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1.
Front Oncol ; 14: 1380527, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841161

RESUMO

The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus, correct GGN recognition and management has become a research focus. Many scholars have explored the underlying mechanism of the indolent progression of GGNs from several perspectives, such as pathological type, genomic mutational characteristics, and immune microenvironment. GGNs have different major mutated genes at different stages of development; EGFR mutation is the most common mutation in GGNs, and p53 mutation is the most abundant mutation in the invasive stage of GGNs. Pure GGNs have fewer genomic alterations and a simpler genomic profile and exhibit a gradually evolving genomic mutation profile as the pathology progresses. Compared to advanced lung adenocarcinoma, GGN lung adenocarcinoma has a higher immune cell percentage, is under immune surveillance, and has less immune escape. However, as the pathological progression and solid component increase, negative immune regulation and immune escape increase gradually, and a suppressive immune environment is established gradually. Currently, regular computer tomography monitoring and surgery are the main treatment strategies for persistent GGNs. Stereotactic body radiotherapy and radiofrequency ablation are two local therapeutic alternatives, and systemic therapy has been progressively studied for lung cancer with GGNs. In the present review, we discuss the characterization of the multidimensional molecular evolution of GGNs that could facilitate more precise differentiation of such highly heterogeneous lesions, laying a foundation for the development of more effective individualized treatment plans.

2.
Nano Lett ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874576

RESUMO

Noncontact sensing technology serves as a pivotal medium for seamless data acquisition and intelligent perception in the era of the Internet of Things (IoT), bringing innovative interactive experiences to wearable human-machine interaction perception networks. However, the pervasive limitations of current noncontact sensing devices posed by harsh environmental conditions hinder the precision and stability of signals. In this study, the triboelectric nanopaper prepared by a phase-directed assembly strategy is presented, which possesses low charge transfer mobility (1618 cm2 V-1 s-1) and exceptional high-temperature stability. Wearable self-powered noncontact sensors constructed from triboelectric nanopaper operate stably under high temperatures (200 °C). Furthermore, a temperature warning system for workers in hazardous environments is demonstrated, capable of nonintrusively identifying harmful thermal stimuli and detecting motion status. This research not only establishes a technological foundation for accurate and stable noncontact sensing under high temperatures but also promotes the sustainable intelligent development of wearable IoT devices under extreme environments.

3.
Indian J Hematol Blood Transfus ; 40(2): 190-195, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38708162

RESUMO

No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01704-8.

4.
Materials (Basel) ; 17(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38730745

RESUMO

The Applications of silica aerogel are limited due to its brittleness and low strength. As a result, it is essential to strengthen and toughen it. Organic nanofibers are one of the preferred reinforcement materials. In this work, we designed and fabricated flexible and compressible nanostructure-assembled aramid nanofiber/silica composites aerogel (ANF/SiO2 aerogel) to improve the mechanical strength and flexibility of silica aerogel without compromising thermal insulation properties. The aramid nanofiber/silica composite aerogels were prepared by immersing the aramid nanofiber wet gel into the silica sol for a certain period of time followed by freeze drying without solvent replacement. The surface modifier 3-aminopropyltriethoxysilane (APTES) was used as a coupling agent to form chemical linkage between the ANF fiber and silica gel. It was observed that APTES can effectively drive the silica sol to infuse into ANF hydrogel, promoting the assembly of silica gel onto the fiber surface and a uniform distribution in the network of ANF. The compressive resilience, thermal stability, and thermal insulation properties of the composite aerogels were evaluated by inducing the silica aerogel into the ANF network to form a protective layer on the fiber and change the pore structure in the ANF network.

5.
ACS Omega ; 9(18): 20196-20205, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737071

RESUMO

Shale reservoirs have diverse mineral types, and analyzing the sensitivity of the mineral composition to shale pores is of great scientific and engineering significance. In this paper, first, X-ray diffraction (XRD) experiments on shale mineral compositions are carried out, and the characteristics of pore structure changes after shale mineral compositions interacted with external fluids (slick water and backflow fluid) are elucidated. Then, the effects of quartz, kaolinite, and pyrite on the pore structure and permeability of shale on the susceptibility to slick water are studied. The results show that (a) quartz and clay minerals are the dominant constituents of each core, with some cores containing minor amounts of plagioclase feldspar and rhodochrosite. (b) The composition of the shale changed significantly following the action of external fluids. The average quartz content of pure shale decreased from 31.62% to 29.1%. The average content of quartz in siliceous shale decreased from 36.53% to 33.5%. The average content of quartz in carbonaceous shale decreased from 9.15% to 8.05%. (c) Factors affecting the sensitivity of shale pore structure and permeability to slick water are mainly quartz, kaolinite, and pyrite. The contents of quartz, kaolinite, and pyrite decreased by an average of 5.1%, 4.6%, and 0.9%, respectively, after slick water action.

