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1.
J Dig Dis ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992957

RESUMEN

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

3.
J Am Coll Surg ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920308

RESUMEN

BACKGROUND: The association between preoperative wearable device step counts and surgical outcomes has not been examined using commercial devices linked to electronic health records (EHR). This study measured the association between daily preoperative step counts and postoperative complications. STUDY DESIGN: Data was obtained using the All of Us (AOU) Research program, a nationwide initiative to collect EHR and health-related data from the population. Included were patients who underwent a surgical procedure included in the National Surgical Quality Improvement Program (NSQIP) targeted procedures dataset. Excluded were patients who did not have available physical activity FitBit data. Primary outcome was the development of a postoperative complication. All analyses were performed in the AOU researcher workbench. RESULTS: Of 27,150 patients who underwent a surgical procedure, 475 participants with preoperative wearable data were included. 74.7% were female and 85.2% were White. The average age was 57.2 years. The overall rate of postoperative complications was 12.6%. Patients averaging fewer than 7,500 daily steps were at increased odds for developing a postoperative complication (OR 1.83, 95% CI [1.01, 3.31]). Following adjustment for age, sex, race, comorbid disease, body mass index (BMI), and relative procedure risk, patients with a baseline average steps/day < 7,500 were at increased odds for postoperative complication (aOR = 2.06, 95% CI [1.05, 4.06]). CONCLUSIONS: This study found an increase in overall postoperative complication rate in patients recording lower average preoperative step counts. Patients with a baseline of less than 7,500 steps per day had increased odds of postoperative complications in this cohort. This data supports the use of wearable devices for surgical risk stratification and suggests step count may measure preoperative fitness.

4.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868873

RESUMEN

BACKGROUND: From June 2021 to July 2021, our hospital confirmed 3 cases of Mycobacterium infection in skin abscesses. All 3 patients underwent thread embedding and weight loss surgery at the same informal beauty institution, with a history of silk protein injection. None of the patients had any other underlying diseases or surgical history. Symptoms and signs show that the disease is acute and the course of the disease is short. All patients have found subcutaneous masses in different parts of the body. In most cases, the masses show redness and swelling, and some of the masses are accompanied by tenderness, wave sensation, and rupture. After some of the masses rupture, purulent secretions can be seen. METHODS: The pus secreted by the skin lesions of the three patients were cultured to a single bacterium, which was identified by MALDI-TOF MS. Multiple locus sequence typing (MLST) was performed using three specific genes (hsp65, rpoB, and secA1) and seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH). The results were queried through the MLST database of Mycobacterium abscess. RESULTS: All three strains of bacteria were Mycobacterium abscess type ST279 massiliense subtype. Three antibacterial drugs including cefmetazole, amikacin, and clarithromycin were administered in combination with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). After 3 - 6 months, there was no obvious redness or swelling in the surrounding tissues of the wound, and no obvious purulent secretions were observed. All patients were cured and discharged from the hospital. After a follow-up of six months, there was no recurrence of the lesions. CONCLUSIONS: Medical institutions must strictly follow infection control guidelines and take preventive measures to prevent such incidents from happening again. ALA-PDT as a combination therapy for nontuberculous Mycobacterium (NTM) skin infections can improve treatment efficacy and shorten antibiotic usage time.


Asunto(s)
Antibacterianos , Brotes de Enfermedades , Infecciones por Mycobacterium no Tuberculosas , Humanos , Femenino , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Adulto , Antibacterianos/uso terapéutico , Enfermedades Cutáneas Bacterianas/epidemiología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Absceso/microbiología , Absceso/epidemiología , Absceso/diagnóstico , Mycobacterium abscessus/aislamiento & purificación , Mycobacterium abscessus/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/efectos de los fármacos
5.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868894

