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1.
Br J Haematol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613241

RESUMO

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

2.
Aging Med (Milton) ; 7(1): 90-95, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38571677

RESUMO

Aging is an extremely intricate and progressive phenomenon that is implicated in many physiological and pathological conditions. Icariin (ICA) is the main active ingredient of Epimedium and has exhibited multiple bioactivities, such as anti-tumor, neuroprotective, antioxidant, anti-inflammatory, and anti-aging properties. ICA could extend healthspan in both invertebrate and vertebrate models. In this review, the roles of ICA in protection from declined reproductive function, neurodegeneration, osteoporosis, aging intestinal microecology, and senescence of cardiovascular system will be summarized. Furthermore, the underlying mechanisms of ICA-mediated anti-aging effects will be introduced. Finally, we will discuss some key aspects that constrain the usage of ICA in clinical practice and the corresponding strategies to solve these issues.

3.
Sci Rep ; 14(1): 7847, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570595

RESUMO

Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a "Bi-directional feature extraction and fusion module" and a "Purification module for feature channel and space" based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.


Assuntos
Aprendizado Profundo , Neoplasias Gástricas , Humanos , Gastroscopia , Neoplasias Gástricas/diagnóstico por imagem , Gastroscópios
5.
J Agric Food Chem ; 72(13): 7010-7020, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38529524

RESUMO

Cyetpyrafen is a recently developed acaricide. The citrus red mite, Panonychus citri (McGregor), has developed significant resistance to cyetpyrafen. However, the molecular mechanism underlying the cyetpyrafen resistance in P. citri remains unclear. Glutathione S-transferases (GSTs) play a critical role in arthropod pesticide resistance. This study showed that GSTs were potentially related to the resistance of P. citri to cyetpyrafen through synergistic experiments and enzyme activity analysis. An omega-family GST gene, PcGSTO1, was significantly up-regulated in the egg, nymph, and adult stages of the cyetpyrafen-resistant strain. Additionally, silencing of PcGSTO1 significantly increased the mortality of P. citri to cyetpyrafen and recombinant PcGSTO1 demonstrated the ability to metabolize cyetpyrafen. Our results indicated that the overexpression of PcGSTO1 is associated with cyetpyrafen resistance in P. citri, and they also provided valuable information for managing resistance in P. citri.


Assuntos
Acaricidas , Tetranychidae , Animais , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Tetranychidae/genética , Tetranychidae/metabolismo , Acaricidas/farmacologia , Acaricidas/metabolismo
6.
Int J Nanomedicine ; 19: 2553-2571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505171

RESUMO

Purpose: Accumulating evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes hold significant potential for the treatment of atherosclerosis. However, large-scale production and organ-specific targeting of exosomes are still challenges for further clinical applications. This study aims to explore the targeted efficiency and therapeutic potential of biomimetic platelet membrane-coated exosome-mimetic nanovesicles (P-ENVs) in atherosclerosis. Methods: To produce exosome-mimetic nanovesicles (ENVs), MSCs were successively extruded through polycarbonate porous membranes. P-ENVs were engineered by fusing MSC-derived ENVs with platelet membranes and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. The stability and safety of P-ENVs were also assessed. The targeted efficacy of P-ENVs was evaluated using an in vivo imaging system (IVIS) spectrum imaging system and immunofluorescence. Histological analyses, Oil Red O (ORO) staining, and Western blot were used to investigate the anti-atherosclerotic effectiveness of P-ENVs. Results: Both ENVs and P-ENVs exhibited similar characteristics to exosomes. Subsequent miRNA sequencing of P-ENVs revealed their potential to mitigate atherosclerosis by influencing biological processes related to cholesterol metabolism. In an ApoE-/- mice model, the intravenous administration of P-ENVs exhibited enhanced targeting of atherosclerotic plaques, resulting in a significant reduction in lipid deposition and necrotic core area. Our in vitro experiments showed that P-ENVs promoted cholesterol efflux and reduced total cholesterol content in foam cells. Further analysis revealed that P-ENVs attenuated intracellular cholesterol accumulation by upregulating the expression of the critical cholesterol transporters ABCA1 and ABCG1. Conclusion: This study highlighted the potential of P-ENVs as a novel nano-drug delivery platform for enhancing drug delivery efficiency while concurrently mitigating adverse reactions in atherosclerotic therapy.


