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1.
PLoS One ; 19(6): e0305670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913637

RESUMO

PURPOSE: To compare the risk of developing subsequent primary lung cancer among cervical cancer patients and the general population. METHODS: Several databases were searched from inception to April 25, 2023. The standard incidence ratios (SIRs) with 95% confidence intervals (CIs) were combined to identify the risk for second primary lung cancer after cervical carcinoma. Subgroup analyses based on the follow-up period, age, degree of malignancy and source of SIR were conducted. All the statistical analyses were performed with STATA 15.0 software. RESULTS: A total of 22 retrospective studies involving 864,627 participants were included. The pooled results demonstrated that cervical cancer patients had a significantly greater risk for lung cancer than did the general population (SIR = 2.63, 95% CI: 2.37-2.91, P<0.001). Furthermore, subgroup analyses stratified by follow-up period (<5 years and ≥5 years), age (≤50 years and <50 years), and degree of malignancy (invasive and in situ) also revealed an increased risk of developing lung cancer among cervical carcinoma patients. CONCLUSION: Cervical cancer patients are more likely to develop subsequent primary lung cancer than the general population, regardless of age, follow-up time or degree of malignancy. However, more high-quality prospective studies are still needed to verify our findings.


Assuntos
Neoplasias Pulmonares , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Feminino , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Segunda Neoplasia Primária/epidemiologia , Incidência , Estudos Retrospectivos , Adulto , Idoso
2.
Nat Commun ; 15(1): 4365, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778052

RESUMO

Biotic-abiotic hybrid photocatalytic system is an innovative strategy to capture solar energy. Diversifying solar energy conversion products and balancing photoelectron generation and transduction are critical to unravel the potential of hybrid photocatalysis. Here, we harvest solar energy in a dual mode for Cu2-xSe nanoparticles biomineralization and seawater desalination by integrating the merits of Shewanella oneidensis MR-1 and biogenic nanoparticles. Photoelectrons generated by extracellular Se0 nanoparticles power Cu2-xSe synthesis through two pathways that either cross the outer membrane to activate periplasmic Cu(II) reduction or are directly delivered into the extracellular space for Cu(I) evolution. Meanwhile, photoelectrons drive periplasmic Cu(II) reduction by reversing MtrABC complexes in S. oneidensis. Moreover, the unique photothermal feature of the as-prepared Cu2-xSe nanoparticles, the natural hydrophilicity, and the linking properties of bacterium offer a convenient way to tailor photothermal membranes for solar water production. This study provides a paradigm for balancing the source and sink of photoelectrons and diversifying solar energy conversion products in biotic-abiotic hybrid platforms.


Assuntos
Biomineralização , Cobre , Água do Mar , Shewanella , Energia Solar , Shewanella/metabolismo , Cobre/química , Cobre/metabolismo , Água do Mar/microbiologia , Água do Mar/química , Salinidade , Purificação da Água/métodos , Nanopartículas/química , Catálise/efeitos da radiação
3.
ACS Nano ; 18(10): 7334-7345, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38421637

RESUMO

All-solid-state batteries (ASSBs) working at room and mild temperature have demonstrated inspiring performances over recent years. However, the kinetic attributes of the interface applicable to the subzero temperatures are still unidentified, restricting the low-temperature interface design and operation. Herein, a host of cathode interfaces are constructed and investigated to unlock the critical interface features required for cryogenic temperatures. The unstable interface between LiNi0.90Co0.05Mn0.05O2 (Ni90) and Li6PS5Cl (LPSC) sulfide solid electrolyte (SE) results in unfavorable cathode-electrolyte interphase (CEI) and sluggish lithium-ion transport across the CEI. After inserting a Li2ZrO3 (LZO) coating layer, the activation energy of the Ni90@LZO/sulfide SE interface can be reduced from 60.19 kJ mol-1 to 41.39 kJ mol-1 owing to the suppressed interfacial reactions. Through replacing the LPSC SE and LZO coating layer by the Li3InCl6 (LIC) halide SE, both a highly stable interface and low activation energy (25.79 kJ mol-1) can be achieved, thus realizing an improved capacity retention (26.9%) at -30 °C for the Ni90/LIC/LPSC/Li-In ASSB. Moreover, theoretical evaluation clarifies that cathode/SE interfaces with high ionic conductivity and low energy barrier are favorable to the Li+ conduction through the interphase and the Li+ transfer across the cathode/interphase interface. These critical understandings may provide guidance for low-temperature interface design in ASSBs.