RESUMEN

BACKGROUND: In July 2023, our hospital confirmed one case of lumbar spine infected complicated by Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was admitted due to lower back pain for 1 year and a hard lump for 3 months. Symptoms and signs: Dressing can be seen fixed on the lower back, with severe bleeding. When the dressing is removed, a hard and protruding lump with a size of 6 cm x 8 cm, a sinus tract can be seen near the mass, with a slightly red wound and a sinus depth of about 3 cm. Light red fluid can be seen flowing out. There are no symptoms such as redness, swelling, or heat in the rest of the lower back, and the patient has no other underlying diseases or surgical history. METHODS: Lumbar magnetic resonance imaging and lumbar CT examination; Percutaneous puncture lumbar vertebral biopsy was performed, and the biopsy tissue was subjected to pathological examination, mNGS (metagenomic next-generation sequencing), and acid-fast staining; Extract pus from the lump for fungal culture and ink staining, and identify the fungi through MALDI-TOF MS. RESULTS: Bone destruction and bone marrow edema in the L5 vertebral body, compression of the spinal canal at the L5 vertebral body level; The pathological results of the biopsy tissue indicate granulomatous lesions. The acid-fast staining of the tissue is positive, and the mNGS of the tissue indicates infection with Mycobacterium tuberculosis. A single fungus was cultured from pus and identified by MALDI-TOF MS as Cryptococcus neoformans. Clinically, isoniazid 0.3 g ivgtt + rifampicin 0.45 g qd po + ethambutol 0.25 g qd po + pyrazinamide 0.75 g qd po + fluconazole 0.3 g qd po was administered for treatment. After 11 days, there was slight pain at the incision site, and the original symptoms were significantly relieved. The wound dressing was fixed in place, dry and without obvious exudation. Improved and discharged, followed up for 3 months with no recurrence of the lesion. CONCLUSIONS: mNGS is an effective identification technique that can be used to accurately diagnose suspected infection cases. MALDI-TOF MS has significant advantages over traditional detection methods in shortening detection time. This case achieved satisfactory treatment results for patients through a reasonable treatment plan, which is of great significance for exploring the diagnosis and treatment of similar disease infections.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Vértebras Lumbares , Mycobacterium tuberculosis , Humanos , Cryptococcus neoformans/aislamiento & purificación , Vértebras Lumbares/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Criptococosis/diagnóstico , Criptococosis/microbiología , Criptococosis/tratamiento farmacológico , Masculino , Tuberculosis de la Columna Vertebral/diagnóstico , Tuberculosis de la Columna Vertebral/microbiología , Imagen por Resonancia Magnética , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
6.
Biomed Pharmacother ; 176: 116936, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38878685

RESUMEN

Myocardial reperfusion injury occurs when blood flow is restored after ischemia, an essential process to salvage ischemic tissue. However, this phenomenon is intricate, characterized by various harmful effects. Tissue damage in ischemia-reperfusion injury arises from various factors, including the production of reactive oxygen species, the sequestration of proinflammatory immune cells in ischemic tissues, the induction of endoplasmic reticulum stress, and the occurrence of postischemic capillary no-reflow. Secretory phospholipase A2 (sPLA2) plays a crucial role in the eicosanoid pathway by releasing free arachidonic acid from membrane phospholipids' sn-2 position. This liberated arachidonic acid serves as a substrate for various eicosanoid biosynthetic enzymes, including cyclooxygenases, lipoxygenases, and cytochromes P450, ultimately resulting in inflammation and an elevated risk of reperfusion injury. Therefore, the activation of sPLA2 directly correlates with the heightened and accelerated damage observed in myocardial ischemia-reperfusion injury (MIRI). Presently, clinical trials are in progress for medications aimed at sPLA2, presenting promising avenues for intervention. Cardiolipin (CL) plays a crucial role in maintaining mitochondrial function, and its alteration is closely linked to mitochondrial dysfunction observed in MIRI. This paper provides a critical analysis of CL modifications concerning mitochondrial dysfunction in MIRI, along with its associated molecular mechanisms. Additionally, it delves into various pharmacological approaches to prevent or alleviate MIRI, whether by directly targeting mitochondrial CL or through indirect means.


Asunto(s)
Cardiolipinas , Daño por Reperfusión Miocárdica , Humanos , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Animales , Cardiolipinas/metabolismo , Fosfolipasas A2 Secretoras/metabolismo
7.
Ann Surg Oncol ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909113

RESUMEN

BACKGROUND: Few studies have examined the performance of artificial intelligence (AI) content detection in scientific writing. This study evaluates the performance of publicly available AI content detectors when applied to both human-written and AI-generated scientific articles. METHODS: Articles published in Annals of Surgical Oncology (ASO) during the year 2022, as well as AI-generated articles using OpenAI's ChatGPT, were analyzed by three AI content detectors to assess the probability of AI-generated content. Full manuscripts and their individual sections were evaluated. Group comparisons and trend analyses were conducted by using ANOVA and linear regression. Classification performance was determined using area under the curve (AUC). RESULTS: A total of 449 original articles met inclusion criteria and were evaluated to determine the likelihood of being generated by AI. Each detector also evaluated 47 AI-generated articles by using titles from ASO articles. Human-written articles had an average probability of being AI-generated of 9.4% with significant differences between the detectors. Only two (0.4%) human-written manuscripts were detected as having a 0% probability of being AI-generated by all three detectors. Completely AI-generated articles were evaluated to have a higher average probability of being AI-generated (43.5%) with a range from 12.0 to 99.9%. CONCLUSIONS: This study demonstrates differences in the performance of various AI content detectors with the potential to label human-written articles as AI-generated. Any effort toward implementing AI detectors must include a strategy for continuous evaluation and validation as AI models and detectors rapidly evolve.

