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1.
Anal Chim Acta ; 1315: 342825, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879210

RESUMO

BACKGROUND: Non-invasive indirect blood glucose monitoring can be realized by detecting low concentrations of glucose (0.05-5 mM) in tears, but sensitive optical indicators are required. The intensity of the phosphorescence of a candidate optical indicator, palladium hematoporphyrin monomethyl ether (Pd-HMME), is increased by oxygen consumption under sealed conditions in the presence of glucose and glucose oxidase. However, the glucose detection limit based on this mechanism is high (800 µM) because the phosphorescence is completely quenched under ambient oxygen conditions and hence a large amount of glucose is required to reduce the oxygen levels such that the phosphorescence signal is detectable. RESULTS: To improve the glucose detection limit of Pd-HMME phosphorescence-based methods, the triplet protector imidazole was introduced, and strong phosphorescence was observed under ambient oxygen conditions. Detectable phosphorescence enhancement occurred at low glucose concentrations (<200 µM). Linear correlation between the phosphorescence intensity and glucose concentration was observed in the range of 30-727 µM (R2 = 99.9 %), and the detection limit was ∼10 µM. The glucose sensor has a fast response time (∼90 s) and excellent selectivity for glucose. SIGNIFICANCE AND NOVELTY: These results indicate the potential of the developed optical indicator for fast, selective, and reliable low-concentration glucose sensing.


Assuntos
Limite de Detecção , Medições Luminescentes , Medições Luminescentes/métodos , Hematoporfirinas/química , Hematoporfirinas/análise , Paládio/química , Glucose/análise , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Glicemia/análise , Imidazóis/química , Técnicas Biossensoriais/métodos , Oxigênio/química , Humanos
2.
Front Microbiol ; 15: 1408645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38894966

RESUMO

Introduction: Carbohydrates, which make up 20 to 25% of tea beverages, are responsible for their flavor and bioactivity. Carbohydrates of pu-erh tea change during microbial fermentation and require further research. In this study, we examined the carbohydrate metabolism and expression of carbohydrate-active enzyme genes during the fermentation of tea leaves with Aspergillus luchuensis. Methods: Widely targeted metabolomics analysis, high-performance anion-exchange chromatography measurements, and transcriptomics were used in this study. Results: After fermentation, the levels of soluble sugar, hemicellulose, lignin, eight monosaccharides, and seven sugar alcohols increased. Meanwhile, the relative contents of polysaccharides, D-sorbitol, D-glucose, and cellulose decreased. High expression of 40 genes encoding 16 carbohydrate enzymes was observed during fermentation (FPKM>10). These genes encode L-iditol 2-dehydrogenase, pectinesterase, polygalacturonase, α-amylase, glucoamylase, endoglucanase, ß-glucosidase, ß-galactosidase, α-galactosidase, α-glucosidase, and glucose-6-phosphate isomerase, among others. Discussion: These enzymes are known to break down polysaccharides and cell wall cellulose, increasing the content of monosaccharides and soluble sugars.

