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1.
Artigo em Inglês | MEDLINE | ID: mdl-38578382

RESUMO

Oxidative stress and apoptosis play crucial roles in myocardial ischemia‒reperfusion injury (MIRI). In this study, we investigated the role of circ_0073932 in MIRI as well as its molecular mechanism. A hypoxia/reoxygenation (H/R) cardiomyocyte model was established with H9C2 cardiomyocytes, and RT-qPCR was used to measure gene expression. We observed that circ_0073932 expression was abnormally increased in the H/R cardiomyocyte model and in blood samples from MIRI patients. Inhibition of circ_0073932 suppressed H/R-induced cell apoptosis, oxidative stress (ROS, LDH and MDA), and p-JNK expression. Dual luciferase reporter assays showed that circ_0073932 targeted the downregulation of miR-493-3p, and miR-493-3p targeted the downregulation of FAF1. Furthermore, si-circ_0073932, an miR-493-3p inhibitor, oe-FAF1, or si-FAF1 were transfected into H9C2 cardiomyocytes to investigate the roles of these factors in MIRI. Our results showed that compared with the H/R group, si-circ_0073932 inhibited H/R-induced cell apoptosis, oxidative stress (ROS, LDH and MDA), and p-JNK expression. These results were reversed by the miR-493-3p inhibitor or oe-FAF1. Finally, a rat model of MIRI was established, and si-circ_0073932 was administered. Inhibition of circ_0073932 reduced the area of myocardial infarction and decreased the levels of apoptosis and oxidative stress by inhibiting the JNK signaling pathway. Our study indicated that circ_0073932 mediates MIRI via miR-493-3p/FAF1/JNK in vivo and in vitro, revealing novel insights into the pathogenesis of MIRI and providing a new target for the clinical treatment of MIRI.

2.
Nat Commun ; 15(1): 3017, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589414

RESUMO

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

3.
FASEB J ; 38(7): e23534, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38597911

RESUMO

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.


Assuntos
Sistema de Sinalização das MAP Quinases , Osteonectina , Animais , Camundongos , Osteonectina/genética , Transdução de Sinais , Divisão Celular Assimétrica , Diferenciação Celular
4.
Nanoscale ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602354

RESUMO

High-throughput biofluid metabolomics analysis for screening life-threatening diseases is urgently needed. However, the high salt content of biofluid samples, which introduces severe interference, can greatly limit the analysis throughput. Here, a new 3-D interconnected hierarchical superstructure, namely a "plasmonic gold-on-silica (Au/SiO2) double-layered aerogel", integrating distinctive features of an upper plasmonic gold aerogel with a lower inert silica aerogel was successfully developed to achieve in situ separation and storage of inorganic salts in the silica aerogel, parallel enrichment of metabolites on the surface of the functionalized gold aerogel, and direct desorption/ionization of enriched metabolites by the photo-excited gold aerogel for rapid, sensitive, and comprehensive metabolomics analysis of human serum/urine samples. By integrating all these unique advantages into the hierarchical aerogel, multifunctional properties were introduced in the SALDI substrate to enable its effective utilization in clinical metabolomics for the discovery of reliable metabolic biomarkers to achieve unambiguous differentiation of early and advanced-stage lung cancer patients from healthy individuals. This study provides insight into the design and application of superstructured nanomaterials for in situ separation, storage, and photoexcitation of multi-components in complex biofluid samples for sensitive analysis.

