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1.
Front Endocrinol (Lausanne) ; 15: 1390725, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161393

RESUMEN

Purpose: To compare the dietary inflammatory index (DII), triglyceride glucose index (TyG), waist triglyceride index (WTI), and body mass index (BMI) in predicting the survival of chronic kidney disease (CKD). Methodology: Inclusion of 23,099 participants from the NHANES database who met specific criteria. Baseline was established using quartiles of DII index. The relationship between DII index, WTI index, TyG index, and BMI index with mortality rate in CKD patients was evaluated using Kaplan-Meier curves. Univariate and multivariate COX regression risk models were used to study the relationship between DII index, WTI index, and TyG index with mortality risk in CKD patients. Stratification of eGFR by age and gender was conducted to investigate the association between DII index, WTI index, and TyG index with mortality risk in CKD patients. Restricted cubic spline analysis was used to study the correlation between DII index, WTI index, and TyG index with mortality risk in CKD patients. Results: The incidence of CKD increased with the increase of DII index, WTI index and TyG index. After multivariable adjustment, the fourth quartile of DII index, TyG index and WTI index showed the highest risk for CKD [DII: hazard ratio (HR) 1.36, 95% confidential interval (CI) (1.23-1.51); TyG: HR 1.21; 95% CI (1.07-1.37); WTI: HR 1.29; 95% CI (1.13-1.46)]. There was no difference in the risk of developing CKD between the obese group (BMI ≥24 kg/m2) and the normal weight group (P>0.05). Conclusion: This study has identified a significant association between elevated DII index, WTI index, and TyG index with the risk of CKD. Furthermore, the DII index demonstrated superior prognostic capability in predicting CKD compared to other indicators.


Asunto(s)
Índice de Masa Corporal , Inflamación , Encuestas Nutricionales , Insuficiencia Renal Crónica , Triglicéridos , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/sangre , Persona de Mediana Edad , Triglicéridos/sangre , Adulto , Inflamación/sangre , Estudios de Cohortes , Glucemia/análisis , Glucemia/metabolismo , Factores de Riesgo , Dieta , Anciano , Circunferencia de la Cintura , Pronóstico
2.
Front Endocrinol (Lausanne) ; 15: 1400939, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109075

RESUMEN

Objective: To investigate the efficacy and safety of Shengjiang powder as a treatment for DKD. Methods: A comprehensive search was performed in eight databases from their inception to December 30, 2023, to identify relevant RCTs. The inclusion criteria were diagnosis of DKD and intervention including TCM that contained Shengjiang powder. Two researchers independently conducted literature screening and data extraction, utilizing the Rob2 tool and GRADE to assess the quality of the RCTs. Meta-analysis was carried out using RevMan 5.4.1 and Stata 15.0. Results: As a result of the search, 23 RCTs comprising 1,682 patients. The interventions resulted in significant reductions in all the assessed indicators: 24-h urinary protein, UAER, mALB, BUN, Scr, FBG, 2hPG, HbA1c, total cholesterol, and Triglycerides. Together the results showed that Shengjiang powder, in conjunction with conventional therapy, is an effective treatment of DKD. Subgroup analyses, considering duration, stage, blood glucose control levels, baseline blood glucose levels, and baseline Scr levels indicated that shorter duration treatment had a greater effect on UAER, 2hPG, and HbA1c. Additionally, Shengjiang powder was more effective in reducing 24-h urinary protein, Scr, and 2hPG in stage IV patients compared to corresponding values at other stages. However, with respect to FBG, the treatment was more effective in stage II/III. Shengjiang powder also, reduced Scr levels significantly in patients with higher baseline Scr and reduced urinary protein excretion with stricter blood glucose control. The interventions had additional lipid-regulating effects in cases with looser blood glucose control and led to a remarkable reduction in BUN and Scr levels in patients with FBG > 11.1 mmol/L. Conclusion: Shengjiang powder may supplement conventional therapy, thus benefiting DKD patients in terms of reducing urinary protein, stabilizing kidney function, and improving blood glucose and lipid metabolism. Considering the significant heterogeneity among studies and limited quality of some reports, our conclusions need to be further verified through analyses utilizing larger, multi-center samples of higher quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024490795.


