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1.
Gerontology ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697041

RESUMO

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCC) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD) and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aim to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from seven electronic databases. The Newcastle Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR=2.02; 95%CI=1.94-2.11), cognitive impairment (adjusted RR=1.72; 95%CI=1.49-1.99), falls (adjusted RR=1.32; 95%CI=1.17-1.50), mortality (adjusted RR=1.66; 95%CI=1.32-2.10); MCR had more prominent predictive efficacy for AD (adjusted RR=2.23; 95%CI=1.81-2.76) compared to VaD (adjusted RR=3.78; 95%CI=0.49-28.95), while excluding analyses from the study that utilized the Timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (HR=1.69; 95%CI=1.08-2.02) and frailty (OR=5.53; 95%CI=1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR=1.22; 95%CI=1.11-1.34 vs. adjusted RR=1.19; 95%CI= 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis, and provide evidence to support future targeted interventions.

2.
J Am Chem Soc ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741463

RESUMO

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6 double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 µA/cm2 from 30.62 µA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and -1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn-Teller distortion of the oxygen octahedron are the main phenomena of the change in electron-orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.

3.
Appl Opt ; 63(9): 2352-2361, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568591

RESUMO

Improving the spectrum efficiency (SE) is an effective method to further enhance the data rate of bandwidth-limited underwater wireless optical communication (UWOC) systems. Non-orthogonal frequency-division multiplexing (NOFDM) with a compression factor of 0.5 can save half of the bandwidth without introducing any inter-carrier-interference (ICI) only if the total number of subcarriers is large enough, and we termed it as half-spectrum OFDM (HS-OFDM). To the best of our knowledge, this is the first reported work on a closed-form HS-OFDM signal in the discrete domain from the perspective of a correlation matrix. Due to the special mathematical property, no extra complex decoding algorithm is required at the HS-OFDM receiver, making it as simple as the conventional OFDM receiver. Compared with traditional OFDM, HS-OFDM can realize the same data rate, but with a larger signal-to-noise ratio (SNR) margin. To fully use the SNR resource of the communication system, we further propose a digital power division multiplexed HS-OFDM (DPDM-HS-OFDM) scheme to quadruple the SE of conventional OFDM for the bandwidth-starved UWOCs. The experimental results show that HS-OFDM can improve the receiver sensitivity by around 4 dB as opposed to conventional 4QAM-OFDM with the same data rate and SE. With the help of the DPDM-HS-OFDM scheme, the data rate of multi-user UWOC can reach up to 4.5 Gbps under the hard-decision forward error correction (HD-FEC) limit of a bit error rate (BER) of 3.8×10-3. Although there is some performance degradation in comparison with single-user HS-OFDM, the BER performance of multi-user DPDM-HS-OFDM is still superior to that of conventional single-user 4QAM-OFDM. Both single-user HS-OFDM and multi-user DPDM-HS-OFDM successfully achieve 2 Gbps/75 m data transmission, indicating that the DPDM-HS-OFDM scheme is of great importance in bandwidth-limited UWOC systems and has guiding significance to underwater wireless optical multiple access.

4.
J Mater Chem B ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682491

RESUMO

Black phosphorus (BPs) nanosheets with their inherent and selective chemotherapeutic effects have recently been identified as promising cancer therapeutic agents, but challenges in surface functionalization hinder satisfactory enhancement of their selectivity between tumors and normal cells. To address this issue, we developed a novel biomineralization-inspired strategy to synthesize CaBPs-Na2FDP@CaCl2 nanosheets, aiming to achieve enhanced and selective anticancer bioactivity along with accelerated osteoblast activity. Benefiting from the in situ mineralization and fructose modification, CaBPs-Na2FDP@CaCl2 exhibited improved pH-responsive degradation behavior and targeted therapy for osteosarcoma. The in vitro results indicated that CaBPs-Na2FDP@CaCl2 exhibited efficient uptake and quick degradation by GLUT5-positive 143B osteosarcoma cells, enhancing BPs-driven chemotherapeutic effects through ATP level disturbance-mediated apoptosis of tumor cells. Moreover, CaBPs-Na2FDP@CaCl2 underwent gradual degradation into PO43-, Ca2+ and fructose in MC3T3-E1 cells, eliminating systemic toxicity. Intracellular Ca2+ bound to calmodulin (CaM), activating Ca2+/CaM-dependent signaling cascades, thereby enhancing osteoblast differentiation and mineralization in pro-osteoblastic cells. In vivo experiments affirmed the anti-tumor capability, inhibition of tumor recurrence and bone repair promotion of CaBPs-Na2FDP@CaCl2. This study not only broadens the application of BPs in bone tumor therapy but also provides a versatile surface functionalization strategy for nanotherapeutic agents.

