RESUMO
Anisotropic nanocrystals such as nanorods (NRs) display unique linearly polarized emission, which is expected to break the external quantum efficiency (EQE) limit of quantum dot-based light-emitting diodes (LEDs). However, the progress in achieving a higher EQE using NRs encounters several challenges, primarily involving a low photoluminescence quantum yield (PLQY) of NRs and imbalanced charge injection in NR-LEDs. In this work, we investigated NR-LEDs based on CdSe/CdZnS/ZnS rod-in-rod NRs with a high PLQY and higher linear polarization compared to those of dot-in-rod NRs. The balanced charge injection is achieved using ZnMgO nanoparticles as the electron transport layer and poly-TPD {poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)benzidine]} as the hole transport layer. Therefore, the NR-LEDs exhibit a maximum EQE of 21.5% and a maximum luminance of >120â¯000 cd/m2 owing to the high level of in-plane transitions with a dipole moment of 90%. The NR-LEDs also have greatly inhibited droop in EQE under a high current density as well as outstanding operation lifetime and cycle stability.
RESUMO
P-type self-doping is known to hamper tin-based perovskites for developing high-performance solar cells by increasing the background current density and carrier recombination processes. In this work, we propose a gradient homojunction structure with germanium doping that generates an internal electric field across the perovskite film to deplete the charge carriers. This structure reduces the dark current density of perovskite by over 2 orders of magnitude and trap density by an order of magnitude. The resultant tin-based perovskite solar cells exhibit a higher power conversion efficiency of 13.3% and excellent stability, maintaining 95% and 85% of their initial efficiencies after 250 min of continuous illumination and 3800 h of storage, respectively. We reveal the homojunction formation mechanism using density functional theory calculations and molecular level characterizations. Our work provides a reliable strategy for controlling the spatial energy levels in tin perovskite films and offers insights into designing intriguing lead-free perovskite optoelectronics.
RESUMO
Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called Leading Eigenvector Dynamics Analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, inter group differences in brain dynamic activity indicators are examined. And the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual regions activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state, and more active in limbic regions activity state and visual regions activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.
RESUMO
BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial. METHODS: In this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria. RESULTS: Our results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: In conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.
Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Animais , Humanos , Camundongos , Eixo Encéfalo-Intestino , Irinotecano/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/farmacologiaRESUMO
BACKGROUND: The hemoglobin glycation index (HGI) is the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, there are still no studies on the correlation between HGI and poor prognosis in patients with critical coronary artery disease. The purpose of this study was to analyze the correlation between HGI and all-cause mortality in patients with critical coronary artery disease using the MIMIC-IV database. METHODS: The HGI was calculated by constructing a linear regression equation between HbA1c and fasting plasma glucose (FPG). A KaplanâMeier survival analysis model was constructed based on the HGI quartiles to clarify the differences in all-cause mortality rates between groups, and the log-rank test was used to assess the differences between groups. The hazard ratio (HR) of HGI as a risk factor for outcome events was assessed using the Cox proportional risk model and restricted cubic spline (RCS), with the Q2 group serving as the reference group. RESULTS: A total of 5260 patients were included in this study. The 30-day mortality rate of the patients was 4.94% and the mortality rate within 365 days was 13.12%. A low HGI was significantly associated with 30-day mortality (HR, 1.96; 95% CI, (1.38, 2.78); P < 0.001) and 365-day mortality (HR, 1.48; 95% CI, (1.19, 1.85); P < 0.001) in patients with critical coronary artery disease in the completely adjusted Cox proportional risk model. In addition, high levels of HGI were associated with 365-day mortality (HR, 1.31; 95% CI, (1.02, 1.69); P < 0.05). RCS analysis revealed a U-shaped relationship between HGI and outcome events. According to the stratified analysis, the interaction test revealed that the correlation between HGI and outcome events remained stable. CONCLUSION: There was a significant correlation between HGI and all-cause mortality in patients with critical coronary artery disease, particularly in those with low HGI. HGI can be used as a potential indicator for assessing the short- and long-term risk of mortality in such patients.
Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Humanos , Hemoglobinas Glicadas , Reação de Maillard , Hemoglobinas/análise , Medição de Risco , Prognóstico , Glicemia/análiseRESUMO
OBJECTIVES: To preliminarily assess the immunogenicity of Mtb-HAg in mice and the synergistic effect provided by HAg when co-immunised with BCG. METHODS: Mice were randomly grouped for different immunisations and then spleens were aseptically removed and lymphocytes were extracted for immediate detection of cytokines transcript levels and stimulation index(SI), cytokine secretion and multifunctional antigen-specific T cells were detected after incubation for different times. RESULTS: HAg extracted from active Mtb is a group of mixed polypeptides with molecular weights of (10-14) kDa. It can significantly stimulate lymphocytes proliferation and increase SI. Injection of HAg alone and in combination with BCG induced significantly higher numbers of multifunctional antigen-specific T cells including CD4+ IFN-γ+, CD4+ IL-2+, CD8+ IFN-γ+, and CD8+ IL-2+ cells than that in BCG-treated mice. Co-immunisation induced the secretion of higher levels of IFN-γ, TNF-α, IL-2 and IL-4 and increased their mRNA expression levels. Significant increases in the transcription levels of IL-10, IL-12 and IL-17 were observed in the co-immunised group with the assistance of HAg. CONCLUSION: We demonstrated that HAg has favourable immunogenicity, triggers a stronger Th1-type immune response and proposed the hypothesis that HAg can be used as a BCG booster to further enhance the benefits of BCG.
Assuntos
Antígenos de Bactérias , Citocinas , Mycobacterium tuberculosis , Animais , Camundongos , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/administração & dosagem , Citocinas/metabolismo , Mycobacterium tuberculosis/imunologia , Mycobacterium bovis/imunologia , Vacina BCG/imunologia , Feminino , Camundongos Endogâmicos BALB C , Imunização/métodos , Proliferação de Células/efeitos dos fármacos , Baço/imunologiaRESUMO
Parasitoids are important components of the natural enemy guild in the biological control of insect pests. They depend on host resources to complete the development of a specific stage or whole life cycle and thus have evolved towards optimal host exploitation strategies. In the present study, we report a specific survival strategy of a fly parasitoid Exorista sorbillans (Diptera: Tachinidae), which is a potential biological control agent for agricultural pests and a pest in sericulture. We found that the expression levels of nitric oxide synthase (NOS) and nitric oxide (NO) production in host Bombyx mori (Lepidoptera: Bombycidae) were increased after E. sorbillans infection. Reducing NOS expression and NO production with an NOS inhibitor (NG-nitro-L-arginine methyl ester hydrochloride) in infected B. mori significantly impeded the growth of E. sorbillans larvae. Moreover, the biosynthesis of 20-hydroxyecdysone (20E) in infected hosts was elevated with increasing NO production, and inhibiting NOS expression lowered 20E biosynthesis. More importantly, induced NO synthesis was required to eliminate intracellular bacterial pathogens that presumably competed for shared host resources. Inhibiting NOS expression down-regulated the transcription of antimicrobial peptide genes and increased the number of bacteria in parasitized hosts. Collectively, this study revealed a new perspective on the role of NO in host-parasitoid interactions and a novel mechanism for parasitoid regulation of host physiology to support its development.
Assuntos
Bombyx , Dípteros , Ecdisterona , Interações Hospedeiro-Parasita , Óxido Nítrico , Animais , Bombyx/genética , Bombyx/microbiologia , Bombyx/parasitologia , Dípteros/fisiologia , Ecdisterona/metabolismo , Larva/crescimento & desenvolvimento , Larva/parasitologia , Larva/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase/genéticaRESUMO
Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.
Assuntos
Doença de Alzheimer , Apoptose , Barreira Hematorretiniana , Camundongos Transgênicos , Retina , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apoptose/efeitos dos fármacos , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Camundongos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Camundongos Endogâmicos C57BL , Humanos , Peptídeos beta-Amiloides/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , MasculinoRESUMO
Mitochondria are pivotal in the modulation of macrophage activation, differentiation, and survival. Furthermore, macrophages are instrumental in the onset and progression of cardiovascular diseases. Hence, it is imperative to investigate the role of mitochondria within macrophages in the context of cardiovascular disease. In this review, we provide an updated description of the origin and classification of cardiac macrophages and also focused on the relationship between macrophages and mitochondria in cardiovascular diseases with respect to (1) proinflammatory or anti-inflammatory macrophages, (2) macrophage apoptosis, (3) macrophage pyroptosis, and (4) macrophage efferocytosis. Clarifying the relationship between mitochondria and macrophages can aid the exploration of novel therapeutic strategies for cardiovascular disease.