3.
Clin Exp Med ; 24(1): 118, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833040

RESUMO

Vitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent. This meta-analysis aimed to investigate the relationship between VDR gene polymorphisms and MM risk. The PubMed, Web of Science, Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), Wanfang Databases (WANFANG) were searched from inception to June 1, 2023, without language restriction or publication preference. Pooled odds ratio (OR) and 95% confidence interval (CI) for each variable were calculated. Leave-one-out sensitivity analysis was performed to determine the source of heterogeneity. Publication bias was assessed using Begg' and Egger's tests, and the trim-and-fill method was used to compensate for publication bias. The correlation meta-analysis was conducted using Comprehensive Meta-Analysis 3.0 and STATA 12.0 software. All the included studies were based on Asian populations and involved four VDR gene polymorphisms, TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410) and FokI (rs2228570). The results showed that TaqI (C vs. T: OR = 1.487, 95% CI 1.052, 2.104, P = 0.025; CC + CT vs. TT: OR = 1.830, 95% CI 1.138, 2.944, P = 0.013), ApaI (T vs. G: OR = 1.292, 95% CI 1.101, 1.517, P = 0.002; TT vs. GG: OR = 1.600, 95% CI 1.106, 2.314, P = 0.013; TG vs. GG: OR 1.305, 95% CI 1.050, 1.622; P = 0.016; TT + TG vs. GG: OR = 1.353, 95% CI 1.103, 1.662, P = 0.004), BsmI (GG vs. AA: OR = 1.918, 95% CI 1.293, 2.844, P = 0.001; GA vs. AA: OR = 1.333, 95% CI 1.058, 1.679, P = 0.015; G vs. A: OR = 1.398, 95% CI 1.180, 1.657, P = 0.000; GG vs. AA + GA: OR = 1.686, 95% CI 1.174, 2.423, P = 0.005), and FokI (T vs. C: OR = 1.687, 95% CI 1.474, 1.931, P = 0.000; TT vs. CC: OR = 2.829, 95% CI 2.066, 3.872, P = 0.000; TC vs. CC: OR = 1.579, 95% CI 1.304, 1.913, P = 0.000, TT + TC vs. CC: OR = 1.771, 95% CI 1.477, 2.125, P = 0.000; TT vs. CC + TC: OR = 2.409, 95% CI 1.814, 3.200, P = 0.000) are associated with MM risk. VDR gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations. Additional studies with large sample sizes and different ethnicities are needed.


Assuntos
Predisposição Genética para Doença , Mieloma Múltiplo , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol , Receptores de Calcitriol/genética , Mieloma Múltiplo/genética , Humanos , Povo Asiático/genética , Estudos de Casos e Controles , Razão de Chances
4.
Angew Chem Int Ed Engl ; : e202409656, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837290

RESUMO

Perovskite quantum dots (QDs) have shown attractive prospects in the field of visible photocatalysis, especially in the synthesis of high value-added chemicals. However, under aerobic conditions, the stable operation of QD catalysts has been limited by the reactive oxygen species (ROS) generated by photoexcitation, especially superoxide species. Here, we propose a strategy of Ce3+ doping in perovskite QDs to guide superoxide species for photocatalytic oxidation reactions. In C(sp3)-H bond oxidation of hydrocarbons, superoxide species were rapidly generated and efficiently utilized on the surface of perovskite QDs, which achieves the stable operation of the catalytic system and obtains a high product conversion rate (15.3 mmol/g/h for benzaldehydes). The mechanism studies show that the strong Ce-oxygen affinity accelerates the relaxation process of photoinduced exciton transfer to superoxide species and inhibits the radiative recombination pathway. This work provides a new idea of utilizing oxygen species on perovskite surface and broadens the design strategy of high-performance QD photocatalysts.

5.
Int J Pharm ; 660: 124330, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866081

RESUMO

Chemodynamic therapy (CDT) is a promising strategy for cancer treatment, however, its application is restricted by low hydrogen peroxide (H2O2) concentration, insufficient reactive oxygen species (ROS) generation, and high glutathione (GSH) levels. Here, we developed an injectable thermosensitive hydrogel (DSUC-Gel) based on "sea urchin-like" copper sulfide nanoparticles (UCuS) loaded with dihydroartemisinin (DHA) and sulfasalazine (SAS) to overcome these limitations of CDT. DSUC was cleaved to release DHA, SAS and Cu2+ under acidic tumor microenvironment to enhance CDT. DHA with peroxide bridge responded to intracellular Fe2+ to alleviate H2O2 deficiency. SAS prevented GSH synthesis by targeting SLC7A11 and inhibited glutathione peroxidase (GPX4) activity to induce endogenous ferroptosis. ROS produced by Fenton-like reaction of Cu2+ promoted lipid peroxidation (LPO) accumulation to promote ferroptosis. Enhanced CDT and ferroptosis induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration. As a result, DSUC-Gel significantly inhibited tumor growth both in vitro and in vivo. Our study provides a novel approach for enhancing anti-tumor efficacy by combining CDT, endogenous ferroptosis and ICD.