4.
Environ Sci Technol ; 58(6): 2598-2614, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38291652

RESUMO

The widespread application of nanotechnology inevitably leads to an increased release of engineered nanoparticles (ENPs) into the environment. Due to their specific physicochemical properties, ENPs may interact with other contaminants and exert combined effects on the microbial community and metabolism of anaerobic digestion (AD), an important process for organic waste reduction, stabilization, and bioenergy recovery. However, the complicated interactions between ENPs and other contaminants as well as their combined effects on AD are often overlooked. This review therefore focuses on the co-occurrence of ENPs and cocontaminants in the AD process. The key interactions between ENPs and cocontaminants and their combined influences on AD are summarized from the available literature, including the critical mechanisms and influencing factors. Some sulfides, coagulants, and chelating agents have a dramatic "detoxification" effect on the inhibition effect of ENPs on AD. However, some antibiotics and surfactants increase the inhibition of ENPs on AD. The reasons for these differences may be related to the interactive effects between ENPs and cocontaminants, changes of key enzyme activities, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS) production, and microbial communities. New scientific opportunities for a better understanding of the coexistence in real world situations are converging on the scale of nanoparticles.


Assuntos
Nanopartículas , Anaerobiose , Nanopartículas/química , Nanotecnologia , Espécies Reativas de Oxigênio
5.
Nat Commun ; 15(1): 939, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296941

RESUMO

Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C-H bonds are unreactive towards electrophiles due to their extremely low acidity (pKa ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the α-amino C-H bonds by up to 1044 times. This makes the α-amino C-H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric α-C-H alkylation of NH2-unprotected primary alkyl amines with allylic carbonates has been achieved. This reaction produces a wide range of chiral homoallylic amines with high enantiopurities. The approach has successfully switched the reactivity between primary alkyl amines and allylic carbonates from intrinsic allylic amination to the α-C-H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38109220

RESUMO

Building two-dimensional (2D) and three-dimensional (3D) micro- and nanofibril structures with designable patterns and functionalities will offer exciting prospects for numerous applications spanning from permeable bioelectronics to tissue engineering scaffolds. This Spotlight on Applications highlights recent technological advances in fiber printing and patterning with functional materials for biointerfacing applications. We first introduce the current state of development of micro- and nanofibers with applications in biology and medical wearables. We then describe our contributions in developing a series of fiber printing techniques that enable the patterning of functional fiber architectures in three dimensions. These fiber printing techniques expand the material library and device designs, which underpin technological capabilities from enabling fundamental studies in cell migration to customizable and ecofriendly fabrication of sensors. Finally, we provide an outlook on the strategic pathways for developing the next-generation bioelectronics and "Fiber-of-Things" (FoT) using nano/micro-fibers as architectural building blocks.

7.
Sci Adv ; 9(45): eadi3245, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37948518

RESUMO

Graph neural networks (GNNs) have recently been used to learn the representations of crystal structures through an end-to-end data-driven approach. However, a systematic top-down approach to evaluate and understand the limitations of GNNs in accurately capturing crystal structures has yet to be established. In this study, we introduce an approach using human-designed descriptors as a compendium of human knowledge to investigate the extent to which GNNs can comprehend crystal structures. Our findings reveal that current state-of-the-art GNNs fall short in accurately capturing the periodicity of crystal structures. We analyze this failure by exploring three aspects: local expressive power, long-range information processing, and readout function. To address these identified limitations, we propose a straightforward and general solution: the hybridization of descriptors with GNNs, which directly supplements the missing information to GNNs. The hybridization enhances the predictive accuracy of GNNs for specific material properties, most notably phonon internal energy and heat capacity, which heavily rely on the periodicity of materials.