8.
Dalton Trans ; 53(20): 8772-8780, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38712840

RESUMEN

A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4'-CH2ONPX)](PF6) (Ir-NPX-1-3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1-3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1-3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1-3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Iridio , Mitocondrias , Naproxeno , Iridio/química , Iridio/farmacología , Naproxeno/farmacología , Naproxeno/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Animales , Ratones , Inflamación/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Línea Celular Tumoral
9.
J Chem Phys ; 160(20)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804487

RESUMEN

Lanthanide-doped upconversion (UC) luminescent materials display multicolor emissions, making them ideal for a variety of applications, such as multi-channel biological imaging, fluorescence encryption, anti-counterfeiting, and 3D display. Manipulating the UC emissions of the luminescent materials with a fixed composition is crucial for their applications. Herein, we propose a facile strategy to achieve pulse-width-dependent multicolor UC emissions in NaYF4:Yb/Er/Tm nanocrystals. Upon excitation with a 980 nm continuous-wave laser diode, Er3+ ions in NaYF4:20%Yb,15%Er,1%Tm nanocrystals exhibited UC emissions with a red-to-green (R/G) ratio of 11.3. Nevertheless, by employing a 980 nm pulse laser with pulse widths from 0.1 to 10 ms, the UC R/G ratio can be easily adjusted from 0.9 to 11.3, resulting in continuous and remarkable color transformation from green, yellow, orange, to red. By virtue of the dynamic luminescence color variation of these NaYF4:20%Yb,15%Er,1%Tm nanocrystals, we demonstrated their potential applications in the areas of anti-counterfeiting and information encryption. These findings provide deep insights into the excited-state dynamics and energy transfer of Er3+ in NaYF4:Yb/Er/Tm nanocrystals upon 980 nm pulse excitation, which may pave the way for designing multicolor UC materials toward versatile applications.

10.
J Inorg Biochem ; 257: 112596, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38759264

RESUMEN

The design and synthesis of a series of metal complexes formed by non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (IBP) and iridium(III), with the molecular formula [Ir(C^N)2bpy(4-CH2OIBP-4'-CH2OIBP)](PF6) (Ir-IBP-1, Ir-IBP-2) (C^N = 2-phenylpyridine (ppy, Ir-IBP-1), 2-(2-thienyl)pyridine (thpy, Ir-IBP-2)) was introduced in this article. Firstly, it was found that the anti-proliferative activity of these complexes was more effective than that of cisplatin. Further research showed that Ir-IBP-1 and Ir-IBP-2 can accumulate in intracellular mitochondria, thereby disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), blocking the G2/M phase of the cell cycle, and inducing cell apoptosis. In terms of protein expression, the expression of COX-2, MMP-9, NLRP3 and Caspase-1 proteins can be downregulated, indicating their ability to anti-inflammatory and overcome immune evasion. Furthermore, Ir-IBP-1 and Ir-IBP-2 can induce immunogenic cell death (ICD) by triggering the release of cell surface calreticulin (CRT), high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Overall, iridium(III)-IBP conjugates exhibit various anti-tumor mechanisms, including mitochondrial damage, cell cycle arrest, inflammatory suppression, and induction of ICD.


Asunto(s)
Antineoplásicos , Apoptosis , Complejos de Coordinación , Ibuprofeno , Iridio , Iridio/química , Iridio/farmacología , Humanos , Ibuprofeno/farmacología , Ibuprofeno/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos
11.
Plants (Basel) ; 13(6)2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38592849

RESUMEN

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings' leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙-, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.

12.
Environ Sci Technol ; 58(15): 6725-6735, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38565876

RESUMEN

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.


Asunto(s)
Cerio , Ozono , Oxidación-Reducción , Metales , Catálisis
13.
Int J Biol Macromol ; 268(Pt 1): 131729, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38653429

RESUMEN

In this case, various characterization technologies have been employed to probe dissociation mechanism of cellulose in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl) system. These results indicate that coordination of DMAc ligands to the Li+-Cl- ion pair results in the formation of a series of Lix(DMAc)yClz (x = 1, 2; y = 1, 2, 3, 4; z = 1, 2) complexes. Analysis of interaction between DMAc ligand and Li center indicate that Li bond plays a major role for the formation of these Lix(DMAc)yClz complexes. And the saturation and directionality of Li bond in these Lix(DMAc)yClz complexes are found to be a tetrahedral structure. The hydrogen bonds between two cellulose chains could be broken at the nonreduced end of cellulose molecule via combined effects of basicity of Cl- ion and steric hindrance of [Li (DMAc)4]+ unit. The unique feature of Li bond in Lix(DMAc)yClz complexes is a key factor in determination of the dissociation mechanism.


