Porous Crystalline Materials Based on Tetrathiafulvalene and Its Analogues: Assembly, Charge Transfer, and Applications.

ConspectusThe directed synthesis and functionalization of porous crystalline materials pose significant challenges for chemists. The synergistic integration of different functionalities within an ordered molecular material holds great significance for expanding its applications as functional materials. The presence of coordination bonds connected by inorganic and organic components in molecular materials can not only increase the structural diversity of materials but also modulate the electronic structure and band gap, which further regulates the physical and chemical properties of molecular materials. In fact, porous crystalline materials with coordination bonds, which inherit the merits of both organic and inorganic materials, already showcase their superior advantages in optical, electrical, and magnetic applications. In addition to the inorganic components that provide structural rigidity, organic ligands of various types serve as crucial connectors in the construction of functional porous crystalline materials. In addition, redox activity can endow organic linkers with electrochemical activity, thereby making them a perfect platform for the study of charge transfer with atom-resolved single-crystal structures, and they can additionally serve as stimuli-responsive sites in sensor devices and smart materials.In this Account, we introduce the synthesis, structural characteristics, and applications of porous crystalline materials based on the famous redox-active units, tetrathiafulvalene (TTF) and its analogues, by primarily focusing on metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). TTF, a sulfur-rich conjugated molecule with two reversible and easily accessible oxidation states (i.e., radical TTF•+ cation and TTF2+ dication), and its analogues boast special electrical characteristics that enable them to display switchable redox activity and stimuli-responsive properties. These inherent properties contribute to the enhancement of the optical, electrical, and magnetic characteristics of the resultant porous crystalline materials. Moreover, delving into the charge transfer phenomena, which is key for the electrochemical process within these materials, uncovers a myriad of potential functional applications. The Account is organized into five main sections that correspond to the different properties and applications of these materials: optical, electrical, and magnetic functionalities; energy storage and conversion; and catalysis. Each section provides detailed discussions of synthetic methods, structural characteristics, the physical and chemical properties, and the functional performances of highlighted examples. The Account also discusses future directions by emphasizing the exploration of novel organic units, the transformation between radical cation TTF•+ and dication TTF2+, and the integration of multifunctionalities within these frameworks to foster the development of smart materials for enhanced performance across diverse applications. Through this Account, we aim to highlight the massive potential of TTF and its analogues-based porous crystals in chemistry and material science.

Active antibiotic resistome in soils unraveled by single-cell isotope probing and targeted metagenomics.

Antimicrobial resistance (AMR) in soils represents a serious risk to human health through the food chain and human-nature contact. However, the active antibiotic-resistant bacteria (ARB) residing in soils that primarily drive AMR dissemination are poorly explored. Here, single-cell Raman-D2O coupled with targeted metagenomics is developed as a culture-independent approach to phenotypically and genotypically profiling active ARB against clinical antibiotics in a wide range of soils. This method quantifies the prevalence (contamination degree) and activity (spread potential) of soil ARB and reveals a clear elevation with increasing anthropogenic activities such as farming and the creation of pollution, thereby constituting a factor that is critical for the assessment of AMR risks. Further targeted sorting and metagenomic sequencing of the most active soil ARB uncover several uncultured genera and a pathogenic strain. Furthermore, the underlying resistance genes, virulence factor genes, and associated mobile genetic elements (including plasmids, insertion sequences, and prophages) are fully deciphered at the single-cell level. This study advances our understanding of the soil active AMR repertoire by linking the resistant phenome to the genome. It will aid in the risk assessment of environmental AMR and guide the combat under the One Health framework.

Polynuclear Cobalt Cluster-Based Coordination Polymers for Efficient Nitrate-to-Ammonia Electroreduction.