8.
Cell Death Discov ; 9(1): 206, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391426

RESUMO

Glioma-associated macrophages (GAMs) are pivotal chains in the tumor immune microenvironment (TIME). GAMs mostly display M2-like phenotypes with anti-inflammatory features related to the malignancy and progression of cancers. Extracellular vesicles derived from immunosuppressive GAMs (M2-EVs), the essential components of the TIME, greatly impact the malignant behavior of GBM cells. M1- or M2-EVs were isolated in vitro, and human GBM cell invasion and migration were reinforced under M2-EV treatment. Signatures of the epithelial-mesenchymal transition (EMT) were also enhanced by M2-EVs. Compared with M1-EVs, miR-146a-5p, considered the key factor in TIME regulation, was deficient in M2-EVs according to miRNA-sequencing. When the miR-146a-5p mimic was added, EMT signatures and the invasive and migratory abilities of GBM cells were correspondingly weakened. Public databases predicted the miRNA binding targets and interleukin 1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were screened as miR-146a-5p binding genes. Bimolecular fluorescent complementation and coimmunoprecipitation confirmed interactions between TRAF6 and IRAK1. The correlation between TRAF6 and IRAK1 was evaluated with immunofluorescence (IF)-stained clinical glioma samples. The TRAF6-IRAK1 complex is the switch and the brake that modulates IKK complex phosphorylation and NF-κB pathway activation, as well as the EMT behaviors of GBM cells. Furthermore, a homograft nude mouse model was explored and mice transplanted with TRAF6/IRAK1-overexpressing glioma cells had shorter survival times while mice transplanted with glioma cells with miR-146a-5p overexpression or TRAF6/IRAK1 knockdown lived longer. This work indicated that in the TIME of GBM, the deficiency of miR-146a-5p in M2-EVs enhances tumor EMT through disinhibition of the TRAF6-IRAK1 complex and IKK-dependent NF-κB signaling pathway providing a novel therapeutic strategy targeting the TIME of GBM.

9.
Water Res ; 237: 119979, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37098286

RESUMO

The conventional oxidation-adsorption methods are effective for the removal of roxarsone (ROX) but are limited by complicated operation, toxic residual oxidant and leaching of toxic metal ions. Herein, we proposed a new approach to improve ROX removal, i.e., using the FeS/sulfite system. Experimental results showed that approximately 100% of ROX (20 mg/L) was removed and more than 90% of the released inorganic arsenic (As(V) dominated) was adsorbed on FeS within 40 min. This FeS/sulfite system was a non-homogeneous activation process, and SO4·-, ·OH and 1O2 were identified as reactive oxidizing species with their contributions to ROX degradation being 48.36%, 27.97% and 2.64%, respectively. Based on density functional theory calculations and HPLC-MS results, the degradation of ROX was achieved by C-As breaking, electrophilic addition, hydroxylation and denitrification. It was also found that the released inorganic arsenic was adsorbed through a combination of outer-sphere complexation and surface co-precipitation, and the generated arsenopyrite (FeAsS), a precursor to ecologically secure scorodite (FeAsO4·2H2O), was served as the foundation for further inorganic arsenic mineralization. This is the first attempt to use the FeS/sulfite system for organic heavy metal removal, which proposes a prospective technique for the removal of ROX.


