patients who consented to clinical registry enrollment at the University of Texas Southwestern and the University of California at Davis. Patients were stratified by idiopathic pulmonary fibrosis (IPF) and non-IPF ILD diagnosis and were substratified by presence or absence of familial pulmonary fibrosis, defined as one or more additional affected family members. Transplant-free survival was compared using multilevel, mixed-effects Cox proportional hazards regression. RESULTS: Of the 1,262 patients included, 534 (42%) had IPF ILD and 728 (58%) had non-IPF ILD. Of those with non-IPF ILD, 18.5% had connective tissue disease, 15.6% had chronic hypersensitivity pneumonitis, and 23.5% had unclassifiable ILD. Familial pulmonary fibrosis was reported in 134 IPF ILD patients (25.1%) and 90 non-IPF ILD patients (12.4%). Those with familial IPF showed an 80% increased risk of death or transplantation compared with those with sporadic IPF (hazard ratio [HR], 1.8; 95% CI, 1.37-2.37; P < .001), whereas those with familial non-IPF ILD showed a twofold increased risk compared with their counterparts with sporadic disease (HR, 2.08; 95% CI, 1.46-2.96; P < .001). Outcome risk among those with familial non-IPF ILD was no different than for those with sporadic IPF ILD (HR, 1.27; 95% CI, 0.89-1.84; P = .19). INTERPRETATION: Patient-reported familial pulmonary fibrosis is predictive of reduced transplant-free survival in IPF and non-IPF ILD patients. Because survival among patients with familial non-IPF ILD approximates that of sporadic IPF ILD, early intervention should be considered for such patients. Until clinical genetic testing is widely available and provides actionable results, family history should be ascertained and considered in risk stratification.

Trisulfide linked cholesteryl PEG conjugate attenuates intracellular ROS and collagen-1 production in a breast cancer co-culture model.

The progression of cancer has been closely-linked with augmentation of cellular reactive oxygen species (ROS) levels and ROS-associated changes in the tumour microenvironment (TME), including alterations to the extracellular matrix and associated low drug uptake. Herein we report the application of a co-culture model to simulate the ROS based cell-cell interactions in the TME using fibroblasts and breast cancer cells, and describe how novel reactive polymers can be used to modulate those interactions. Under the co-culture conditions, both cell types exhibited modifications in behaviour, including significant overproduction of ROS in the cancer cells, and elevation of the collagen-1 secretion and stained actin filament intensity in the fibroblasts. To examine the potential of using reactive antioxidant polymers to intercept ROS communication and thereby manipulate the TME, we employed H2S-releasing macromolecular conjugates which have been previously demonstrated to mitigate ROS production in HEK cells. The specific conjugate used, mPEG-SSS-cholesteryl (T), significantly reduced ROS levels in co-cultured cancer cells by approximately 50%. This reduction was significantly greater than that observed with the other positive antioxidant controls. Exposure to T was also found to downregulate levels of collagen-1 in the co-cultured fibroblasts, while exhibiting less impact on cells in mono-culture. This would suggest a possible downstream effect of ROS-mitigation by T on stromal-tumour cell signalling. Since fibroblast-derived collagens modulate crucial steps in tumorigenesis, this ROS-associated effect could potentially be harnessed to slow cancer progression. The model may also be beneficial for interrogating the impact of antioxidants on naturally enhanced ROS levels, rather than relying on the application of exogenous oxidants to simulate elevated ROS levels.

Trisulfide-Bearing PEG Brush Polymers Donate Hydrogen Sulfide and Ameliorate Cellular Oxidative Stress.

A potential approach to combat cellular dysfunction is to manipulate cell communication and signaling pathways to restore physiological functions while protecting unaffected cells. For instance, delivering the signaling molecule H2S to certain cells has been shown to restore cell viability and re-normalize cell behavior. We have previously demonstrated the ability to incorporate a trisulfide-based H2S-donating moiety into linear polymers with good in vitro releasing profiles and demonstrated their potential for ameliorating oxidative stress. Herein, we report two novel series of brush polymers decorated with higher numbers of H2S-releasing segments. These materials contain two trisulfide-based monomers co-polymerized with oligo(ethylene glycol methyl ether methacrylate) via reversible addition-fragmentation chain-transfer polymerization. The macromolecules were characterized to have a range of trisulfide densities with similar, well-defined molecular weight distribution, good H2S-releasing profiles, and high cellular tolerance. Using an amperometric technique, the H2S liberated and total sulfide release were found to depend on concentrations and chemical nature of triggering molecules (glutathione and cysteine) and, importantly, the position of reactive groups within the brush structure. Notably, when introduced to cells at well-tolerated doses, two macromolecular donors which have the same proportion as of the H2S-donating monomer (30%) but differ in releasing moiety location show similar cellular H2S-releasing kinetics. These donors can restore reactive oxygen species levels to baseline values, when polymer pretreated cells are exposed to exogenous oxidants (H2O2). Our work opens up a new aspect in preparing H2S macromolecule donors and their application to arresting cellular oxidative cascades.

