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1.
J Anesth ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581580

RESUMO

PURPOSE: Present study was designed to investigate the association between muscular tissue desaturation and acute kidney injury (AKI) in older patients undergoing major abdominal surgery. METHOD: A total of 253 patients (≥ 65 years old) who underwent abdominal surgery with expected duration ≥ 2 h were enrolled. Muscular tissue oxygen saturation (SmtO2) was monitored at quadriceps and bilateral flanks during surgery. Muscular desaturation was defined as SmtO2 < 90% baseline lasting for > 60 s. The primary outcome was the incidence of AKI within postoperative 7 days. The association between muscular desaturation and AKI was analyzed by multivariable logistic regression model. The secondary outcomes indicated the other complications within postoperative 30 days. RESULTS: Among 236 patients, 44 (18.6%) of them developed AKI. The incidence of muscular desaturation at quadriceps was 28.8% (68/236). Patients with muscular desaturation had higher incidence of AKI than those without desaturation (27.9% [19/68], vs. 14.9% [25/168], P = 0.020). After adjustment of confounders, multivariable analysis showed that muscular desaturation at quadriceps was significantly associated with an increased risk of AKI (OR = 2.84, 95% CI 1.21-6.67, P = 0.016). Muscular desaturations at left and right flank were also associated with an increased risk of AKI (OR = 6.38, 95% CI 1.78-22.89, P = 0.004; OR = 8.90, 95% CI 1.42-45.63; P = 0.019, respectively). Furthermore, patients with muscular desaturation may have a higher risk of pulmonary complications, sepsis and stroke at 30-day follow-up. CONCLUSION: Muscular desaturation was associated with postoperative AKI in older patients undergoing major abdominal surgery which may serve as a predictor of AKI.

2.
Arthritis Res Ther ; 26(1): 71, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493104

RESUMO

OBJECTIVE: Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms. METHODS: TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1ß was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo. RESULTS: TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration. CONCLUSION: Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.


Assuntos
Osteoartrite , Humanos , Osteoartrite/metabolismo , Cartilagem/metabolismo , Inflamação/patologia , Condrócitos/metabolismo , DNA Mitocondrial , RNA Interferente Pequeno/metabolismo
3.
Nat Commun ; 15(1): 1888, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424092

RESUMO

Stacking order plays a crucial role in determining the crystal symmetry and has significant impacts on electronic, optical, magnetic, and topological properties. Electron-phonon coupling, which is central to a wide range of intriguing quantum phenomena, is expected to be intricately connected with stacking order. Understanding the stacking order-dependent electron-phonon coupling is essential for understanding peculiar physical phenomena associated with electron-phonon coupling, such as superconductivity and charge density waves. In this study, we investigate the effect of stacking order on electron-infrared phonon coupling in graphene trilayers. By using gate-tunable Raman spectroscopy and excitation frequency-dependent near-field infrared nanoscopy, we show that rhombohedral ABC-stacked trilayer graphene has a significant electron-infrared phonon coupling strength. Our findings provide novel insights into the superconductivity and other fundamental physical properties of rhombohedral ABC-stacked trilayer graphene, and can enable nondestructive and high-throughput imaging of trilayer graphene stacking order using Raman scattering.