Asunto(s)
Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Humanos , Glucemia/análisis , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Medicina Tradicional China/métodos , Polvos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
3.
Bioorg Med Chem ; 111: 117864, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39116711

RESUMEN

As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 µM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón , Tiofenos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Animales , Tiofenos/farmacología , Tiofenos/química , Tiofenos/síntesis química , Regulación Alostérica/efectos de los fármacos , Ratones , Humanos , Relación Estructura-Actividad , Estructura Molecular , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Insulina/metabolismo , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/síntesis química , Fosfato de Sitagliptina/química
4.
Front Cell Dev Biol ; 12: 1435064, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100097

RESUMEN

Background: Metronidazole (MTZ) is among the first-line drugs against the human gastric pathogen Helicobacter pylori (H. pylori). MTZ is used as a prodrug that is activated by an oxygen-insensitive enzyme NADPH nitroreductase (RdxA). Loss-of-function mutations in rdxA make H. pylori MTZ resistant; however, experimental proof is lacking. Methods: We collected 139 gastric biopsy samples from patients suspected of H. pylori infection in Shanghai, and amplified Hp-specific rdxA gene from 134 samples. All these rdxA genes were sequenced and phylogenetically compared. The effect of mutations on RdxA function was measured by expressing them in Escherichia coli DH5α by using the MTZ sensitivity test. Results: In total, 134 gastric biopsy samples were identified as H. pylori positive. Of the 134 samples, 74 and 6 had point mutations at the various sites or promoter region of rdxA, generating truncated and extended fused proteins, respectively. The remaining 54 were full-length with single nucleotide variation (SNV) compared with the wild-type RdxA from H. pylori, with 49 clustering with hpEastAsia, 3 with hpEurope, and 2 with hpNEAfrica. All 134 rdxA were expressed in E. coli DH5α; 22 and 112 resultant strains showed MTZ-sensitive and MTZ-resistant phenotypes, respectively. Comparative analysis of single nucleotide polymorphisms (SNPs) in the functional and inactivated RdxA revealed 14 novel mutations in RdxA, 5 of which conferred MTZ resistance: S18F, D59S, L62I, S79N, and A187V. Conclusion: The occurrence of MTZ resistance induced by site-mutation of RdxA in patients with H. pylori infection was 83.6% (112/134) in the Shanghai region. The major form of loss-of-function mutation was truncation of RdxA translation at a rate of 58/112 (51.8%). Molecular detection reliably determined the resistance of H. pylori to MTZ. Thus, the functional mutants involved in MTZ resistance facilitate clinical diagnosis and medication based on sequence analysis.

5.
Expert Opin Drug Discov ; : 1-24, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38994606

RESUMEN

INTRODUCTION: Abundant evidence suggests that the overexpression of CDK2-cyclin A/E complex disrupts normal cell cycle regulation, leading to uncontrolled proliferation of cancer cells. Thus, CDK2 has become a promising therapeutic target for cancer treatment. In recent years, insights into the structures of the CDK2 catalytic site and allosteric pockets have provided notable opportunities for developing more effective clinical candidates of CDK2 inhibitors. AREA COVERED: This article reviews the latest CDK2 inhibitors that have entered clinical trials and discusses the design and discovery of the most promising new preclinical CDK2 inhibitors in recent years. Additionally, it summarizes the development of allosteric CDK2 inhibitors and CDK2-targeting PROTACs. The review encompasses strategies for inhibitor and PROTAC design, structure-activity relationships, as well as in vitro and in vivo biological assessments. EXPERT OPINION: Despite considerable effort, no CDK2 inhibitor has yet received FDA approval for marketing due to poor selectivity and observed toxicity in clinical settings. Future research must prioritize the optimization of the selectivity, potency, and pharmacokinetics of CDK2 inhibitors and PROTACs. Moreover, exploring combination therapies incorporating CDK2 inhibitors with other targeted agents, or the design of multi-target inhibitors, presents significant promise for advancing cancer treatment strategies.