Assuntos
Aterosclerose , Exossomos , Células-Tronco Mesenquimais , Camundongos , Animais , Exossomos/metabolismo , Biomimética , Fusão de Membrana , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Colesterol/metabolismo , Células-Tronco Mesenquimais/metabolismo
7.
Fa Yi Xue Za Zhi ; 40(1): 30-36, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500458

RESUMO

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.


Assuntos
Espectrometria de Massas em Tandem , Água , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Formiatos , Extração em Fase Sólida/métodos
8.
Fa Yi Xue Za Zhi ; 40(1): 37-42, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500459

RESUMO

OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.


Assuntos
3,4-Metilenodioxianfetamina , Anfetaminas , N-Metil-3,4-Metilenodioxianfetamina , Ratos , Animais , Anfetamina , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , 3,4-Metilenodioxianfetamina/análise , Toxicocinética , Solução Salina
9.
Heliyon ; 10(5): e27166, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449604

RESUMO

Platelets play a pivotal role in many physiological and pathological processes, with their special targeting/adhering properties towards infarcted myocardium, injured or dysfunctional endothelium, and growing thrombus. Leveraging the site-targeting/adhering property, a variety of platelet-inspired targeting delivery(PITD)designs have been developed, the majority of which are reached by hitchhiking live platelets, cloaking nanoparticles with platelet membranes and mimicking platelet functions. With PITD, drugs or regenerative cells can directly reach targeted sites with minimized systematical distribution thus being of great clinical benefits. Coronary heart disease (CHD) is a major health burden worldwide. Plenty of PITD designs have shown promising outcomes for the treatment of CHD in preclinical models, especially in thrombolysis and post-percutaneous coronary intervention (post-PCI) anti-restenosis. Besides, PITD applications in cardiac protection and atherosclerotic plaque imaging are also under investigation. What's more, the potential benefits of PITD in the field of cell-based therapy are also attracting growing attention since it may resolve the problem of low arriving and retention efficiency, which are also particularly discussed in this review. In brief, our focus is putting on PITD strategies designed for the treatment of CHD, which hopefully can facilitate further optimization of this direction.

10.
Appl Environ Microbiol ; 90(3): e0211023, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38391210

RESUMO

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.


Assuntos
Nostoc , Raios Ultravioleta , Humanos , Biomassa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Nostoc/metabolismo , Fotossíntese/fisiologia
11.
Phys Rev Lett ; 132(4): 040404, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335337

RESUMO

We consider the preparation of matrix product states (MPS) on quantum devices via quantum circuits of local gates. We first prove that faithfully preparing translation-invariant normal MPS of N sites requires a circuit depth T=Ω(logN). We then introduce an algorithm based on the renormalization-group transformation to prepare normal MPS with an error ε in depth T=O[log(N/ε)], which is optimal. We also show that measurement and feedback leads to an exponential speedup of the algorithm to T=O[loglog(N/ε)]. Measurements also allow one to prepare arbitrary translation-invariant MPS, including long-range non-normal ones, in the same depth. Finally, the algorithm naturally extends to inhomogeneous MPS.