5.
Heliyon ; 10(6): e27701, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38515659

RESUMO

Countries face exasperating and inclement climate worldwide. Food and feed security could be their paramount life objective. The study aimed to investigate the impact of selenium on the protein content and distribution in different parts of rice. For this purpose, advanced selenium biofortified breeding material developed after generations of breeding efforts was investigated at the field area, rice research institute, Chengdu, China during cropping season 2021-22. The accumulation and distribution of selenium and protein contents were observed in various fractions of selenium-enriched rice (Z3057B) and positive control (727). The correlation studies for selenium and protein quantification leads to the optimization of the breeding material and relevance in virtue. The rice fractions indicated rice embryo retains highest selenium contents, which gradually decreases in succession (other rice parts). The difference in protein content between the embryo and endosperm of Se-enriched rice is significant, while that between embryo and aleurone layer is not obvious. The selenium protein was found with molecular weight of 13.6-122.6 kDa. The protein of each molecular weight is found to bind with selenium, but the binding strength of selenium is negatively correlated with the molecular weight of protein. The 67.5% of the total selenium sticks with protein having molecular weight less than 38.8 kDa. In summary, protein with low molecular weight (13.4 kDa) binds maximum selenium and accounts for highest total protein content (40.76%).

7.
Nat Mater ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491148

RESUMO

The conventional fabrication of bulk van der Waals (vdW) materials requires a temperature above 1,000 °C to sinter from the corresponding particulates. Here we report the near-room-temperature densification (for example, ∼45 °C for 10 min) of two-dimensional nanosheets to form strong bulk materials with a porosity of <0.1%, which are mechanically stronger than the conventionally made ones. The mechanistic study shows that the water-mediated activation of van der Waals interactions accounts for the strong and dense bulk materials. Initially, water adsorbed on two-dimensional nanosheets lubricates and promotes alignment. The subsequent extrusion closes the gaps between the aligned nanosheets and densifies them into strong bulk materials. Water extrusion also generates stresses that increase with moulding temperature, and too high a temperature causes intersheet misalignment; therefore, a near-room-temperature moulding process is favoured. This technique provides an energy-efficient alternative to design a wide range of dense bulk van der Waals materials with tailored compositions and properties.

8.
Front Cardiovasc Med ; 11: 1324345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476381

RESUMO

Objective: Cell division cycle 42 (CDC42) regulates CD4+ T-cell differentiation and participates in vascular stiffness and atherosclerosis and is involved in the progression of Stanford type B aortic dissection (TBAD). This study aimed to explore the correlation between serum CDC42 level and CD4+ T cell subsets and in-hospital mortality in TBAD patients. Methods: Serum CDC42 and peripheral blood T-helper (Th) 1, Th2, and Th17 cells were detected in 127 TBAD patients by enzyme-linked immunosorbent assay and flow cytometry, respectively. Serum CDC42 was also quantified in 30 healthy controls. Results: Serum CDC42 was decreased in TBAD patients vs. healthy controls (median [interquartile range (IQR)]: 418.0 (228.0-761.0) pg/ml vs. 992.0 (716.3-1,445.8) pg/ml, P < 0.001). In TBAD patients, serum CDC42 was negatively correlated with Th17 cells (P = 0.001), but not Th1 (P = 0.130) or Th2 cells (P = 0.098). Seven (5.5%) patients experienced in-hospital mortality. Serum CDC42 was reduced in patients who experienced in-hospital mortality vs. those who did not (median (IQR): 191.0 (145.0-345.0) pg/ml vs. 451.5 (298.3-766.8) pg/ml, P = 0.006). By receiver operating characteristic analysis, serum CDC42 showed a good ability for estimating in-hospital mortality [area under curve = 0.809, 95% confidence interval (CI) = 0.662-0.956]. By the multivariate logistic regression analysis, elevated serum CDC42 [odd ratio (OR) = 0.994, 95% CI = 0.998-1.000, P = 0.043] was independently correlated with lower risk of in-hospital mortality, while higher age (OR = 1.157, 95% CI = 1.017-1.316, P = 0.027) was an independent factor for increased risk of in-hospital mortality. Conclusion: Serum CDC42 negatively associates with Th17 cells and is independently correlated with decreased in-hospital mortality risk in TBAD patients.

9.
ACS Appl Mater Interfaces ; 16(10): 12321-12331, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38431875

RESUMO

Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.


Assuntos
Hemostáticos , Polifenóis , Hemostáticos/farmacologia , Hemostáticos/química , Microesferas , Hemostasia , Antibacterianos/farmacologia , Antibacterianos/química , Géis/farmacologia , Amido/química
11.
Proc Natl Acad Sci U S A ; 121(11): e2316544121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442155

RESUMO

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.