Assuntos
Arsênio , Roxarsona , Adsorção , Estudos Prospectivos , Oxirredução
10.
Front Surg ; 10: 1039615, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36865627

RESUMO

Objective: To compare the clinicopathological features and perioperative outcomes of video-assisted mediastinoscopy esophagectomy (VAME) compared to video-assisted thoracoscopy esophagectomy (VATE) in esophageal cancer. Methods: We comprehensively searched online databases (PubMed, Embase, Web of Science and Wiley online library) to find available studies exploring the clinicopathological features and perioperative outcomes between VAME and VATE in esophageal cancer. Relative risk (RR) with 95% confidence interval (CI) and standardized mean difference (SMD) with 95% CI were used to evaluate the perioperative outcomes and clinicopathological features. Results: A total of seven observational studies and one randomized controlled trial involving 733 patients were considered eligible for this meta-analysis, of which 350 patients underwent VAME in contrast to 383 patients underwent VATE. Patients in the VAME group had more pulmonary comorbidities (RR = 2.18, 95% CI 1.37-3.46, P = 0.001). The pooled results showed that VAME shortened the operation time (SMD = -1.53, 95% CI -2.308--0.76, P = 0.000), and retrieved less total lymph nodes (SMD = -0.70, 95% CI -0.90--0.50, P = 0.000). No differences were observed in other clinicopathological features, postoperative complications or mortality. Conclusions: This meta-analysis revealed that patients in the VAME group had more pulmonary disease before surgery. The VAME approach significantly shortened the operation time and retrieved less total lymph nodes and did not increase intra- or postoperative complications.

12.
Brain Sci ; 13(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36831773

RESUMO

Multi-omics expression datasets obtained from multiple public databases were used to elucidate the biological function of TK1 and its effects on clinical outcomes. The Kaplan-Meier curve, a predictive nomogram mode, and the time-dependent receiver operating characteristic (ROC) curve were established to assess the role of TK1 expression in glioma prognosis. TK1 was overexpressed in glioma compared with normal samples, and patients with elevated expression of TK1 had poor overall survival. The ROC curves indicated a high diagnostic value of TK1 expression in patients of glioma; the areas under the ROC curve (AUC) were 0.682, 0.735, and 0.758 for 1 year, 3 years, and 5 years of glioma survival, respectively. For a model based on TK1 expression and other clinical characteristics, the values of AUC were 0.864, 0.896, and 0.898 for 1 year, 3 years, and 5 years, respectively. Additionally, the calibration curve indicated that the predicted and observed areas at 1 year, 3 years, and 5 years of survival were in excellent agreement. Three types of TK1 alterations-missense mutations, splice mutations, and amplifications-were identified in 25 of 2706 glioma samples. The TK1-altered group had better overall survival than the unaltered group. Single-cell function analysis showed that TK1 was positively associated with proliferation, the cell cycle, DNA repair, DNA damage, and epithelial-mesenchymal transition in glioma. Immunoinfiltration analysis indicated that TK1 expression might play different roles in low-grade glioma and glioblastoma multiforme tumor microenvironments, but TK1 expression was positively associated with activated CD4 and Th2, regardless of tumor grade. In summary, our findings identified TK1 as a novel marker for predicting clinical outcomes and a potential target for glioma.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 292: 122394, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36736047

RESUMO

Reliable origin certification methods are essential for the protection of high-value genuine medicinal material with designated origins and geographical indication (GI) products. Aconiti Lateralis Radix Praeparata (Fuzi), one well-known traditional Chinese medicine and geographical indication products have remarkable efficacy and wide clinical application, with high demand in domestic and international markets. The efficacy and price of Fuzi from different origins vary, and it is difficult for the general public to accurately identify them through traditional experience. The mass spectrometry detection technology based on the plant metabolomics is tedious and lengthy in test sample preparation, complicated in operation, long in detection time, and low in reproducibility. As a sophisticated, green, fast, and low-loss detection technique, infrared spectroscopy is integrated by machine learning to bring new ways for quality regulation and control of traditional Chinese medicines. An analytical method based on mid-infrared spectroscopy combined with a random forest algorithm was developed to verify the geographical origin of authentic herbs and/or GI products. The method successfully predicted and classified three varieties of Chinese GI Fuzi and four varieties of non-GI Fuzi. In this study, an environment-friendly traceability strategy with fast analysis, low sample loss and high precision was used to provide a new strategy for identifying the origin of Fuzi.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Reprodutibilidade dos Testes , Algoritmo Florestas Aleatórias , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Aconitum/química , Análise Espectral
14.
ACS Nano ; 17(5): 4999-5013, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36812031