6.
Heliyon ; 10(10): e31492, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38807870

RESUMO

Background: We developed a novel minimally invasive transapical beating-heart septal myectomy (TA-BSM) procedure for patients with midventricular obstruction (MVO), without the aid of cardiopulmonary bypass. This study aims to describe the TA-BSM procedure for the relief of MVO and to detail the clinical outcomes in these patients. Methods: Sixty-one patients receiving TA-BSM for MVO were included: isolated MVO (n = 12) and combined MVO and subaortic obstruction (n = 49). We reviewed the electronic medical record to collect information on preoperative, intraoperative, and postoperative parameters. Results: The intraventricular pressure gradient after the resection was largely attenuated. On the catheter measurement, the median resting and provoked gradient decreased by 29.0 and 71.0 mm Hg, respectively. Likewise, the resting intraventricular gradient was successfully reduced from 58.0 to 11.0 mm Hg, and the maximal intraventricular gradient was reduced from 88.0 to 20.0 mm Hg at 6 months follow-up. In addition, all patients showed significantly improved MR and 37 of 42 patients with preoperative MR grade ≥2+ showed MR grade ≤1+ after TA-BSM. During the follow-up, no death was observed and no one had HCM-related rehospitalization. All patients reported improvement in symptoms and the mean New York Heart Association class improved from 3.0 (IQR, 3.0-3.0) preoperatively to 1.0 (IQR, 1.0-1.0) at 6 months follow-up. Conclusions: The TA-BSM procedure is a valuable therapy to relieve MVO, improving hemodynamics and providing satisfactory clinical outcomes. The procedure can also preserve favorable outcomes for patients with MVO and concomitant subaortic obstruction.

7.
Bioorg Chem ; 148: 107436, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735265

RESUMO

BACKGROUND: Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest. AIM OF THE STUDY: This study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs. METHODS: The cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2's antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model. RESULTS: FLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects. CONCLUSION: The study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.


Assuntos
Antineoplásicos , Apoptose , Camptotecina , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Camptotecina/farmacologia , Camptotecina/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Animais , Camundongos , Apoptose/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Camundongos Nus , Células Tumorais Cultivadas , Linhagem Celular Tumoral
8.
Carbohydr Res ; 540: 109121, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692248

RESUMO

Precise and selective modification of carbohydrates is a critical strategy in producing diverse carbohydrate derivatives for exploiting their functions. We disclosed a simple, efficient, and highly regioselective and stereoselective protocol to controllable amination of 2-nitroglycals under mild conditions in 5 min. A range of 3-amino-carbohydrates including 3-arylamino-2-nitro-glycals and 1,3-di-amino-carbohydrate derivatives were obtained in good to excellent yield with excellent stereoselectivity. The produced 3-amino-2-nitro-glycals can be used as a precursor for further transformation.


Assuntos
Nitrocompostos , Aminação , Estereoisomerismo , Estrutura Molecular , Nitrocompostos/química , Nitrocompostos/síntese química , Carboidratos/química , Carboidratos/síntese química
9.
Pathobiology ; : 1-14, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718783

RESUMO

INTRODUCTION: Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. METHODS: Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole-slide images (WSIs) and is composed of two deep learning models to locate the lymph nodes and detect cancers. RESULTS: It achieved an area under the receiver operating characteristic curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 WSIs from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical centre, with an AUC of 0.925. CONCLUSION: Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

10.
Cancer Res Commun ; 4(5): 1351-1362, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38695555

RESUMO

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomic sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 patients with mucosal melanoma, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared with NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of patients with PMME and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T-cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma. SIGNIFICANCE: This study investigated the intricate epigenetic factor of mucosal melanomas contributed to the differential immune checkpoint inhibitor response, and found that PMME exhibited a global hypermethylation pattern and lower gene expression in comparison to NEMM. TERT hypermethylation may contribute to the favorable responses observed in patients with mucosal melanoma undergoing immunotherapy.


Assuntos
Metilação de DNA , Epigênese Genética , Melanoma , Humanos , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Epigênese Genética/genética , Metilação de DNA/genética , Masculino , Feminino , Idoso , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Mucosa/imunologia , Mucosa/patologia , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Telomerase/genética
11.
Sensors (Basel) ; 24(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38793843

RESUMO

Edge computing provides higher computational power and lower transmission latency by offloading tasks to nearby edge nodes with available computational resources to meet the requirements of time-sensitive tasks and computationally complex tasks. Resource allocation schemes are essential to this process. To allocate resources effectively, it is necessary to attach metadata to a task to indicate what kind of resources are needed and how many computation resources are required. However, these metadata are sensitive and can be exposed to eavesdroppers, which can lead to privacy breaches. In addition, edge nodes are vulnerable to corruption because of their limited cybersecurity defenses. Attackers can easily obtain end-device privacy through unprotected metadata or corrupted edge nodes. To address this problem, we propose a metadata privacy resource allocation scheme that uses searchable encryption to protect metadata privacy and zero-knowledge proofs to resist semi-malicious edge nodes. We have formally proven that our proposed scheme satisfies the required security concepts and experimentally demonstrated the effectiveness of the scheme.