RESUMO
Prostate cancer (PC) is the fifth leading cause of cancer-related deaths among men worldwide. Prostate-specific membrane antigen (PSMA), a molecular target of PC, is clinically used for the treatment and diagnosis of PC using radioligand approaches. However, no PSMA-based chemotherapies have yet been approved by the FDA. Here, we present a novel therapeutic approach using PSMA-targeted 2-deoxyglucose-dendrimer (PSMA-2DG-D) for targeted delivery of a potent tyrosine kinase inhibitor, cabozantinib (Cabo), selectively to PC cells. PSMA-2DG-D demonstrates intracellular localization in PSMA (+) PC cells through PSMA-mediated internalization. This PSMA-specific targeting translates to enhanced efficacy of Cabo compared to the free drug when conjugated to PSMA-2DG-D. Furthermore, systemically administered fluorescently labeled PSMA-2DG-D-Cy5 specifically targets PSMA (+) tumors with minimal off-target accumulation in the PC3-PIP tumor xenograft mouse model. This demonstrates that the PSMA-2DG-D platform is a promising new delivery system for potent chemotherapeutics, where systemic side effects are a significant concern.
RESUMO
In the past decade, metal halide materials have been favored by many researchers because of their excellent physical and chemical properties under thermal, electrical, and light stimuli, such as ferroelectricity, dielectric, nonlinearity, fluorescence, and semiconductors, greatly promoting their application in optoelectronic devices. In this study, we successfully constructed an unleaded organic-inorganic hybrid perovskite crystal: [Cl-C6H4-(CH2)2NH3]3SbBr6 (1), which underwent a high-temperature reversible phase transition near Tp = 368 K. The phase transition behavior of 1 was characterized by differential scanning calorimetry, accompanied by a thermal hysteresis of 6 K. In addition, variable-temperature Raman spectroscopy analysis and PXRD further verified the sensitivity of 1 to temperature and the phase transition from low symmetry to high symmetry. Temperature-dependent dielectric testing shows that 1 can be a sensitive switching dielectric constant switching material. Remarkably, 1 exhibits strong photoluminescence emission with a wavelength of 478 nm and a narrow band gap of 2.7 eV in semiconductors. As the temperature increases and decreases, fluorescence undergoes significant changes, especially near Tc, which further confirms the reversible phase transition of 1. All of these findings provide new avenues for designing and assembling new phase change materials with high Tp and photoluminescence properties.
RESUMO
Little is known about the impacts of specific chemical components on cardiovascular hospitalizations. We examined the relationships of PM2.5 chemical composition and daily hospitalizations for cardiovascular disease in 184 Chinese cities. Acute PM2.5 chemical composition exposures were linked to higher cardiovascular disease hospitalizations on the same day and the percentage change of cardiovascular admission was the highest at 1.76% (95% CI, 1.36-2.16%) per interquartile range increase in BC, followed by 1.07% (0.72-1.43%) for SO42-, 1.04% (0.63-1.46%) for NH4+, 0.99% (0.55-1.43%) for NO3-, 0.83% (0.50-1.17%) for OM, and 0.80% (0.34%-1.26%) for Cl-. Similar findings were observed for all cause-specific major cardiovascular diseases, except for heart rhythm disturbances. Short-term exposures to PM2.5 chemical composition were related to higher admissions and showed diverse impacts on major cardiovascular diseases.
RESUMO
Short-term exposure to particles with aerodynamic diameters less than 2.5 µm (PM2.5) and ozone (O3) are important risk factors for human health. Despite the awareness of reducing attributable health burden, region-specific and source-specific strategies remain less explored due to the gap between precursor emissions and health effects. In this study, we isolate the health burden of individual sector sources of PM2.5 and O3 precursors, nitrogen oxides (NOx) and volatile organic compounds (VOCs), across the globe. Specifically, we estimate mortalities attributable to short-term exposure using machine-learning-based daily exposure estimates and quantify sectoral impacts using chemical transport model simulations. Globally, short-term exposure to PM2.5 and O3 result in 713.5 (95% Confidence Interval: 598.8-843.3) thousand and 496.3 (371.3-646.1) thousand mortalities in 2019, respectively, of which 12.5% are contributed by fuel-related NOx emissions from transportation, energy, and industry. Sectoral impacts from anthropogenic NOx and VOC emissions on health burden vary significantly among seasons and regions, requiring a target shift from transportation in winter to industry in summer for East Asia, for instance. Emission control and health management are additionally complicated by unregulated natural influences during climatic events. Fire-sourced NOx and VOC emissions, respectively, contribute to 8.5 (95% CI: 6.2-11.7) thousand and 4.8 (3.6-5.9) thousand PM2.5 and O3 mortalities, particularly for tropics with high vulnerability to climate change. Additionally, biogenic VOC emissions during heatwaves contribute to 1.8 (95% CI: 1.5-2.2) thousand O3-introduced mortalities, posing challenges in urban planning for high-income regions, where biogenic contributions to health burden during heatwaves are 13% of anthropogenic contributions annually. Our study provides important implications for temporally dynamic and sector-targeted emission control and health management strategies, which are of urgency under the projection of continuously increasing energy consumption and changing climate.