4.
Acta Biochim Biophys Sin (Shanghai) ; 56(3): 356-365, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38419499

RESUMO

Currently, platinum agents remain the mainstay of chemotherapy for ovarian cancer (OC). However, cisplatin (DDP) resistance is a major reason for chemotherapy failure. Thus, it is extremely important to elucidate the mechanism of resistance to DDP. Here, we establish two DDP-resistant ovarian cancer cell lines and find that caseinolytic protease P (CLPP) level is significantly downregulated in DDP-resistant cell lines compared to wild-type ovarian cancer cell lines (SK-OV-3 and OVcar3). Next, we investigate the functions of CLPP in DDP-resistant and wild-type ovarian cancer cells using various assays, including cell counting kit-8 assay, western blot analysis, immunofluorescence staining, and detection of reactive oxygen species (ROS) and apoptosis. Our results show that CLPP knockdown significantly increases the half maximal inhibitory concentration (IC 50) and mitophagy of wild-type SK-OV-3 and OVcar3 cells, while CLPP overexpression reduces the IC 50 values and mitophagy of DDP-resistant SK-OV-3 and OVcar3 cells. Next, we perform database predictions and confirmation experiments, which show that heat shock protein family A member 8 (HSPA8) regulates CLPP protein stability. The dynamic effects of the HSPA8/CLPP axis in ovarian cancer cells are also examined. HSPA8 increases mitophagy and the IC 50 values of SK-OV-3 and OVcar3 cells but inhibits their ROS production and apoptosis. In addition, CLPP partly reverses the effects induced by HSPA8 in SK-OV-3 and OVcar3 cells. In conclusion, CLPP increases DDP resistance in ovarian cancer by inhibiting mitophagy and promoting cellular stress. Meanwhile, HSPA8 promotes the degradation of CLPP protein by regulating its stability.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Endopeptidase Clp , Proteínas de Choque Térmico HSC70/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
5.
Clin Oral Investig ; 28(3): 172, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400913

RESUMO

OBJECTIVES: To investigate the clinical outcomes of endodontic microsurgery in complicated cases presenting with large or through-and-through lesions. MATERIALS AND METHODS: We retrospectively collected and analyzed preoperative, intraoperative, and follow-up data from 143 complicated cases that underwent endodontic microsurgery. Clinical outcomes were assessed in terms of tooth survival and surgery success. Cox regression analysis was used to evaluate the survival rate and identify associated risk factors. Additionally, the success rate was compared across different postoperative periods, and potential factors contributing to surgical failure were identified through binary logistic regression. RESULTS: The overall survival and success rates were 93.0% and 91.7%, respectively. The Cox regression model identified four risk factors affecting tooth survival, including apicoectomy of four teeth (HR = 35.488; P = 0.0002), an open apex observed on preoperative radiographs (HR = 6.300; P = 0.025), the performance of guided tissue regeneration technique (HR = 8.846; P = 0.028), and a palatal surgical approach (HR = 8.685; P = 0.030). The success rate demonstrated an initial increase in the early postoperative period (from 0.5 to 2 years; P = 5.8124e-30), followed by stabilization (from 2 to 9 years; P = 0.298). Surgery success rate significantly declined when apicoectomy involved four teeth (OR = 109.412; P = 0.002). CONCLUSIONS: Endodontic microsurgery demonstrates satisfactory outcomes in complicated cases, maintaining a stable success rate after two years. However, tooth survival and surgery success are significantly compromised when apicoectomy involves four teeth. Factors such as guided tissue regeneration, an open apex, and the palatal surgical approach are associated with an increased risk of tooth extraction. CLINICAL RELEVANCE: Despite achieving acceptable outcomes in complicated cases, endodontic microsurgery is adversely affected by the apicoectomy of four teeth.


Assuntos
Apicectomia , Microcirurgia , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Resultado do Tratamento , Microcirurgia/métodos , Apicectomia/métodos
6.
Chem Commun (Camb) ; 60(12): 1634-1637, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38234223

RESUMO

Li- and Mn-rich layered oxides (LMLOs) are regarded as the most promising cathode materials for Li-ion batteries (LIBs), but they suffer from poor rate capability. Herein, a promising and practical method (i.e. a hydroxide coprecipitation method in combination with a microwave heating process) is developed to controllably synthesize cobalt-free Li[Li0.2Ni0.2Mn0.6]O2 with a layered/spinel heterostructure (LLNMO-LS). The cathode made of the LLNMO-LS delivers an excellent electrochemical performance, demonstrating a discharge capacity of 147 mA h g-1 at 10C.

7.
Nat Mater ; 23(4): 506-511, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38191633

RESUMO

Surface plasmon polaritons and phonon polaritons offer a means of surpassing the diffraction limit of conventional optics and facilitate efficient energy storage, local field enhancement and highsensitivity sensing, benefiting from their subwavelength confinement of light. Unfortunately, losses severely limit the propagation decay length, thus restricting the practical use of polaritons. While optimizing the fabrication technique can help circumvent the scattering loss of imperfect structures, the intrinsic absorption channel leading to heat production cannot be eliminated. Here, we utilize synthetic optical excitation of complex frequency with virtual gain, synthesized by combining the measurements made at multiple real frequencies, to compensate losses in the propagations of phonon polaritons with dramatically enhanced propagation distance. The concept of synthetic complex frequency excitation represents a viable solution to the loss problem for various applications including photonic circuits, waveguiding and plasmonic/phononic structured illumination microscopy.

