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1.
Heliyon ; 10(15): e35157, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170129

RESUMO

Background: The role of Mast cells has not been thoroughly explored in the context of prostate cancer's (PCA) unpredictable prognosis and mixed immunotherapy outcomes. Our research aims to employs a comprehensive computational methodology to evaluate Mast cell marker gene signatures (MCMGS) derived from a global cohort of 1091 PCA patients. This approach is designed to identify a robust biomarker to assist in prognosis and predicting responses to immunotherapy. Methods: This study initially identified mast cell-associated biomarkers from prostate adenocarcinoma (PRAD) patients across six international cohorts. We employed a variety of machine learning techniques, including Random Forest, Support Vector Machine (SVM), Lasso regression, and the Cox Proportional Hazards Model, to develop an effective MCMGS from candidate genes. Subsequently, an immunological assessment of MCMGS was conducted to provide new insights into the evaluation of immunotherapy responses and prognostic assessments. Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and pathway analysis to explore the biological pathways and mechanisms associated with MCMGS. Results: MCMGS incorporated 13 marker genes and was successful in segregating patients into distinct high- and low-risk categories. Prognostic efficacy was confirmed by survival analysis incorporating MCMGS scores, alongside clinical parameters such as age, T stage, and Gleason scores. High MCMGS scores were correlated with upregulated pathways in fatty acid metabolism and ß-alanine metabolism, while low scores correlated with DNA repair mechanisms, homologous recombination, and cell cycle progression. Patients classified as low-risk displayed increased sensitivity to drugs, indicating the utility of MCMGS in forecasting responses to immune checkpoint inhibitors. Conclusion: The combination of MCMGS with a robust machine learning methodology demonstrates considerable promise in guiding personalized risk stratification and informing therapeutic decisions for patients with PCA.

2.
Adv Sci (Weinh) ; : e2402550, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119875

RESUMO

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

3.
Adv Healthc Mater ; : e2401563, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39086039

RESUMO

Bullous keratopathy, a condition severely impacting vision and potentially leading to corneal blindness, necessitates corneal transplantation. However, the shortage of donor corneas and complex surgical procedures drive the exploration of tissue-engineered corneal endothelial layers. This study develops a transparent, amphiphilic, and cell-free membrane for corneal endothelial replacement. The membrane, securely attached to the posterior surface of the cornea, is created by mixing hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethylacrylate (EGDMA) in a 10:1 ratio. A 50 µL volume is used to obtain a 60 µm hydrophobic membrane on both sides, with one side treated with a polyvinylpyrrolidone (PVP) solution. The resulting membrane is transparent, foldable, biocompatible, amphiphilic, and easily handled. When exposed to 20% sulfur hexafluoride (SF6), the hydrophilic side of the membrane adheres tightly to the corneal Descemet's membrane, preventing water absorption into the corneal stroma, and thus treating bullous keratopathy. Histological test confirms its effectiveness, showing normal corneal structure and low inflammation when implanted in rabbits for up to 100 d. This study showcases the potential of this membrane as a viable option for corneal endothelial replacement, offering a novel approach to address donor tissue scarcity in corneal transplantation.

4.
World J Clin Cases ; 12(22): 5184-5188, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39109019

RESUMO

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

5.
World J Gastrointest Surg ; 16(7): 2088-2095, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39087131

RESUMO

BACKGROUND: Bariatric surgery is one of the most effective ways to treat morbid obesity, and postoperative nausea and vomiting (PONV) is one of the common complications after bariatric surgery. At present, the mechanism of the high incidence of PONV after weight-loss surgery has not been clearly explained, and this study aims to investigate the effect of surgical position on PONV in patients undergoing bariatric surgery. AIM: To explore the effect of the operative position during bariatric surgery on PONV. METHODS: Data from obese patients, who underwent laparoscopic sleeve gastrectomy (LSG) in the authors' hospital between June 2020 and February 2022 were divided into 2 groups and retrospectively analyzed. Multivariable logistic regression analysis and the t-test were used to study the influence of operative position on PONV. RESULTS: There were 15 cases of PONV in the supine split-leg group (incidence rate, 50%) and 11 in the supine group (incidence rate, 36.7%) (P = 0.297). The mean operative duration in the supine split-leg group was 168.23 ± 46.24 minutes and 140.60 ± 32.256 minutes in the supine group (P < 0.05). Multivariate analysis revealed that operative position was not an independent risk factor for PONV (odds ratio = 1.192, 95% confidence interval: 0.376-3.778, P = 0.766). CONCLUSION: Operative position during LSG may affect PONV; however, the difference in the incidence of PONV was not statistically significant. Operative position should be carefully considered for obese patients before surgery.