RESUMO

Laser reduction of polymers has recently been explored to rapidly and inexpensively synthesize high-quality graphitic and carbonaceous materials. However, in past work, laser-induced graphene has been restricted to semiaromatic polymers and graphene oxide; in particular, poly(acrylonitrile) (PAN) is claimed to be a polymer that cannot be laser-reduced successfully to form electrochemically active material. In this work, three strategies to surmount this barrier are employed: (1) thermal stabilization of PAN to increase its sp2 content for improved laser processability, (2) prelaser treatment microstructuring to reduce the effects of thermal stresses, and (3) Bayesian optimization to search the parameter space of laser processing to improve performance and discover morphologies. Based on these approaches, we successfully synthesize laser-reduced PAN with a low sheet resistance (6.5 Ω sq-1) in a single lasing step. The resulting materials are tested electrochemically, and their applicability as membrane electrodes for vanadium redox flow batteries is demonstrated. This work demonstrates electrodes that are processed in air, below 300 °C, which are cycled stably over 2 weeks at 40 mA cm-2, motivating further development of laser reduction of porous polymers for membrane electrode applications such as RFBs.

15.
Signal Transduct Target Ther ; 8(1): 82, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36828823

RESUMO

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose/metabolismo , Tuberculose/microbiologia , Mycobacterium tuberculosis/metabolismo , Splicing de RNA , Macrófagos/metabolismo , Biomarcadores , Enzimas de Conjugação de Ubiquitina/metabolismo , Cinesinas/metabolismo , Fatores de Processamento de Serina-Arginina
16.
Anal Bioanal Chem ; 415(2): 345-356, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36350342

RESUMO

Bear bile powder (BBP) is one of the most famous traditional Chinese medicines derived from animals. It has a long history of medicinal use and is widely used in the treatment of hepatobiliary and ophthalmic diseases. Due to its similar morphological characterizations and chemical composition compared with other bile powders, it is difficult to accurately identify its authenticity. In addition, there are very few methods that could analyze the geographical origins of BBP. In this study, elemental analysis isotope ratio mass spectrometry (EA-IRMS) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine stable isotope ratios and elemental contents, respectively. Combined these variables with chemometrics, the discrimination models were established successfully for identifying the authenticity and geographical origins of BBP. Meanwhile, the discrimination markers were identified by calculating the variable importance for the projection (VIP) value of each variable. A total of 13 discrimination markers (δ13C, δ15N, C, Li, Mg, K, Ca, Cr, Ni, Zn, As, Se, and Sr) were used to further establish the fingerprint of BBP. According to similarity analysis, the authenticity and geographical origins of BBP could be identified without chemometrics. In conclusion, the present study established a reliable method for authenticity identification and origin traceability of BBP, which will provide references for the quality control of bile medicines.


Assuntos
Ursidae , Animais , Pós , Bile , Isótopos/química , Espectrometria de Massas/métodos
17.
Stem Cells ; 41(1): 77-92, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36208284

RESUMO

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.