6.
J Acoust Soc Am ; 156(1): 359-368, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38994905

RESUMEN

A noise attenuation performance test was conducted on earmuffs using a recoilless weapon launch platform in a confined space, along with two acoustic test fixtures (ATFs). The overpressure at the ATF's effective tympanic membrane comprised direct sound at 185 dB sound pressure level (SPL) and reflected sound at 179 dB SPL. Wearing earmuffs reduced these peaks to 162 dB SPL and 169 dB SPL, respectively. The reflected sound from walls was defined as delayed sound. An analytical model for earmuff noise attenuation simulated their effectiveness. The simulation revealed that when the earmuffs attenuated delayed sound, the acoustic impedance of acoustic leakage and the acoustic impedance of the earmuff material decreased by 96% and 50%, respectively. The negative overpressure zone between direct and delayed sound decreased the earmuffs' fit against the ATF. Additionally, the enclosed volume between the earmuff and the ear canal decreased by 12%. After the installation of bandages on the earmuffs, the overpressure peak of delayed sound was reduced by 5 dB. Furthermore, the acoustic impedance of the earmuff's sound leakage path and the acoustic impedance of the earmuff material deformation path increased by 100% and 809%, respectively.


Asunto(s)
Acústica , Dispositivos de Protección de los Oídos , Presión , Humanos , Diseño de Equipo , Ruido , Sonido , Armas de Fuego , Adulto , Masculino , Factores de Tiempo , Modelos Teóricos
7.
Environ Sci Technol ; 58(28): 12685-12696, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38959026

RESUMEN

Fabrication of robust isolated atom catalysts has been a research hotspot in the environment catalysis field for the removal of various contaminants, but there are still challenges in improving the reactivity and stability. Herein, through facile doping alkali metals in Pt catalyst on zirconia (Pt-Na/ZrO2), the atomically dispersed Ptδ+-O(OH)x- associated with alkali metal via oxygen bridge was successfully fabricated. This novel catalyst presented remarkably higher CO and hydrocarbon (HCs: C3H8, C7H8, C3H6, and CH4) oxidation activity than its counterpart (Pt/ZrO2). Systematically direct and solid evidence from experiments and density functional theory calculations demonstrated that the fabricated electron-rich Ptδ+-O(OH)x- related to Na species rather than the original Ptδ+-O(OH)x-, serving as the catalytically active species, can readily react with CO adsorbed on Ptδ+ to produce CO2 with significantly decreasing energy barrier in the rate-determining step from 1.97 to 0.93 eV. Additionally, owing to the strongly adsorbed and activated water by Na species, those fabricated single-site Ptδ+-O(OH)x- linked by Na species could be easily regenerated during the oxidation reaction, thus considerably boosting its oxidation reactivity and durability. Such facile construction of the alkali ion-linked active hydroxyl group was also realized by Li and K modification which could guide to the design of efficient catalysts for the removal of CO and HCs from industrial exhaust.


Asunto(s)
Oxidación-Reducción , Circonio , Catálisis , Circonio/química , Álcalis/química , Platino (Metal)/química
8.
Int Immunopharmacol ; 139: 112707, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39032472

RESUMEN

Telmisartan, an angiotensin II type 1 receptor (AT1R) blocker, exhibits broad anti-tumor activity. However, in vitro, anti-proliferative effects are shown at doses far beyond the therapeutic plasma concentration. Considering the role of tumor microenvironment in glioma progression, glioma-astrocyte co-cultures were employed to test the anti-tumor potential of low-dose telmisartan. When a high dose was required for a direct anti-proliferative effect on glioma cell lines, a low dose significantly inhibited glioma cell proliferation and migration in the co-culture system. Under co-culture conditions, upregulated IL-6 expression in astrocytes played a critical role in glioma progression. Silencing IL-6 in astrocytes or IL-6R in glioma cells reduced proliferation and migration. Telmisartan (5 µM) inhibited astrocytic IL-6 expression, and its anti-tumor effects were reversed by silencing IL-6 or IL-6R and inhibiting signal transducer and activator of transcription 3 (STAT3) activity in glioma cells. Moreover, the telmisartan-driven IL-6 downregulation was not imitated by losartan, an AT1R blocker with little capacity of peroxisome proliferator-activated receptor-gamma (PPARγ) activation, but was eliminated by a PPARγ antagonist, indicating that the anti-glioma effects of telmisartan rely on its PPARγ agonistic activity rather than AT1R blockade. This study highlights the importance of astrocytic IL-6-mediated paracrine signaling in glioma growth and the potential of telmisartan as an adjuvant therapy for patients with glioma, especially those with hypertension.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II , Astrocitos , Proliferación Celular , Técnicas de Cocultivo , Glioma , Interleucina-6 , PPAR gamma , Factor de Transcripción STAT3 , Telmisartán , Telmisartán/farmacología , Telmisartán/uso terapéutico , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Interleucina-6/metabolismo , Glioma/tratamiento farmacológico , Glioma/metabolismo , Glioma/patología , Humanos , Proliferación Celular/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , PPAR gamma/metabolismo , Comunicación Paracrina/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Receptores de Interleucina-6/metabolismo , Losartán/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Microambiente Tumoral/efectos de los fármacos
9.
J Mater Chem B ; 12(31): 7532-7542, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38995372