6.
Reproduction ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39102452

RESUMO

Testosterone deficiency in humans can be caused by depressive symptoms; however, the causes of this deficiency are incompletely understood. This study demonstrates that male mice with depression-like symptoms due to chronic unpredictable mild stress (CUMS) show reduced serum testosterone levels and disrupted sexual behaviors. However, the observed testosterone reductions were not caused by apoptosis of Leydig cells. Oil red O staining revealed that lipid droplets were dramatically decreased in Leydig cells, suggesting that defects in cholesterol uptake might be related to testosterone-deficiency in depression-like mice. To investigate the potential mechanism, lipid homeostasis was examined by liquid chromatography tandem mass spectrometry. The results revealed that higher levels of sphingomyelins (SM 8:0;2O/28:1, 18:0;2O/22:2, 33:0;3O, 33:1;2O) were linked to decreased cholesterol levels. Further investigation indicated that testosterone biosynthesis from cholesterol in Leydig cells was impaired by downregulation of Ldlr, SR-BI, LHR, and P450scc. Elevated levels of interferon signaling associated pathways in depression-like mice testes may also contribute to decreased testosterone level. Taken together, these findings provide a novel understanding of male reproductive problems under psychological stress and suggest that cholesterol uptake might be a causal factor in reduced testosterone production in depression-like mice.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39169663

RESUMO

BACKGROUND AND AIMS: Extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferred therapeutic approaches for painful chronic pancreatitis (CP) with pancreatic stones. This study aimed to report the short- and long-term outcomes following P-ESWL and ERCP in a large cohort with CP. METHODS: Patients with painful CP and pancreatic stones >5 mm in size, who underwent P-ESWL and subsequent ERCP between March 2011 and June 2018, were included in this retrospective-prospective mixed observational study. The total stone clearance rates were recorded. All patients were followed up until the end of March 2024, with the visual analogue scale (VAS) for pain, pain type, quality-of-life scores and other relevant information recorded. RESULTS: A total of 2071 patients underwent P-ESWL, and 93.1% of them subsequently underwent ERCP during the study period. Patients were followed up for an average of 11.8 years from the onset of CP and 6.7 years from the first P-ESWL procedure. Complete stone clearance was achieved in 73.7% of the patients. At the end of the follow-up period, 70.1% of the patients achieved complete pain remission. Significant pain type conversion and lower VAS scores were observed in the patients after treatment. Quality-of-life scores and body mass indices increased after P-ESWL and ERCP. CONCLUSIONS: P-ESWL and ERCP are effective and minimally invasive treatments for pancreatic stones in patients with painful CP. Most patients achieved complete pain relief, and pain-type conversion was common after treatment. (ClinicalTrials.gov: NCT05916547).

