Epigenome-850K-wide profiling reveals peripheral blood differential methylation in term low birth weight.

Aim: We investigate the genome-wide DNA methylation (DNAm) patterns of term low birth weight (TLBW) neonates. Methods: In the discovery phase, we assayed 32 samples (TLBW/control:16/16) using the EPIC 850k BeadChip Array. Targeted pyrosequencing of in 60 samples (TLBW/control:28/32) using targeted pyrosequencing during the replication phase. Results: The 850K array identified TLBW-associated 144 differentially methylated positions (DMPs) and 149 DMRs. Nearly 77% DMPs exhibited hypomethylation, located in the opensea and gene body regions. The most significantly enriched pathway in KEGG is sphingolipid metabolism (hsa00600), and the genes GALC and SGMS1 related to this pathway both show hypomethylation. Conclusion: Our analysis provides evidence of genome-wide DNAm alterations in TLBW. Further investigations are needed to elucidate the functional significance of these DNAm changes.

This study looked at the DNA of babies born after 37 weeks of pregnancy but weighing less than 2500 grams. We found that these babies had lower levels of DNA methylation, which might change how their bodies handle fats.

Association of urinary metal element with semen quality: a cross-sectional study from Eastern China.

The effect of metallic elements on semen quality remains controversial, with limited evidence on the effects of metal mixtures. We conducted a study involving 338 participants from multiple centers in Eastern China, measuring 17 urinary metals and semen quality parameters. Our analysis used various statistical models, including multivariate logistic and linear regression, Bayesian Kernel Machine Regression, and weighted quantile sum models, to examine the associations between metal levels and semen quality. Logistic regression showed that higher urinary lead was associated with increased risk of abnormal sperm concentration (OR = 1.86, p = 0.021), arsenic to higher abnormal progressive motility risk (OR = 1.49, p = 0.027), and antimony to greater abnormal total motility risk (OR = 1.37, p = 0.018). Conversely, tin was negatively correlated with the risk of abnormal progressive motility (OR = 0.76, p = 0.012) and total motility (OR = 0.74, p = 0.003), respectively. Moreover, the linear models showed an inverse association between barium and sperm count, even after adjusting for other metals (ß = - 0.32, p < 0.001). Additionally, the WQS models showed that the metal mixture may increase the risk of abnormal total motility (ßWQS = 0.55, p = 0.046). In conclusion, semen quality may be adversely affected by exposure to metals such as arsenic, barium, lead, and antimony. The combined effect of the metal mixture appears to be particularly impaired total motility.

Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort.

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Prevalence of mental health symptoms and associated risk factors among healthcare workers in specialized COVID-19 hospitals in Anyang, China: A cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.

A Self-Cascade Oxygen-Generating Nanomedicine for Multimodal Tumor Therapy.

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.

Na0.4MnO2/MXene nanocomposites as cathodes for high-performance aqueous zinc-ion batteries.

The distinctive configuration of MnO2 renders it an exceptionally promising candidate for cathode materials for aqueous zinc-ion batteries (ZIBs). However, its practical utilization is constrained by the sluggish diffusion kinetics of Zn2+ and the capacity degradation resulting from lattice distortions occurring during charge and discharge cycles. To address these challenges, Na0.4MnO2@MXene with a typical 2 × 4 tunnel structure has been successfully synthesized by a simple hydrothermal method in the presence of 5 M NaCl. The nanorods are about 56 nm in diameter. The zinc-ion batteries (ZIBs) with Na0.4MnO2@MXene displays a specific capacity of 324.6 mA h g-1 at 0.2 A g-1, and have a high reversible capacity of 153.8 mA h g-1 after 1000 charge-discharge cycles at 2 A g-1 with a capacity retention of 91.4%. The unique morphology endows abundant electrochemical active sites and facile ion diffusion kinetics, that contribute to the high specific capacity and stability. The Na0.4MnO2@MXene with a 2 × 4 tunnel structure is a promising candidate as an electrode material for ZIBs.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition.

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

Cohort profile: migraine exposures and cardiovascular health in Hong Kong Chinese women (MECH-HK).

