Comparative metabolomics reveals how the severity of predation by the invasive insect Cydalima perspectalis modulates the metabolism re-orchestration of native Buxus sempervirens.

The recent biological invasion of box tree moth Cydalima perspectalis on Buxus trees has a major impact on European boxwood stands through severe defoliation. This can hinder further regrowth and threaten survival of populations. In a mesocosm approach and controlled larval density over a 2-month period, responses of B. sempervirens essential and specialized metabolites were characterized using metabolomics, combining 1H-NMR and LC-MS/MS approaches. This is the first metabolome depiction of major Buxus responses to boxwood moth invasion. Under severe predation, remaining green leaves accumulate free amino acids (with the noticeable exception of proline). The leaf trans-4-hydroxystachydrine and stachydrine reached 10-13% and 2-3% (DW), while root content was lower but also modulated by predation level. Larval predation promoted triterpenoid and (steroidal) alkaloid synthesis and diversification, while flavonoids did not seem to have a relevant role in Buxus resistance. Our results reveal the concomitant responses of central and specialized metabolism, in relation to severity of predation. They also confirm the potential of metabolic profiling using 1H-NMR and LC-MS to detect re-orchestration of metabolism of native boxwood after severe herbivorous predation by the invasive box-tree moth, and thus their relevance for plant-insect relationships and ecometabolomics.

Cost analysis of establishing and operating the first human milk bank at Da Nang Hospital for Women and Children in Vietnam: an activity-based costing ingredients study.

BACKGROUND: Breastfeeding is the biological norm for feeding infants and young children. When mothers' breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam. METHODS: An activity-based costing ingredients (ABC-I) approach was employed, with the cost perspective from service provision agencies (specifically, the project conducted at Da Nang Hospital for Women and Children and Development Partners). Estimated financial costs, based on actual expenditures, were measured in 2023 local currency and then converted to 2023 US dollars (USD). We examined three scenarios: 1) direct start-up costs + indirect start-up costs + implementation costs, 2) direct start-up costs + implementation costs, and 3) capital costs + implementation costs over the 6.5 years of operation. RESULTS: The total start-up cost was USD 616,263, with total expenditure on direct activities at USD 228,131 and indirect activities at USD 388,132. Investment in equipment accounted for the largest proportion (USD 84,213). The monthly costs of Da Nang HMB were USD 25,217, 14,565, and 9,326, corresponding to scenarios 1, 2, and 3, respectively. Over HMB's 6.5 years of operation, on average, the unit costs were USD 166, USD 96, and USD 62 for DHM received and USD 201, USD 116, and USD 74 for pasteurized DHM meeting specified criteria in the corresponding scenarios. Unit costs were highest in the initial six months, decreased, and reached their lowest levels after a year. Then, the unit costs experienced an increase in late 2020 and early 2021. CONCLUSION: Although the unit cost of DHM in Da Nang HMB is comparable to that in certain neighboring countries, intentional measures to reduce disposal rates, improve HMB efficiency, motivate more community-based donors, and establish an HMB service network should be implemented to lower costs.

In vitro anti-leukemia, antioxidant, and anti-inflammatory properties of Lantana camara.

It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.

Risk factors for early mortality from lung cancer: evolution over the last 20 years in the French nationwide KBP cohorts.

BACKGROUND: The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years. MATERIALS AND METHODS: The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. In this study, we analyzed data on patient and tumor characteristics from participants in the KBP-2020 cohort and compared the characteristics of patients who died within 3 months of diagnosis with those of all other patients within the cohort. We also carried out a comparative analysis with the KBP-2000 and KBP-2010 cohorts. RESULTS: Overall, 8999 patients from 82 centers were included in the KBP-2020 cohort. Three-month survival data were available for 8827 patients, of whom 1792 (20.3%) had died. Risk factors for early mortality were: male sex, age >70 years, symptomatic disease at diagnosis, ever smoker, weight loss >10 kg, poor Eastern Cooperative Oncology Group performance status (≥1), large-cell carcinoma or not otherwise specified, and stage ≥IIIC disease. The overall 3-month mortality rate was found to have decreased significantly over the last 20 years, from 24.7% in KBP-2000 to 23.4% in KBP-2010 and 20.3% in KBP-2020 (P < 0.0001). CONCLUSION: Early mortality among patients with lung cancer has significantly decreased over the last 20 years which may reflect recent improvements in treatments. However, early mortality remained extremely high in 2020, particularly when viewed in light of improvements in longer-term survival. Delays in lung cancer diagnosis and management could contribute to this finding.