6.
Cancer Res ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775809

RESUMO

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted Smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional targeted therapies represent a promising direction for developing improved anti-Hh therapies. In this study, we integrated epigenetic/transcriptional-targeted small-molecule library screening with CRISPR/Cas9 knockout library screening and identified CDK9 and CDK12, two transcription elongation regulators, as therapeutic targets for antagonizing aberrant Hh activation and overcoming SMOi resistance. Inhibition of CDK9 or CDK12 potently suppressed Hh signaling and tumor growth in various SMOi responsive or resistant Hh-driven tumor models. Systemic epigenomic profiling elucidated the Hh-driven super-enhancer (SE) landscape and identified IRS1, encoding a critical component and cytoplasmic adaptor protein of the IGF pathway, as an oncogenic Hh-driven SE target gene and effective therapeutic target in Hh-driven tumor models. Collectively, this study identifies SE-driven transcriptional dependencies that represent promising therapeutic vulnerabilities for suppressing the Hh pathway and overcoming SMOi resistance. As CDK9 and IRS inhibitors have already entered human clinical trials for cancer treatment, these findings provide comprehensive preclinical support for developing trials for Hh-driven cancers.

7.
Polymers (Basel) ; 16(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38794572

RESUMO

Self-melting ice asphalt pavement materials inhibit pavement freezing and improve driving safety. This paper aims to study the long-term salt release characteristics of self-melting ice asphalt mixtures and the impact on pavement after complete salt release. Firstly, a method to accelerate the rapid release of salt based on the Los Angeles abrasion tester. Then, long-term salt release patterns were elucidated under the influence of deicing agent dosage, type of asphalt, and type of gradation. Finally, a quantitative analysis of the pavement performance after complete salt release is conducted. The results indicate that the release efficiency of the Los Angeles abrasion tester method has increased by 91 times compared to the magnetic stirrer immersion flushing method and by 114 times compared to the natural soaking method. The SBS-modified self-melting ice asphalt mixture possesses a longer duration of salt release, but the uniformity of salt release is inferior. Salt release duration is directly proportional to the dosage of deicing agents. SMA-13 self-melting ice asphalt mixture exhibits poorer uniformity in salt release. After complete salt release, high-temperature stability of self-melting ice asphalt mixtures decreased by 31.6%, low-temperature performance decreased by 15.4%, water stability decreased by 26.7%, and fatigue life decreased by 35.9%.

9.
Small ; : e2402998, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716678

RESUMO

Aqueous zinc-based batteries (AZBs) are promising energy storage solutions with remarkable safety, abundant Zn reserve, cost-effectiveness, and relatively high energy density. However, AZBs still face challenges such as anode dendrite formation that reduces cycling stability and limited cathode capacity. Recently, low-dimensional metal-organic frameworks (LD MOFs) and their derivatives have emerged as promising candidates for improving the electrochemical performance of AZBs owing to their unique morphologies, high structure tunability, high surface areas, and high porosity. However, clear guidelines for developing LD MOF-based materials for high-performance AZBs are scarce. In this review, the recent progress of LD MOF-based materials for AZBs is critically examined. The typical synthesis methods and structural design strategies for improving the electrochemical performance of LD MOF-based materials for AZBs are first introduced. The recent noteworthy research achievements are systematically discussed and categorized based on their applications in different AZB components, including cathodes, anodes, separators, and electrolytes. Finally, the limitations are addressed and the future perspectives are outlined for LD MOFs and their derivatives in AZB applications. This review provides clear guidance for designing high-performance LD MOF-based materials for advanced AZBs.