8.
Acta Parasitol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162923

RESUMO

BACKGROUND: Toxoplasma gondii, a globally distributed zoonotic obligate intracellular parasite, infects a wide array of mammals, including humans, sheep, and birds. As a unique sheep breed in southwestern China, Yunnan semi-fine wool sheep occupies an important position in animal husbandry in Zhaotong due to its strong adaptability, high reproductive rate, and excellent wool quality. Lambs infected with T. gondii are prone to neurological symptoms and growth retardation, while T. gondii infection in ewes can cause abortions, stillbirths, and deformities, thus affecting sheep reproduction and sheep product quality. Meanwhile, mutton and dairy products contaminated with T. gondii can become potential sources of human infection, potentially threatening public health and safety. METHOD: To understand the T. gondii infection in semi-fine wool sheep in Zhaotong, Yunnan Province, 586 blood samples were collected and subjected to indirect hemagglutination assay (IHA) for T. gondii antibodies, and the infection-related factors were analyzed through cross-sectional analysis. In the meantime, nested PCR was conducted on a total of 217 samples collected from 31 rodents caught in and around the sheep breeding ground to test the T. gondii B1 gene in rodent tissues. RESULTS: A total of 94 sera tested positive for T. gondii antibodies, with a total positive rate of 16.04% (94/586) (95% CI: 14.77-20.89). Cross-sectional statistical analysis on factors related to semi-fine wool sheep infection rate, including sampling season, sex, age, and weight, suggested that age (< 6 months: 23.81%; 6-12 months: 11.74%; > 12 months: 15.83%) was a significant factor explaining the infection rate differences (P = 0.003 < 0.05, χ2 = 11.62, df = 2). Thus, age was considered a key risk factor for T. gondii infection in this study (odds ratio, OR = 2.35, 95% CI: 1.42-3.87). Nested PCR analysis on 217 (heart, liver, spleen, lung, kidney, brain, and muscle) tissues from the 31 rodents indicated that 11 tested positive. The total infection rate of rodents in and around the breeding ground was 35.48% (11/31), and 14 samples tested positive, with a positive infection rate of 6.45% (14/217). CONCLUSION: The T. gondii infection rates of semi-fine wool sheep and rodents from their breeding environment in Zhaotong, Yunnan Province, were high, necessitating enhanced prevention, control, and treatment measures to ensure the healthy breeding of semi-fine wool sheep and veterinary public health and safety.

9.
Nano Lett ; 24(33): 10210-10218, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39105760

RESUMO

Assembling active materials into dense electrodes is a promising way to obtain high-volumetric-capacitance supercapacitors, but insufficient ion channels in the dense structure lead to a low rate capability. Herein, a dense and robust wood electrode with a large MXene volumetric mass loading (1.25 g cm-3) and abundant ion diffusion channels is designed via a facile capillary-force-driven self-densification strategy. Specifically, MXene is assembled onto a wood cell wall, endowing the wood electrode with good electrical conductivity (86 S cm-1) and high electrochemical activity (5.9 F cm-2 at 1 mA cm-2). Notably, the oriented channels along with spaces between adjacent microfibrils recast after densification ensure efficient ion transport for the wood electrode, achieving an excellent rate capability with a high capacitance retention of 77% from 1 to 20 mA cm-2. Meanwhile, the capillary force induces self-densification on the softened wood cell wall, resulting in a highly compact and robust structure for the wood electrode.

11.
Inorg Chem ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190538

RESUMO

The pursuit of highly efficient electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of paramount importance for water splitting. However, it is still a formidable task in Mo2C-based materials because of the agglomeration and strong Mo-H binding of Mo2C units. Herein, a novel CeOCl-CeO2/Mo2C heterostructure nesting within a three-dimensional porous nitrogen-doped carbon matrix has been designed and used for catalyzing HER via simultaneous morphology and heterointerface engineering. As expected, the optimal CeOCl-CeO2(0.2)/Mo2C@3DNC exhibits impressive HER activity, with a low overpotential of 156 mV at a current density of 10 mA cm-2 coupled with a slight Tafel slope of 62.20 mV dec-1. Introducing a Ce promoter, that is CeOCl and CeO2, would endow the interface with an internal electric field and electron redistribution between CeOCl-CeO2 and Mo2C induced by the heterogeneous work function difference. Moreover, experimental investigation and density functional calculations confirm that the CeOCl-CeO2/Mo2C heterointerface can downshift the d-band center of the active Mo center, weakening the strength of the Mo-H coupling. This proposed concept, engineering Ce-based promoters into active entities involved in the heterostructure to modulate intermediate adsorption, offers a great opportunity for the design of superior electrocatalysts for energy conversion.