Mechanistic and kinetic insights of the formation of allene and propyne from the C3H3 reaction with water.

CONTEXT: Allene (H2C = C = CH2) and propyne (CH3-C≡CH) are important compounds in the combustion chemistry. They can be created from the reaction of proparyl radicals with water. In this study, therefore, a computational study into the C3H3 + H2O potential energy landscape has been carefully conducted. The computed results indicate that the reaction paths forming the products (allene: CH2CCH2 + •OH) and (propyne: HCCCH3 + •OH) prevail under the 300-2000 K temperature range, where the latter is much more predominant compared to the former. However, these two products are not easily formed under ambient conditions due to the high energy barriers. In the 300 - 2000 K temperature range, the branching ratio for the propyne + •OH product declines from 100 to 86%, whereas the allene + •OH product shows an increase, reaching 14% at 2000 K. The overall bimolecular rate constant of the title reaction can be presented by the modified Arrhenius expression of ktotal = 1.94 × 10-12 T0.14 exp[(-30.55 kcal.mol-1)/RT] cm3 molecule-1 s-1. The total rate constant at the ambient conditions in this work, 2.37 × 10-34 cm3 molecule-1 s-1, was found to be over five orders of magnitude lower than the total rate constant of the C3H3 + NH3 reaction, 7.98 × 10-29 cm3 molecule-1 s-1, calculated by Hue et al. (Int. J. Chem. Kinet. 2020, 4(2), 84-91). The results in this study contribute to elucidating the mechanism of allene and propylene formation from the C3H3 + H2O reaction, and they can be used for modeling C3H3-related systems under atmospheric and combustion conditions. METHODS: All the geometric structures of the C3H3 + H2O system were optimized by the B3LYP method in conjunction with the 6-311 + + G(3df,2p) basis set. Single-point energies of these species were calculated at the CCSD(T)/6-311 + + G(3df,2p) level of theory. The CCSD(T)/CBS level has also been used to compute single-point energies for the two major reaction channels (C3H3 + H2O → allene + •OH and C3H3 + H2O → propyne + •OH). Rate constants and branching ratios of the key reaction channels were calculated in the 300-2000 K temperature interval using the Chemrate software based on the transition state theory (TST) with Eckart tunneling corrections.

Assessing and forecasting collective urban heat exposure with smart city digital twins.

Due to population growth, climate change, and the urban heat island effect, heat exposure is becoming an important issue faced by urban built environments. Heat exposure assessment is a prerequisite for mitigation measures to reduce the impact of heat exposure. However, there is limited research on urban heat exposure assessment approaches that provides fine-scale spatiotemporal heat exposure information, integrated with meteorological status and human collective exposure as they move about in cities, to enable proactive heat exposure mitigation measures. Smart city digital twins (SCDTs) provide a new potential avenue for addressing this gap, enabling fine spatiotemporal scales, human-infrastructure interaction modeling, and predictive and decision support capabilities. This study aims to develop and test an SCDT for collective urban heat exposure assessment and forecasting. Meteorological sensors and computer vision techniques were implemented in Columbus, Georgia, to acquire temperature, humidity, and passersby count data. These data were then integrated into a collective temperature humidity index. A time-series prediction model and a crowd simulation were employed to predict future short-term heat exposures based on the data accumulated by this SCDT and to support heat exposure mitigation efforts. The results demonstrate the potential of SCDT to enhance public safety by providing city officials with a tool for discovering, predicting, and, ultimately, mitigating community exposure to extreme heat.

Recyclable and Biobased Vitrimers for Carbon Fibre-Reinforced Composites-A Review.