10.
J Cancer ; 15(11): 3441-3451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817851

RESUMO

Background: Chemoresistance is a key reason for treatment failure in colorectal cancer (CRC) patients. The tumor microenvironment of chemoresistant CRC is distinctly immunosuppressive, although the underlying mechanisms are unclear. Methods: The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method. The in-situ expression of transient receptor potential channel 5 (TRPC5) and fibroblast activation protein (FAP) in the CRC tissues was examined by immunohistochemistry. TRPC5 expression levels in the HCT8 and HCT116 cell lines and the corresponding 5-fluorouracil (5-FU)-resistant cell lines (HCT8R and HCT116R) were analyzed by western blotting and RT-PCR. Exosomes were isolated from the HCT8R and HCT116R cells and incubated with colorectal normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs)markers were detected. NFs were also incubated with exosomes isolated from TRPC5-knockdown HCT8R cells, and the changes in intracellular Ca2+ levels and C-X-C motif chemokine ligand 12 (CXCL12) secretion were analyzed. Results: TRPC5 and FAP expression showed positive correlation in the datasets. Immunostaining of CRC tissue specimens further revealed that high TRPC5 and FAP expressions were significantly associated with worse tumor regression. Furthermore, chemoresistant CRC cells expressed higher levels of TRPC5 compared to the chemosensitive cells, and knocking down TRPC5 reversed chemoresistance. Exosomes derived from CRC cells induced the transformation of NFs to CAFs. However, TRPC5-exosomes derived from chemoresistant CRC cells can promote CAFs to secrete more CXCL12. Conclusion: Chemoresistant CRC cells can induce CAFs activation and promote CXCL12 secretion through exosomal TRPC5.

11.
Sci Total Environ ; 931: 172993, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38719056

RESUMO

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM2.5). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China. Ambient PM2.5 levels were continuously monitored at a fixed station from 2013 to 2015. Serum cytokine levels were measured to assess systemic inflammation. Multiple bioactive lipids in the ARA pathway and three subtypes of C1P were quantified in blood samples. Mediation analyses were performed to test the hypotheses. We observed that PM2.5 exposure was positively associated with inflammatory cytokines and the three subtypes of C1P. Mediation analyses showed that C1P significantly mediated the associations of ARA and 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET), an ARA metabolite, with PM2.5 exposure. ARA, 5, 6-DHET, and leukotriene B4 mediated systemic inflammatory response to PM2.5 exposure. For example, C1P C16:0 (a subtype of C1P) mediated a 12.9 % (95 % confidence interval: 3.7 %, 32.5 %) increase in ARA associated with 3-day moving average PM2.5 exposure, and ARA mediated a 27.1 % (7.8 %, 61.2 %) change in interleukin-8 associated with 7-day moving average PM2.5 exposure. Our study indicates that bioactive lipids in the ARA and sphingolipid metabolic pathways may mediate systemic inflammation after PM2.5 exposure.


Assuntos
Poluentes Atmosféricos , Inflamação , Material Particulado , Material Particulado/toxicidade , Humanos , Inflamação/induzido quimicamente , Poluentes Atmosféricos/toxicidade , Masculino , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Pequim , Feminino , Idoso , Citocinas/sangue , Citocinas/metabolismo , Ácido Araquidônico/metabolismo , Ceramidas , Pessoa de Meia-Idade , Lipídeos/sangue
12.
Artigo em Inglês | MEDLINE | ID: mdl-38748524

RESUMO

Vision-and-language navigation requires an agent to navigate in a photo-realistic environment by following natural language instructions. Mainstream methods employ imitation learning (IL) to let the agent imitate the behavior of the teacher. The trained model will overfit the teacher's biased behavior, resulting in poor model generalization. Recently, researchers have sought to combine IL and reinforcement learning (RL) to overcome overfitting and enhance model generalization. However, these methods still face the problem of expensive trajectory annotation. We propose a hierarchical RL-based method-discovering intrinsic subgoals via hierarchical (DISH) RL-which overcomes the generalization limitations of current methods and gets rid of expensive label annotations. First, the high-level agent (manager) decomposes the complex navigation problem into simple intrinsic subgoals. Then, the low-level agent (worker) uses an intrinsic subgoal-driven attention mechanism for action prediction in a smaller state space. We place no constraints on the semantics that subgoals may convey, allowing the agent to autonomously learn intrinsic, more generalizable subgoals from navigation tasks. Furthermore, we design a novel history-aware discriminator (HAD) for the worker. The discriminator incorporates historical information into subgoal discrimination and provides the worker with additional intrinsic rewards to alleviate the reward sparsity. Without labeled actions, our method provides supervision for the worker in the form of self-supervision by generating subgoals from the manager. The final results of multiple comparison experiments on the Room-to-Room (R2R) dataset show that our DISH can significantly outperform the baseline in accuracy and efficiency.

