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1.
JMIR Public Health Surveill ; 10: e57437, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267352

RESUMO

Background: Personality has an impact on the health-related quality of life (HRQoL) of older adults. However, the relationship and mechanisms of the 2 variables are controversial, and few studies have been conducted on older adults. Objective: The aim of this study was to explore the relationship between personality and HRQoL and the mediating and moderating roles of sleep quality and place of residence in this relationship. Methods: A total of 4123 adults 60 years and older were from the Psychology and Behavior Investigation of Chinese Residents survey. Participants were asked to complete the Big Five Inventory, the Brief version of the Pittsburgh Sleep Quality Index, and EQ-5D-5L. A backpropagation neural network was used to explore the order of factors contributing to HRQoL. Path analysis was performed to evaluate the mediation hypothesis. Results: As of August 31, 2022, we enrolled 4123 older adults 60 years and older. Neuroticism and extraversion were strong influencing factors of HRQoL (normalized importance >50%). The results of the mediation analysis suggested that neuroticism and extraversion may enhance and diminish, respectively, HRQoL (index: ß=-.262, P<.001; visual analog scale: ß=-.193, P<.001) by increasing and decreasing brief version of the Pittsburgh Sleep Quality Index scores (neuroticism: ß=.17, P<.001; extraversion: ß=-.069, P<.001). The multigroup analysis suggested a significant moderating effect of the place of residence (EQ-5D-5L index: P<.001; EQ-5D-5L visual analog scale: P<.001). No significant direct effect was observed between extraversion and EQ-5D-5L index in urban older residents (ß=.037, P=.73). Conclusions: This study sheds light on the potential mechanisms of personality and HRQoL among older Chinese adults and can help health care providers and relevant departments take reasonable measures to promote healthy aging.


Assuntos
Personalidade , Qualidade de Vida , Humanos , Masculino , Estudos Transversais , Qualidade de Vida/psicologia , Feminino , Idoso , China/epidemiologia , Pessoa de Meia-Idade , Análise de Mediação , Idoso de 80 Anos ou mais , Inquéritos e Questionários , Qualidade do Sono , População do Leste Asiático
2.
Comput Biol Med ; 181: 109076, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39216405

RESUMO

BACKGROUND: Knowledge feature (KF) with clear physiological significance of photoplethysmography are widely used in predicting blood pressure. However, KF primarily focus on local information of photoplethysmography, which may struggle to capture the overall characteristics. METHODS: Firstly, functional data analysis (FDA) was introduced to extract two types of data feature (DF). Furthermore, data-knowledge co-driven feature (DKCF) was proposed by combining FDA and constraints of KF. Finally, random forest, ada boost, gradient boosting, support vector machine and deep neural network were adopted, to compare the abilities of KF, DFs and DKCF in predicting blood pressure with two datasets (A published dataset and a self-collected dataset). RESULTS: Under the premise of extracting only 9 features, the average mean absolute errors (MAE) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) obtained by DKCF are both the smallest in dataset 1. In dataset 2, DKCF acquires the smallest MAE in predicting SBP and obtains the second smallest MAE in predicting DBP. CONCLUSIONS: The results demonstrate that low-dimensional DKCF of photoplethysmography is closely correlated with blood pressure, which may serve as an important indicator for health assessment.


Assuntos
Pressão Sanguínea , Fotopletismografia , Humanos , Fotopletismografia/métodos , Pressão Sanguínea/fisiologia , Masculino , Feminino , Determinação da Pressão Arterial/métodos , Adulto , Máquina de Vetores de Suporte , Redes Neurais de Computação , Pessoa de Meia-Idade
3.
Clin Transl Radiat Oncol ; 48: 100818, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39091465

RESUMO

Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0-8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1-34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0-15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

4.
Small ; : e2403399, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39045897

RESUMO

Ammonia (NH3) synthesis via the nitrate reduction reaction (NO3RR) offers a competitive strategy for nitrogen cycling and carbon neutrality; however, this is hindered by the poor NO3RR performance under high current density. Herein, it is shown that boron-doped Ti3C2Tx MXene nanosheets can highly efficiently catalyze the conversion of NO3RR-to-NH3 at ambient conditions, showing a maximal NH3 Faradic efficiency of 91% with a peak yield rate of 26.2 mgh-1 mgcat. -1, and robust durability over ten consecutive cycles, all of them are comparable to the best-reported results and exceed those of pristine Ti3C2Tx MXene. More importantly, when tested in a flow cell, the designed catalyst delivers a current density of ‒1000 mA cm-2 at a low potential of ‒1.18 V versus the reversible hydrogen electrode and maintains a high NH3 selectivity over a wide current density range. Besides, a Zn-nitrate battery with the catalyst as the cathode is assembled, which achieves a power density of 5.24 mW cm-2 and a yield rate of 1.15 mgh-1 mgcat. -1. Theoretical simulations further demonstrate that the boron dopants can optimize the adsorption and activation of NO3RR intermediates, and reduce the potential-determining step barrier, thus leading to an enhanced NH3 selectivity.

