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1.
Front Bioeng Biotechnol ; 12: 1343294, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333080

RESUMO

Polyetheretherketone (PEEK) has been one of the most promising materials in bone tissue engineering in recent years, with characteristics such as biosafety, corrosion resistance, and wear resistance. However, the weak bioactivity of PEEK leads to its poor integration with bone tissues, restricting its application in biomedical fields. This research effectively fabricated composite porous scaffolds using a combination of PEEK, nano-hydroxyapatite (nHA), and carbon fiber (CF) by the process of fused deposition molding (FDM). The experimental study aimed to assess the impact of varying concentrations of nHA and CF on the biological performance of scaffolds. The incorporation of 10% CF has been shown to enhance the overall mechanical characteristics of composite PEEK scaffolds, including increased tensile strength and improved mechanical strength. Additionally, the addition of 20% nHA resulted in a significant increase in the surface roughness of the scaffolds. The high hydrophilicity of the PEEK composite scaffolds facilitated the in vitro inoculation of MC3T3-E1 cells. The findings of the study demonstrated that the inclusion of 20% nHA and 10% CF in the scaffolds resulted in improved cell attachment and proliferation compared to other scaffolds. This suggests that the incorporation of 20% nHA and 10% CF positively influenced the properties of the scaffolds, potentially facilitating bone regeneration. In vitro biocompatibility experiments showed that PEEK composite scaffolds have good biosafety. The investigation on osteoblast differentiation revealed that the intensity of calcium nodule staining intensified, along with an increase in the expression of osteoblast transcription factors and alkaline phosphatase activities. These findings suggest that scaffolds containing 20% nHA and 10% CF have favorable properties for bone induction. Hence, the integration of porous PEEK composite scaffolds with nHA and CF presents a promising avenue for the restoration of bone defects using materials in the field of bone tissue engineering.

2.
J Am Chem Soc ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335733

RESUMO

The unstable electrode-electrolyte interface and the narrow electrochemical window of normal electrolytes hinder the potential application of high-voltage sodium metal batteries. These problems are actually related to the solvation structure of the electrolyte, which is determined by the competition between cations coordinated with anions or solvent molecules. Herein, we design an electrolyte incorporating ethyl (2,2,2-trifluoroethyl) carbonate and fluoroethylene carbonate, which facilitates a pronounced level of cation-anion coordination within the solvation sheath by enthalpy changes to reduce the overall coordination of cation-solvents and increase sensitivity to salt concentration. Such an electrolyte regulated by competitive coordination leads to highly reversible sodium plating/stripping with extended cycle life and a high Coulombic efficiency of 98.0%, which is the highest reported so far in Na||Cu cells with ester-based electrolytes. Moreover, 4.5 V high-voltage Na||Na3V2(PO4)2F3 cells exhibit a high rate capability up to 20 C and an impressive cycling stability with an 87.1% capacity retention after 250 cycles with limited Na. The proposed strategy of solvation structure modification by regulating the competitive coordination of the cation provides a new direction to achieve stable sodium metal batteries with high energy density and can be further extended to other battery systems by controlling enthalpy changes of the solvation structure.

3.
Nat Commun ; 15(1): 1321, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351029

RESUMO

Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.


Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias Ovarianas , Humanos , Feminino , Proteínas/metabolismo , Neoplasias Ovarianas/genética , Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , Proteases Específicas de Ubiquitina/metabolismo
4.
J Biol Chem ; : 105762, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367665

RESUMO

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL.

