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1.
Front Microbiol ; 15: 1473441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351297

RESUMO

Background: We aim to establish a gestational diabetes mellitus (GDM) mouse model with mice fed with a high-fat diet (HFD) in comparison with pregnant mice with normal blood glucose levels to investigate the role of intestinal microbiota in the development of HFD-induced GDM. Methods: We divided healthy 6-week-old female C57BL mice into an HFD-induced GDM group and a normal diet group. Their bacterial flora and metabolites in intestinal fecal exosomes were co-analyzed using 16 s multi-region sequencing and compared. Findings: Alpha (α) diversity was lower within the model group compared to the control group. Beta (ß) diversity was significantly different between the two groups. The relative abundances of Lactobacillus, Actinomyces, Rothia, and Bacteroidetes were significantly different between the two groups. Fermentation and nitrate consumption were significantly higher in the GDM group. Multiple bacteria were associated with glycerophosphocholine, S-methyl-5'-thioadenosine, quinolinate, galactinol, deoxyadenosine, DL-arginine, and 2-oxoadenic acid. Interpretation: Imbalances in the production of Lactobacillus, Bacteroidetes, Actinomyces, and Rothia and their related metabolites may lead to metabolic disturbances in GDM. These indicators may be used to assess changes affecting the intestinal microbiota during pregnancy and thus help modulate diet and alter blood glucose.

2.
Anal Sci ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363137

RESUMO

The present article introduced an natural enzyme-covered/amino-modified Pd-Pt bimetallic-doped zeolitic imidazolate framework (NAPPZ) for ultrasensitive and specific detection of glucose. The dodecahedral nanomaterial zeolitic imidazolate framework (ZIF-8)-loaded Pd-Pt bimetallic nanoparticles endowed the composite with peroxidase-like activity. The modification with glucose oxidase (GOx) facilitated the rapid access of H2O2 produced through glucose oxidation to the Pd-Pt nanoparticles vicinity reducing diffusion. GOx specifically catalyzes the transformation of glucose into H2O2, which then H2O2 rapidly migrates to the Pd-Pt nanoparticles, catalyzing the oxidation of colorless o-phenylenediamine into the orange-yellow product 2,3-diaminophenazine. Based on the aforementioned cascade reaction, the NAPPZ and NAPPZ based on ChOx were utilized for detecting glucose in human urine samples and cholesterol in milk, respectively. The NAPPZ strategy presented a broad detection range (20-1100 µmol L-1) and a low detection limit (15.9 µmol L-1) for glucose, and the NAPPZ based on ChOx strategy approach offered a broad detection range (10-500 µmol L-1) and low detection limit (6.4 µmol L-1) for cholesterol. Therefore, this novel method holds significant potential in the areas of clinical diagnostics and food safety.

3.
Cell Biosci ; 14(1): 127, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39385301

RESUMO

BACKGROUND: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. We have previously shown a tumor suppressive role of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1), which is targeted for degradation upon phosphorylation at S14 (pCASTOR1) in multiple types of cancer. This study focuses on the predictive value of pCASTOR1 in lung adenocarcinoma (LUAD) patients with KRAS mutations. RESULTS: Employing a newly developed pCASTOR1 specific antibody, we found that tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells (P < 0.05). Higher pCASTOR1 scores predicted poorer overall survival (OS) (HR = 3.3, P = 0.0008) and relapse-free survival (RFS) (HR = 3.0, P = 0.0035) in male patients with KRAS mutations. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations, akin to late-stage patients. CONCLUSION: Elevated pCASTOR1 scores serve as biomarkers predicting poorer OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39343626