The electrocatalytic nitrate reduction reaction (NITRR) holds great promise for purifying wastewater and producing valuable ammonia (NH3). However, the lack of efficient electrocatalysts has impeded the achievement of highly selective NH3 synthesis from the NITRR. In this study, we report the design and synthesis of two polynuclear Co-cluster-based coordination polymers, {[Co2(TCPPDA)(H2O)5]·(H2O)9(DMF)} and {Co1.5(TCPPDA)[(CH3)2NH2]·(H2O)6(DMF)2} (namely, NJUZ-2 and NJUZ-3), which possess distinct coordination motifs with well-defined porosity, high-density catalytic sites, accessible mass transfer channels, and nanoconfined chemical environments. Benefitting from their intriguing multicore metal-organic coordination framework structures, NJUZ-2 and NJUZ-3 exhibit remarkable catalytic activities for the NITRR. At a potential of -0.8 V (vs. RHE) in an H-type cell, they achieve an optimal Faradaic efficiency of approximately 98.5% and high long-term durability for selective NH3 production. Furthermore, the electrocatalytic performance is well maintained even under strongly acidic conditions. When operated under an industrially relevant current density of 469.9 mA cm-2 in a flow cell, a high NH3 yield rate of up to 3370.6 mmol h-1 g-1cat. was observed at -0.5 V (vs. RHE), which is 20.1-fold higher than that obtained in H-type cells under the same conditions. Extensive experimental analyses, in combination with theoretical computations, reveal that the great enhancement of the NITRR activity is attributed to the preferential adsorption of NO3- and the reduction in energy input required for the hydrogenation of *NO3 and *NO2 intermediates.

Dynamic Interchain Motion in 1D Tetrathiafulvalene-Based Coordination Polymers for Highly Sensitive Molecular Recognition.

The application of electrically conductive 1D coordination polymers (1D CPs) in nanoelectronic molecular recognition is theoretically promising yet rarely explored due to the challenges in their synthesis and optimization of electrical properties. In this regard, two tetrathiafulvalene-based 1D CPs, namely [Co(m-H2TTFTB)(DMF)2(H2O)]n (Co-m-TTFTB), and {[Ni(m-H2TTFTB)(CH3CH2OH)1.5(H2O)1.5]·(H2O)0.5}n (Ni-m-TTFTB) are successfully constructed. The shorter S···S contacts between the [M(solvent)3(m-H2TTFTB)]n chains contribute to a significant improvement in their electrical conductivities. The powder X-ray diffraction (PXRD) under different organic solvents reveals the flexible and dynamic structural characteristic of M-m-TTFTB, which, combined with the 1D morphology, lead to their excellent performance for sensitive detection of volatile organic compounds. Co-m-TTFTB achieves a limit of detection for ethanol vapor down to 0.5 ppm, which is superior to the state-of-the-art chemiresistive sensors based on metal-organic frameworks or organic polymers at room temperature. In situ diffuse reflectance infrared Fourier transform spectroscopy, PXRD measurements and density functional theory calculations reveal the molecular insertion sensing mechanism and the corresponding structure-function relationship. This work expands the applicable scenario of 1D CPs and opens a new realm of 1D CP-based nanoelectronic sensors for highly sensitive room temperature gas detection.

Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

AIM: To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. METHODS: This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. RESULTS: During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. CONCLUSIONS: Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

Bimetal-Organic Frameworks Incorporating Both Hard and Soft Base Active Sites for Heavy Metal Ion Capture.

The design and synthesis of stable porous materials capable of removing both hard and soft metal ions pose a significant challenge. In this study, a novel metal-organic framework (MOF) adsorbent named CdK-m-COTTTB was developed. This MOF material was constructed using sulfur-rich m-cyclooctatetrathiophene-tetrabenzoate (m-H4COTTTB) as the organic ligand and oxygen-rich bimetallic clusters as the inorganic nodes. The incorporation of both soft and hard base units within the MOF structure enables effective removal of various heavy metal ions, including both soft and hard acid species. In single-component experiments, the adsorption capacity of CdK-m-COTTTB for Pb2+, Tb3+, and Zr4+ ions reached levels of 636.94, 432.90, and 357.14 mg·g-1, respectively, which is comparable to specific MOF absorbents. The rapid adsorption process was found to be chemisorption. Furthermore, CdK-m-COTTTB exhibited the capability to remove at least 12 different metal ions in both separate and multicomponent solutions. The material demonstrated excellent acid-base stability and renewability, which are advantageous for practical applications. CdK-m-COTTTB represents the first reported pristine MOF material for the removal of both hard and soft acid metal ions. This work serves as inspiration for the design and synthesis of porous crystalline materials that can efficiently remove diverse heavy metal pollutants.