5.
Sci Total Environ ; 920: 171046, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38369151

RESUMO

Food security, water scarcity, and excessive fossil energy use pose considerable challenges to sustainable agriculture. To understand how rain-fed farming systems on the Loess Plateau, China, reconcile yield increases with ecological conservation, we conducted an integrated evaluation based on the denitrification-decomposition (DNDC) model, agricultural statistics data using the Food-Energy-Water (FEW) nexus indicator. The results showed that maize yields with ridge-furrow plastic film mulching (PFM) were 3479, 8942, and 11,124 kg ha-1 under low (50 kg N ha-1), medium (200 kg N ha-1), and high (350 kg N ha-1) nitrogen (N) fertilizer rates, respectively, and that PFM increased yield and water use efficiency (WUE) by 110-253 % and 166-205 % compared to using no mulching (control, CK), respectively. Plastic film mulching also increased net energy (126-436 %), energy use efficiency (81-578 %), energy productivity (100-670 %), and energy profitability (126-994 %), and nitrogen fertilizer, compound fertilizer, and diesel fuel consumption by agricultural machinery were the main energy inputs. The PFM system reduced water consumption during the maize growing season and the green water footprint and gray water footprint decreased by 66-74 % and 44-68 %, respectively. The FEW nexus indicator, based on a high production at low environmental cost scenario, was greater under the PFM system and had the widest spatial distribution area at the medium-N application rate. Among the environmental factors, the nexus indicator was negatively correlated with precipitation (-0.37), air temperature (-0.36), and the aridity index (-0.36), but positively correlated with elevation (0.17). Our results suggest that the PFM system promotes resource-saving while increasing yields and moves dryland agriculture in an environmentally friendly direction, thus promoting the sustainable development of agroecosystems.

6.
Int J Parasitol Parasites Wildl ; 23: 100912, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38375444

RESUMO

Soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with worldwide distributions. As one representative group of Argasidae, the genus Argas has an important vectorial role in transmitting zoonotic diseases. However, our knowledge of the subgenus Argas in China is still limited, as most literature only lists occurrence records or describes specific case reports without providing detailed morphological characteristics and further molecular data. This study aims to characterize Argas vulgaris through complete mitochondrial sequencing and morphological diagnostic techniques based on a batch of adult specimens collected from Ningxia Hui Autonomous Regions (NXHAR), North China. The morphology and microstructures of Ar. vulgaris and other lectotypes of argasid ticks in the subgenus Argas were also observed using a stereomicroscope. Following DNA extraction and sequencing, a complete mitochondrial sequence of Ar. vulgaris was assembled and analyzed within a phylogenetic context. The 14,479 bp mitogenome of Ar. vulgaris consists of 37 genes, including 13 genes for protein coding, two for ribosomal RNA, 22 for transfer RNA, and one for control region (D-loops). Phylogenetic analysis of Ar. vulgaris showed 98.27%-100% nucleotide identity with Ar. japonicus, indicating a close relationship between the two tick species. The morphological diagnostic features to differentiate Ar. vulgaris from other ticks within the subgenus Argas included the location of the anus and setae on the anterior lip of the female genital aperture. This study provided high-resolution scanning electron microscope images of female Ar. vulgaris and corresponding molecular data, representing valuable resources for future accurate species identification.

7.
Anal Chem ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377587

RESUMO

Identification of degradation products and pathways is crucial for investigating emerging pollutants and evaluation of wastewater treatment methods. Nontargeted analysis is a powerful tool to comprehensively investigate the degradation pathways of organic pollutants in real-world wastewater samples but often generates large data sets, making it difficult to effectively locate the exact information on interests. Herein, to efficiently establish the linkages among compounds in the same degradation pathways, we introduce a compound similarity network (CSN) as a novel data mining strategy for LC-MS-based nontargeted analysis of complex wastewater samples. Different from molecular networks that cluster compounds based on MS/MS spectra similarity, our CSN strategy harnesses molecular fingerprints to establish linkages among compounds and thus is spectra-independent. The effectiveness of CSN was demonstrated by nontargeted identification of degradation pathways and products of organic pollutants in leather industrial wastewater that underwent laboratory-scale activated carbon adsorption (ACD) and ozonation treatments. Utilizing CSN in interpreting nontargeted data, we tentatively annotated 4324 compounds in the untreated leather industrial wastewater, 3246 after ACD, and 3777 after ACD/ozonation. We located 145 potential degradation pathways of organic pollutants in the ACD/ozonation process using CSN and validated 7 pathways with 15 chemical standards. CSN also revealed 5 clusters of emerging pollutants, from which 3 compounds were selected for in vitro cytotoxicity study to evaluate their potential biohazards as new pollutants. As CSN offers an efficient way to connect massive compounds and to find multiple degradation pathways in a high-throughput manner, we anticipate that it will find wide applications in nontargeted analysis of diverse environmental samples.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38342488