RESUMEN

Hydrophilic peptides (HPs) play a critical role in the pathogenesis of hepatocellular carcinoma (HCC). However, the comprehensive and in-depth high-throughput analysis of specific changes in HPs associated with HCC remains unrealized, due to the complex nature of biological fluids and the challenges of mining complex patterns in large data sets. The clinical diagnosis of HCC still lacks a non-destructive and accurate classification method, given the limited specificity of widely used biomarkers. To address these challenges, we have established a multifunctional platform that integrates artificial intelligence computation, hydrophilic interaction extraction of HPs, and MALDI-MS testing. This platform aims to achieve highly sensitive HP fingerprinting for accurate diagnosis of HCC. The method not only facilitates efficient detection of HPs, but also achieves a remarkable 100.00% diagnostic accuracy for HCC in a test cohort, supported by machine learning algorithms. By constructing a panel of HPs with 10 characteristic features, we achieved 98% accuracy in the test cohort for rapid diagnosis and identified 62 HPs deeply involved in pathways related to liver diseases. This integrated strategy provides new research directions for future biomarker studies as well as early diagnosis and individualized treatment of HCC.


Asunto(s)
Inteligencia Artificial , Carcinoma Hepatocelular , Interacciones Hidrofóbicas e Hidrofílicas , Neoplasias Hepáticas , Nanoestructuras , Péptidos , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Humanos , Péptidos/química , Nanoestructuras/química , Biomarcadores de Tumor/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Masculino
10.
Front Oncol ; 14: 1336763, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903724

RESUMEN

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. Objective: The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Methods: Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. Results: In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Conclusions: Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

11.
Transl Cancer Res ; 13(5): 2094-2107, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38881939

RESUMEN

Background: Angiogenesis of the tumor microenvironment (TME) can promote the proliferation and metastases of colon cancer (CC). However, there is a lack of bioinformatics analysis to comprehensively clarify the molecular characteristics, immune interaction characteristics and predictive values of angiogenesis characteristics in CC patients. This study aimed to perform a comprehensive elucidation of the correlation between angiogenesis and CC for the purpose of improving the clinical management of CC. Methods: Angiogenesis-associated genes (AAGs) were evaluated in the population of CC patients from the Cancer Genome Atlas database and Gene Expression Omnibus dataset. The expression, prognostic role, and immune cell infiltration of AAGs were assessed first. And then we established the AAGs score to further explore the prognosis and treatment response of angiogenesis characteristics in individual patient. Results: Totally, we identified two different molecular subtypes of angiogenesis, and there was a significant difference in the background of genome, expression profiles, prognosis, and characteristics of TME between two subtypes. And the AAGs score was independently associated with over survival in CC patients, the prognostic value was significant and confirmed in the entire cohort. And we also constructed a nomogram based on the risk score and clinical parameters to maximize the predictive ability of the risk score. Additionally, the AAGs score was significantly correlated with the tumor mutation burden score, cancer stem cell score and drug sensitivity. Conclusions: Our study elucidated the role of angiogenesis characteristics in CC and the AAGs score could help clinicians plan for individual management with chemotherapy agents and promote the development of immunotherapy in CC. Prospective studies need to be conducted to further confirm our findings.