Economic and environmental concerns over the accumulation of end-of-life carbon fibre composite waste have led to increased attention to sustainable materials with low environmental impact. Over decades of research, vitrimers, a modern class of covalent adaptable networks, have bridged the gap between thermoplastics and thermosets. With the distinguishing feature of dynamic covalent bonds, vitrimers can be rearranged and reprocessed within their existing network structures in response to external stimuli such as heat or light. This poses a unique solution to repairing damaged composites, extending their service life, and reducing post-consumer waste. However, the synthesis of vitrimers often requires petrochemical consumption, which increases their carbon footprint. Using bio-based materials could be a promising solution to reduce the reliance on petrochemicals and their related pollution. This review compiles the contemporary requirements for bio-based vitrimers regarding their properties, scalability, and recycling features. This article also presents a comprehensive overview of the pathways to produce sustainable bio-based vitrimers and an overview of promising studies showing the potential uses of bio-derived vitrimers on carbon fibre composite productions.

Selective C-H Activation of Molecular Nanodiamonds via Photoredox Catalysis.

While substituted adamantanes have widespread use in medicinal chemistry, materials science, and ligand design, the use of diamantanes and higher diamondoids is limited to a much smaller number. Selective functionalization beyond adamantane is challenging, as the number of very similar types of C-H bonds (secondary, 2°, and tertiary, 3°) increases rapidly, and H atom transfer does not provide a general solution for site selectivity. We report a method using pyrylium photocatalysts that is effective for nanodiamond functionalization in up to 84% yield with exclusive 3° selectivity and moderate levels of regioselectivity between 3° sites. The proposed mechanism involving photooxidation, deprotonation, and radical C-C bond formation is corroborated through Stern-Volmer luminescence quenching, cyclic voltammetry, and EPR studies. Our photoredox strategy offers a versatile approach for the streamlined synthesis of diamondoid building blocks.

Lighting the way: recent developments and applications in molecular optogenetics.

Molecular optogenetics utilizes genetically encoded, light-responsive protein switches to control the function of molecular processes. Over the last two years, there have been notable advances in the development of novel optogenetic switches, their utilization in elucidating intricate signaling pathways, and their progress toward practical applications in biotechnological processes, material sciences, and therapeutic applications. In this review, we discuss these areas, offer insights into recent developments, and contemplate future directions.

Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children.

BACKGROUND: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described. OBJECTIVE: Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures. METHODS: Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12-month, n = 73; 36-month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort. RESULTS: In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß = 2.04; P = .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R2 = 0.055; P = .0001) and dominant bacterial genus (R2 = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes (R2 = 0.019; P = .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment. CONCLUSION: Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years.

In Search of a Gold Standard Tool for Assessing Knowledge of Stroke: A Systematic Review.

BACKGROUND: Knowledge of stroke is essential to empower people to reduce their risk of these events. However, valid tools are required for accurate and reliable measurement of stroke knowledge. We aimed to systematically review contemporary stroke knowledge assessment tools and appraise their content validity, feasibility, and measurement properties. METHODS: The protocol was registered in PROSPERO (CRD42023403566). Electronic databases (MEDLINE, PsycInfo, CINAHL, Embase, Scopus, Web of Science) were searched to identify published articles (1 January 2015-1 March 2023), in which stroke knowledge was assessed using a validated tool. Two reviewers independently screened titles and abstracts prior to undertaking full-text review. COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methods guided the appraisal of content validity (relevance, comprehensiveness, comprehensibility), feasibility, and measurement properties. RESULTS: After removing duplicates, the titles and abstracts of 718 articles were screened; 323 reviewed in full; with 42 included (N = 23 unique stroke knowledge tools). For content validity, all tools were relevant, two were comprehensive, and seven were comprehensible. Validation metrics were reported for internal consistency (n = 20 tools), construct validity (n = 17 tools), cross-cultural validity (n = 15 tools), responsiveness (n = 9 tools), reliability (n = 7 tools), structural validity (n = 3 tools), and measurement error (n = 1 tool). The Stroke Knowledge Test met all content validity criteria, with validation data for six measurement properties (n = 3 rated "Sufficient"). CONCLUSION: Assessment of stroke knowledge is not standardised and many tools lacked validated content or measurement properties. The Stroke Knowledge Test was the most comprehensive but requires updating and further validation for endorsement as a gold standard.