RESUMO

BACKGROUND: The pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of nirmatrelvir (NMV) are unknown in Chinese patients with COVID-19. OBJECTIVES: To understand the PK, as well as PK-PD characteristics of NMV for optimizing the dose in Chinese patients with COVID-19. METHODS: We enrolled 141 participants who received NMV 300 mg/ritonavir (RTV) 100 mg b.i.d. for 5 days. The NMV concentrations were analyzed using 251 blood samples. PK/PD of NMV was investigated in these COVID-19 patients using a nonlinear mixed-effects model. RESULTS: The patients had a mean age of 82 years (range, 34-97). The absorption rate constant and apparent clearance of NMV in this Chinese cohort were 0.253 h-1 and 6.83 L/h, respectively, similar to Caucasian patients. No covariates affected NMV clearance. Predicted peak (Cmax ) and trough concentration (Cmin ) under 300 mg NMV/100 mg RTV b.i.d. were 4004 and 1498 ng/mL, respectively. Although higher AUC and Cmin were weakly associated with a slight increase in the number of cycle threshold (CT) of viral genes, no significant correlation was found, indicating a weak relationship between drug exposure and efficacy (CT). CONCLUSIONS: In all, our findings suggest no ethnic PK differences, a weak and clinically insignificant relationship between drug exposure and efficacy, suitable dosage for Chinese patients (including the elderly) based on PK parameters, and the need for further studies to determine optimal regimens for high-risk patients due to inter-individual variability.

9.
Cell Death Dis ; 15(2): 111, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316760

RESUMO

Osteoclasts consume an amount of adenosine triphosphate (ATP) to perform their bone resorption function in the development of osteoporosis. However, the mechanism underlying osteoclast energy metabolism has not been fully elucidated. In addition to glucose, glutamine (Glu) is another major energy carrier to produce ATP. However, the role of Glu metabolism in osteoclasts and the related molecular mechanisms has been poorly elucidated. Here we show that Glu is required for osteoclast differentiation and function, and that Glu deprivation or pharmacological inhibition of Glu transporter ASCT2 by V9302 suppresses osteoclast differentiation and their bone resorptive function. In vivo treatment with V9302 improved OVX-induced bone loss. Mechanistically, RNA-seq combined with in vitro and in vivo experiments suggested that Glu mediates the role of IL-17 in promoting osteoclast differentiation and in regulating energy metabolism. In vivo IL-17 treatment exacerbated OVX-induced bone loss, and this effect requires the participation of Glu or its downstream metabolite α-KG. Taken together, this study revealed a previously unappreciated regulation of IL-17 on energy metabolism, and this regulation is Glu-dependent. Targeting the IL-17-Glu-energy metabolism axis may be a potential therapeutic strategy for the treatment of osteoporosis and other IL-17 related diseases.


Assuntos
Reabsorção Óssea , Osteoporose , Humanos , Osteoclastos/metabolismo , Glutamina/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Reabsorção Óssea/metabolismo , Osteoporose/metabolismo , Metabolismo Energético , Trifosfato de Adenosina/metabolismo , Diferenciação Celular , Ligante RANK/metabolismo , Osteogênese
10.
Polymers (Basel) ; 16(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38337239

RESUMO

This study explores the impact of resin-missing defects on the mechanical properties of composite laminates through experimental and finite element methods. Specimens with varying defect contents (5.3%, 8.0%, 10.7%, 13.3%, and 16.7%) were prepared via Vacuum Assistant Resin Infusion process. Experimental tests were conducted with the assistance of Digital Image Correlation measurements to illustrate the impact of resin-missing defects on failure characteristics. The experimental results indicate that the existence of resin-missing defects altered the stress distribution, increased the local stress, and reduced the tensile strength of the composite laminate. The DIC results indicate that the presence of defects weakens the matrix, leading to premature damage and deterioration. Numerical modeling with a progressive damage analysis method was developed to simulate the failure process and the influence of the resin-missing defects. The simulation results agree well with the experimental results, and the maximum error was 3.06%. The failure modes obtained from finite elements are consistent with the experimental and DIC results. Furthermore, a study was conducted on how the location of resin-missing defects affects the mechanical properties of composite laminates. The findings suggest that defects situated at the edges or on the surface of the material have a more significant impact on the tensile strength.