Assuntos
Poluentes Atmosféricos , Ozônio , Material Particulado , Humanos , Exposição Ambiental , Compostos Orgânicos Voláteis , Óxidos de NitrogênioRESUMO
A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O3) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O3 and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O3; 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O3 exposures ranged from 1.029 to 1.107 compared with low-level O3, while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O3 and heat wave exposures, which were generally greater with higher levels of the O3 exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O3 and heat wave. Women and older adults were more vulnerable to the exposure to O3 and heat wave exposure. Exposure to both O3 and heat wave was significantly associated with an increased odds of CVD mortality, and O3 and heat wave can interact synergistically to trigger CVD deaths.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Ozônio , Humanos , Feminino , Idoso , Ozônio/análise , Doenças Cardiovasculares/epidemiologia , Poluentes Atmosféricos/análise , Estudos Cross-Over , Temperatura Alta , China/epidemiologia , Poluição do Ar/análise , Exposição Ambiental/análise , Material Particulado/análiseRESUMO
Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 µg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 µg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hipersensibilidade Alimentar , Rinite Alérgica , Criança , Pré-Escolar , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Estudos Transversais , Rinite Alérgica/epidemiologia , China/epidemiologia , Exposição Ambiental/análise , Poluição do Ar/análiseRESUMO
BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.
Assuntos
Aminopiridinas , Benzamidas , Ciclopropanos , Inibidores da Fosfodiesterase 4 , Psoríase , Índice de Gravidade de Doença , Creme para a Pele , Humanos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciclopropanos/uso terapêutico , Psoríase/tratamento farmacológico , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Benzamidas/efeitos adversos , Benzamidas/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inibidores da Fosfodiesterase 4/administração & dosagem , Inibidores da Fosfodiesterase 4/efeitos adversos , Resultado do Tratamento , Creme para a Pele/administração & dosagem , Creme para a Pele/efeitos adversos , Doença Crônica , Idoso , Esquema de Medicação , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Hypothyroidism is a major manifestation of autoimmune thyroid diseases (AITD). We previously reported that a low selenium (Se) status was linked to an elevated prevalence of thyroid diseases. We hypothesized that Se status may also influence the restoration of thyroid function. Thus, this study aimed to investigate the factors affecting the recovery of thyroid function in patients with (sub-)clinical hypothyroidism, with a specific focus on Se status. METHODS: We conducted a 6-year prospective cohort study comparing two counties with different Se concentrations. Demographic and disease data were collected from 1,190 individuals (549 Se-adequate and 641 Se-deficient) who completed a follow-up study in 2019. In addition, urinary iodine (I) levels, thyroid function, and serum and nail Se levels were measured. Logistic regression was used to investigate the relationship between Se deficiency and recovery of thyroid function. RESULTS: Sex and smoking status was similar between the two counties studied. Thyroid function recovery rate was significantly higher in Se-deficient counties (46.0% vs. 30.6%, P = 0.008). In the multivariate analysis, our results show that female sex (odds ratio [OR] (95% confidence interval [CI]) = 1.875 (1.080-3.257), P = 0.026] and increasing age [OR (95%CI) = 1.028(1.007-1.049), P = 0.009] were associated with the recovery rate. Additionally, our study revealed that while Se status was significant in the univariate analysis, this association appeared to disappear in the multivariate analysis. CONCLUSIONS: Female sex and increasing age have unfavorable effects on the recovery of thyroid function in patients over 30 years of age with (sub-) clinical hypothyroidism.