5.
Front Endocrinol (Lausanne) ; 15: 1278504, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686203

RESUMO

Objective: The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. Results: The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). Conclusion: In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.


Assuntos
Criopreservação , Transferência Embrionária , Endométrio , Resultado da Gravidez , Taxa de Gravidez , Fluxo Pulsátil , Artéria Uterina , Humanos , Feminino , Gravidez , Transferência Embrionária/métodos , Adulto , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiologia , Estudos de Casos e Controles , Fluxo Pulsátil/fisiologia , Endométrio/irrigação sanguínea , Endométrio/diagnóstico por imagem , Fertilização in vitro/métodos , Estudos Retrospectivos
6.
PLoS Biol ; 22(3): e3002515, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512963

RESUMO

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.


Assuntos
Proteínas de Drosophila , MicroRNAs , Animais , Feminino , Drosophila/genética , Drosophila/metabolismo , Ovário/metabolismo , Proteínas de Drosophila/metabolismo , Nicho de Células-Tronco/genética , Diferenciação Celular/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Células-Tronco/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Comunicação , Drosophila melanogaster/metabolismo , Células Germinativas/metabolismo
7.
Opt Express ; 32(5): 8081-8091, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439474

RESUMO

A digital pre-distortion (DPD) scheme based on an adaptive-memory-length look-up table (AML-LUT) is proposed and experimentally demonstrated in a four-level pulse amplitude modulation (4-PAM) underwater optical wireless communication (UOWC) system. By implementing adaptive memory length for each pattern in the AML-LUT-based DPD, the size of the AML-LUT can be significantly reduced without sacrificing performance compared to both the full-size LUT and the multi-symbol simplified look-up table (MSS-LUT)-based DPDs. The performance of the proposed AML-LUT-based DPD is experimentally evaluated for a 625 Mbit/s 4-PAM UOWC over 1 m transmission length. Experimental results show that compared with the full-size LUT with a memory length of 7 (LUT-7)-based DPD, the proposed AML-LUT-based DPD (i) incurs a marginal power penalty of 0.5 dB at both the 7% hard-decision forward error correction (HD-FEC) and KP4-FEC threshold limits, while simultaneously reducing the implementation complexity (i.e., the LUT size) by 93%; (ii) achieves comparable transmission performance compared to the MSS-LUT-based DPD, while reducing the implementation complexity by 89%; and (iii) shows great potential for high-speed, low-complexity and memory-efficient intensity modulation and direct detection (IM/DD) UOWC and short-reach optical interconnects.

8.
Inorg Chem ; 63(12): 5709-5717, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38484381

RESUMO

The electron transport layer (ETL) plays an important role in determining the conversion efficiency and stability of perovskite solar cells (PSCs). Here, TiO2 thin film was prepared by irradiating diisopropoxy diacetylacetone titanium precursor thin film with 172 nm vacuum ultraviolet (VUV) at a low temperature. The prepared TiO2 thin film has higher electron mobility and conductivity. As it is used as an ETL for MAPbI3 PSCs, its band structure is better matched with the perovskite, and at the same time, due to the good interface contact, more uniform perovskite crystals are formed. Most importantly, a large number of hydroxyl radicals were formed during VUV irradiation of the precursor film, which made up for the oxygen defect present on the surface of the TiO2 thin film, and were adsorbed to the film surface. These hydroxyl groups form hydrogen bonds with methylammonium (MA) components on the MAPbI3 buried surface, thus promoting the transfer of photogenerated electrons at the MAPbI3/ETL interface. The power conversion efficiency of PSCs fabricated in air with the ETL prepared by VUV irradiation is 20.46%, which is higher than that of the contrast solar cell based on the sintered ETL (17.96%).

9.
iScience ; 27(3): 109147, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38433901

RESUMO

Aiming at the current SPI (solder paste inspection) system for printing solder paste similar defects detection accuracy is not high, the system intelligence degree is low and so on, design a for the solder paste similar defects and combined with phase modulation profile measurement technique and improve the YOLOX intelligent detection system. The core of the system is the improved YOLOX depth model based on s-mosica and kt-iou algorithms proposed in this paper. The experimental results show that the proposed s-mosica and kt-iou algorithms can effectively improve the detection accuracy of printed solder paste, and when combined with the YOLOX model, the best 90.33% detection accuracy is obtained, which is better than the detection performance of the existing algorithms in the same scenario, and it provides an effective and feasible reference program for the design of the SPI high-precision intelligent detection system.