11.
Drug Metab Rev ; : 1-30, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38311829

RESUMO

Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, four have been withdrawn from the market due to severe hepatotoxicity, and others carry boxed warnings for idiosyncratic liver toxicity. The clinical and economic implications of antidepressant-induced liver injury are substantial, but the underlying mechanisms remain elusive. Drug-induced liver injury may involve the host immune system, the parent drug, or its metabolites, and reactive drug metabolites are one of the most commonly referenced risk factors. Although the precise mechanism by which toxicity is induced may be difficult to determine, identifying reactive metabolites that cause toxicity can offer valuable insights for decreasing the bioactivation potential of candidates during the drug discovery process. A comprehensive understanding of drug metabolic pathways can mitigate adverse drug-drug interactions that may be caused by elevated formation of reactive metabolites. This review provides a comprehensive overview of the current state of knowledge on antidepressant bioactivation, the metabolizing enzymes responsible for the formation of reactive metabolites, and their potential implication in hepatotoxicity. This information can be a valuable resource for medicinal chemists, toxicologists, and clinicians engaged in the fields of antidepressant development, toxicity, and depression treatment.

12.
J Surg Case Rep ; 2024(2): rjae069, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38370599

RESUMO

Retroperitoneal appendiceal perforation presents unique challenges in surgical management due to the complex nature of the retroperitoneal space. We present a case of a 57-year-old male with retroperitoneal appendiceal perforation, characterized by the presence of a large amount of gas in the retroperitoneal space. Emergent laparoscopic surgery was performed to address the retroperitoneal involvement. In retroperitoneal appendiceal perforation, surgical intervention and postoperative drainage are of great significance to prevent septic shock. The interconnectedness of the retroperitoneal space with other body regions is highlighted, underscoring the potential for severe complications. This case emphasizes the need for a tailored approach to managing retroperitoneal appendiceal perforation, preventing potential complications associated with this condition.

13.
Front Med (Lausanne) ; 11: 1336640, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371508

RESUMO

Objective: To investigate the performance of multiparametric magnetic resonance imaging (MRI)-based radiomics models in differentiating early stage of cervical cancer (Stage I-IIa vs. IIb-IV). Methods: One hundred patients with cervical cancer who underwent preoperative MRI between June 2020 and March 2022 were retrospectively enrolled. Training (n = 70) and testing cohorts (n = 30) were assigned by stratified random sampling. The clinical and pathological features, including age, histological subtypes, tumor grades, and node status, were compared between the two cohorts by t-test or chi-square test. Radiomics features were extracted from each volume of interest (VOI) on T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps. The data balance of the training cohort was resampled by synthesizing minority oversampling techniques. Subsequently, the adiomics signatures were constructed by the least absolute shrinkage and selection operator algorithm and minimum-redundancy maximum-relevance with 10-fold cross-validation. Logistic regression was applied to predict the cervical cancer stages (low [I-IIa]) and (high [IIb-IV] FIGO stages). The receiver operating characteristic curve (area under the curve [AUC]) and decision curve analysis were used to assess the performance of the radiomics model. Results: The characteristics of age, histological subtypes, tumor grades, and node status were not significantly different between the low [I-IIa] and high [IIb-IV] FIGO stages (p > 0.05 for both the training and test cohorts). Three models based on T2WI, ADC maps, and the combined were developed based on six radiomics features from T2WI and three radiomics features from ADC maps, with AUCs of 0.855 (95% confidence interval [CI], 0.777-0.934) and 0.823 (95% CI, 0.727-0.919), 0.861 (95% CI, 0.785-0.936) and 0.81 (95% CI, 0.701-0.918), 0.934 (95% CI, 0.884-0.984) and 0.902 (95% CI, 0.832-0.972) in the training and test cohorts. Conclusion: The radiomics models combined T2W and ADC maps had good predictive performance in differentiating the early stage from locally advanced cervical cancer.