12.
Cochrane Database Syst Rev ; 2: CD007859, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319008

RESUMO

BACKGROUND: Initial arch wires are the first arch wires inserted into fixed appliance at the beginning of orthodontic treatment. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which are most efficient and which cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is the third update of a Cochrane review first published in 2010. OBJECTIVES: To assess the effects of initial arch wires for the alignment of teeth with fixed orthodontic braces, in terms of the rate of tooth alignment, amount of root resorption accompanying tooth movement, and intensity of pain experienced by patients during the initial alignment stage of treatment. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, Embase, and two ongoing trials registries on 4 July 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of different initial arch wires used to align teeth with fixed orthodontic braces. We included people with full-arch fixed orthodontic appliances on the upper arch, lower arch, or both arches. DATA COLLECTION AND ANALYSIS: Two independent review authors were responsible for study selection, data extraction, and assessment of risk of bias in included studies. We contacted corresponding authors of included studies to obtain missing information. We resolved disagreements by discussion between the review authors. Our main outcomes were alignment rate (movement of teeth in mm), root resorption, time to alignment, and intensity of pain measured on a 100-mm visual analogue scale (VAS). We pooled data from studies with similar interventions and outcomes using random-effects models. We reported mean differences (MDs) with 95% confidence intervals (CIs) for continuous data, risk ratios (RRs) with 95% CIs for dichotomous data, and alignment rate ratios with 95% CIs for time-to-event data. Two independent review authors assessed the certainty of evidence. We resolved disagreements by discussion between the review authors. MAIN RESULTS: We included 29 RCTs with 1915 participants (2581 arches) in this review. Studies were generally small (sample sizes ranged from 14 to 200 participants). Duration of follow-up varied between three days and six months. Eleven studies received funding, six received no funding, and 12 provided no information about funding sources. We judged eight studies at high risk of bias, nine at low risk, and 12 at unclear risk. We grouped the studies into six main comparisons. Multistrand stainless steel wires versus wires composed of other materials Six studies with 409 participants (545 arches) evaluated multistrand stainless steel (StSt) wires versus wires composed of other materials. We are very uncertain about the effect of multistrand StSt wires versus other wires on alignment rate (4 studies, 281 participants, 417 arches; very low-certainty evidence). There may be little to no difference between multistrand StSt wires and other wires in terms of intensity of pain (MD -2.68 mm, 95% CI -6.75 to 1.38; 2 studies, 127 participants, 127 arches; low-certainty evidence). Conventional nickel-titanium wires versus superelastic nickel-titanium wires Four studies with 266 participants (274 arches) evaluated conventional nickel-titanium (NiTi) wires versus superelastic NiTi wires. There may be little to no difference between the different wire types in terms of alignment rate (124 participants, 124 arches, 2 studies; low-certainty evidence) and intensity of pain (MD -0.29 mm, 95% CI -1.10 to 0.52; 2 studies, 142 participants, 150 arches; low-certainty evidence). Conventional nickel-titanium wires versus thermoelastic copper-nickel-titanium wires Three studies with 210 participants (210 arches) evaluated conventional Ni-Ti versus thermoelastic copper-nickel-titanium (CuNiTi) wires. We are very uncertain about the effects of the different arch wires on alignment rate (1 study, 66 participants, 66 arches; very low-certainty evidence). There may be little to no difference between conventional NiTi wires and thermoelastic CuNiTi wires in terms of time to alignment (alignment rate ratio 1.30, 95% CI 0.68 to 2.50; 1 study, 60 participants, 60 arches; low-certainty evidence). Superelastic nickel-titanium wires versus thermoelastic nickel-titanium wires Twelve studies with 703 participants (936 arches) evaluated superelastic NiTi versus thermoelastic NiTi wires. There may be little to no difference between superelastic NiTi wires and thermoelastic NiTi wires in alignment rate at four weeks (MD -0.28 mm, 95% CI 0.62 to 0.06; 5 studies, 183 participants, 183 arches; low-certainty evidence). We are very uncertain about the effects of the different wires on root resorption (2 studies, 52 participants, 312 teeth; very low-certainty evidence). Superelastic NiTi wires compared with thermoelastic NiTi wires may result in a slight increase in time to alignment (MD 0.5 months, 95% CI 0.21 to 0.79; 1 study, 32 participants, 32 arches; low-certainty evidence) but are probably associated with a slight increase in intensity of pain (MD 6.96 mm, 95% CI 1.82 to 12.10; 3 studies, 94 participants, 138 arches, moderate-certainty evidence). Single-strand superelastic nickel-titanium wires versus coaxial superelastic nickel-titanium wires Three studies with 104 participants (104 arches) evaluated single-strand superelastic NiTi versus coaxial superelastic NiTi wires. Use of single-strand superelastic NiTi wires compared with coaxial superelastic NiTi wires probably results in a slight reduction in alignment rate at four weeks (MD -2.64 mm, 95% CI -4.61 to -0.67; 2 studies, 64 participants, 64 arches, moderate-certainty evidence). Different sizes of nickel-titanium wires Two studies with 149 participants (232 arches) compared different types of NiTi wires. There may be little to no difference between different sizes of NiTi wires in terms of pain (low-certainty evidence). AUTHORS' CONCLUSIONS: Superelastic NiTi wires probably produce slightly more pain after one day than thermoelastic NiTi wires, and single-strand superelastic NiTi wires probably have a lower alignment rate over four weeks compared with coaxial superelastic NiTi wires. All other evidence on alignment rate, root resorption, time to alignment, and pain is of low or very low certainty in all comparisons. Therefore, there is insufficient evidence to determine whether any particular arch wire material or size is superior to any other. The findings of this review are imprecise and unreliable; well-designed larger studies are needed to give better estimates of the benefits and harms of different arch wires. Orthodontists should exercise caution when interpreting the findings of this review and be prepared to adapt their treatment plans based on individual patient needs.