10.
J Food Sci ; 89(4): 2450-2464, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462851

RESUMO

Fermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)-induced UC were investigated via 16S rRNA sequencing and non-targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro-inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS-induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Metabólicas , Animais , Camundongos , Lactobacillus , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , RNA Ribossômico 16S , Ácido Butírico , Bifidobacterium , Firmicutes , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo
11.
Nano Lett ; 24(7): 2196-2202, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329428

RESUMO

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

12.
iScience ; 27(2): 108811, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303695

RESUMO

MicroRNA (miRNA) plays physiologically and pathologically important roles in post-transcriptional regulation. Although miRNA has been suggested to dynamically interact with cellular organelles, the dynamicity of intracellular miRNA behavior has remained unclear. Here, by introducing fluorescently labeled pre-miRNA into living cells, we improved the miRNA visualization method using exogenous miRNA precursors. Through the combination of our miRNA visualization method and single-molecule sensitive fluorescence microscopy, we quantitatively analyzed the process of miRNA maturation. Furthermore, single-particle tracking of fluorescent miRNA in cells revealed the directed movements of miRNA on cytoskeletal components (i.e., microtubules and actin filaments). Our results also suggest that cytoskeleton-dependent miRNA trafficking is associated with the interaction of miRNAs with the nucleus and the endoplasmic reticulum/Golgi apparatus. Our method should facilitate the elucidation of the mechanism and physiological significance of the subcellular localization and organelle interaction of miRNA.

13.
Int J Surg ; 110(3): 1699-1710, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181123

RESUMO

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.


Assuntos
Imunoterapia , Melanoma , Humanos , Carga Tumoral , Autoria , Bibliometria , Microambiente Tumoral
14.
J Sci Food Agric ; 104(6): 3776-3787, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294418

RESUMO

BACKGROUND: Melons (Cucumis melo L.) are among the most commonly consumed fruits but they are highly susceptible to mechanical damage and rot during storage and transportation. New processed products are needed to avoid postharvest fruit loss and to increase health benefits. Fermentation is an effective means of utilizing the nutrients and improving flavor. RESULTS: Fermented melon juice (MJ) was prepared using three potential probiotics Lactiplantibacillus plantarum CICC21824 (LP), Lactiplantibacillus plantarum GB3-2 (LG), and Lactiplantibacillus pentosus XZ-34 (LX). The nutrition, flavor characteristics, and digestive properties of different fermented MJs were compared. The results demonstrated that, in comparison with mono-fermentation, mixed fermentation by LG and LX could increase the level of organic acids and phenolic acids. Correspondingly, antioxidant capacity was improved significantly and positively correlated with p-coumaric acid and cinnamic acid content. The production of alcohols and acids was more strongly enhanced by mixed culture fermentation, whereas mono-fermentation reduced the content of esters, especially ethyl acetate and isopropyl acetate. Aldehydes and ketones increased significantly in fermented MJ, and damascenone and heptanal could be the characteristic aroma compounds. CONCLUSION: Mixed fermented MJ provides more beneficial phytochemicals, better flavor, and stronger antioxidant properties than mono-fermentation. © 2024 Society of Chemical Industry.


Assuntos
Antioxidantes , Cucurbitaceae , Fermentação , Antioxidantes/química , Cucurbitaceae/metabolismo , Frutas/química , Álcoois/análise
15.
Nat Metab ; 6(2): 238-253, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38278946

RESUMO

Biphasic glucose-stimulated insulin secretion (GSIS) is essential for blood glucose regulation, but a mechanistic model incorporating the recently identified islet ß cell heterogeneity remains elusive. Here, we show that insulin secretion is spatially and dynamically heterogeneous across the islet. Using a zinc-based fluorophore with spinning-disc confocal microscopy, we reveal that approximately 40% of islet cells, which we call readily releasable ß cells (RRßs), are responsible for 80% of insulin exocytosis events. Although glucose up to 18.2 mM fully mobilized RRßs to release insulin synchronously (first phase), even higher glucose concentrations enhanced the sustained secretion from these cells (second phase). Release-incompetent ß cells show similarities to RRßs in glucose-evoked Ca2+ transients but exhibit Ca2+-exocytosis coupling deficiency. A decreased number of RRßs and their altered secretory ability are associated with impaired GSIS progression in ob/ob mice. Our data reveal functional heterogeneity at the level of exocytosis among ß cells and identify RRßs as a subpopulation of ß cells that make a disproportionally large contribution to biphasic GSIS from mouse islets.