Enhanced laser-induced damage performance of all-glass metasurfaces for energetic pulsed laser applications.

To fabricate optical components with surface layers compatible with high-power laser applications that may operate as antireflective coatings, polarization rotators, or harness physical anisotropy for other uses, metasurfaces are becoming an appealing candidate. In this study, large-beam (1.05 cm diameter) 351-nm laser-induced damage testing was performed on an all-glass metasurface structure composed of cone-like features with a subwavelength spacing of adjacent features. These structures were fabricated on untreated fused silica glass and damage tested, as were structures that were fabricated on fused silica glass that experienced a preliminary etching process to remove the surface Beilby layer that is characteristic of polished fused silica. The laser-induced damage onset for structures on untreated fused silica glass was 19.3J⋅c m -2, while the sample that saw an initial pretreatment etch exhibited an improved damage onset of 20.4J⋅c m -2, only 6% short of the reference pretreated glass damage onset of 21.7J⋅c m -2. For perspective, the National Ignition Facility operational average fluence at this wavelength and pulse length is about 10J/c m 2. At a fluence of 25.5J⋅c m -2, the reference (pretreated) fused silica initiated 5.2 damage sites per m m 2, while the antireflective metasurface sample with a preliminary etching process treatment initiated 9.8 damage sites per m m 2. These findings demonstrate that substrate-engraved metasurfaces are compatible with high energy and power laser applications, further broadening their application space.

The Influence of Comorbidities, General Health Status, and Self-Care Self-Efficacy on COVID-19 Symptoms During the Omicron Wave.

Background The emergence of the less virulent COVID-19 strains such as Omicron and its subvariants shifted the paradigm of COVID-19 treatment from inpatient treatment to regular outpatient care. The individual health determinants affecting COVID-19 disease severity among vulnerable adults treated in outpatient settings are an under-researched area. Methods This study conducted in an outpatient COVID-19 antibody infusion center employed a cross-sectional survey design to explore the impact of comorbidities, general health status, and self-care self-efficacy on COVID-19 symptom severity. We recruited 120 COVID-19-positive participants over 40 years of age, of which 117 completed the study with 87 providing complete data. After the screening and consenting process, the participants completed the following surveys in a secure REDCap survey software (Vanderbilt University, Nashville, USA) on an iPad (Apple Inc., Cupertino, USA): 1) sociodemographic questionnaire, 2) Charlson Comorbidity Index (CCI) to capture comorbidities, 3) Medical Outcomes Study Short-Form (SF-12) to assess general health including physical (PCS) and mental (MCS) health subscales, 4) Self-Care Self-Efficacy Scale (SCSES) to measure self-care self-efficacy, and 5) the COVID-19 Symptom rating scale (COVID-19 SRS). Statistical analysis used were Chi-square and Pearson correlations.  Results As evidenced by CCI, the top five comorbidities were hypertension (42%), diabetes mellitus (31%), pulmonary disease (19%), depression (14%), and solid tumors (11%). Age was statistically significantly correlated to comorbidity burden (p<0.0001). Severe COVID-19 symptoms reported were fatigue, myalgia, cough, runny nose, and sore throat. The general health status measure (SF-12) subscales showed that the patient's mental component summary (MCS) was more statistically significant to COVID-19 symptom severity than the physical component summary (PCS). The MCS demonstrated a statistically significant correlation with fatigue and myalgia (p<0.0001), headache and breathing difficulties (p<0.001), nausea/vomiting (p<0.01), and abdominal pain/diarrhea (p<0.05). The PCS showed a lesser statistically significant correlation with fatigue, myalgia, headaches (p<0.01), fever/chills, cough, congestion/runny nose, night sweats, breathing difficulties, nausea/vomiting, and abdominal pain/diarrhea (p<0.05). Interestingly, the 'loss of smell' which is the hallmark symptom of COVID-19 was the only symptom that showed a statically significant correlation with the Charlson Comorbidity Index (p<0.05), and it did not show any association with either mental (SF-12 MCS) or physical (SF-12 PCS) health status. The SF-12 MCS also showed a statistically significant correlation with a diagnosis of depression (p< 0.01), validating it as a true measure of mental health among vulnerable adults. The SCSES was not correlated with any of the COVID-19 symptoms. Conclusions The patient's general health status, especially mental health was more statistically significant to COVID-19 symptoms. The COVID-19 hallmark symptom of 'loss of smell' was the only symptom that showed statistical significance with comorbidities. Within the limitations of a cross-sectional survey design and convenient sampling methods, this study calls to tailor general health status, especially mental health, and cumulative comorbidity burden to risk assessment/risk stratification of COVID-19 care.