Assuntos
Vesículas Extracelulares , MicroRNAs , Células Satélites de Músculo Esquelético , Fibras Musculares Esqueléticas , Comunicação , MicroRNAs/genética , Regeneração/genética
12.
Nature ; 628(8008): 515-521, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509374

RESUMO

The convergence of topology and correlations represents a highly coveted realm in the pursuit of new quantum states of matter1. Introducing electron correlations to a quantum spin Hall (QSH) insulator can lead to the emergence of a fractional topological insulator and other exotic time-reversal-symmetric topological order2-8, not possible in quantum Hall and Chern insulator systems. Here we report a new dual QSH insulator within the intrinsic monolayer crystal of TaIrTe4, arising from the interplay of its single-particle topology and density-tuned electron correlations. At charge neutrality, monolayer TaIrTe4 demonstrates the QSH insulator, manifesting enhanced nonlocal transport and quantized helical edge conductance. After introducing electrons from charge neutrality, TaIrTe4 shows metallic behaviour in only a small range of charge densities but quickly goes into a new insulating state, entirely unexpected on the basis of the single-particle band structure of TaIrTe4. This insulating state could arise from a strong electronic instability near the van Hove singularities, probably leading to a charge density wave (CDW). Remarkably, within this correlated insulating gap, we observe a resurgence of the QSH state. The observation of helical edge conduction in a CDW gap could bridge spin physics and charge orders. The discovery of a dual QSH insulator introduces a new method for creating topological flat minibands through CDW superlattices, which offer a promising platform for exploring time-reversal-symmetric fractional phases and electromagnetism2-4,9,10.

13.
Zhen Ci Yan Jiu ; 49(2): 103-109, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38413030

RESUMO

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.


Assuntos
Pontos de Acupuntura , Eletroacupuntura , Ratos , Animais , Ratos Sprague-Dawley , Ratos Wistar , Dor , Neurônios , Inflamação/terapia , Analgésicos/efeitos adversos , Medula Espinal
14.
Cardiovasc Diabetol ; 23(1): 67, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350936

RESUMO

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.


Assuntos
Insuficiência Cardíaca , Hiperglicemia , Humanos , Prognóstico , Volume Sistólico , Biomarcadores , Hiperglicemia/diagnóstico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos
15.
Ageing Res Rev ; 96: 102248, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408490

RESUMO

Temporal lobe epilepsy (TLE) is the most common form of epileptic syndrome. It has been established that due to its complex pathogenesis, a considerable proportion of TLE patients often progress to drug-resistant epilepsy. Ferroptosis has emerged as an important neuronal death mechanism in TLE, which is primarily influenced by lipid accumulation and oxidative stress. In previous studies of ferroptosis, more attention has been focused on the impact of changes in the levels of proteins related to the redox equilibrium and signaling pathways on epileptic seizures. However, it is worth noting that the oxidative-reduction changes in different organelles may have different pathophysiological significance in the process of ferroptosis-related diseases. Mitochondria, as a key organelle involved in ferroptosis, its structural damage and functional impairment can lead to energy metabolism disorders and disruption of the excitatory inhibitory balance, significantly increasing the susceptibility to epileptic seizures. Therefore, secondary mitochondrial dysfunction in the process of ferroptosis could play a crucial role in TLE pathogenesis. This review focuses on ferroptosis and mitochondria, discussing the pathogenic role of ferroptosis-related mitochondrial dysfunction in TLE, thus aiming to provide novel insights and potential implications of ferroptosis-related secondary mitochondrial dysfunction in epileptic seizures and to offer new insights for the precise exploration of ferroptosis-related therapeutic targets for TLE patients.


Assuntos
Epilepsia do Lobo Temporal , Ferroptose , Doenças Mitocondriais , Humanos , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Convulsões/complicações , Convulsões/metabolismo , Convulsões/patologia , Mitocôndrias/metabolismo , Doenças Mitocondriais/complicações , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia
16.
J Integr Med ; 22(1): 32-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38310025

RESUMO

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.