8.
J Environ Sci (China) ; 139: 364-376, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105062

RESUMO

Dissolved organic matter (DOM) and iron minerals widely existing in the natural aquatic environment can mediate the migration and transformation of organic pollutants. However, the mechanism of interaction between DOM and iron minerals in the microbial degradation of pollutants deserves further investigation. In this study, the mechanism of 17 alpha-ethinylestradiol (EE2) biodegradation mediated by humic acid (HA) and three kinds of iron minerals (goethite, magnetite, and pyrite) was investigated. The results found that HA and iron minerals significantly accelerated the biodegradation process of EE2, and the highest degradation efficiency of EE2 (48%) was observed in the HA-mediated microbial system with pyrite under aerobic conditions. Furthermore, it had been demonstrated that hydroxyl radicals (HO•) was the main active substance responsible for the microbial degradation of EE2. HO• is primarily generated through the reaction between hydrogen peroxide secreted by microorganisms and Fe(II), with aerobic conditions being more conducive. The presence of iron minerals and HA could change the microbial communities in the EE2 biodegradation system. These findings provide new information for exploring the migration and transformation of pollutants by microorganisms in iron-rich environments.


Assuntos
Matéria Orgânica Dissolvida , Poluentes Ambientais , Ferro , Minerais , Substâncias Húmicas , Etinilestradiol/análise , Oxirredução
9.
J Endod ; 50(1): 96-105, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37890613

RESUMO

Nonsurgical endodontic teeth treatment with severe pulp canal obliteration poses challenges, primarily locating canals. By combining 3-dimensional reconstruction and spatial location registration, the dynamic navigation technique uses an optical tracking system to guide the clinician to drill in real time according to the predesigned path until access to the canal is established. Several in vitro studies and case reports have shown that calcified canal location with dynamic navigation system (DNS) is more accurate and efficient, yet the technique has limitations. In 4 cases with 7 teeth, this work presents manipulation process and clinical outcomes of DNS helping in calcified canal location. We performed handpiece adaptation and elucidated the failure to locate the canals with DNS in 2 teeth, resulting in canal geometry alteration and canal path deviation. Subsequently, the more experienced endodontist located the canals by combining cone-beam computed tomographic imaging and dental operating microscopy. All patients were completely asymptomatic after treatment. At the 1-year follow-up visit, the bone healing of periapical lesions progressed well according to the periapical radiography or cone-beam computed tomographic imaging. These findings indicate that DNS is a promising technique for locating calcified canals; however, it needs to be refined before clinical use.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Cavidade Pulpar , Humanos , Cavidade Pulpar/diagnóstico por imagem , Cavidade Pulpar/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Molar , Assistência Odontológica , Tratamento do Canal Radicular
10.
Nanoscale ; 15(46): 18858-18863, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37966341

RESUMO

Structural reconstruction of electrocatalysts to generate metal hydroxide/oxyhydroxide species is critical for an efficient oxygen evolution reaction (OER), but the controllable regulation of the reconstruction process still remains a challenge. Given the designable nature of metal-organic frameworks (MOFs), herein, we have reported a localized structure disordering strategy to accelerate the structural reconstruction of Ni-BDC to generate NiOOH for boosting the OER. The Ni-BDC nanosheets were modified by Fe3+ and urea to form cracks, which could promote the accessibility of the Ni sites by the electrolyte and thus promote the reconstruction to form NiOOH. In addition, the interaction between Ni2+ and Fe3+ allows the electron flow from Ni2+ to Fe3+, further enhancing the NiOOH generation. As a result, the optimized sample exhibits excellent OER activity with a small overpotential of 251 mV at 10 mA cm-2, which is superior to most of the MOF-based OER catalysts reported previously. This work provides a controllable strategy to regulate the structural reconstruction for promoting the OER, which could provide important guidance for the development of more efficient OER electrocatalysts.