Assuntos
Hipotireoidismo , Selênio , Doenças da Glândula Tireoide , Humanos , Feminino , Adulto , Seguimentos , Estudos Prospectivos , Hipotireoidismo/epidemiologiaRESUMO
ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.
Assuntos
ATP Citrato (pro-S)-Liase , Neoplasias , Humanos , ATP Citrato (pro-S)-Liase/metabolismo , Neoplasias/metabolismo , Metabolismo dos LipídeosRESUMO
Preventing soil nitrogen (N) losses driven by microbial nitrification and denitrification contributes to improving global environmental concerns caused by NO3--N leaching and N2O emission. Quorum sensing (QS) signals regulate nitrification and denitrification of N-cycling bacteria in pure culture and water treatment systems, and mediate the composition of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in activated sludge. However, whether disrupting QS could prevent soil N losses remains unclear. This study explored the feasibility of applying quorum sensing inhibitors (QSIs) as an innovative strategy to reduce N losses from agricultural soils. The two QSIs, penicillic acid and 4-iodo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]-benzeneacetamide (4-iodo PHL), were more effective in reducing N losses than traditional inhibitors, including N-(n-butyl) thiophosphoric triamide and 3,4-dimethylpyrazole phosphate. After 36 days of aerobic incubation, penicillic acid and 4-iodo PHL inhibited nitrification by 39% and 68%, respectively. The inhibitory effects are attributed to the fact that 4-iodo PHL decreased the abundance of archaeal and bacterial amoA genes, as well as the relative abundance of Candidatus Nitrocosmicus (AOA), Candidatus Nitrososphaera (AOA), and Nitrospira (nitrite-oxidizing bacteria/comammox), while penicillic acid reduced archaeal amoA abundance and the relative abundance of Nitrosospira (AOB) and the microbes listed above. Penicillic acid also strongly inhibited denitrification (33%) and N2O emissions (61%) at the peak of N2O production (day 4 of anaerobic incubation) via decreasing nitrate reductase gene (narG) abundance and increasing N2O reductase gene (nosZ) abundance, respectively. Furthermore, the environmental risks of QSIs to microbial community structure and network stability, CO2 emissions, and soil animals were acceptable. Overall, QSIs have application potential in agriculture to reduce soil N losses and the associated effect on climate change. This study established a new method to mitigate N losses from the perspective of QS, and can serve as important basis of decreasing the environmental risks of agricultural non-point source pollution.
Assuntos
Betaproteobacteria , Solo , Animais , Solo/química , Nitrogênio , Amônia , Ácido Penicílico , Percepção de Quorum , Microbiologia do Solo , Bactérias/genética , Archaea , OxirreduçãoRESUMO
Available evidence suggests that air pollutants can cause stroke, but little research has investigated the confounding effects of urban-rural differences. Here, we investigated the urban-rural difference in the correlation between particulate matter (PM2.5 and PM10) exposure and stroke. This cohort study was based on a prospective multi-city community-based cohort (Guizhou Population Health Cohort Study (GPHCS)) in Guizhou Province, China. A total of 7988 eligible individuals (≥18 years) were enrolled with baseline assessments from November 2010 to December 2012, and follow-up was completed by June 2020. Two major particulate matters (PMs, including PM2.5 and PM10) were assessed monthly from 2000 by using satellite-based spatiotemporal models. The risk of stroke was estimated using a Cox proportional hazard regression model. The association between particulate matters' exposure and stroke in different areas (total, urban, and rural) and the potential modification effect of comorbidities (hypertension, diabetes, and dyslipidemia) and age (≤65/>65 years) were examined using stratified analyses. The risk of stroke increased for every 10 µg/m3 increase in mean PMs' concentrations during the previous 1 year at the residential address (HR: 1.26, 95%CI: 1.24, 1.29 (PM2.5); HR: 1.13, 95%CI: 1.11, 1.15 (PM10)). The presence of diabetes and dyslipidemia increased the risk of PM10-induced stroke in whole, urban, and rural areas. Specifically, people living in rural areas were more likely to experience the effects of PMs in causing a stroke. The risk of stroke due to PMs was statistically increased in the young and older populations living in rural areas. In conclusion, long-term exposure to PMs increased the risk of stroke and such association was more pronounced in people living in rural areas with lower income levels. Diabetes and dyslipidemia seemed to strengthen the association between PMs and stroke.