PURPOSE: Evidence about the associations of migraine features with cardiovascular risk profiles in Chinese population is lacking. The Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort was constructed to investigate longitudinal migraine features and their cardiovascular implications in Hong Kong Chinese women. PARTICIPANTS: We enrolled 4221 Hong Kong Chinese women aged 30 years or above from October 2019 to December 2020. Demographics, reproductive information, lifestyle factors, disease history, blood lipids and glucose, anthropometrics and body compositions were measured during baseline and follow-up. Migraine diagnosis followed the International Classification of Headache Disorders-3 criteria. Migraine features were longitudinally tracked using a migraine diary and summarised by a wide range of epidemiological metrics. Cardiovascular health was assessed using the Framingham risk score (FRS). FINDINGS TO DATE: From October 2021 to June 2023, 3455 women completed the first follow-up measurement. The retention rate was 81.9%. The average age at baseline was 54.40 years. The mean blood glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were 6.44 mmol/L, 65.06 mg/dL and 102.40 mg/dL, respectively. The average FRS was 0.06. Participants had a 10.3% prevalence of migraine or probable migraine. After 1.27 years of follow-up, the median migraine attack frequency was 0.99 attacks/month, with an incidence rate of 2.55 attacks/person-month and a median duration of 7.70 hours/attack. Sleep problems (64.7%) and stress (54.0%) were the top triggers, while prevalent accompanying symptoms were nausea (67.4%), photophobia (39.9%), phonophobia (30.0%) and vomiting (26.2%). Migraine auras included blurred visions (59.6%), flashing lights (41.3%), blind spots (33.0%), pins and needles (6.4%) and halo (1.8%). FUTURE PLANS: The follow-up for the cohort will be implemented every 2 years. MECH-HK will provide unique longitudinal data on migraine features in Hong Kong women. The linkage between migraine features and cardiovascular disease risk progression will be identified by a long-term observation.

Is high exposure to antisocial media content associated with increased participation in malicious online trolling? exploring the moderated mediation model of hostile attribution bias and empathy.

Malicious online trolling is prevalent among Chinese college students and has recently garnered extensive attention from researchers due to the substantial harm it causes to the victims and the damage it inflicts on the online environment. Most previous studies have focused on examining how personal traits related to malicious online trolling. Further comprehensive research is needed to explore the mechanisms linking external environmental factors (antisocial media exposure) and malicious online trolling. A total of 1259 Chinese college students completed questionnaires regarding malicious online trolling, antisocial media exposure, hostile attribution bias, and empathy. The results indicated a positive association between antisocial media exposure and malicious online trolling among Chinese college students, with hostile attribution bias serving as a mediating factor. Furthermore, the direct and mediated paths between antisocial media exposure and malicious online trolling were moderated by empathy. Specifically, as the level of empathy increased among college students, the relations between the variables all weakened. Excessive exposure to antisocial media content among college students may trigger hostile attribution bias and lead to more malicious online trolling behavior. However, the relation between antisocial media exposure and malicious online trolling, hostile attribution bias and malicious online trolling, was attenuated when college students' empathy levels were high.

Broadband and fabrication-tolerant 3-dB couplers with topological valley edge modes.

3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

Blood mercury mediates the associations between fish consumption and serum uric acid levels among Chinese adults: A nationally representative study.

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

ß-CsHg2I5, a compound with rare [Hg2I5] dimers and large optical anisotropy.