12.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167206, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38718848

RESUMEN

The long noncoding RNA growth arrest-specific 5 (lncRNA Gas5) is implicated in various kidney diseases. In this study, we investigated the lncRNA Gas5 expression profile and its critical role as a potential biomarker in the progression of chronic kidney disease. Subsequently, we assessed the effect of lncRNA Gas5 deletion on renal fibrosis induced by unilateral ureteral obstruction (UUO). The results indicated that loss of lncRNA Gas5 exacerbates UUO-induced renal injury and extracellular matrix deposition. Notably, the deletion of lncRNA Gas5 had a similar effect on control mice. The fibrogenic phenotype observed in mice lacking lncRNA Gas5 correlates with peroxisome proliferator-activated receptor (PPAR) signaling pathway activation and aberrant cytokine and chemokine reprogramming. Single-cell RNA sequencing analysis revealed key transcriptomic features of fibroblasts after Gas5 deletion, revealing heterogeneous cellular states suggestive of a propensity for renal fibrosis. Our findings indicate that lncRNA Gas5 regulates the differentiation and activation of immune cells and the transcription of key genes in the PPAR signaling pathway. These data offer novel insights into the involvement of lncRNA Gas5 in renal fibrosis, potentially paving the way for innovative diagnostic and therapeutic targets.


Asunto(s)
Fibrosis , ARN Largo no Codificante , Análisis de la Célula Individual , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Fibrosis/genética , Ratones , Perfilación de la Expresión Génica , Masculino , Obstrucción Ureteral/patología , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo , Riñón/patología , Riñón/metabolismo , Transcriptoma , Transducción de Señal/genética , Ratones Endogámicos C57BL , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Ratones Noqueados , Fibroblastos/metabolismo , Fibroblastos/patología , Enfermedades Renales/genética , Enfermedades Renales/patología , Enfermedades Renales/metabolismo
13.
PLoS One ; 19(4): e0299496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38573890

RESUMEN

As video platforms such as Douyin, also known as TikTok's Chinese version, continue to grow, there is an increasing interest in the study of green advertising videos to understand their audiovisual features and their impact on audience engagement. In this research, we specifically focus on green advertising within the automotive industry. Drawing on literature from sustainability, green advertising, and communication studies, we identified seven audiovisual aspects and three persuasive strategies pertinent to green automotive advertising videos. Utilizing a mixed-methods video analysis framework, we analyzed a dataset of 2,553 green automotive advertising videos on Douyin over three years from 15 June 2020 to 15 June 2023. These videos exhibited higher loudness, a faster pace, and longer durations compared to their non-green counterparts. We categorized three distinct types of green advertising videos on Douyin and established that specific audiovisual features and persuasive strategies are significantly correlated with audience engagement levels. This study not only delineates the audiovisual characteristics of green automotive advertising in China's digital space but also contributes to the broader discourse on sustainable marketing practices on social networks like TikTok. The findings extend image-centric research to video content and provide marketers with data-driven insights for crafting effective content creation strategies on Douyin.

14.
Cancer Cell Int ; 24(1): 129, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582841

RESUMEN

BACKGROUND: The objective of this study was to determine the role and regulatory mechanism of miR-380 in cholangiocarcinoma. METHODS: The TargetScan database and a dual-luciferase reporter assay system were used to determine if LIS1 was a target gene of miR-380. The Cell Counting Kit 8 assay, flow cytometry, and Transwell assay were used to detect the effects of miR-380 and LIS1 on the proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. Western blotting was used to determine the effect of miR-380 on MMP-2/p-AKT. Immunohistochemistry detected the regulatory effect of miR-380 on the expression of MMP-2/p-AKT/LIS1. RESULTS: Expression of miR-380 in cholangiocarcinoma was decreased but expression of LIS1 was increased. LIS1 was confirmed to be a target gene of miR-380. Transfection with miR-380 mimics inhibited the proliferation, S-phase arrest, and invasion of HCCC-9810/HuCCT1/QBC939 cells, and LIS1 reversed these inhibitory effects. miR-380 inhibitor promoted proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. si-LIS1 salvaged the promotive effect of miR-380 inhibitor. Overexpression of miR-380 inhibited expression of MMP-2/p-AKT/LIS1, but miR-380 inhibitor promoted their expression. CONCLUSION: An imbalance of miR-380 expression is closely related to cholangiocarcinoma, and overexpression of miR-380 inhibits the expression of MMP-2/p-AKT by directly targeting LIS1.