Spatiotemporal Changes of Antibiotic Resistance, Potential Pathogens, and Health Risk in Kindergarten Dust.

The microorganisms present in kindergartens are extremely important for children's health during their three-year preschool education. To assess the risk of outdoor dust in kindergartens, the antibiotic resistome and potential pathogens were investigated in dust samples collected from 59 kindergartens in Xiamen, southeast China in both the winter and summer. Both high-throughput quantitative PCR and metagenome analysis revealed a higher richness and abundance of antibiotic resistance genes (ARGs) in winter (P < 0.05). Besides, the bloom of ARGs and potential pathogens was evident in the urban kindergartens. The co-occurrence patterns among ARGs, mobile genetic elements (MGEs), and potential pathogens suggested some bacterial pathogens were potential hosts of ARGs and MGEs. We found a large number of high-risk ARGs in the dust; the richness and abundance of high-risk ARGs were higher in winter and urban kindergartens compared to in summer and peri-urban kindergartens, respectively. The results of the co-occurrence patterns and high-risk ARGs jointly reveal that urbanization will significantly increase the threat of urban dust to human beings and their risks will be higher in winter. This study unveils the close association between ARGs/mobile ARGs and potential pathogens and emphasizes that we should pay more attention to the health risks induced by their combination.

Insights into the Antibacterial Properties of Complement Peptides C3a, C4a, and C5a across Vertebrates.

Complement peptides C3a, C4a, and C5a are important components of innate immunity in vertebrates. Although they diverged from a common ancestor, only C3a and C4a can act as antibacterial peptides in Homo sapiens, suggesting that C5a has evolved into a purely chemotactic molecule; however, the antibacterial properties of C3a, C4a, and C5a across vertebrates still require elucidation. In this article, we show that, unlike those in H. sapiens, Mus musculus C3a, C4a, and C5a all possess antibacterial activities, implying that the antibacterial properties of C3a, C4a, and C5a have evolved divergently in vertebrates. The extremely different net charge, a key factor determining the antibacterial activities of cationic antimicrobial peptides, of vertebrate C3a, C4a, and C5a supports this speculation. Moreover, the antibacterial activity of overlapping peptides covering vertebrate C3a, C4a, and C5a further strongly supports the speculation, because their activity is positively correlated with the net charge of source molecules. Notably, the structures of C3a, C4a, and C5a are conserved in vertebrates, and the inactive overlapping peptides can become antibacterial peptides if mutated to possess enough net positive charges, indicating that net charge is the only factor determining the antibacterial properties of vertebrate C3a, C4a, and C5a. More importantly, many vertebrate C3a-, C4a-, and C5a-derived peptides possess high antibacterial activities yet exhibit no hemolytic activities, suggesting the application potential in anti-infective therapy. Taken together, our findings reveal that vertebrate C3a, C4a, and C5a are all sources of antibacterial peptides that will facilitate the design of excellent peptide antibiotics.

Insights into the Antibacterial Properties of Complement Peptides C3a, C4a, and C5a across Vertebrates.