5.
Chin J Cancer Res ; 36(3): 306-321, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988489

RESUMO

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

6.
Chem Commun (Camb) ; 60(66): 8728-8731, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39072368

RESUMO

Herein, we show that P-doped Ti3C2Tx MXene nanosheets can effectively catalyze the NO3RR-to-NH3 conversion with a high faradaic efficiency of 95% and a yield rate of 5.39 mg h-1 mgcat.-1. Moreover, the catalyst achieves an impressive high current density of -1200 mA cm-2 at a low potential of -1.51 V, accompanied by an NH3 productivity of 123.5 mg h-1 mgcat.-1. Theoretical calculations further reveal that phosphorous dopants facilitate the adsorption and activation of reactants/intermediates and thus lower the energy barrier.

7.
Nat Commun ; 15(1): 4470, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796520

RESUMO

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.

8.
Physiol Plant ; 176(3): e14321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686595

RESUMO

Increasing density is an effective way to enhance wheat (Triticum aestivum L.) yield under limited cultivated areas. However, the physiological mechanisms underlying the reduction in grain weight when density increased are still unclear. Three field experiments were conducted during the 2014-2019 growing seasons to explore the physiological mechanisms by which polyamines affect grain weight formation. The results showed that when wheat planting density exceeded 450 × 104 seedlings ha-1 and 525 × 104 seedlings ha-1, wheat yield tended to decrease. Compared to moderate density (DM, 450 × 104 seedlings ha-1), the filling rate of inferior grains was reduced before 25 days after anthesis (DAA) and the active filling period was shortened by 6.4%-7.4% under high density (DH, 600 × 104 seedlings ha-1), resulting in a loss of 1000-grain weight by 5.4%-8.1%. DH significantly reduced sucrose and starch content in inferior grains at the filling stage. Meanwhile, DH inhibited the activity of key enzymes involved in polyamine synthesis [SAMDC (EC 4.1.1.50) and SpdSy (EC 2.5.1.16)] and induced the activity of ethylene (ETH) precursor synthase, resulting in a significant decrease in endogenous spermidine (Spd) content in inferior grains, but a significant increase in ETH release rate. Post-flowering application of exogenous Spd increased the accumulation of sucrose and starch in the inferior grains and positively regulated the filling and grain weight of the inferior grains, whereas exogenous ETH had a negative effect. Overall, Spd may affect wheat grain weight at high planting density by promoting the synthesis of sucrose and starch in inferior grains.


Assuntos
Grão Comestível , Espermidina , Amido , Sacarose , Triticum , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Triticum/fisiologia , Espermidina/metabolismo , Amido/metabolismo , Sacarose/metabolismo , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
9.
BMC Pulm Med ; 24(1): 146, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509516

RESUMO

OBJECTIVE: Transbronchial biopsy is a safe manner with fewer complications than percutaneous transthoracic needle biopsy; however, the current diagnostic yield is still necessitating further improvement. We aimed to evaluate the diagnostic yield of using virtual bronchoscopic navigation (VBN) and cone-beam CT (CBCT) for transbronchial biopsy and to investigate the factors that affected the diagnostic sensitivity. METHODS: We retrospectively investigated 255 patients who underwent VBN-CBCT-guided transbronchial biopsy at our two centers from May 2021 to April 2022. A total of 228 patients with final diagnoses were studied. Patient characteristics including lesion size, lesion location, presence of bronchus sign, lesion type and imaging tool used were collected and analyzed. Diagnostic yield was reported overall and in groups using different imaging tools. RESULTS: The median size of lesion was 21 mm (range of 15.5-29 mm) with 46.1% less than 2 cm in diameter. Bronchus sign was present in 87.7% of the patients. The overall diagnostic yield was 82.1%, and sensitivity for malignancy was 66.3%. Patients with lesion > 2 cm or with bronchus sign were shown to have a significantly higher diagnostic yield. Four patients had bleeding and no pneumothorax occurred. CONCLUSION: Guided bronchoscopy with VBN and CBCT was an effective diagnostic method and was associated with a high diagnostic yield in a safe manner. In addition, the multivariant analysis suggested that lesion size and presence of bronchus sign could be a predictive factor for successful bronchoscopic diagnosis.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Biópsia/métodos , Tomografia Computadorizada de Feixe Cônico , Brônquios/patologia , Broncoscopia/métodos
10.
Anal Chim Acta ; 1298: 342380, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462337