15.
Sci Total Environ ; 928: 172345, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38621537

RESUMEN

Fine particulate matter (PM2.5) causes millions of premature deaths each year worldwide. Oxidative potential (OP) has been proposed as a better metric for aerosol health effects than PM2.5 mass concentration alone. In this study, we report for the first time online measurements of PM2.5 OP in wintertime Beijing and surroundings based on a dithiothreitol (DTT) assay. These measurements were combined with co-located PM chemical composition measurements to identify the main source categories of aerosol OP. In addition, we highlight the influence of two distinct pollution events on aerosol OP (spring festival celebrations including fireworks and a severe regional dust storm). Source apportionment coupled with multilinear regression revealed that primary PM and oxygenated organic aerosol (OOA) were both important sources of OP, accounting for 41 ± 12 % and 39 ± 10 % of the OPvDTT (OP normalized by the sampled air volume), respectively. The small remainder was attributed to fireworks and dust, mainly resulting from the two distinct pollution events. During the 3.5-day spring festival period, OPvDTT spiked to 4.9 nmol min-1 m-3 with slightly more contribution from OOA (42 ± 11 %) and less from primary PM (31 ± 15 %). During the dust storm, hourly-averaged PM2.5 peaked at a very high value of 548 µg m-3 due to the dominant presence of dust-laden particles (88 % of total PM2.5). In contrast, only mildly elevated OPvDTT values (up to 1.5 nmol min-1 m-3) were observed during this dust event. This observation indicates that variations in OPvDTT cannot be fully explained using PM2.5 alone; one must also consider the chemical composition of PM2.5 when studying aerosol health effects. Our study highlights the need for continued pollution control strategies to reduce primary PM emissions, and more in-depth investigations into the source origins of OOA, to minimize the health risks associated with PM exposure in Beijing.

16.
Nature ; 628(8008): 569-575, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570681

RESUMEN

Shuotheriids are Jurassic mammaliaforms that possess pseudotribosphenic teeth in which a pseudotalonid is anterior to the trigonid in the lower molar, contrasting with the tribosphenic pattern of therian mammals (placentals, marsupials and kin) in which the talonid is posterior to the trigonid1-4. The origin of the pseudotribosphenic teeth remains unclear, obscuring our perception of shuotheriid affinities and the early evolution of mammaliaforms1,5-9. Here we report a new Jurassic shuotheriid represented by two skeletal specimens. Their complete pseudotribosphenic dentitions allow reidentification of dental structures using serial homology and the tooth occlusal relationship. Contrary to the conventional view1,2,6,10,11, our findings show that dental structures of shuotheriids can be homologized to those of docodontans and partly support homologous statements for some dental structures between docodontans and other mammaliaforms6,12. The phylogenetic analysis based on new evidence removes shuotheriids from the tribosphenic ausktribosphenids (including monotremes) and clusters them with docodontans to form a new clade, Docodontiformes, that is characterized by pseudotribosphenic features. In the phylogeny, docodontiforms and 'holotherians' (Kuehneotherium, monotremes and therians)13 evolve independently from a Morganucodon-like ancestor with triconodont molars by labio-lingual widening their posterior teeth for more efficient food processing. The pseudotribosphenic pattern passed a cusp semitriangulation stage9, whereas the tribosphenic pattern and its precursor went through a stage of cusp triangulation. The two different processes resulted in complex tooth structures and occlusal patterns that elucidate the earliest diversification of mammaliaforms.