12.
Sheng Li Xue Bao ; 76(4): 561-575, 2024 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-39192789

RESUMO

As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays a crucial role in regulating intracellular protein folding, translation and assembly. Multiple quality control mechanisms in the ER ensure accurate modification of proteins in the ER lumen are accurately modified, thus maintaining calcium homeostasis, oxidative stress, cellular senescence and apoptosis. These mechanisms include ER stress (ERS), ER autophagy (ER-phagy, ERPA) and ER-associated degradation (ERAD). Intervertebral disc degeneration (IDD) is an age-related degenerative disease of the spine. Although the pathogenesis of IDD has not been fully elucidated, emerging evidence suggests that the ER quality control system may be involved in its progression. Previous studies have focused on mitochondrial quality control and its related mechanisms in diseases, with limited systematic summaries on the ER quality control system. In this paper, we comprehensively reviewed the molecular mechanisms of the ER quality control system and investigated its association with IDD. In addition, we summarized the potential therapeutic strategies targeting the ER quality control system to attenuate IDD progression, offering new insights into the pathogenesis and regenerative repair strategies of IDD.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Degeneração do Disco Intervertebral , Humanos , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/fisiopatologia , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/fisiologia , Autofagia/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Animais , Degradação Associada com o Retículo Endoplasmático/fisiologia
13.
Brain Res ; 1844: 149169, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39179194

RESUMO

OBJECTIVE: Depression and insomnia frequently co-occur, but the neural mechanisms between patients with varying degrees of these conditions are not fully understood. The specific topological features and connectivity patterns of this co-morbidity have not been extensively studied. This study aimed to investigate the topological characteristics of topological characteristics and functional connectivity of brain networks in depressed patients with insomnia. METHODS: Resting-state functional magnetic resonance imaging data from 32 depressed patients with a high level of insomnia (D-HI), 35 depressed patients with a low level of insomnia (D-LI), and 81 healthy controls (HC) were used to investigate alterations in brain topological organization functional networks. Nodal and global properties were analyzed using graph-theoretic techniques, and network-based statistical analysis was employed to identify changes in brain network functional connectivity. RESULTS: Compared to the HC group, both the D-HI and D-LI groups showed an increase in the global efficiency (Eglob) values, local efficiency (Eloc) was decreased in the D-HI group, and Lambda and shortest path length (Lp) values were decreased in the D-LI group. At the nodal level, the right parietal nodal clustering coefficient (NCp) values were reduced in D-HI and D-LI groups compared to those in HC. The functional connectivity of brain networks in patients with D-HI mainly involves default mode network (DMN)-cingulo-opercular network (CON), DMN-visual network (VN), DMN-sensorimotor network (SMN), and DMN-cerebellar network (CN), while that in patients with D-LI mainly involves SMN-CON, SMN-SMN, SMN-VN, and SMN-CN. The values of the connection between the midinsula and postoccipital gyrus was negatively correlated with scores for early awakening in D-HI. CONCLUSION: These findings may contribute to our understanding of the underlying neuropsychological mechanisms in depressed patients with insomnia.

14.
Sci Total Environ ; 951: 175519, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39168342

RESUMO

The antiepileptic drug carbamazepine (CBZ) has been widely detected in freshwater, yet its toxic actions in fish at multiple endpoints and the subsequent recovery patterns of the impacted are less discussed. This study investigated the bioaccumulation, physiological and behavioral changes of crucian carp (Carassius carassius) following CBZ exposure (G1 = 6.15 µg/L, G2 = 61.5 µg/L, G3 = 615 µg/L, G4 = 6150 µg/L) and subsequent recovery. Our results showed that CBZ was more likely to accumulate in the liver and brain than in the gills. A concentration-dependent phenomenon was observed; however, the residual CBZ decreased to similar levels after recovery. The behavioral indicators (i.e. feeding, social and spontaneous swimming) were significantly inhibited after 7-days of CBZ exposure, and only recovered at low concentration treatment (G1) after 7-days recovery in CBZ-free water. The acetylcholinesterase (AChE) activity in the brain and superoxide dismutase (SOD) activity in the liver and gills were induced after CBZ exposure and returned to normal levels after 7-days of recovery. In contrast, the inhibition of catalase (CAT) activity caused by CBZ exposure persisted in the high concentration treatment (G4) after recovery. Furthermore, correlation analysis indicated that changes in feeding behavior were closely related to the variation of CBZ concentrations in tissues, and the persistence of abnormal swimming and social behavior was closely related to gill CAT activity. These findings contribute to explore the toxic mechanisms of CBZ and highlight the recovery process and connections between various endpoints.