RESUMO

Herbicides have been extensively used around the world, which poses a potential hazard to humans and wildlife. Accurate detection of herbicides is crucial for the environment and human health. Herein, a simple and sensitive fluorescence sensor array was constructed for discrimination and identification of herbicides. Fluorescent gold nanoclusters modified with 11-mercaptoundecanoic acid or reduced glutathione were prepared, respectively. Metal ions quenched the fluorescence of nanoclusters through coordination and leading to the aggregation of gold nanoclusters. The addition of auxin herbicides (2,4-dichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid, decamba, picloram, quinclorac) restored the fluorescence of nanoclusters with different degrees. The mechanism study showed auxin herbicides can bind with metal ions and re-disperse the gold nanoclusters from the aggregation state. The "on-off-on" fluorescent sensor array was constructed basic on above detection mechanism. Combined with principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods, auxin herbicides are well separated on 2D/3D PCA score plots and HCA dendrogram in the range of 40-500 µm. In addition, the fluorescence sensor array performed successful in detecting real samples and blind samples. The developed sensor system shows a promising in practical detection of herbicides.


Assuntos
Herbicidas , Nanopartículas Metálicas , Humanos , Ouro , Fluorescência , Corantes Fluorescentes , Ácidos Indolacéticos , Íons , Espectrometria de Fluorescência/métodos
11.
Int J Oncol ; 64(4)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38391024

RESUMO

Human epidermal growth factor receptor 2 (HER2)+ gastric cancer (GC) is a distinct subtype of GC, accounting for 10­20% of all cases of GC. Although the development of the anti­HER2 monoclonal antibody trastuzumab has markedly improved response rates and prognosis of patients with HER2+ advanced GC (AGC), drug resistance remains a considerable challenge. Therefore, dynamic monitoring of HER2 expression levels can facilitate the identification of patients who may benefit from targeted therapy. Besides trastuzumab, DS­8201 and RC48 have been applied in the treatment of HER2+ AGC, and several novel anti­HER2 therapies are undergoing preclinical/clinical trials. At present, combination immunotherapy with anti­HER2 agents is used as the first­line treatment of this disease subtype. New promising approaches such as chimeric antigen receptor T­cell immunotherapy and cancer vaccines are also being investigated for their potential to improve clinical outcomes. The current review provides new insights that will guide the future application of anti­HER2 therapy by summarizing research progress on targeted therapy drugs for HER2+ AGC and combination treatments.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Trastuzumab/uso terapêutico , Receptor ErbB-2/metabolismo , Antineoplásicos/uso terapêutico , Prognóstico , Imunoterapia
12.
Braz J Med Biol Res ; 57: e13192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38381884

RESUMO

The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.


Assuntos
Adenocarcinoma , Eritrodermia Ictiosiforme Congênita , Erros Inatos do Metabolismo Lipídico , Doenças Musculares , Receptor de Morte Celular Programada 1 , Humanos , Metástase Linfática/patologia , Células Dendríticas , Adenocarcinoma/patologia
13.
Front Pharmacol ; 15: 1274209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410129

RESUMO

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK's role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.

14.
Braz. j. med. biol. res ; 57: e13192, fev.2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1534072

RESUMO

Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.

15.
Adv Sci (Weinh) ; 11(4): e2305016, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037482

RESUMO

With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next-generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high-quality thin films of molecular ferroelectrics. To address the above issue, a volume-confined method is utilized to achieve ultrasmooth single-crystal molecular ferroelectric thin films at the sub-centimeter scale, with the thickness controlled in the range of 100-1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two-dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high-performance devices based on molecular ferroelectric thin films.

16.
Adv Mater ; 36(11): e2307518, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38041802

RESUMO

On the path of persisting Moore's Law, one of the biggest obstacles is the "Boltzmann tyranny," which defines the lower limit of power consumption of individual transistors. Negative capacitance (NC) in ferroelectrics could provide a solution and has garnered significant attention in the fields of nanoelectronics, materials science, and solid-state physics. Molecular ferroelectrics, as an integral part of ferroelectrics, have developed rapidly in terms of both performance and functionality, with their inherent advantages such as easy fabrication, mechanical flexibility, low processing temperature, and structural tunability. However, studies on the NC in molecular ferroelectrics are limited. In this study, the focus is centered on the fabricated high-quality thin films of trimethylchloromethyl ammonium trichlorocadmium(II), and a pioneering investigation on their NC responses is conducted. The findings demonstrate that the NC exhibited by molecular ferroelectrics is comparable to that of conventional HfO2 -based ferroelectrics. This underscores the potential of molecular material systems for next-generation electronic devices.