14.
JAMA Pediatr ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372979
15.
ChemSusChem ; : e202400295, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38362788

RESUMO

Ongoing research to develop advanced electrocatalysts for the oxygen evolution reaction (OER) is needed to address demand for efficient energy conversion and carbon-free energy sources. In the OER process, acidic electrolytes have higher proton concentration and faster response than alkaline ones, but their harsh strongly acidic environment requires catalysts with greater corrosion and oxidation resistance. At present, iridium oxide (IrO2) with its strong stability and excellent catalytic performance is the catalyst of choice for the anode side of commercial PEM electrolysis cells. However, the scarcity and high cost of iridium (Ir) and the unsatisfactory activity of IrO2 hinder industrial scale application and the sustainable development of acidic OER catalytic technology. This highlights the importance of further research on acidic Ir-based OER catalysts. In this review, recent advances in Ir-based acidic OER electrocatalysts are summarized, including fundamental understanding of the acidic OER mechanism, recent insights into the stability of acidic OER catalysts, highly efficient Ir-based electrocatalysts, and common strategies for optimizing iridium-based catalysts. The future challenges and prospects of developing highly effective Ir-based catalysts are also discussed.

16.
Cancer Rep (Hoboken) ; 7(2): e1971, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351528

RESUMO

BACKGROUND: Cancer is the leading cause of death among Asian Americans, who often face barriers to cancer care. Cancer supportive care needs among Asian Americans remain understudied. AIMS: We examined cancer supportive care needs and participant factors correlated with these needs, identified profiles of supportive care needs, and examined whether needs profiles are associated with quality of life among Asian American adults. METHODS AND RESULTS: We recruited 47 Asian American adults with colorectal, liver, or lung cancer who spoke Chinese, English, or Vietnamese, and were starting or undergoing cancer treatment. We assessed cancer supportive care needs in four domains: cancer information, daily living, behavioral health, and language assistance. Hierarchical cluster analysis was used to identify clusters of participants based on their supportive need profiles to further examine the association between need profiles and quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy. Participants (mean age = 57.6) included 72% males and 62% spoke English less than very well. Older participants (age ≥ 65) and those with annual income <$50K reported higher daily living needs. Men and younger participants (age < 50) reported higher behavioral health needs. We found three clusters displaying distinct cancer supportive need profiles: Cluster 1 (28% of the sample) displayed high needs across all domains; Cluster 2 (51%) had low needs across all domains; and Cluster 3 (21%) had high needs for cancer information and daily living. Cluster 1 participants reported the lowest QoL. CONCLUSION: Cancer supportive care needs among Asian American patients with colorectal, liver, and lung cancer were associated with patient characteristics and QoL. Understanding cancer supportive care needs will inform future interventions to improve care and QoL for Asian American patients with cancer. CLINICALTRIALS: gov Identifier: NCT03867916.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Pulmonares , Navegação de Pacientes , Portais do Paciente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asiático , Neoplasias Colorretais/terapia , Internet , Neoplasias Pulmonares/terapia , Qualidade de Vida , Neoplasias Hepáticas/terapia
17.
Sci Total Environ ; 918: 170668, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38320701