11.
Ying Yong Sheng Tai Xue Bao ; 34(11): 3127-3134, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997424

RESUMO

We investigated the responses of community structure of soil arthropods to yak and Tibetan sheep grazing based on a manipulated grazing experiment at the alpine meadow livestock Adaptive Management Platform, which locates in Haiyan County, Qinghai Province. The results showed that the obtained soil arthropods belonged to 26 families, 8 orders, and 4 classes, with Acaroidae and Oribatida as the dominant groups. Yak and Tibetan sheep grazing decreased the abundance but increased Shannon index, Margalef index and Pielou index of soil arthropods. Yak grazing significantly increased the quantity of the predatory soil arthropod groups. Yak and Tibetan sheep gra-zing significantly increased the quantity of the detritivore soil arthropod groups, but did not affect the quantity of the omnivorous and phytophagous soil arthropod groups. Yak and Tibetan sheep grazing significantly reduced the abundance of soil mites. Soil bulk density, available potassium, and available nitrogen were the main abiotic factors affecting soil arthropods community composition.


Assuntos
Artrópodes , Humanos , Animais , Bovinos , Ovinos , Tibet , Pradaria , Solo/química , China
12.
Immunobiology ; 228(6): 152765, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38029515

RESUMO

BACKGROUND: Mesenchymal stromal cells (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and hemorrhagic shock (THS)-induced ALI. METHODS: ALI model induced by THS was constructed by fractures plus abdominal trauma plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 106 ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated. RESULTS: Administration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1ß, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue. CONCLUSION: Our data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Choque Hemorrágico , Ratos , Animais , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/terapia , Pulmão/patologia , Células-Tronco Mesenquimais/metabolismo , Anti-Inflamatórios , RNA Mensageiro
13.
Adv Mater ; : e2308481, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902720

RESUMO

In this study, perovskite oxides La0.3 Ca0.6 Ni0.05 Mnx Ti0.95- x O3- γ (x = 0, 0.05, 0.10) are investigated as potential solid oxide electrolysis cell cathode materials. The catalytic activity of these cathodes toward CO2 reduction reaction is significantly enhanced through the exsolution of highly active Ni nanoparticles, driven by applying a current of 1.2 A in 97% CO2 - 3% H2 O. The performance of La0.3 Ca0.6 Ni0.05 Ti0.95 O3-γ is notably improved by co-doping with Mn. Mn dopants enhance the reducibility of Ni, a crucial factor in promoting the in situ exsolution of metallic nanocatalysts in perovskite (ABO3 ) structures. This improvement is attributed to Mn dopants enabling more flexible coordination, resulting in higher oxygen vacancy concentration, and facilitating oxygen ion migration. Consequently, a higher density of Ni nanoparticles is formed. These oxygen vacancies also improve the adsorption, desorption, and dissociation of CO2 molecules. The dual doping strategy provides enhanced performance without degradation observed after 133 h of high-temperature operation, suggesting a reliable cathode material for CO2 electrolysis.

14.
Acta Biochim Pol ; 70(4): 865-873, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37883680

RESUMO

BACKGROUND: Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. METHODS: (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. RESULTS: The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. CONCLUSION: Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.


Assuntos
Anestesia , Delírio , Humanos , Idoso , Ratos , Masculino , Animais , Camundongos , Lactente , Delírio/epidemiologia , Delírio/etiologia , Delírio/psicologia , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Encéfalo , Anestesia/efeitos adversos , Ubiquitina-Proteína Ligases
15.
Front Neurol ; 14: 1162168, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840941