17.
Transl Res ; 266: 1-15, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37433392

RESUMO

Diabetic lipo-toxicity is a fundamental pathophysiologic mechanism in DM and is now increasingly recognized a key determinant of DKD. Targeting lipid metabolic disorders is an important therapeutic strategy for the treatment of DM and its complications, including DKD. This study aimed to explore the molecular mechanism of lipid metabolic regulation in kidney, especially renal PTECs, and elucidate the role of lipid metabolic related molecule lipin-1 in diabetic lipid-related kidney damage. In this study, lipin-1-deficient db/db mouse model and STZ/HFD-induced T2DM mouse model were used to determine the effect of lipin-1 on DKD development. Then RPTCs and LPIN1 knockdown or overexpressed HK-2 cells induced by PA were used to investigate the mechanism. We found that the expression of lipin-1 increased early and then decreased in kidney during the progression of DKD. Glucose and lipid metabolic disorders and renal insufficiency were found in these 2 types of diabetic mouse models. Interestingly, lipin-1 deficiency might be a pathogenic driver of DKD-to-CKD transition, which could further accelerate the imbalance of renal lipid homeostasis, the dysfunction of mitochondrial and energy metabolism in PTECs. Mechanistically, lipin-1 deficiency resulted in aggravated PTECs injury to tubulointerstitial fibrosis in DKD by downregulating FAO via inhibiting PGC-1α/PPARα mediated Cpt1α/HNF4α signaling and upregulating SREBPs to promote fat synthesis. This study provided new insights into the role of lipin-1 as a regulator for maintaining lipid homeostasis in the kidney, especially PTECs, and its deficiency led to the progression of DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Doenças Metabólicas , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Rim/patologia , Modelos Animais de Doenças , Lipídeos , Ácidos Graxos , Doenças Metabólicas/patologia , Diabetes Mellitus/patologia , Compostos Orgânicos
18.
Cell Res ; 33(11): 835-850, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37726403

RESUMO

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Serina/metabolismo , Linhagem Celular Tumoral
19.
Am J Health Behav ; 47(3): 510-519, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37596749

RESUMO

Objectives: In this study, we investigate the relationships among personal well-being, self-esteem, supervisor support, life satisfaction, and happiness in a sample of nurses. In this study, we also investigate the mediating role of life satisfaction. Methods: Present research was quantitative in nature and the research design was cross-sectional. Data were collected from a convenience sample of nurses working in hospitals by using a self-administered survey. We used partial least square-structural equation modeling (PLS-SEM) for the assessment of statistical significance of the proposed model. Results: We found a statistically significant and positive relationship between personal well-being, life satisfaction, and happiness. Similarly, self-esteem and supervisor support positively affected life satisfaction. Conclusion: Our research adds to the present literature on the factors that affect happiness among nurses. The study also adds to the current literature on PLS-SEM in terms of the assessment of mediation and direct relationships. Our findings are helpful for decision-makers in the health sector in developing happiness and life satisfaction among nurses. These results are also valuable for academicians for their future studies.


Assuntos
Felicidade , Análise de Mediação , Recursos Humanos de Enfermagem , Satisfação Pessoal , Humanos , Estudos Transversais , Satisfação no Emprego , Recursos Humanos de Enfermagem/psicologia , Reprodutibilidade dos Testes , Autoimagem , Autorrelato , Apoio Social , Inquéritos e Questionários , Pessoa de Meia-Idade , Idoso
20.
Inorg Chem ; 62(30): 11809-11816, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37466947

RESUMO

Metal-organic frameworks (MOFs) built from fluorescent ligands frequently exhibit enhanced fluorescence when doped with inert ligands. This study focuses on a MOF of the UiO-68 structure, which is built from a fluorescent dibenzoate-anthracene ligand doped with a dibenzoate-benzene ligand. Our investigation aims to understand the mechanism behind the doping-enhanced emission of this MOF. We rule out several possible mechanisms, including exciton coupling, electron transfer between ligand and metal center, and ligand intersystem crossing induced by the metal center. Inhibition of the interligand charge transfer is considered a possible way to enhance emission. Furthermore, we propose that the conformational change of the anthracene-based ligand in the MOF cavity is also a way for enhancement. Our molecular dynamics simulations of the MOF structure filled with solvents reveal that the steric crowding in the cavity induces a conformational change at different doping levels, affecting the rate of intersystem crossing of the ligand.

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