13.
Org Lett ; 26(23): 5010-5015, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38819192

RESUMO

Two fully fused acceptor-donor-acceptor (A-D-A) architecture conjugated derivatives (NPF and NCF) comprising an electron-withdrawing naphthalimide (NMI) and two different electron-donating cores, phenanthrene and carbazole, respectively, were conveniently synthesized by bismuth(III)-catalyzed selective cyclization of vinyl ethers. Compared with their corresponding single bond-linked A-D-A molecules NPS and NCS, both having a moderately twisted aromatic configuration, the ring fusion strategy leads to fully coplanar conjugated skeletons and greatly changes the electronic structures, photophysical properties, self-assembling behaviors, and molecular packing motifs. In particular, the naphthalimide/carbazole derivative NCF exhibits intriguing 2D brickwork packing and significantly enhanced self-assembling properties.

14.
Materials (Basel) ; 17(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38793263

RESUMO

Cementitious composites are ubiquitous in construction, and more and more research is focused on improving mechanical properties and environmental effects. However, the jury is still out on which material can achieve low-carbon and high-performance cementitious composites. This article compares the mechanical and environmental performance of zero-dimensional fullerenes, one-dimensional carbon nanotubes (CNTs), two-dimensional graphene oxide (GO), and three-dimensional nano-graphite platelets (NGPs) on cementitious composites. The literature review shows that two-dimensional (2D) GO has the best mechanical and environmental performance, followed by 3D NGPs, 1D CNTs, and 0D fullerenes. Specifically, GO stands out for its lower energy consumption (120-140 MJ/kg) and CO2 emissions (0.17 kg/kg). When the optimal dosage (0.01-0.05 wt%) of GO is selected, due to its high specific surface area and strong adhesion to the matrix, the compressive strength of the cementitious composites is improved by nearly 50%. This study will help engineers and researchers better utilize carbon-based nanomaterials and provide guidance and direction for future research in related fields.

15.
Int J Gen Med ; 17: 1695-1705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706745

RESUMO

Background: Anti-claudin (CLDN) 18.2 therapy has been proven to be effective in treating advanced gastric cancer with negative human epidermal growth factor receptor 2 (HER-2). This study purposed to investigate the relationship of CLDN 18.2 expression with prognosis of HER-2-positive gastric cancer patients. Objective: To investigate the expression of claudin (CLDN) 18.2 in Human epidermal growth factor receptor 2 (HER-2) positive gastric cancer patients after radical resection and its relationship with gastric cancer prognosis. Methods: A total of 55 postoperative HER-2-positive gastric cancer patients were included in this study. CLDN 18.2 protein was detected by immunohistochemistry, and detailed clinical and pathological information was collected. Factors considered potentially important in the univariate analysis were included in the multivariate analysis, which involved COX regression to find the independent prognostic factors affecting disease-free survival (DFS). Results: Immunohistochemistry showed that different levels of CLDN 18.2 protein were expressed in HER-2 positive gastric cancer tissues, and the Chi-square analysis showed that the expression level of CLDN 18.2 was significantly correlated with the lymph node stage. Higher expression levels of CLDN 18.2 were found in patients with lymph node positivity and were associated with poor prognosis in HER-2-positive gastric cancer patients. Gastric cancer patients with low and high expressions of CLDN 18.2 had postoperative median DFS of 38.5 months (95% confidence interval (CI) 28.8-48.2 months) and 12.1 months (95% CI, 11.7-41.0 months), respectively. Conclusion: High expression of CLDN 18.2 in HER-2 positive gastric cancer is associated with poor prognosis, and the optimal treatment mode for this population is worth exploring after the approval of anti-CLDN 18.2 drugs.