12.
Int J Biol Macromol ; : 132410, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38821799

RESUMO

Retrogradation is a critical step in the physical production of resistant starch. This study aimed to examine the effects of isothermal and temperature-cycled retrogradation on the structural, physicochemical properties, and digestibility of resistant starch type-III (RS3) under various thermal conditions. To create RS3, normal maize starch (NM) and Hylon VII (HAM) were treated by autoclave-microwave and then retrograded at isothermal (4 °C) or various temperature conditions (4/10 °C, 4/20 °C, 4/30 °C, 4/40 °C, and 4/50 °C). We found that temperature-cycled retrogradation possessed greater potential than isothermal retrogradation for producing short-range ordering and crystalline structures of RS3. Also, retrograded starch prepared via temperature cycling exhibited higher double helix content, lower amorphous content, reduced swelling power, and less amylose leaching in water. Furthermore, the starch digestibility was affected by structural alterations, which were more significant in HAM-retrograded starch. While, HAM-4-40 (39.27 %) displayed the highest level of resistant starch (RS).

13.
Sci Rep ; 14(1): 8367, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600221

RESUMO

Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.


Assuntos
Lesões Encefálicas Traumáticas , Epilepsia Pós-Traumática , Humanos , Animais , Epilepsia Pós-Traumática/etiologia , Astrócitos/metabolismo , Transcriptoma , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo , Convulsões , Perfilação da Expressão Gênica , Modelos Animais de Doenças
14.
JACS Au ; 4(3): 974-984, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38559736

RESUMO

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

15.
J Am Heart Assoc ; 13(9): e033488, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38639362

RESUMO

BACKGROUND: Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. METHODS AND RESULTS: A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. CONCLUSIONS: Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.


Assuntos
Doenças das Artérias Carótidas , Lipoproteína(a) , Placa Aterosclerótica , Humanos , Masculino , Lipoproteína(a)/sangue , Feminino , Pessoa de Meia-Idade , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/sangue , Idoso , Medição de Risco , Placa Aterosclerótica/epidemiologia , Incidência , Fatores de Tempo , Fatores de Risco , Biomarcadores/sangue , Fatores de Risco de Doenças Cardíacas , AVC Isquêmico/epidemiologia , AVC Isquêmico/sangue , AVC Isquêmico/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia
16.
Comput Struct Biotechnol J ; 23: 1144-1153, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38510975

RESUMO

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

17.
ACS Pharmacol Transl Sci ; 7(3): 630-640, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481681

RESUMO

Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residues of F149, Q156, V163, and K164 of the second intracellular loop played a vital role in determining MC4R constitutive activity. This study provided novel insights into functional evolution and identified a key motif essential for constitutive modulation of MC4R signaling.

18.
J Geriatr Cardiol ; 21(2): 211-218, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38544493

RESUMO

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

19.
Adv Physiol Educ ; 48(2): 378-384, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38420666

RESUMO

To improve the physical education experience for students, this study investigates the idea of an integrated solution based on a smart campus for physical education. Within the physical education curriculum, the study focuses on the integration of smart fitness monitoring and wearables, interactive fitness equipment and gamification, mobile applications and customized workout plans, smart facilities, indoor navigation, and data-driven curriculum enhancements. The data gathered from a study involving two groups of students, an experimental group with access to smart campus solutions and a control group without such access, was analyzed using an organized and component-based framework. The data study looks at how the smart campus solutions affect the students' academic performance, fitness levels, motivation, and adherence to exercise regimens. The analyzed findings point to a few advantages of using smart campus technologies in physical education. Compared to the control group, students in the experimental group showed higher levels of academic performance, increased motivation, improved exercise adherence, and fitness. Students who had access to smart campus solutions reported much better experiences with physical education overall. The results imply that smart campus technologies have the potential to produce a physical education learning environment that is more interesting, focused on the needs of the students, and effective. Smart campus solutions help optimize curriculum design, boost motivation, and enhance academic performance by utilizing data-driven insights and personalized learning experiences.NEW & NOTEWORTHY This study investigates the idea of an integrated solution based on a smart campus for physical education. Within the physical education curriculum, the study focuses on the integration of smart fitness monitoring and wearables, interactive fitness equipment and gamification, mobile applications and customized workout plans, smart facilities, indoor navigation, and data-driven curriculum enhancements.


Assuntos
Currículo , Educação Física e Treinamento , Humanos , Educação Física e Treinamento/métodos , Feminino , Masculino , Universidades , Adulto Jovem , Estudantes/psicologia , Motivação , Aplicativos Móveis
20.
Org Lett ; 26(7): 1332-1337, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38330288

RESUMO

We disclosed a Ni/CPA cocatalyzed protocol to access diverse C-acyl glycosides under mild conditions with broad functional group compatibility through the coupling of readily available glycosyl bromides and carboxylic esters. The potential application of the methodology was demonstrated by the C-acyl glycosylation of bioactive molecules and the transformation of products to a variety of value-added molecules. Mechanistic studies revealed that CPA might serve as a bifunctional H-bond catalyst to activate carboxylic esters and nickel catalyst.

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