RESUMO

OBJECTIVES: This study aimed to investigate the association between preoperative red blood cell distribution width (RDW) levels and liver injury (LI) after cardiac surgery, to highlight RDW's usefulness in the early identification and intervention for patients at high risk of LI. DESIGN: A retrospective observational study. SETTING: A university-affiliated teaching hospital and tertiary referral center. PARTICIPANTS: Adult patients who underwent cardiac and aortic aneurysm surgery at Changhai Hospital in 2021. INTERVENTIONS: Postoperative LI was defined by increased liver enzyme levels and/or hyperbilirubinemia, noted from the time of surgery to discharge. Logistic regression analyses were conducted to examine the RDW-LI relationship, with stratified analyses based on age, gender, and anemia. Survival within 30 days was assessed using the Kaplan-Meier method, with survival curve differences analyzed via the log-rank test. The study included 3 sets of sensitivity analyses. MEASUREMENTS AND MAIN RESULTS: Postoperative LI was observed in 75 patients (10%). Multivariate regression analysis showed a significant association between high RDW levels and postoperative LI (adjusted odds ratio, 3.25; p = 0.033; 95% confidence intefal, 1.10-9.63), even after adjusting for all covariates. This association remained consistent across 3 sets of sensitivity analyses. Subgroup analysis showed men had a higher correlation with LI (p for interaction = 0.041). Kaplan-Meier analysis indicated a significantly lower survival rate in the LI group (76%) compared with the non-LI group (99.6%; p < 0.001). CONCLUSIONS: Preoperative RDW levels are significantly associated with postoperative LI. RDW could serve as a significant useful marker for early detection and intervention in patients at high risk of LI, thereby potentially improving patient outcomes.

5.
Anal Chem ; 96(37): 15031-15041, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39226180

RESUMO

Metformin (MET) is currently the first-line treatment for type 2 diabetes mellitus (T2DM). However, overdose and long-term use of MET may induce a serious liver injury. What's worse, diagnosis of MET-induced liver injury remains challenging in clinic. Although several probes have been reported for imaging MET-induced liver injury utilizing upregulated hepatic H2S as a biomarker, they are still at risk of nonspecific activation in complex physiological environments and rely on light excitation with limited imaging depth. Herein, we rationally designed and developed a dual-locked probe, DPA-H2S, for precise imaging of MET-induced liver injury by H2S-activated sonoafterglow luminescence. DPA-H2S is a small molecule consisting of a sonosensitizer protoporphyrin IX (PpIX) and an afterglow substrate that is dual-locked with a H2S-responsive 2,4-dinitrobenzene group and a 1O2-responsive electron-rich double bond. When employing DPA-H2S for imaging of MET-induced liver injury in vivo, since the PpIX moiety can produce 1O2 in situ at the liver site under focused ultrasound (US) irradiation, the two locks of DPA-H2S can be specifically activated by the highly upregulated H2S at the liver injury sites and the in situ generated 1O2, respectively. Thus, the sonoafterglow signal of DPA-H2S is significantly turned on, enabling precise imaging of the MET-induced liver injury. In vitro results showed that, through H2S-activated sonoafterglow luminescence, DPA-H2S was capable of imaging H2S with good sensitivity and high selectivity and realized deep tissue imaging (∼20 mm, signal-to-background ratio (SBR) = 3.4). Furthermore, we successfully applied DPA-H2S for precise in vivo imaging of MET-induced liver injury. We anticipate that our dual-locked probe, DPA-H2S, may serve as a promising tool in assisting the diagnosis of MET-induced liver injury in clinics and informing the clinical utilization of MET in the near future.


Assuntos
Metformina , Animais , Camundongos , Metformina/química , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Humanos , Protoporfirinas/química , Imagem Óptica , Sulfeto de Hidrogênio/análise , Sulfeto de Hidrogênio/química , Fígado/diagnóstico por imagem , Fígado/metabolismo , Luminescência
6.
Curr Neurovasc Res ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39279112

RESUMO

BACKGROUND: Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT). METHODS: From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model. RESULTS: Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR. CONCLUSION: Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

7.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4022-4030, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39307737

RESUMO

In recent years, the incidence and mortality rates of cardiovascular diseases in China have kept rising, with no significant reduction in disease burden observed. Percutaneous coronary intervention(PCI) is an effective approach for treating coronary artery disease. Drug-eluting stents and drug-coated balloons are currently the most common PCI devices used in clinical practice. However, challenges with restenosis and late-stage thrombotic events persist. Inhibiting the proliferation of vascular smooth muscle cells while enhancing endothelial cell activity is crucial for reducing restenosis and preventing thrombosis, and it remains a challenge in research. The active compounds and extracts of traditional Chinese medicine(TCM), particularly the combinations of active compounds in coatings, possess multi-target potential and serve as a supplement to coatings prepared from synthetic compounds. This review elucidates the application of TCM active compounds(such as arsenic trioxide, paclitaxel, hirudin, tetramethylpyrazine, emodin, oxymatrine, and curcumin), combinations of TCM active compounds(paclitaxel/hirudin, geniposide/baicalin), and TCM extracts(such as Curcumae Rhizoma extract and Tripterygium hypoglaucum extract) in the coatings for PCI devices in recent years. Furthermore, this review expounds the current challenges and future prospects in this field, giving insights into the innovation of PCI devices.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Animais , Medicina Tradicional Chinesa , Intervenção Coronária Percutânea/instrumentação , Stents Farmacológicos
8.
CNS Neurosci Ther ; 30(9): e70018, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252474