Assuntos
Insulinas Bifásicas , Células Secretoras de Insulina , Camundongos , Animais , Secreção de Insulina , Insulinas Bifásicas/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Exocitose/fisiologia
16.
Cardiovasc Diabetol ; 23(1): 19, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195474

RESUMO

AIMS: Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known. In present study, we aimed to investigate whether Mel alleviated DCM via regulation of VEGF-B and explored its underlying mechanisms. METHODS AND RESULTS: We found that Mel significantly alleviated cardiac dysfunction and improved autophagy of cardiomyocytes in type 1 diabetes mellitus (T1DM) induced cardiomyopathy mice. VEGF-B was highly expressed in DCM mice in comparison with normal mice, and its expression was markedly reduced after Mel treatment. Mel treatment diminished the interaction of VEGF-B and Glucose-regulated protein 78 (GRP78) and reduced the interaction of GRP78 and protein kinase RNA -like ER kinase (PERK). Furthermore, Mel increased phosphorylation of PERK and eIF2α, then up-regulated the expression of ATF4. VEGF-B-/- mice imitated the effect of Mel on wild type diabetic mice. Interestingly, injection with Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration of GSK2656157 (GSK), an inhibitor of phosphorylated PERK abolished the protective effect of Mel on DCM. Furthermore, rapamycin, an autophagy agonist displayed similar effect with Mel treatment; while 3-Methyladenine (3-MA), an autophagy inhibitor neutralized the effect of Mel on high glucose-treated neonatal rat ventricular myocytes. CONCLUSIONS: These results demonstrated that Mel attenuated DCM via increasing autophagy of cardiomyocytes, and this cardio-protective effect of Mel was dependent on VEGF-B/GRP78/PERK signaling pathway.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Melatonina , Humanos , Camundongos , Ratos , Animais , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Miócitos Cardíacos , Fator B de Crescimento do Endotélio Vascular , Melatonina/farmacologia , Chaperona BiP do Retículo Endoplasmático , Diabetes Mellitus Experimental/tratamento farmacológico , Transdução de Sinais , Autofagia , Glucose
17.
Life Sci ; 338: 122396, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38171413

RESUMO

Lung adenocarcinoma (LUAD) is highly lethal tumor; understanding immune response is crucial for current effective treatment. Research investigated immunogenic cell death (ICD) impact on LUAD through 75 ICD-related genes which encompass cell damage, endoplasmic reticulum stress, microenvironment, and immunity. Transcriptome data and clinical info were analyzed, revealing two ICD-related clusters: B, an immune osmotic subgroup, had better prognosis, stronger immune signaling, and higher infiltration, while A represented an immune-deficient subgroup. Univariate Cox analysis identified six prognostic genes (AGER, CD69, CD83, CLEC9A, CTLA4, and NT5E), forming a validated risk score model. It was validated across datasets, showing predictive performance. High-risk group had unfavorable prognosis, lower immune infiltration, and higher chemotherapy sensitivity. Conversely, low-risk group had better prognosis, higher immune infiltration, and favorable immunotherapy response. The key gene NT5E was examined via immunohistochemistry, with higher expression linked to poorer prognosis. NT5E was predominantly expressed in B cells, fibroblasts, and endothelial cells, correlated with immune checkpoints. These outcomes suggest that NT5E can serve as a LUAD therapeutic target. The study highlights gene predictive value, offers an efficient tumor assessment tool, guides clinical treatment strategies, and identifies NT5E as therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Células Endoteliais , Morte Celular Imunogênica , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Microambiente Tumoral
18.
Sci Rep ; 14(1): 1568, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238494

RESUMO

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Nomogramas , Colangiocarcinoma/cirurgia , Fatores de Risco , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Internet , Programa de SEER , Prognóstico , Estadiamento de Neoplasias
19.
Angew Chem Int Ed Engl ; 63(1): e202316384, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38009454

RESUMO

Photocatalytic nitrogen fixation using solar illumination under ambient conditions is a promising strategy for production of the indispensable chemical NH3 . However, due to the catalyst's limitations in solar energy utilization, loss of hot electrons during transfer, and low nitrogen adsorption and activation capacity, the unsatisfactory solar-to-chemical conversion (SCC) efficiencies of most photocatalysts limit their practical applications. Herein, cerium oxide nanosheets with abundant strain-VO defects were anchored on Au hollow nanomushroom through atomically sharp interfaces to construct a novel semiconductor/plasmonic metal hollow nanomushroom-like heterostructure (denoted cerium oxide-AD/Au). Plasmonic Au extended the absorption of light from the visible to the second near-infrared region. The superior interface greatly enhanced the transfer efficiency of hot electrons. Abundant strain-VO defects induced by interfacial compressive strain promoted adsorption and in situ activation of nitrogen, and such synergistic promotion of strain and VO defects was further confirmed by density functional theory calculations. The judicious structural and defect engineering co-promoted the efficient nitrogen photofixation of the cerium oxide-AD/Au heterostructures with a SCC efficiency of 0.1 % under simulated AM 1.5G solar illumination, which is comparable to the average solar-to-biomass conversion efficiency of natural photosynthesis by typical plants, thus exhibiting significant potential as a new candidate for artificial photosynthesis.

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