Complement peptides C3a, C4a, and C5a are important components of innate immunity in vertebrates. Although they diverged from a common ancestor, only C3a and C4a can act as antibacterial peptides in Homo sapiens, suggesting that C5a has evolved into a purely chemotactic molecule; however, the antibacterial properties of C3a, C4a, and C5a across vertebrates still require elucidation. In this article, we show that, unlike those in H. sapiens, Mus musculus C3a, C4a, and C5a all possess antibacterial activities, implying that the antibacterial properties of C3a, C4a, and C5a have evolved divergently in vertebrates. The extremely different net charge, a key factor determining the antibacterial activities of cationic antimicrobial peptides, of vertebrate C3a, C4a, and C5a supports this speculation. Moreover, the antibacterial activity of overlapping peptides covering vertebrate C3a, C4a, and C5a further strongly supports the speculation, because their activity is positively correlated with the net charge of source molecules. Notably, the structures of C3a, C4a, and C5a are conserved in vertebrates, and the inactive overlapping peptides can become antibacterial peptides if mutated to possess enough net positive charges, indicating that net charge is the only factor determining the antibacterial properties of vertebrate C3a, C4a, and C5a. More importantly, many vertebrate C3a-, C4a-, and C5a-derived peptides possess high antibacterial activities yet exhibit no hemolytic activities, suggesting the application potential in anti-infective therapy. Taken together, our findings reveal that vertebrate C3a, C4a, and C5a are all sources of antibacterial peptides that will facilitate the design of excellent peptide antibiotics.

Diallyl disulfide antagonizes DJ-1 mediated proliferation, epithelial-mesenchymal transition, and chemoresistance in gastric cancer cells.

Diallyl disulfide (DADS), an organic component of allicin abstracted from garlic, possesses multi-target antitumor activity. DJ-1 performs a vital function in promoting AKT aberrant activation via down-regulating phosphatase and tensin homologue (PTEN) in tumors. It is unknown the involvement of DJ-1 in epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells. The purpose of this study is to investigate whether diallyl disulfide (DADS) intervenes in the role of DJ-1 in GC. Based on the identification that the correlation between high DJ-1 and low PTEN expression in GC was implicated in clinical progression, we illuminated that down-regulation of DJ-1 by DADS aided in an increase in PTEN expression and a decrease in phosphorylated AKT levels, which was in line with the results manifested in the DJ-1 knockdown and overexpressed cells, concurrently inhibiting proliferation, EMT, migration, and invasion. Furthermore, the antagonistic effects of DADS on DJ-1 were observed in in vivo experiments. Additionally, DADS mitigated the DJ-1-associated drug resistance. The current study revealed that DJ-1 is one of potential targets for DADS, which hopefully provides a promising strategy for prevention and adjuvant chemotherapy of GC.

Long-term seawall barriers lead to the formation of an urban coastal lagoon with increased antibiotic resistome.

Urbanization has increased the spread of antibiotic resistance genes (ARGs) impacting urban aquatic ecosystems and threatening human health. However, an overview of the antibiotic resistome in artificial coastal lagoons formed by coastal seawall construction is unclear. This study investigated the resistome of sediment in a coastal lagoon, established for over 60 years and found that the composition of the resistome in the lagoon sediments associated with the seawall significantly differed from that of marine sediment external to the seawall. Moreover, the diversity, number, relative abundance, and absolute abundance of the antibiotic resistome in the lagoon sediments were significantly higher compared to marine sediment. Network analyses revealed that more co-occurrences were found in lagoon sediment between bacterial communities, ARGs and mobile genetic elements (MGEs) than in marine sediments, suggesting that bacteria in lagoon sediments may be associated with multiple antibiotic resistances. Random forest and structural equation models showed that an increase in the absolute abundance of MGEs had a concomitant effect on the absolute abundance and diversity of ARGs, whereas increasing salinity decreased the absolute abundance of ARGs. This study provides a basis to assess the risk of resistome diffusion and persistence in an artificial coastal lagoon.

Topologically Tunable Conjugated Metal-Organic Frameworks for Modulating Conductivity and Chemiresistive Properties for NH3 Sensing.