RESUMO

OBJECTIVE: Nowadays, the prevalence of cognitive impairment in women has gradually increased, especially in postmenopausal women. There were few studies on the mechanistic effects of iron exposure on neurotoxicity in postmenopausal women. The aim of this study is to investigate the effect of iron accumulation on cognitive ability in ovariectomized mice and its possible mechanism and to provide a scientific basis for the prevention of cognitive dysfunction in postmenopausal women. METHODS: Female C57BL/6N ovariectomized model mice were induced with ferric citrate (FAC). The mice were randomly divided into 5 groups: control, sham, ovariectomized (Ovx), Ovx + 50 mg/kg FAC (Ovx + l), and Ovx + 100 mg/kg FAC (Ovx + h). The impact of motor and cognitive function was verified by a series of behavioral tests. The levels of serum iron parameters, malondialdehyde, and superoxide dismutase were measured. The ultrastructure of mice hippocampal microglia was imaged by transmission electron microscopy. The differential expression of hippocampal proteins was analyzed by Tandem Mass Tag labeling. RESULTS: Movement and cognitive function in Ovx + l/Ovx + h mice were significantly decreased compared to control and Sham mice. Then, iron exposure caused histopathological changes in the hippocampus of mice. In addition, proteomic analysis revealed that 29/27/41 proteins were differentially expressed in the hippocampus when compared by Ovx vs. Sham, Ovx + l vs. Ovx, as well as Ovx + h vs. Ovx + l groups, respectively. Moreover, transferrin receptor protein (TFR1) and divalent metal transporter 1 (DMT1) protein expression were significantly increased in the iron accumulation mice model with ovariectomy. CONCLUSION: Iron exposure could cause histopathological damage in the hippocampus of ovariectomised mice and, by altering hippocampal proteomics, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice.


Assuntos
Modelos Animais de Doenças , Compostos Férricos , Hipocampo , Ferro , Camundongos Endogâmicos C57BL , Ovariectomia , Animais , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Ferro/metabolismo , Compostos Férricos/toxicidade , Compostos Férricos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Transtornos Cognitivos/patologia , Transtornos Cognitivos/induzido quimicamente , Superóxido Dismutase/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Receptores da Transferrina/metabolismo
9.
Nat Commun ; 15(1): 8148, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289379

RESUMO

In computational molecular and materials science, determining equilibrium structures is the crucial first step for accurate subsequent property calculations. However, the recent discovery of millions of new crystals and super large twisted structures has challenged traditional computational methods, both ab initio and machine-learning-based, due to their computationally intensive iterative processes. To address these scalability issues, here we introduce DeepRelax, a deep generative model capable of performing geometric crystal structure relaxation rapidly and without iterations. DeepRelax learns the equilibrium structural distribution, enabling it to predict relaxed structures directly from their unrelaxed ones. The ability to perform structural relaxation at the millisecond level per structure, combined with the scalability of parallel processing, makes DeepRelax particularly useful for large-scale virtual screening. We demonstrate DeepRelax's reliability and robustness by applying it to five diverse databases, including oxides, Materials Project, two-dimensional materials, van der Waals crystals, and crystals with point defects. DeepRelax consistently shows high accuracy and efficiency, validated by density functional theory calculations. Finally, we enhance its trustworthiness by integrating uncertainty quantification. This work significantly accelerates computational workflows, offering a robust and trustworthy machine-learning method for material discovery and advancing the application of AI for science.