16.
Chin Herb Med ; 16(2): 263-273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38706820

RESUMO

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

17.
World J Clin Cases ; 12(11): 1900-1908, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660542

RESUMO

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT. This review elucidates the risks, mechanisms, reliable markers, and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

18.
Nucleic Acids Res ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634789

RESUMO

Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging and are targets of DNA damage response. Although we and others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about the role of telomere lengths in cardiomyocyte. Here, we demonstrate that in heart failure patient cardiomyocytes, telomeres are shortened compared to healthy controls. We generated isogenic human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) with short telomeres (sTL-CMs) and normal telomeres (nTL-CMs) as model. Compared to nTL-CMs, short telomeres result in cardiac dysfunction and expression of senescent markers. Using Hi-C and RNASeq, we observe that short telomeres induced TAD insulation decrease near telomeric ends and this correlated with a transcription upregulation in sTL-CMs. FOXC1, a key transcription factor involved in early cardiogenesis, was upregulated in sTL-CMs and its protein levels were negatively correlated with telomere lengths in heart failure patients. Overexpression of FOXC1 induced hiPSC-CM aging, mitochondrial and contractile dysfunction; knockdown of FOXC1 rescued these phenotypes. Overall, the work presented demonstrate that increased chromatin accessibility due to telomere shortening resulted in the induction of FOXC1-dependent expression network responsible for contractile dysfunction and myocardial senescence.

19.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602742

RESUMO

Prior investigations have established that the manipulation of neural activity has the potential to influence both rapid eye movement and non-rapid eye movement sleep. Low-intensity retinal ultrasound stimulation has shown effectiveness in the modulation of neural activity. Nevertheless, the specific effects of retinal ultrasound stimulation on rapid eye movement and non-rapid eye movement sleep, as well as its potential to enhance overall sleep quality, remain to be elucidated. Here, we found that: In healthy mice, retinal ultrasound stimulation: (i) reduced total sleep time and non-rapid eye movement sleep ratio; (ii) changed relative power and sample entropy of the delta (0.5-4 Hz) in non-rapid eye movement sleep; and (iii) enhanced relative power of the theta (4-8 Hz) and reduced theta-gamma coupling strength in rapid eye movement sleep. In Alzheimer's disease mice with sleep disturbances, retinal ultrasound stimulation: (i) reduced the total sleep time; (ii) altered the relative power of the gamma band during rapid eye movement sleep; and (iii) enhanced the coupling strength of delta-gamma in non-rapid eye movement sleep and weakened the coupling strength of theta-fast gamma. The results indicate that retinal ultrasound stimulation can modulate rapid eye movement and non-rapid eye movement-related neural activity; however, it is not beneficial to the sleep quality of healthy and Alzheimer's disease mice.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Entropia , Nível de Saúde , Luz , Qualidade do Sono
20.
Opt Express ; 32(6): 10527-10534, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571261

RESUMO

In the traditional dry etching process for photonic device fabrication, the etching effect is influenced in many ways, usually resulting in relatively large sidewall roughness and high transmission loss. In this study, an effective method, namely the secondary coating method, is proposed to reduce the transmission loss of a Ge-Sb-Se chalcogenide waveguide and increase the quality factor (Q-factor) of a Ge-Sb-Se chalcogenide micro-ring resonator. The Ge-Sb-Se waveguide and micro-ring resonator are fabricated by ultraviolet exposure/electron beam lithography and inductively coupled plasma etching technology. Afterward, a 10 nm-thick Ge-Sb-Se thin film is deposited by thermal evaporation. The measurements show that after secondary coating, the sidewall roughness of the waveguide is reduced from 11.96 nm to 6.52 nm, with the transmission loss reduced from 2.63± 0.19 dB/cm to 1.86± 0.11 dB/cm at 1.55 µm wavelength. Keeping an equal coupling condition with equal radius and coupling distance, the Q-factor of the micro-ring resonator is improved by 47.5% after secondary coating. All results indicate that the secondary coating method is a feasible way to generate low-loss and high Q-factor integrated chalcogenide photonic devices.

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