Electrically conductive metal-organic frameworks (cMOFs) have garnered significant attention in materials science due to their potential applications in modern electrical devices. However, achieving effective modulation of their conductivity has proven to be a major challenge. In this study, we have successfully prepared cMOFs with high conductivity by incorporating electron-donating fused thiophen rings in the frameworks and extending their π-conjugated systems through ring-closing reactions. The conductivity of cMOFs can be precisely modulated ranging from 10-3 to 102 S m-1 by regulating their dimensions and topologies. Furthermore, leveraging the inherent tunable electrical properties based on topology, we successfully demonstrated the potential of these materials as chemiresistive gas sensors with an outstanding response toward 100 ppm NH3 at room temperature. This work not only provides valuable insights into the design of functional cMOFs with different topologies but also enriches the cMOF family with exceptional conductivity properties.

Dynamic Bond-Directed Synthesis of Stable Mesoporous Metal-Organic Frameworks under Room Temperature.

Stable metal-organic frameworks (MOFs) with mesopores (2-50 nm) are promising platforms for immobilizing nanosized functional compounds, such as metal-oxo clusters, metal-sulfide quantum dots, and coordination complexes. However, these species easily decompose under acidic conditions or high temperatures, hindering their in situ encapsulation in stable MOFs, which are usually synthesized under harsh conditions involving excess acid modulators and high temperatures. Herein, we report a route for the room-temperature and acid-modulator-free synthesis of stable mesoporous MOFs and MOF catalysts with acid-sensitive species encapsulated: (1) we initially construct a MOF template by connecting stable Zr6 clusters with labile Cu-bipyridyl moieties; (2) Cu-bipyridyl moieties are subsequently exchanged by organic linkers to afford a stable version of Zr-MOFs; (3) acid-sensitive species, including polyoxometalates (POMs), CdSeS/ZnS quantum dots, and Cu-coordination cages, can be encapsulated in situ into the MOFs during step 1. The room-temperature synthesis allows the isolation of mesoporous MOFs with 8-connected Zr6 clusters and reo topology as kinetic products, which are inaccessible by traditional solvothermal synthesis. Furthermore, acid-sensitive species remain stable, active, and locked within the frameworks during MOF synthesis. We observed high catalytic activity for VX degradation by the POM@Zr-MOF catalysts as a result of the synergy between redox-active POMs and Lewis-acidic Zr sites. The dynamic bond-directed method will accelerate the discovery of large-pore stable MOFs and offer a mild route to avoid the decomposition of catalysts during MOF synthesis.

Observing multiple processes of backward-phase-matching spontaneous parametric downconversion in a single-periodic crystal.

A nonlinear process based on backward quasi-phase matching (BQPM) can be used to realize mirrorless optical parametric oscillation, the generation of paired photons with a separable joint spectral amplitude and narrow wavelength bandwidth, and the preparation of counterpropagating polarization-entangled photons, which shows distinct advantages over some applications based on forward quasi-phase matching. In this work, three types of BQPM in a bulk periodically poled potassium titanyl phosphate crystal with a single period are theoretically analyzed. Experimentally, the harmonic wave generated by second-harmonic generation in type 0 and type I exhibits a narrow bandwidth of 15.5 GHz. Furthermore, photon pairs generated by spontaneous parametric downconversion in all types of BQPM (type 0, type I, and type II) at 7th order are observed and characterized. Their coincidence-to-accidental ratios are all greater than 5 × 103 in the pump power range from 10 mW to 500 mW. This research lays the foundation for further applications of BQPM in nonlinear optics, quantum optics, and quantum information processing.