Polymers with Dithiobenzoate End Groups Constitutively Release Hydrogen Sulfide upon Exposure to Cysteine and Homocysteine.

Dithioesters are well-established as efficient reversible addition-fragmentation chain transfer (RAFT) agents. More recently, certain small molecule dithioesters have been reported to release the biological signaling molecule hydrogen sulfide (H2S) upon exposure to cysteine. Herein, we examine the propensity of polymers synthesized using RAFT with a dithioester chain transfer agent to release H2S via reaction of cysteine with constitutive dithioester end-groups. Homocysteine-triggered release of H2S from these materials is also observed, with evidence suggesting that the mechanism is analogous to the reaction with cysteine.

Lack of Knowledge about Sexually Transmitted Diseases (STDs): Implications for STDs Prevention and Care among Dermatology Patients in an Urban City in Vietnam.

Sexually transmitted diseases (STDs) are a substantial global burden of diseases, especially in developing countries. Lack of awareness of STDs may lead to a delay in treatment. This study aimed to assess knowledge about STDs and the associated factors among dermatological patients. A cross-sectional study was conducted among 622 patients at Vietnam National Hospital of Dermatology and Venereology (NHD). Structured questionnaires were used to investigate the knowledge about STDs. A multivariate Tobit regression was employed to determine factors associated with knowledge about STDs. The percentage of patients knowing that syphilis was an STD was highest (57.8%), followed by herpes warts (57.7%) and HIV/AIDS (57.4%). By contrast, 26.6% and 17.2% of patients knew that chlamydia and hepatitis C were STDs. The most commonly stated symptom of STDs was purulent genital (53.5%). Nearly two-thirds of participants were aware of the curability of STDs, and 34.7% knew about vaccines for STDs. Living with partners, young age, and acquired knowledge of STDs via the Internet, social networks, and health staff were positively related to having better knowledge about STDs. Based on the results of this study, peer education, informal conversations within clusters, mass community campaigns through the Internet and social networks, and the use of online health care providers should be promoted in order to improve awareness of STDs.

Pathogen screening and prognostic factors in children with severe ARDS of pulmonary origin.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most lethal diseases encountered in the pediatric intensive care unit (PICU). The etiological pathogens and prognostic factors of severe ARDS of pulmonary origin in children with respiratory virus infections were prospectively investigated. METHODS: Enrolled children fulfilled the following criteria: (1) PICU admission; (2) age of 1 month to 16 years; (3) diagnosis of infectious pneumonia and respiratory virus infection; and (4) development of severe ARDS within 72 h after PICU admission. Pathogens were detected in the blood and tracheal lavage fluid using molecular techniques and a conventional culture system. The serum levels of inflammatory mediators on the day of PICU admission were examined. RESULTS: Fifty-seven patients (32 boys; median age, 9 months) were enrolled. Multiple virus infections, co-infection with bacteria/fungus, and bacteremia/fungemia were observed in 60%, 49%, and 32% of children, respectively. Adenovirus-B, measles virus, and cytomegalovirus were detected predominantly in tracheal lavage fluid. There were no statistically significant differences between non-survivors and survivors regarding the types of pathogen, incidence of multiple virus infection, gender, age, clinical features, and treatment. The serum levels of interferon (IFN)-γ and the IFN-γ/interleukin (IL)-10 ratio were higher in non-survivors. CONCLUSIONS: IFN-γ upregulation as detected on the day of PICU admission was found to be one of the possible prognostic factors affecting a fatal outcome. These results suggest that modulation of inflammatory responses is critical for the clinical management of children with ARDS.