Sex differences in the association between stroke risk factors and pre-clinical predictors of stroke in the childhood determinants of Adult Health study.

BACKGROUND AND AIMS: It is unclear why blood pressure (BP), metabolic markers and smoking increase stroke incidence in women more than men. We examined these associations with carotid artery structure and function in a prospective cohort study. METHODS: Participants in the Australian Childhood Determinants of Adult Health study at ages 26-36 years (2004-06) were followed-up at 39-49 years (2014-19). Baseline risk factors included smoking, fasting glucose, insulin, systolic and diastolic BP. Carotid artery plaques, intima-media thickness [IMT], lumen diameter and carotid distensibility [CD] were assessed at follow up. Log binomial and linear regression with risk factor × sex interactions predicted carotid measures. Sex-stratified models adjusting for confounders were fitted when significant interactions were identified. RESULTS: Among 779 participants (50% women), there were significant risk factor × sex interactions with baseline smoking, systolic BP and glucose associated with carotid measures in women only. Current smoking was associated with incidence of plaques (RRunadjusted 1.97 95% CI 1.4, 3.39), which reduced when adjusted for sociodemographics, depression, and diet (RRadjusted 1.82 95% CI 0.90, 3.66). Greater systolic BP was associated with lower CD adjusted for sociodemographics (ßadjusted -0.166 95% CI -0.233, -0.098) and hypertension with greater lumen diameter (ßunadjusted 0.131 95% CI 0.037, 0.225), which decreased when adjusted for sociodemographics, body composition and insulin (ßadjusted 0.063 95% CI -0.052, 0.178). Greater glucose (ßunadjusted -0.212 95% CI -0.397, -0.028) was associated with lower CD, which decreased when adjusted for sociodemographics, BP, depression and polycystic ovary syndrome (ßadjusted -0.023 95% CI -0.249, 0.201). CONCLUSIONS: Smoking, SBP and glucose affect carotid structure and function more in women than men with some of this risk due to co-occurring risk factors.

Birefringent Glass-Engraved Tilted Pillar Metasurfaces for High Power Laser Applications.

Birefringent materials-which are highly needed in high power laser systems-may be limited in usage due to the laser-induced damage threshold of traditional birefringent materials. This work reports here on all-glass metasurfaces, fabricated by angled etching through sacrificial metal nanoparticle (NP) etching masks, for generation of effective birefringence in the formed layer. As a result, a fused silica metasurface, monolithic to the underlying substrate, is demonstrated to exhibit a birefringence of 6.57° under 375 nm illumination. Full-wave analysis shows a good agreement with the measurement and presents potential paths forward to increasing the effective metasurface birefringence. This is the first demonstration, to the best of knowledge, of an etching technique to obtain the resulting tilted pillar-like nanofeatures. The anisotropy of the metasurface nanoelements along the two window in-plane major axes presents different effective paths for the two polarizations and thus generates birefringence in a nonbirefringent material. Additionally, the imparted anisotropy lends itself to manipulation of physical properties of the surface as well, with metasurface feature orientation suppressing water flow along one principal axis and giving rise to water flow steering capabilities.

Mechanistic and Kinetic Approach on the Propargyl Radical (C3H3) with the Criegee Intermediate (CH2OO).