Hg-based compounds show abundant structural diversity and distinguished properties. Herein, a new phase transition compound CsHg2I5 was reported. The high-temperature phase ß-CsHg2I5 with rare [Hg2I5] dimers was synthesized by the flux method at 573 K, and it shows a reversible phase transition at a low temperature of ∼100 K to form the low-temperature phase α-CsHg2I5. The two phases crystallize in the same P21/c space group, with different crystal structures. ß-CsHg2I5 is composed of rare [Hg2I5] dimers and [CsI11] polyhedral units, while α-CsHg2I5 is composed of [Hg4I11] and [CsI10] units. The experimental band gap of ß-CsHg2I5 was found to be 2.58 eV. Owing to the presence of [Hg2I5]∞ pseudo-layers, ß-CsHg2I5 exhibits large optical anisotropy with a calculated birefringence of 0.132@1064 nm. Meanwhile, ß-CsHg2I5 is a congruent compound and the congruent point is ∼481 K. Theoretical calculations indicate that the rare [Hg2I5] dimer is a nonlinear active unit, which can be used as a new fundamental building block for the design of advanced nonlinear optical materials. Moreover, a CsI-HgI2 pseudo-binary diagram was drawn. The results enrich the structural diversity of Hg-based halides and give some insights into the development of new functional materials based on rare [Hg2I5] dimers.

Planetary Health Diet Index and risk of total and cause-specific mortality in three prospective cohorts.

BACKGROUND: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. OBJECTIVES: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States. METHODS: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts. CONCLUSIONS: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts.

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

BACKGROUND: Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. METHODS: We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. CONCLUSION: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Structural equation model analysis of the effect of visceral fat on osteoporosis.

BACKGROUND: Osteoporosis is a considerable public health challenge in Moyu County, Xinjiang. Here, we evaluated the influencing factors of osteoporosis in this region. METHODS: We recruited 7,761 participants and randomized them into normal and osteoporotic populations based on T-score. The effects of general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet on osteoporosis were analyzed. Furthermore, a structural equation model was constructed to uncover the direct and indirect influencing factors of osteoporosis. RESULTS: Among the participants, 1,803 (23.23%) had normal bone mass while 1,496 (19.28%) had osteoporosis. The univariate analysis showed significant differences in the general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet. Stratification based on age (45 years) and body mass index (BMI) (18.5 kg/m2) showed variations in the body composition between the two groups; however, the visceral fat differed significantly. Logistic regression analysis affirmed the association of visceral fat index as it was included in all equations, except for age and female menopause. The structural equation exhibited that the general conditions, body composition, and, calcium sources, and exercise were direct factors of osteoporosis, while respiratory exposure and daily diet were indirect factors. The standardized path coefficient was highest in general conditions, followed by body composition, and lastly, calcium sources and exercise. CONCLUSION: Obesity, besides age and female menopause, is also an influencing factor of osteoporosis. The visceral fat index plays a vital role in osteoporosis. Our findings may provide experimental evidence for early prevention and treatment of osteoporosis.

1-Trinitromethyl-3,5-dinitro-4-nitroaminopyrazole: Intramolecular Full Nitration and Strong Intermolecular H-Bonds toward Highly Dense Energetic Materials.

Full nitration is one of the most effective strategies used in synthesizing high-density energetic materials, but this strategy has reached its limit because the resultant compounds cannot be further functionalized. To overcome this limitation, we present the synergistic action of full nitration and strong intermolecular H-bonding in designing and synthesizing 1-trinitromethyl-3,5-dinitro-4-nitroaminopyrazole (DNTP) with a density that exceeds those of the reported monocyclic CHON compounds. The detonation velocity and specific impulse of DNTP exceed those of 1-trinitromethyl-3,4,5-trinitropyrazole (TTP), HMX, and ADN.

Opportunity and Challenge of Advanced Porous Sorbents for PFAS Removal.

Per- and polyfluoroalkyl substances (PFASs), comprising over 9,000 persistent synthetic organic contaminants, are extensively found in the environment and pose significant risks to both human and ecological health. Among the strategies for addressing PFAS contamination, adsorption processes have proven to be cost-effective. Traditional sorbents such as ion-exchange resins and activated carbon have been found to exhibit low adsorption capacities and slow equilibration times. Recent innovations in porous materials, including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and porous organic polymers (POPs), however, offer significant improvements in the efficiency of PFAS adsorption. This review thoroughly examines the latest advancements in these materials, analyzing their mechanisms of adsorption, and concludes by suggesting directions for future research that could further enhance their effectiveness in PFAS management.

Evolutionary genomic analyses of canine E. coli infections identify a relic capsular locus associated with resistance to multiple classes of antimicrobials.

Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. IMPORTANCE: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system.