RESUMO

Background: Upper limb function reconstruction has been an important issue in the field of stroke rehabilitation. Due to the complexity of upper extremity dysfunction in stroke patients, the clinical efficacy produced by central or peripheral stimulation alone is limited. For this reason, our group has proposed acupuncture synchronized rehabilitation therapy (ASRT), i.e., simultaneous scalp acupuncture and intradermal acupuncture during rehabilitation. Pre-experiments results showed that this therapy can effectively improve the motor and sensory functions of upper limbs in post-stroke patients, but the clinical efficacy and safety of ASRT need to be further verified, and whether there is a synergistic effect between scalp acupuncture and intradermal acupuncture also needs to be studied in depth. Therefore, we designed a randomized controlled trial to compare the efficacy and safety of different therapies to explore a more scientific "synchronous treatment model." Methods: This is a single-center, randomized controlled trial using a 2 × 2 factorial design. We will recruit 136 stroke survivors with upper extremity dysfunction and randomize them into four groups (n = 34). All subjects will undergo routine treatment, based on which the Experimental Group 1: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb; Experimental Group 2: rehabilitation training of the affected upper limb synchronized with focal-side scalp acupuncture treatment, and Experimental Group 3: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb synchronized with focal-side scalp acupuncture treatment; Control Group: rehabilitation training of the affected upper limb only. The intervention will last for 4 weeks, 5 times a week. Both acupuncture treatments will be performed according to the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The primary outcome indicators for this trial are Fugl-Meyer Assessment-Upper Extremity and Somatosensory Evoked Potential. Secondary outcome indicators include Wolf Motor Function Test, Upper Extremity Function Test, revised Nottingham Sensory Assessment Scale, Diffusion Tensor Imaging, and Modified Barthel Index. The incidence of adverse events will be used as the indicator of safety. Discussion: The study will provide high-quality clinical evidence on whether ASRT improves upper limb motor and sensory function and activities of daily living (ADL) in stroke patients, and determine whether scalp acupuncture and intradermal acupuncture have synergistic effects. Clinical trial registration: https://www.chictr.org.cn/, Chinese Clinical Trial Registry [ChiCTR2200066646].

16.
Mol Biol Rep ; 50(11): 9249-9261, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37812357

RESUMO

Paraquat (PQ) is a widely used and highly toxic pesticide that is often actively ingested and causes pulmonary fibrosis in patients. Ferroptosis is a regulated form of non-apoptotic cell death associated with iron-dependent lipid peroxidation. Previous studies have shown that ferroptosis is involved in the occurrence and development of acute lung injury (ALI). In this study, a model rat with inflammatory response, oxidative stress, lipid peroxidation, and pulmonary fibrosis was successfully established by PQ administration. The occurrence of ferroptosis in PQ model rats was confirmed by TUNEL staining, iron ion detection, and Ferroptosis related biomarkers detection. Western blotting (WB) and real-time PCR (RT-PCR) showed that the expression of Keap1 was significantly up-regulated and the expression of Nrf2 was significantly down-regulated in the lung tissue of PQ rats. Further transcriptomics and proteomics confirmed: (1) Enrichment of molecular processes related to iron ion binding; (2) Keap1 may promote Nrf2 ubiquitination and lead to Nrf2 degradation; (3) There is functional enrichment in ferroptosis related pathways. Our results suggest that PQ can regulate Keap1/Nrf2 signaling pathway, leading to increased lipid peroxidation and abnormal iron uptake, thereby inducing iron death and exacerbating the progression of pulmonary fibrosis. Our study provides new insights into PQ-induced pulmonary fibrosis.


Assuntos
Ferroptose , Fibrose Pulmonar , Humanos , Ratos , Animais , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Transdução de Sinais , Ferro/metabolismo
17.
Biomed Chromatogr ; 37(12): e5751, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37772369

RESUMO

In order to facilitate therapeutic drug monitoring of tacrolimus and cyclosporine A in clinical practice, a simple, rapid, robust, sensitive and specific LC-MS/MS assay was developed and validated for the simultaneous determination of tacrolimus and cyclosporine A in human whole blood. Erythrocytes were destroyed using internal standard solution with 10% (w/v) zinc sulfate in water. The analytes were extracted from 100 µl of whole blood by protein precipitation with acetonitrile. Chromatographic separation was conducted on a Kinetex PFP column (60°C) by a gradient elution with a flow rate of 0.450 ml/min in 2.5 min. Quantitative analysis was performed using electrospray ionization and multiple reaction monitoring in positive ionization mode. The method was fully validated as per current guidelines on bioanalytical methodologies of the US Food and Drug Administration and European Medicines Agency. The method developed was applied successfully in analyzing clinical samples from patients administered tacrolimus or cyclosporine A. The sample treatment procedure was rationalized and improved to fulfill the complete target extraction. The chromatography conditions were optimized to achieve rapid and accurate quantification of both analytes. This method may be beneficial as a constructive input for the therapeutic drug monitoring of tacrolimus and cyclosporine A in obtaining individualized therapy.