The detailed reaction mechanism and kinetics of the C3H3 + CH2OO system have been thoroughly investigated. The CBS-QB3 method in conjunction with the ME/vRRKM theory has been applied to figure out the potential energy surface and rate constants for the C3H3 + CH2OO system. The C3H3 + CH2OO reaction leading to the CH2-[cyc-CCHCHOO] + H product dominates compared to the others. Rate constants of the reaction are dependent on temperatures (300-2000 K) and pressures (1-76,000 Torr), for which the rate constant of the channel C3H3 + CH2OO → CH2-[cyc-CCHCHOO] + H decreases at low pressures (1-76 Torr), but it increases with rising temperature if the pressure P ≥ 760 Torr. Rate constants of the three reaction channels C3H3 + CH2OO → CHCCH2CHO + OH, C3H3 + CH2OO → OCHCHCHCHO + H, and C3H3 + CH2OO → CHCHCHO + CH2O fluctuate with temperatures. The branching ratio of the C3H3 + CH2OO → CH2-[cyc-CCHCHOO] + H channel is the highest, accounting for 51-98.7% in the temperature range of 300-2000 K and 760 Torr pressure, while those of the channels forming the products PR10 (OCHCHCHCHO + H) and PR11 (CHCHCHO + CH2O) are the lowest, less than 0.1%, indicating that the contribution of these two reaction paths to the title reaction is insignificant. The proposed temperature- and pressure-dependent rate constants, together with the thermodynamic data of the species involved, can be confidently used for modeling CH2OO-related systems under atmospheric and combustion conditions.

Reactions of Methyl Radicals with Aniline Acting as Hydrogen Donors and as Methyl Radical Acceptors.

The present investigation theoretically reports the comprehensive kinetic mechanism of the reaction between aniline and the methyl radical over a wide range of temperatures (300-2000 K) and pressures (76-76,000 Torr). The potential energy surface of the C6H5NH2 + CH3 reaction has been established at the CCSD(T)//M06-2X/6-311++G(3df,2p) level of theory. The conventional transition-state theory (TST) was utilized to calculate rate constants for the elementary reaction channels, while the stochastic RRKM-based master equation framework was applied for the T- and P-dependent rate-coefficient calculation of multiwell reaction paths. Hindered internal rotation and Eckart tunneling treatments were included. The H-abstraction from the -NH2 group of aniline (to form P1 (C6H5NH + CH4)) has been found to compete with the CH3-addition on the C atom at the ortho site of aniline (to form IS2) with the atmospheric rate expressions (in cm3 molecule-1 s-1) as ka1 = 7.5 × 10-23 T3.04 exp[(-40.63 ± 0.29 kJ·mol-1)/RT] and kb2 = 2.29 × 10-3 T-3.19 exp[(-56.94 ± 1.17 kJ·mol-1)/RT] for T = 300-2000 K and P = 760 Torr. Even though rate constants of several reaction channels decrease with increasing pressures, the total rate constant ktotal = 7.71 × 10-17 T1.20 exp[(-40.96 ± 2.18 kJ·mol-1)/RT] of the title reaction still increases as the pressure increases in the range of 76-76,000 Torr. The calculated enthalpy changes for some species are in good agreement with the available experimental data within their uncertainties (the maximum deviation between theory and experiment is ∼11 kJ·mol-1). The T1 diagnostic and spin contamination analysis for all species involved have also been observed. This work provides sound quality rate coefficients for the title reaction, which will be valuable for the development of detailed combustion reaction mechanisms for hydrocarbon fuels.

Association Between Risk Factors in Childhood and Sex Differences in Prevalence of Carotid Artery Plaques and Intima-Media Thickness in Mid-Adulthood in the Childhood Determinants of Adult Health Study.