15.
Biosens Bioelectron ; 264: 116656, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39133993

RESUMO

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.


Assuntos
Técnicas Biossensoriais , Hidrogéis , Superóxidos , Humanos , Superóxidos/análise , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Hidrogéis/química , Matriz Extracelular/química , Técnicas de Cultura de Células/instrumentação , Simulação de Ausência de Peso , Desenho de Equipamento , Corantes Fluorescentes/química , Dispositivos Lab-On-A-Chip , Ausência de Peso , Estresse Oxidativo
16.
Environ Sci Technol ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155565

RESUMO

Ammonia (NH3) slip from diesel vehicle aftertreatment systems and internal combustion engines fueled by NH3 or NH3/H2 poses serious environmental problems. Ag-based catalysts are widely used for the selective catalytic oxidation of NH3 to N2 (NH3-SCO), and their performance is greatly dependent on the state of Ag, which is influenced by the anchoring sites on the support. Despite efforts to identify the direct anchoring sites of metal atoms on TiO2, conflicting views persist. Here, we compared the correlation between Ag dispersion and the content of hydroxyl (OH) groups or defects on TiO2 and conducted density functional theory (DFT) calculations, and the results confirmed that the surface OH groups of TiO2 serve as the direct anchoring sites for Ag. By modulating the OH group content through thermal induction, the optimal OH group content on TiO2-800 resulted in more metallic Ag nanoparticles (Ag0 NPs) in larger sizes, leading to the development of an excellent NH3-SCO catalyst. Moreover, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), kinetic studies, and DFT calculations suggested that more Ag0 NPs in larger sizes on 10Ag/TiO2-800 were conducive to O2 activation and NH3 dissociation. Our findings provide new insights for designing efficient NH3-SCO catalysts, and OH groups as direct anchoring sites could be extended to other metals and supports for the rational design of catalysts.

17.
J Agric Food Chem ; 72(31): 17343-17355, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39024058

RESUMO

ERAP1 is an emerging target for a large subclass of severe autoimmune diseases known as "MHC-I-opathy", together with tumor immunity. Nevertheless, effective inhibitors targeting ERAP1 remain a challenge. In this study, a novel food-derived natural product ERAP1-targeting inhibitor, carnosic acid, was identified, and to our knowledge, it is one of the best active compounds among the highly selective inhibitors targeting the orthosteric site of ERAP1. The results reveal that carnosic acid could bind strongly, like a key to the ERAP1 active site in the biased S1' pocket, which is different from the binding mode of the existing orthosteric site inhibitors. HLA-B27-mediated cell modeling validated that carnosic acid has the activity to reverse the AS-associated cellular phenotype brought on by ERAP1 through inhibition. Our findings provide insights into the design of potent inhibitors against the ERAP1 orthosteric site and the discovery of a key direct target of carnosic acid.


Assuntos
Abietanos , Aminopeptidases , Apresentação de Antígeno , Antígenos de Histocompatibilidade Menor , Abietanos/farmacologia , Abietanos/química , Humanos , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/química , Antígenos de Histocompatibilidade Menor/metabolismo , Antígenos de Histocompatibilidade Menor/imunologia , Apresentação de Antígeno/efeitos dos fármacos , Aminopeptidases/antagonistas & inibidores , Aminopeptidases/imunologia , Aminopeptidases/metabolismo , Aminopeptidases/química , Ligação Proteica , Sítios de Ligação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular
18.
J Am Chem Soc ; 146(31): 21335-21347, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39049158