Association between N-acetylcysteine treatment and in-hospital mortality in adult patients with acquired thrombotic thrombocytopenic purpura: a cohort study.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a fatal hematologic disease. Despite the currently high standards of care, some patients who develop refractory or recurrent disease still have a poor prognosis. Although N-acetylcysteine (NAC) is recommended for the treatment of aTTP, its use in aTTP treatment is still controversial. We aimed to evaluate the association of NAC with mortality in patients with aTTP. This was a retrospective cohort study of patients with aTTP with in-hospital mortality as the primary outcome and time to platelet recovery and neurological recovery as secondary outcomes. We used multifactorial COX regression analysis to check for an association of NAC with mortality. Moreover, we performed a sensitivity analysis check the stability of our results. Finally, 89 patients with aTTP were enrolled. After adjusting for potential confounders, we found NAC to be associated with 75% lower in-hospital mortality (HR = 0.25, 95% CI = 0.1-0.64). The results of sensitivity analyses performed remained stable as the risk of in-hospital mortality in patients reduced in patients with comorbid neurological symptoms (HR = 0.23, 95% CI = 0.06-0.89). However, NAC use did not affect the time to platelet recovery (HR = 1.19, 95% CI = 0.57-2.5) or neurological recovery (HR = 0.32, 95% CI = 0.08-1.25) in patients with aTTP. NAC treatment reduces in-hospital mortality in patients with aTTP but does not shorten the time to platelet recovery or neurological recovery.

Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study.

AIM: To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. MATERIALS AND METHODS: We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose-response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. RESULTS: Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose-response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]). CONCLUSIONS: Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank.

AIMS: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.

Increasing Antimicrobial Resistance and Potential Human Bacterial Pathogens in an Invasive Land Snail Driven by Urbanization.

Our understanding of the role urbanization has in augmenting invasive species that carry human bacterial pathogens and antimicrobial resistance (AMR) remains poorly understood. Here, we investigated the gut bacterial communities, antibiotic resistance genes (ARGs) and potential antibiotic-resistant pathogens in giant African snails (Achatina fulica) collected across an urbanization gradient in Xiamen, China (n = 108). There was a lack of correlation between the microbial profiles of giant African snails and the soils of their habitats, and the resistome and human-associated bacteria were significantly higher than those of native snails as well as soils. We observed high diversity (601 ARG subtypes) and abundance (1.5 copies per 16S rRNA gene) of giant African snail gut resistome. Moreover, giant African snails in more urban areas had greater diversity and abundance of high-risk ARGs and potential human bacterial pathogens (e.g., ESKAPE pathogens). We highlight that urbanization significantly impacted the gut microbiomes and resistomes of these invasive snails, indicating that they harbor greater biological contaminants such as ARGs and potential human bacterial pathogens than native snails and soils. This study advances our understanding of the effect of urbanization on human bacterial pathogens and AMR in a problematic invasive snail and should help combat risks associated with invasive species under the One Health framework.

Characterization of LTr1 derived from cruciferous vegetables as a novel anti-glioma agent via inhibiting TrkA/PI3K/AKT pathway.

Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC50 values of 1.97, 1.84, and 2.03 µM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg-1 ·d-1, i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway.

Validation of the Thai Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) among young adults.

BACKGROUND: The Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) is a consistent and comprehensive instrument to assess symptoms of specific internet-use disorders including those related to gaming, shopping, pornography use disorder, social networks use and gambling considering criteria in the eleventh revision of the International Classification of Diseases (ICD-11). However, to date, there is little evidence supporting instruments assessing major types of specific internet use disorders in Thailand. The aim of this present study was to assess the psychometric properties of the ACSID-11 among Thai young adults. METHODS: A total of 612 participants were recruited. A confirmatory factor analysis (CFA) examined construct validity of the ACSID-11. Cronbach's α and McDonald's ω were used to assess reliability of the ACSID-11. Pearson correlations examined relationships between ACSID-11 domains and Internet Gaming Disorder Scale-Short Form (IGDS9-SF) scores. RESULTS: The CFA supported validity of the Thai version of the ACSID-11 and a four-factor structure. Specific domains of the Thai ACSID-11, particularly gaming, were positively and significantly correlated with IGDS9-SF scores. CONCLUSIONS: Data indicate that the Thai version of the ACSID-11 is a valid and reliable instrument to assess major types of specific internet use disorders. Additional studies are needed to further examine the validity and reliability of the Thai ACSID-11.