Assuntos
Ligas , Braquetes Ortodônticos , Reabsorção da Raiz , Humanos , Níquel , Titânio , Reabsorção da Raiz/etiologia , Aço Inoxidável , Cobre , Braquetes Ortodônticos/efeitos adversos , Dor
13.
Transl Res ; 269: 64-75, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38395391

RESUMO

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

14.
Heliyon ; 10(3): e24802, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318059

RESUMO

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients' clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85-160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3-4.5) days. The median hospitalization expense for these patients was 3848 (3781-4145) USD. The median number of lymph node yielded was 10.5 (8-15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

15.
ACS Appl Mater Interfaces ; 16(8): 10398-10406, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38380978

RESUMO

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

16.
Front Nutr ; 11: 1327164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379541

RESUMO

Amomum villosum Lour. (A. villosum), known as Sharen in China, is widely used for culinary and medicinal purposes due to containing a diverse set of bioactive compounds. In this study, the optimum ethanol extraction process was optimized and the composition and biological activities (antioxidant and antitumor) of five different fractions (dichloromethane, petroleum ether, ethyl acetate, n-butanol and H2O) extracted from the ethanol extract of A. villosum were investigated. The results showed that the optimal extraction conditions were extraction temperature 80°C, extraction time 120 min, ethanol concentration 40% and solid-liquid ratio 1:25 g/mL. Moreover, 35 bioactive compounds were successfully identified by UPLC-ESI-QTOF-MS/MS from five factions for the first time, including 12 phenolic acids and derivatives, 2 organic acids, 12 flavonoids and derivatives, 2 oxylipins and 7 proanthocyanidins. Among them, ethyl acetate fraction (Fr-EtOAc) exhibited the highest content of total phenolic (374.01 mg GAE/g DW) and flavonoid (93.11 mg RE/g DW), where vanillic acid, catechin, epicatechin and protocatechuic acid were the predominant phenolic compounds that accounting for 81.65% of the quantified bioactive compounds. In addition, Fr-EtOAc demonstrated excellent total antioxidant activity (IC50 of DPPH and ABTS assays were 0.23, 0.08 mg/mL, respectively, and FRAP assay was 322.91 mg VCE/100 g DW) and antitumor activity (1,000 µg/mL, 79.04% inhibition rate). The results could provide guidance for the industrial production and application of A. villosum.

17.
Cell Mol Life Sci ; 81(1): 88, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349408

RESUMO

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.


Assuntos
Fibrilação Atrial , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas de Transporte/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , Espécies Reativas de Oxigênio , Tiorredoxinas/genética
19.
PLoS One ; 19(1): e0296817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38271399

RESUMO

The school students are facing mental health issues, and their performance is not improving in China. Health education policies are not implemented at the school level in China. However, scholars focus on college students' health education, but the school student is neglected. The research's primary objective is to answer the question: What is the impact of health education on the psychological well-being of school students? A sample of 549 10th grade students is collected from China's public and private sector institutes. The partial least square-structural equation modelling (PLS-SEM) is employed to analyze the data. The outcomes highlighted that the impact of health education is significant on the psychological well-being of school students in China. Furthermore, the study introduced that the moderating role of sustainable health exercise and sports participation is critical as it positively influences the relationship between health education and psychological wellbeing. This research improves literature as the novel contribution are highlighted in theory. Furthermore, the government education policies must be reframed under the light of this research' findings to improve students' health.


Assuntos
Educação Física e Treinamento , Esportes , Humanos , Exercício Físico , Instituições Acadêmicas , Estudantes/psicologia
20.
Biochem Biophys Res Commun ; 695: 149373, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38176170

RESUMO

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3'-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC.


Assuntos
Neoplasias Colorretais , Proteínas de Ligação a RNA , Receptores Virais , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Edição de RNA/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/metabolismo
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