RESUMO

The formation and preservation of the active phase of the catalysts at the triple-phase interface during CO2 capture and reduction is essential for improving the conversion efficiency of CO2 electroreduction toward value-added chemicals and fuels under operational conditions. Designing such ideal catalysts that can mitigate parasitic hydrogen generation and prevent active phase degradation during the CO2 reduction reaction (CO2RR), however, remains a significant challenge. Herein, we developed an interfacial engineering strategy to build a new SnOx catalyst by invoking multiscale approaches. This catalyst features a hierarchically nanoporous structure coated with an organic F-monolayer that modifies the triple-phase interface in aqueous electrolytes, substantially reducing competing hydrogen generation (less than 5%) and enhancing CO2RR selectivity (∼90%). This rationally designed triple-phase interface overcomes the issue of limited CO2 solubility in aqueous electrolytes via proactive CO2 capture and reduction. Concurrently, we utilized pulsed square-wave potentials to dynamically recover the active phase for the CO2RR to regulate the production of C1 products such as formate and carbon monoxide (CO). This protocol ensures profoundly enhanced CO2RR selectivity (∼90%) compared with constant potential (∼70%) applied at -0.8 V (V vs RHE). We further achieved a mechanistic understanding of the CO2 capture and reduction processes under pulsed square-wave potentials via in situ Raman spectroscopy, thereby observing the potential-dependent intensity of Raman vibrational modes of the active phase and CO2RR intermediates. This work will inspire material design strategies by leveraging triple-phase interface engineering for emerging electrochemical processes, as technology moves toward electrification and decarbonization.

19.
Environ Sci Technol ; 58(31): 13624-13635, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39051940

RESUMO

Cohorts of pregnant women in 2018 and 2020 were selected to explore prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Maternal serum during the whole pregnancy (first to third trimesters) and matched cord serum were collected for the analysis of 50 PFAS. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS) were the dominant PFAS in both the maternal and cord serum. The median ∑PFAS concentration was 14.18 ng/mL, and the ∑PFAS concentration was observed to decline from the first trimester to the third trimester. The transplacental transfer efficiencies (TTE) of 29 PFAS were comprehensively assessed, and a "U"-shaped trend in TTE values with increasing molecular chain length of perfluoroalkyl carboxylic acid (PFCA) was observed in this study. Moreover, the maternal concentrations of 9-chlorohexadecafluoro-3-oxanonane-1-sulfonic acid (6:2 Cl-PFESA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), PFOS, and hexafluoropropylene oxide dimer acid (HFPO-DA) in the 2020 cohort were significantly lower than those in the 2018 cohort, declining by about 23.85-43.2% from 2018 to 2020 (p < 0.05). Higher proportions of emerging PFAS were observed in fetuses born in 2020. This birth cohort was collected during the COVID-19 epidemic period. The change in the PFAS exposure scene might be in response to the different exposure profiles of the 2018 and 2020 cohorts, which are attributed to the impact of COVID-19 on the social activities and environment of pregnant women. Finally, by application of a multiple informant model, the third trimester was identified as the critical window of vulnerability to PFAS exposure that affects birth weight and birth length.


Assuntos
Fluorocarbonos , Humanos , Feminino , Gravidez , Adulto , COVID-19/epidemiologia , Ácidos Alcanossulfônicos , Estudos de Coortes , Exposição Materna , Poluentes Ambientais , Caprilatos
20.
J Environ Manage ; 366: 121743, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39053377

RESUMO

The carbon emissions trading (CET) policy internalises the cost of carbon emission reductions borne by companies, which will affect the companies' investment and management decisions. From a micro perspective, this paper analyzes the impact on company investment expenditure and its transmission mechanism by implementing the CET policy. Based on panel data of China's A-share listed companies from eight carbon-intensive industries spanning 2010 to 2020, the time-varying difference-in-difference model and its extended model are used to evaluate the impact of the policy in the pilot areas. The results show that: first, based on the cost effect and legality theories, CET policy can reduce the investment expenditure of the companies by 71.95%. Second, CET policy reduces corporate investment expenditures by increasing corporate debt financing costs. When debt financing costs increase by 120.25%, the investment expenditures will reduce by 2.56% indirectly while the intermediary effect of equity financing costs is not significant. Finally, with the implementation of CET policy, the inhibitory effect on corporate investment expenditures has gradually increased. CET policy has a more significant inhibitory effect on investment expenditures of nonstate-owned companies and small-scale companies. The results have passed the robustness test and provide evidence for the policy-maker to balance microeconomic entity development and carbon reduction, and for companies to make optimization investment and financing decisions in response to policy shocks effectively.


Assuntos
Carbono , Investimentos em Saúde , China , Indústrias/economia , Política Ambiental/economia
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