11.
HPB (Oxford) ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39271376

RESUMO

BACKGROUND: When considering hepatectomy for elderly HCC patients, it's essential to assess surgical safety and survival benefits. This study investigated the impact of preoperative frailty, assessed with the Clinical Frailty Scale (CFS), on outcomes for octogenarians undergoing HCC hepatectomy. METHODS: A retrospective cohort study of octogenarians who had hepatectomy for HCC between 2010 and 2022 at 16 hepatobiliary centers was conducted. Patients were categorized as frail or non-frail based on preoperative CFS, with frailty defined as CFS ≥5. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), with perioperative outcomes as secondary endpoints. RESULTS: Among 240 octogenarians, 105 were characterized as being frail. Frail patients had a higher incidence of postoperative 30-day morbidity and postoperative 30-day and 90-day mortality versus non-frail patients. Meanwhile, 5-year OS, RFS and CSS among frail patients were lower compared with non-frail patients. Univariable and multivariable analysis revealed that preoperative frailty was an independent risk factor of postoperative 30-day morbidity (OR: 2.060), OS (HR: 2.384), RFS (HR: 2.190) and CSS (HR: 2.203). CONCLUSION: Preoperative frailty, as assessed by the CFS, was strongly associated with both short-term outcomes and long-term survival among octogenarians undergoing hepatectomy for HCC. Incorporating frailty assessment into the preoperative evaluation may help optimize patient selection and perioperative care.

12.
Ther Adv Med Oncol ; 16: 17588359241273026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39229468

RESUMO

Background: Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). Objectives: To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. Design: A multicenter, open-label, phase Ib trial. Methods: Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1-2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3-5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. Results: A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%-93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%-87.5% for lower doses; grade 4, 46.7% and 4.2%-20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%-54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5-82.6) and patients progressing after ET (53.3%; 95% CI 26.6-78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9-46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9-24.1) with fulvestrant. Conclusion: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration: ClinicalTrials.gov identifier: NCT03481998.

13.
PLoS One ; 19(9): e0308943, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39231188

RESUMO

Complex steerable pyramid (CSP) performs well when applied to magnify subtle motions of structures for observing the dynamic characteristics of facilities. However, the impact of the types and parameters of CSP filters upon the performance of phase-based optical flow (PBOF) in measuring motion parameters has not been systematically studied. The purpose of this study is to comprehensively evaluate the impact of different CSP filter types (Octave, HalfOctave, SmoothHalfOctave, and QuarterOctave) and parameters on the performance of PBOF in measuring motion parameters. Firstly, by measuring simulated translational motion, the influence of the CSP's down-sampling rates on the displacement measurement accuracy of PBOF is analyzed to determine appropriate settings. Subsequently, the effective displacement measurement interval and accuracy of PBOF using the CSP are studied through simulated and experimental translational motion measurements. Further, the vibration parameter's accuracy is analyzed through simulated periodic vibration measurements. Finally, the characteristics of PBOF using the four kinds of CSP and practical considerations are discussed. Simulation and experimental results demonstrate that when using middle-level filters within the effective level range of HalfOctave, PBOF achieves the best overall displacement measurement performance. Additionally, this method can easily integrate with signal processing techniques in analyzing structural dynamic characteristics under field conditions.


Assuntos
Fluxo Óptico , Movimento (Física) , Simulação por Computador , Vibração
14.
Molecules ; 29(17)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39275019