Background The origins of sex differences in cardiovascular diseases are not well understood. We examined the contribution of childhood risk factors to sex differences in adult carotid artery plaques and intima-media thickness (carotid IMT). Methods and Results Children in the 1985 Australian Schools Health and Fitness Survey were followed up when they were aged 36 to 49 years (2014-19, n=1085-1281). Log binomial and linear regression examined sex differences in adult carotid plaques (n=1089) or carotid IMT (n=1283). Childhood sociodemographic, psychosocial, and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were examined using purposeful model building with additional adjustment for equivalent adult risk factors in sensitivity analyses. Women less often had carotid plaques (10%) than men (17%). The sex difference in the prevalence of plaques (relative risk [RR] unadjusted 0.59 [95% CI, 0.43 to 0.80]) was reduced by adjustment for childhood school achievement and systolic blood pressure (RR adjusted 0.65 [95% CI, 0.47 to 0.90]). Additional adjustment for adult education and systolic blood pressure further reduced sex difference (RR adjusted 0.72 [95% CI, 0.49 to 1.06]). Women (mean±SD 0.61±0.07) had thinner carotid IMT than men (mean±SD 0.66±0.09). The sex difference in carotid IMT (ß unadjusted -0.051 [95% CI, -0.061 to -0.042]) reduced with adjustment for childhood waist circumference and systolic blood pressure (ß adjusted -0.047 [95% CI, -0.057 to -0.037]) and further reduced with adjustment for adult waist circumference and systolic blood pressure (ß adjusted -0.034 [95% CI, -0.048 to -0.019]). Conclusions Some childhood factors contributed to adult sex differences in plaques and carotid IMT. Prevention strategies across the life course are important to reduce adult sex differences in cardiovascular diseases.

MUC5AC Genetic Variation Is Associated With Tuberculous Meningitis Cerebral Spinal Fluid Cytokine Responses and Mortality.

BACKGROUND: The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes. METHODS: Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with tumor necrosis factor (TNF) concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality. RESULTS: MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF (P = 1.8 × 10-8) and IFN-γ (P = 2.3 × 10-6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03-1.49; P = .02), but not pulmonary tuberculosis (OR, 1.11, 95% CI, .98-1.25; P = .10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank P = .005) in a Vietnam discovery cohort (n = 210), an independent Vietnam validation cohort (n = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank P = .02), and an Indonesia validation cohort (n = 468, 127/287, 44.3% vs 65/181, 35.9%; log-rank P = .06). CONCLUSIONS: MUC5AC variants may contribute to immune changes that influence TBM outcomes.

Probiotic-educated Tregs are more potent than naïve Tregs for immune tolerance in stressed new-born mice.

When new-born mice are subjected to acute maternal separation stress, cow-milk based formula feeding, and brief recurrent hypoxia with cold stress, they develop gut inflammation similar to the phenotype of neonatal necrotizing enterocolitis, characterised by an increase in gut mucosal effector T (Teffs) and reduced Foxp3+ regulatory T (Tregs) cells. The imbalance can be prevented by probiotic Limosilactobacillus reuteri DSM 17938 (LR 17938). We hypothesised that LR 17938 could potentiate a tolerogenic function of Tregs. To analyse whether LR 17938 can educate Tregs to improve their tolerogenic potency during neonatal stress, we isolated T cells (Tregs and Teffs) from 'donor' mice fed with either LR 17938 (107 cfu) or control media. The cells were adoptively transferred (AT) by intraperitoneal injection (5 × 105 cells/mouse) to new-born (d5) recipient mice. Mice were then separated from their dams, fed formula by gavage, and exposed to hypoxia and cold stress (NeoStress) for 4 days. We analysed the percentage of Tregs in CD4+T helper cells in the intestine (INT) and mesenteric lymph nodes (MLN) of recipient mice. We found that: (1) the percentage of Tregs in the INT and MLN following NeoStress were significantly reduced compared to dam-fed unstressed mice; (2) AT of either naïve Tregs or LR-educated Tregs to mice with Neostress increased the percentage of Tregs in the INT and MLN compared to the percentage in NeoStress mice without Treg treatment; however, LR-educated Tregs increased the Tregs significantly more than naïve Tregs; and (3) AT of LR-educated Tregs reduced pro-inflammatory CD44+Foxp3-NonTregs and inflammatory CX3CR1+ dendritic cells in the intestinal mucosa of NeoStress mice. In conclusion, adoptive transfer of Tregs promotes the generation of and/or migration of endogenous Tregs in the intestinal mucosa of recipient mice. Importantly, probiotic-educated Tregs are more potent than naïve Tregs to enhance immune tolerance following neonatal stress.