Asunto(s)
Acetamidas , Celulosa , Cloruro de Litio , Celulosa/química , Acetamidas/química , Cloruro de Litio/química , Litio/química , Enlace de Hidrógeno
14.
Shock ; 61(6): 915-923, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38662592

RESUMEN

ABSTRACT: ß 3 -adrenergic receptor (ß 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of ß 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of ß 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that ß 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of ß 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with ß 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8, and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of ß 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous ß 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.


Asunto(s)
Apoptosis , Miocitos Cardíacos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Receptores Adrenérgicos beta 3 , Sepsis , Transducción de Señal , Animales , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Apoptosis/efectos de los fármacos , Sepsis/metabolismo , Ratas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Receptores Adrenérgicos beta 3/metabolismo , Lipopolisacáridos/toxicidad , Agonistas de Receptores Adrenérgicos beta 3/farmacología , Línea Celular , Etanolaminas
15.
Adv Sci (Weinh) ; 11(24): e2307754, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38605600

RESUMEN

Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross-presentation, the progress with neoantigen peptide-based vaccines has obviously lagged in clinical trials. Here, a stapling peptide-based nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the nucleic acid adjuvant-antigen conjugate. This nano-vaccine stimulates a strong tumor-specific T cell response by activating antigen presentation and toll-like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co-delivery to the draining lymph nodes, the nano-vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long-term anti-tumor memory. Moreover, the injection of nano-vaccine with signal neoantigen eliminates the established MC-38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide-based nano-vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti-tumor immune response for the neoantigen peptide-based personalized tumor immunotherapy.


Asunto(s)
Antígenos de Neoplasias , Vacunas contra el Cáncer , Inmunoterapia , Medicina de Precisión , Animales , Ratones , Inmunoterapia/métodos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Antígenos de Neoplasias/inmunología , Medicina de Precisión/métodos , Péptidos/inmunología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Línea Celular Tumoral , Nanopartículas/química , Humanos , Femenino , Neoplasias/inmunología , Neoplasias/terapia , Sistemas de Liberación de Medicamentos/métodos
16.
Chem Asian J ; 19(12): e202400184, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38628038

RESUMEN

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

17.
ACS Chem Biol ; 19(5): 1161-1168, 2024 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-38662199

RESUMEN

Targeted protein degradation is becoming more and more important in the field of drug development. Compared with proteasomal-based degraders, lysosomal-based degraders have a broader target spectrum of targets, which have been demonstrated to have great potential, especially in degrading undruggable proteins. Recently, we developed a programmable and facile screening PROTAC development platform based on peptide self-assembly termed split-and-mix PROTAC (SM-PROTAC). In this study, we applied this technology for the development of lysosome-based degraders, named a split-and-mix chaperone-mediated autophagy-based degrader (SM-CMAD). We successfully demonstrated SM-CMAD as a universal platform by degrading several targets, including ERα, AR, MEK1/2, and BCR-ABL. Different from other lysosomal-based degraders, SM-CMAD was capable of facile screening with programmable ligand ratios. We believe that our work will promote the development of other multifunctional molecules and clinical translation for lysosomal-based degraders.


Asunto(s)
Lisosomas , Proteolisis , Lisosomas/metabolismo , Proteolisis/efectos de los fármacos , Humanos , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Autofagia/efectos de los fármacos
18.
World J Psychiatry ; 14(2): 225-233, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38464777

RESUMEN

Depression is a common mental health disorder. With current depression detection methods, specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment. Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized. Specialized physicians usually require extensive training and experience to capture changes in these features. Advancements in deep learning technology have provided technical support for capturing non-biological markers. Several researchers have proposed automatic depression estimation (ADE) systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening. This article summarizes commonly used public datasets and recent research on audio- and video-based ADE based on three perspectives: Datasets, deficiencies in existing research, and future development directions.

19.
Chem Commun (Camb) ; 60(27): 3725-3728, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38482888

RESUMEN

Chemical labeling methods for proteins are highly researched. Herein, we introduced ß-carbonyl sulfonium compounds for selective cysteine modification in proteins within biological systems. Structural tuning led to sulfonium-based probes with high reactivity and selectivity. These probes show excellent biocompatibility, cell uptake, and specificity towards cysteine profiling in live cells.


Asunto(s)
Cisteína , Compuestos de Sulfonio , Cisteína/química , Proteínas/química , Compuestos de Sulfonio/química
20.
Trials ; 25(1): 196, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38504343

RESUMEN

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Obesidad Infantil , Niño , Humanos , Obesidad Infantil/diagnóstico , Obesidad Infantil/terapia , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/terapia , Sobrepeso , Estilo de Vida , Índice de Masa Corporal , Ensayos Clínicos Controlados Aleatorios como Asunto
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