Assuntos
Recuperação de Oócitos , Dor Pós-Operatória , Estimulação Elétrica Nervosa Transcutânea , Humanos , Pontos de Acupuntura , Recuperação de Oócitos/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Feminino
17.
ACS Synth Biol ; 13(3): 958-962, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377571

RESUMO

Lanthanides, a series of 15 f-block elements, are crucial in modern technology, and their purification by conventional chemical means comes at a significant environmental cost. Synthetic biology offers promising solutions. However, progress in developing synthetic biology approaches is bottlenecked because it is challenging to measure lanthanide binding with current biochemical tools. Here we introduce LanTERN, a lanthanide-responsive fluorescent protein. LanTERN was designed based on GCaMP, a genetically encoded calcium indicator that couples the ion binding of four EF hand motifs to increased GFP fluorescence. We engineered eight mutations across the parent construct's four EF hand motifs to switch specificity from calcium to lanthanides. The resulting protein, LanTERN, directly converts the binding of 10 measured lanthanides to 14-fold or greater increased fluorescence. LanTERN development opens new avenues for creating improved lanthanide-binding proteins and biosensing systems.


Assuntos
Elementos da Série dos Lantanídeos , Elementos da Série dos Lantanídeos/metabolismo , Cálcio/metabolismo , Proteínas
18.
Bioorg Chem ; 145: 107222, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401359

RESUMO

Ubiquitination is a representative post-translational modification that tags target proteins with ubiquitin to induce protein degradation or modify their functions. Deubiquitinating enzymes (DUBs) play a crucial role in reversing this process by removing ubiquitin from target proteins. Among them, USP2a has emerged as a promising target for cancer therapy due to its oncogenic properties in various cancer types, but its inhibitors have been limited. In this study, our aim was to optimize the structure of ML364, a USP2a inhibitor, and synthesize a series of its derivatives to develop potent USP2a inhibitors. Compound 8v emerged as a potential USP2a inhibitor with lower cytotoxicity compared to ML364. Cellular assays demonstrated that compound 8v effectively reduced the levels of USP2a substrates and attenuated cancer cell growth. We confirmed its direct interaction with the catalytic domain of USP2a and its selective inhibitory activity against USP2a over other USP subfamily proteins (USP7, 8, or 15). In conclusion, compound 8v has been identified as a potent USP2a inhibitor with substantial potential for cancer therapy.


Assuntos
Endopeptidases , Ubiquitina , Endopeptidases/química , Proteólise , Ubiquitina/metabolismo , Ubiquitinação
19.
BMC Cardiovasc Disord ; 24(1): 85, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310248

RESUMO

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , 60589 , Veias Pulmonares/cirurgia , Pontuação de Propensão , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Hemorragia/etiologia , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações
20.
Angew Chem Int Ed Engl ; 63(12): e202318461, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38302835

RESUMO

Photocatalytic selective oxidation under visible light presents a promising approach for the sustainable transformation of biomass-derived wastes. However, achieving both high conversion and excellent selectivity poses a significant challenge. In this study, two valuable trioses, glyceraldehyde and dihydroxyacetone, are produced from glycerol over Cuδ+ -decorated WO3 photocatalyst in the presence of H2 O2 . The photocatalyst exhibits a remarkable five-fold increase in the conversion rate (3.81 mmol ⋅ g-1 ⋅ h-1 ) while maintaining a high selectivity towards two trioses (46.4 % to glyceraldehyde and 32.9 % to dihydroxyacetone). Through a comprehensive analysis involving X-ray photoelectron spectroscopy measurements with and without light irradiation, electron spin resonance spectroscopy, and isotopic analysis, the critical role of Cu+ species has been explored as efficient hole acceptors. These species facilitate charge transfer, promoting glycerol oxidation by photoholes, followed by coupling with OH- , which are subsequently dehydrated to yield the desired glyceraldehyde and dihydroxyacetone.

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