Asunto(s)
Evolución Biológica , Fósiles , Mamíferos , Diente , Animales , Euterios/anatomía & histología , Mamíferos/anatomía & histología , Mamíferos/clasificación , Mamíferos/fisiología , Marsupiales/anatomía & histología , Diente Molar/anatomía & histología , Diente Molar/fisiología , Filogenia , Diente/anatomía & histología , Diente/fisiología , Masticación
17.
J Med Chem ; 67(8): 6687-6704, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38574002

RESUMEN

In the face of escalating metabolic disease prevalence, largely driven by modern lifestyle factors, this study addresses the critical need for novel therapeutic approaches. We have identified the sodium-coupled citrate transporter (NaCT or SLC13A5) as a target for intervention. Utilizing rational drug design, we developed a new class of SLC13A5 inhibitors, anchored by the hydroxysuccinic acid scaffold, refining the structure of PF-06649298. Among these, LBA-3 emerged as a standout compound, exhibiting remarkable potency with an IC50 value of 67 nM, significantly improving upon PF-06649298. In vitro assays demonstrated LBA-3's efficacy in reducing triglyceride levels in OPA-induced HepG2 cells. Moreover, LBA-3 displayed superior pharmacokinetic properties and effectively lowered triglyceride and total cholesterol levels in diverse mouse models (PCN-stimulated and starvation-induced), without detectable toxicity. These findings not only spotlight LBA-3 as a promising candidate for hyperlipidemia treatment but also exemplify the potential of targeted molecular design in advancing metabolic disorder therapeutics.


Asunto(s)
Hiperlipidemias , Humanos , Animales , Ratones , Hiperlipidemias/tratamiento farmacológico , Células Hep G2 , Relación Estructura-Actividad , Simportadores/antagonistas & inhibidores , Simportadores/metabolismo , Masculino , Hipolipemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/uso terapéutico , Hipolipemiantes/farmacocinética , Descubrimiento de Drogas , Ratones Endogámicos C57BL , Triglicéridos/sangre , Triglicéridos/metabolismo , Diseño de Fármacos
18.
Eur J Med Chem ; 270: 116333, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38569434

RESUMEN

Cushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we delve into recent advances in understanding the pathogenesis of CS and explore therapeutic options by conducting a critical analysis of potential drug targets and candidates. Additionally, we provide an overview of the design strategy employed in previously reported candidates, along with a summary of structure-activity relationship (SAR) analyses and their biological efficacy. This review aims to contribute valuable insights to the evolving landscape of CS research, shedding light on potential avenues for therapeutic development.


Asunto(s)
Síndrome de Cushing , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Humanos , Síndrome de Cushing/tratamiento farmacológico , Síndrome de Cushing/etiología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/complicaciones , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Desarrollo de Medicamentos , Hidrocortisona/uso terapéutico
19.
Ultrason Sonochem ; 104: 106818, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38452710

RESUMEN

In this study, we systematically investigated the emulsifying capabilities of myofibrillar protein (MP)- and MP peptide (MPP)-based conjugates synthesized through intensification techniques: water bath (WB), microwave, ultrasound, and the combined ultrasound-microwave (UM) methods. Compared with WB, microwave, and ultrasound treatments, the combined UM treatment greatly promoted the glycation reaction because ultrasound and microwave mutually reinforced modification effects. The resultant conjugate structure tended to unfold with more flexible conformation and homogeneous morphology. Moreover, the emulsifying properties of conjugates developed with single and combined ultrasound-assisted glycation displayed substantial improvement, and pre-hydrolysis further enhanced these performances, as observed in the Principal Component Analysis as well. Remarkably, MPP grafted by maltodextrin with the assistance of a combined UM field produced the smallest and most uniform emulsion system, positioning it as the most efficient emulsifier among all the fabricated glycoconjugates. Our study highlighted the potential of synergistically applying ultrasound and microwave techniques to develop a well-performance glycation with an ideal conjugate structure, in which they would be associated into a strong film that provided the robust physical barrier, creaming stability, heat retention, and oxidation resistance. These findings offered a basis for better utilizing complex ultrasonic technology to develop novel and improved MP-based food products.


Asunto(s)
Emulsionantes , Microondas , Polisacáridos , Emulsionantes/química , Proteínas , Emulsiones/química , Péptidos
20.
Bioresour Technol ; 397: 130508, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38431057

RESUMEN

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.


Asunto(s)
Chlorella , Microalgas , Humanos , Microalgas/metabolismo , Biocombustibles , Carbono/metabolismo , Proteínas/metabolismo , Biomasa
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