RESUMO

BACKGROUND: Transient receptor potential (TRP) ankyrin 1 (TRPA1) could mediate ozone-induced lung injury. Optic Atrophy 1 (OPA1) is one of the significant mitochondrial fusion proteins. Impaired mitochondrial fusion, resulting in mitochondrial dysfunction and ferroptosis, may drive the onset and progression of lung injury. In this study, we examined whether TRPA1 mediated ozone-induced bronchial epithelial cell and lung injury by activating PI3K/Akt with the involvement of OPA1, leading to ferroptosis. METHODS: Wild-type, TRPA1-knockout (KO) mice (C57BL/6 J background) and ferrostatin-1 (Fer-1)-pretreated mice were exposed to 2.5 ppm ozone for 3 h. Human bronchial epithelial (BEAS-2B) cells were treated with 1 ppm ozone for 3 h in the presence of TRPA1 inhibitor A967079 or TRPA1-knockdown (KD) as well as pharmacological modulators of PI3K/Akt-OPA1-ferroptosis. Transcriptome was used to screen and decipher the differential gene expressions and pathways. Oxidative stress, inflammation and ferroptosis were measured together with mitochondrial morphology, function and dynamics. RESULTS: Acute ozone exposure induced airway inflammation and airway hyperresponsiveness (AHR), reduced mitochondrial fusion, and enhanced ferroptosis in mice. Similarly, acute ozone exposure induced inflammatory responses, altered redox responses, abnormal mitochondrial structure and function, reduced mitochondrial fusion and enhanced ferroptosis in BEAS-2B cells. There were increased mitochondrial fusion, reduced inflammatory responses, decreased redox responses and ferroptosis in ozone-exposed TRPA1-KO mice and Fer-1-pretreated ozone-exposed mice. A967079 and TRPA1-KD enhanced OPA1 and prevented ferroptosis through the PI3K/Akt pathway in BEAS-2B cells. These in vitro results were further confirmed in pharmacological modulator experiments. CONCLUSION: Exposure to ozone induces mitochondrial dysfunction in human bronchial epithelial cells and mouse lungs by activating TRPA1, which results in ferroptosis mediated via a PI3K/Akt/OPA1 axis. This supports a potential role of TRPA1 blockade in preventing the deleterious effects of ozone.


Assuntos
Ferroptose , Lesão Pulmonar , Doenças Mitocondriais , Oximas , Ozônio , Humanos , Camundongos , Animais , Lesão Pulmonar/induzido quimicamente , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ozônio/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/induzido quimicamente , Células Epiteliais , Doenças Mitocondriais/metabolismo , Pulmão/metabolismo , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/farmacologia , Canal de Cátion TRPA1/metabolismo
18.
ACS Macro Lett ; : 252-259, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334272

RESUMO

Unnatural polysaccharide analogs and their biological activities and material properties have attracted considerable research interest. However, these efforts often encounter challenges, especially those related to synthetic complexity and scalability. Here, we report the chemical synthesis of unnatural (1→6)-polysaccharides using levoglucosenone (LGO) and dihydrolevoglucosenone (Cyrene), which are derived from cellulose. Using a versatile monomer synthesis from LGO and Cyrene and cationic ring-opening polymerization, (1→6)-polysaccharides with various tailored substituent patterns are obtained. Additionally, environmentally benign and easy-to-handle organic Brønsted acid catalysts are investigated. This study demonstrates well-controlled first-order polymerization kinetics for the reactive (1S,5R)-6,8-dioxabicyclo[3,2,1]octane (DBO) monomer. The synthesized (1→6)-polysaccharides exhibit high thermal stability and form amorphous solids under ambient conditions, which could be processed into highly transparent self-standing films. Additionally, these polymers exhibit excellent closed-loop chemical recyclability. This study provides an important approach to explore the chemical spaces of unnatural polysaccharides and contributes to the development of sustainable polymer materials from abundant biomass resources.

19.
Inorg Chem ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355102

RESUMO

Upgrading ethanol to n-butanol as biofuels is an important topic for sustainable chemistry. Herein, a Cp*Ir complex bearing a functional 2,2'-carbonylbibenzimidazole ligand [Cp*Ir(2,2'-COBiBzImH2)Cl][Cl] was designed and synthesized. In the presence of a catalyst (0.1 mol %) and Cs2CO3 (6 mol %), the highest yield of updated n-butanol is up to 37% with 80% selectivity. NH units in the ligand are crucially important for the catalytic activity of the iridium complex.

20.
Respir Res ; 25(1): 67, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317146

RESUMO

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Humanos , Animais , Camundongos , MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pulmão/metabolismo , Envelhecimento , Fibroblastos/metabolismo , Senescência Celular/genética , Fator 1 de Resposta a Butirato/metabolismo
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