Assuntos
Proteínas de Membrana , Células-Tronco Neurais , Humanos , Proteínas de Membrana/genética , Hipóxia Celular , Hipóxia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Autofagia , Células-Tronco Neurais/metabolismo , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
18.
Mol Pharmacol ; 103(3): 188-198, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36456191

RESUMO

A dopamine D2 receptor mutation was recently identified in a family with a novel hyperkinetic movement disorder. That allelic variant D2-I212F is a constitutively active and G protein-biased receptor. We now describe mice engineered using CRISPR-Cas9-mediated gene editing technology to carry the D2-I212F variant. Drd2I212F mice exhibited gait abnormalities resembling those in other mouse models of chorea and/or dystonia and had striatal D2 receptor expression that was decreased approximately 30% per Drd2I212F allele. Electrically evoked inhibitory postsynaptic conductances in midbrain dopamine neurons and striatum from Drd2I212F mice, caused by G protein activation of potassium channels, exhibited slow kinetics (e.g., approximately four- to sixfold slower decay) compared with Drd2 +/+ mice. Current decay initiated by photolytic release of the D2 antagonist sulpiride from CyHQ-sulpiride was also ∼fourfold slower in midbrain slices from Drd2I212F mice than Drd2 +/+ mice. Furthermore, in contrast to Drd2 +/+ mice, in which dopamine is several-fold more potent at neurons in the nucleus accumbens than in the dorsal striatum, reflecting activation of Gα o versus Gα i, dopamine had similar potencies in those two brain regions of Drd2I212F mice. Repeated cocaine treatment, which decreases dopamine potency in the nucleus accumbens of Drd2 +/+ mice, had no effect on dopamine potency in Drd2 I212F mice. The results demonstrate the pathogenicity of the D2-I212F mutation and the utility of this mouse model for investigating the role of pathogenic DRD2 variants in early-onset hyperkinetic movement disorders. SIGNIFICANCE STATEMENT: The first dopamine receptor mutation to cause a movement disorder, D2-I212F, was recently identified. The mutation makes receptor activation of G protein-mediated signaling more efficient. To confirm the pathogenesis of D2-I212F, this study reports that mice carrying this mutation have gait abnormalities consistent with the clinical phenotype. The mutation also profoundly alters D2 receptor expression and function in vivo. This mouse model will be useful for further characterization of the mutant receptor and for evaluation of potential therapeutic drugs.


Assuntos
Dopamina , Transtornos dos Movimentos , Receptores de Dopamina D2 , Animais , Humanos , Camundongos , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Marcha/genética , Hipercinese , Mutação , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Sulpirida
19.
Cell Death Dis ; 13(11): 966, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396625

RESUMO

Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.


Assuntos
Hipóxia , Mitofagia , Humanos , Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Mitofagia/fisiologia , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo
20.
Materials (Basel) ; 15(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36363192

RESUMO

In this paper, a series of eutectic hydrated salts was obtained by mixing Na2HPO4·12H2O (DHPD) with K2HPO4·3H2O (DHPT) in different proportions. With the increase in the content of DHPT, the phase transition temperature and melting enthalpy of eutectic hydrated salts decreased gradually. Moreover, the addition of appropriate deionized water improved the thermal properties of eutectic hydrated salts. Colloidal silicon dioxide (SiO2) was selected as the support carrier to adsorb eutectic hydrated salts, and the maximum content of eutectic hydrated salts in composite PCMs was 70%. When the content of the nucleating agent (Na2SiO3·9H2O) was 5%, the supercooling degree of composite PCMs was reduced to the minimum of 1.2 °C. The SEM and FT-IR test results showed that SiO2 and eutectic hydrated salts were successfully combined, and no new substances were formed. When the content of DHPT was 3%, the phase transition temperature and melting enthalpy of composite PCMs were 26.5 °C and 145.3 J/g, respectively. The results of thermogravimetric analysis and heating-cooling cycling test proved that composite PCMs had good thermal reliability and stability. The application performance of composite PCMs in prefabricated temporary houses was investigated numerically. The results indicated that PCM panels greatly increased the Grade I thermal comfort hours and reduced energy consumption. Overall, the composite PCM has great development potential building energy conservation.

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