RESUMO

To meet the demands for high-temperature performance and lightweight materials in aerospace engineering, the Au-Ni solder is often utilized for joining dissimilar materials, such as Ti3Al-based alloys and Ni-based high-temperature alloys. However, the interaction between Ti and Ni can lead to the formation of brittle phases, like Ti2Ni, TiNi, and TiNi3, which diminish the mechanical properties of the joint and increase the risk of crack formation during the welding process. Cu doping has been shown to enhance the mechanical properties and high-temperature stability of the Au-Ni brazed joint's central area. Due to the difficulty in accurately controlling the solid solution content of Cu in the Au-Ni alloy, along with the high cost of Au, traditional experimental trial-and-error methods are insufficient for the development of Au-based solders. In this study, first principles calculations based on density functional theory were employed to analyze the effect of Cu content on the stability of the Au-2.0Ni-xCu (x = 0, 0.25, 0.5, 0.75, 1.0, 1.25 wt%) alloy phase structure. The thermal properties of the alloy were determined using Gibbs software fitting. The results indicate that the Au-2.0Ni-0.25Cu alloy exhibits the highest plastic toughness (B/G = 5.601, ν = 0.416, Cauchy pressure = 73.676 GPa) and a hardness of 1.17 GPa, which is 80% higher than that of Au-2.0Ni. This alloy balances excellent strength and plastic toughness, meeting the mechanical performance requirements of brazed joints. The constant pressure specific heat capacity (Cp) of the Au-2.0Ni-xCu alloy is higher than that of Au-2.0Ni and increases with Cu content. At 1000 K, the Cp of the Au-2.0Ni-0.25Cu alloy is 35.606 J·mol-1·K-1, which is 5.88% higher than that of Au-2.0Ni. The higher Cp contributes to enhanced high-temperature stability. Moreover, the linear expansion coefficient (CTE) of the Au-2.0Ni-0.25Cu alloy at 1000 K is 8.76 × 10-5·K-1, only 0.68% higher than Au-2.0Ni. The lower CTE helps to reduce the risk of solder damage caused by thermal stress. Therefore, the Au-2.0Ni-0.25Cu alloy is more suitable for brazing applications in high-temperature environments due to its excellent mechanical properties and thermal stability. This study provides a theoretical basis for the performance optimization and engineering application of the Au-2.0Ni-xCu alloy as a gold-based solder.

15.
ACS Appl Mater Interfaces ; 16(38): 50229-50237, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39264898

RESUMO

Targeted delivery systems combined with the stimuli-responsive release of drug molecules hold noteworthy promise for precision medicine, enabling treatments with enhanced effectiveness and reduced adverse effects. An ideal drug delivery platform with versatile targeting moieties, the capability of combinational payloads, and simple preparation is highly desirable. Herein, we developed pH-sensitive fluorescent self-assembled complexes (SACs) of a galactose-functionalized G-quadruplex (G4) and a coumarin carboxamidine derivative as a targeted delivery platform through the nanoprecipitation method. These SACs selectively targeted hepatocellular carcinoma (HepG2) cells in fluorescence imaging after a short incubation and exerted specific anticancer effects in an appropriate dose range. Co-delivery of 1 µM prodrug floxuridine oligomers and 16 µg/mL SACs (minimal hemolytic effect) significantly reduced the cytotoxicity of the nucleoside anticancer drug on normal cells (NIH/3T3), kept up to 70% alive after 72-h incubation, and improved anticancer efficacy compared to SACs alone. This strategy can be extended to ratiometric multidrug delivery through self-assembly for targeted combinational therapy.


Assuntos
Quadruplex G , Humanos , Quadruplex G/efeitos dos fármacos , Células Hep G2 , Camundongos , Animais , Células NIH 3T3 , Corantes Fluorescentes/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Floxuridina/química , Floxuridina/farmacologia , Galactose/química , Cumarínicos/química , Cumarínicos/farmacologia
16.
Cell Signal ; 124: 111430, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39312989

RESUMO

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.

17.
Nanoscale ; 16(38): 17974-17983, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39235787

RESUMO

When multilayer graphene (MLG) is subjected to a vertical electric field, electrons traverse across the layers and its interlayer electrical conductance and shielding effect exhibit remarkable diversity, leading to exotic phenomena and diverse applications in photoelectric devices. The rearrangement of electrons induced by this external field is aptly described by polarizability, which quantifies the electronic response to the applied field. In this work, we have developed a polarizability decomposition scheme based on field-induced electron density variations computed using a first-principles approach. This scheme allows us to isolate the inter- and intra-layer contributions from the total polarizability of twisted multilayer graphene (TMG) quantum dots. The inter- and intra-layer counterparts reflect the charge transfer (CT) and field shielding effects among the layers, respectively. While the strongest shield effect is observed between the outermost two layers, the largest CT change is noted in the outermost layers, but small or nearly zero CT changes in the inner layers. Significant CT and shielding effects are observed not only in strongly coupled Bernal stacking, but also in the structures misaligned from full-(AA)N stacking by a small and size-dependent twist angle. The dielectric behaviors of the TMG quantum dots of a few layers are layer-dependent and different from those of typical dielectrics. Moreover, both the shielding and CT effects exhibit variation with thickness, twist angle and disc size, suggesting controllable conductive/dielectric conversion in the vertical direction. Considering the inter- and intralayer polarizability, our study addresses the precise modulation of interlayer conductance and shielding effect for TMG quantum dots, essential for microstructure design and performance manipulation of MLG-based photoelectric devices.