Assuntos
Ciclosporina , Tacrolimo , Humanos , Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos
18.
ACS Nano ; 17(18): 18616-18628, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37713681

RESUMO

P2-type layered transition-metal (TM) oxides, NaxTMO2, are highly promising as cathode materials for sodium-ion batteries (SIBs) due to their excellent rate capability and affordability. However, P2-type NaxTMO2 is afflicted by issues such as Na+/vacancy ordering and multiple phase transitions during Na-extraction/insertion, leading to staircase-like voltage profiles. In this study, we employ a combination of high Na content and Li dual-site substitution strategies to enhance the structural stability of a P2-type layered oxide (Na0.80Li0.024[Li0.065Ni0.22Mn0.66]O2). The experimental results reveal that these approaches facilitate the oxidation of Mn ions to a higher valence state, thereby affecting the local environment of both TM and Na ions. The resulting modification in the local structure significantly improves the Na-ion storage capabilities as required for cathode materials in SIBs. Furthermore, it induces a solid-solution reaction and enables nearly zero-strain operation (ΔV = 0.7%) in the Na0.80Li0.024[Li0.065Ni0.22Mn0.66]O2 cathode during cycling. The assembled full cells demonstrate an exceptional rate performance, with a retention rate of 87% at 10 C compared to that of 0.1 C, as well as an ultrastable cycling capability, maintaining a capacity retention of 73% at 2 C after 1000 cycles. These findings offer valuable insights into the electronic and structural chemistry of ultrastable cathode materials with "zero-strain" Na-ion storage.

19.
Front Microbiol ; 14: 1257521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744903

RESUMO

Grazing by local livestock is the traditional human practice in Qinghai-Tibetan Plateau grassland, and moderate intensity grazing can maintain high productivity and diversity of alpine grassland. Grazing ecosystems are often nitrogen-limited, but N2-fixing communities in response to yak grazing and Tibetan sheep grazing in Qinghai-Tibetan Plateau grassland have remained underexplored. In this study, we applied quantitative PCR quantitation and MiSeq sequencing of nifH under yak grazing and Tibetan grazing through a manipulated grazing experiment on an alpine grassland. The results showed that the grazing treatments significantly increased the soil ammonium nitrogen (AN) and total phosphorus (TP), but reduced the diazotrophs abundance. Compared with no grazing treatment, the composition of diazotrophs could be maximally maintained when the ratio of yak and Tibetan sheep were 1:2. The foraging strategies of grazing livestock reduced the legumes biomass, and thus reduced the diazotrophs abundance. Data analysis suggested that the direct key factors in regulating diazotrophs are AN and TP, and the changes of these two soil chemical properties were affected by the dung and urine of herbivore assemblages. Overall, these results indicated that the mixed grazing with a ratio of yak to Tibetan sheep as 1:2 can stabilize the soil diazotrophsic community, suggesting that MG12 are more reasonable grazing regimes in this region.

20.
J Fungi (Basel) ; 9(9)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37755057

RESUMO

In grassland ecosystems, the occurrence and transmission of foliar fungal diseases are largely dependent on grazing by large herbivores. However, whether herbivores that have different body sizes differentially impact foliar fungal diseases remains largely unexplored. Thus, we conducted an 8-year grazing experiment in an alpine grassland on the Qinghai-Tibet Plateau in China and tested how different types of livestock (sheep (Ovis aries), yak (Bos grunniens), or both)) affected foliar fungal diseases at the levels of both plant population and community. At the population level, grazing by a single species (yak or sheep) or mixed species (sheep and yak) significantly decreased the severity of eight leaf spot diseases. Similarly, at the community level, both single species (yak or sheep) and mixed grazing by both sheep and yak significantly decreased the community pathogen load. However, we did not find a significant difference in the community pathogen load among different types of livestock. These results suggest that grazing by large herbivores, independently of livestock type, consistently decreased the prevalence of foliar fungal diseases at both the plant population and community levels. We suggest that moderate grazing by sheep or yak is effective to control the occurrence of foliar fungal diseases in alpine grasslands. This study advances our knowledge of the interface between disease ecology, large herbivores, and grassland science.

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