18.
J Agric Food Chem ; 72(39): 21869-21876, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39288071

RESUMO

Based on previous research, this study synthesized 24 compounds by splicing the substructures of the indolyl group and the isothiocyanate group. Alternaria alternata, Phytophthora capsici, Botrytis cinerea, and Valsa mali were used to test the activity of the target compounds. At 100 µg/mL, compounds 8, 13, 14, and 17 exhibited excellent inhibitory effects of more than 80% on P. capsici, B. cinerea, and V. mail. The EC50 values of compounds 13 and 14 were 0.64 and 2.08 µg/mL, respectively. Potted antifungal activity demonstrated that compounds 13 and 14 had a protective effect of around 80% against B. cinerea at 200 µg/mL. Further physiological and biochemical studies on B. cinerea revealed that compound 13 thickened cell walls and caused mitochondrial vacuolization. Moreover, theoretical calculations indicated that the charge distribution of indolyl isothiocyanate compounds played a crucial role in the observed fungicidal activity. In summary, this study provided fundamental reference data for the derivative synthesis of these indolyl isothiocyanate compounds.


Assuntos
Botrytis , Fungicidas Industriais , Isotiocianatos , Phytophthora , Isotiocianatos/farmacologia , Isotiocianatos/química , Isotiocianatos/síntese química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Fungicidas Industriais/síntese química , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Phytophthora/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Testes de Sensibilidade Microbiana , Fungos/efeitos dos fármacos
19.
Environ Sci Ecotechnol ; 22: 100474, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39247805

RESUMO

Improving electrification feasibility is essential for reducing emissions from non-electric energy sources, thereby enhancing air quality and public health. Concurrently, climate mitigation actions, such as carbon pricing policies, have significant potential to alleviate increasing carbon dioxide (CO2) and other co-emitted air pollutants. However, the interactions between climate policy and the improvement of electrification feasibility at the provincial level remain unclear, collectively impacting the net-zero transition of energy-intensive sectors. Here we combine a technologically rich economic-energy-environment model with air quality modeling across China to examine the health, climate, and economic implications of large-scale upgrades in electrification feasibility and climate policies from 2017 to 2030. The results indicate that advancing electrification feasibility, coupled with adopting carbon pricing policies, is likely to facilitate a transition towards electricity-dominant energy systems. Improved electrification feasibility is projected to yield a 7-25% increase in nationwide climate benefits and a 5-14% increase in health benefits by 2030. These incremental benefits, coupled with reduced economic costs, result in a 22-68% increase in net benefits. However, regionally, improvements in electrification feasibility will lead to heightened power demand and unintended emissions from electric energy production in certain provinces (e.g., Nei Mongol) due to the coal-dominated power system. Additionally, in major coal-producing provinces like Shanxi and Shaanxi, enhanced electrification feasibility exacerbates the negative economic impacts of climate policies. This study provides quantitative insights into how improving electrification feasibility reshapes energy evolution and the benefit-cost profile of climate policy at the provincial level. The findings underscore the necessity of a well-designed compensation scheme between affected and unaffected provinces and coordinated emission mitigation across the power and other end-use sectors.

20.
Child Care Health Dev ; 50(5): e13329, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39245883

RESUMO

BACKGROUND: The increased trends in psychological distress and mental illness have been of great significance in public health concerns. The study aimed to investigate the proportion and correlates of meeting 24-h movement guidelines (including moderate to vigorous physical activity, screen time and sleep duration) and the associations between 24-h movement guidelines met and mental well-being and psychological distress in a large sample of Chinese students. METHODS: All participants received a physical examination and filled out questionnaires in this study. Chi-square tests were used to analyse the proportion of reaching 24-h guidelines by gender and logistic regression was used to analyse correlates of meeting 24-h guidelines. Two binary logistic regression models were used to analyse the association between meeting 24-h guidelines and mental well-being and psychological distress. The back-propagation artificial neural network was used to describe the importance of the independent variables. RESULTS: The findings revealed a generally low rate of meeting the 24-h movement guidelines, particularly concerning moderate to vigorous physical activity (16.5%). Meeting all three guidelines was related to better mental health in both boys and girls. Particularly, meeting screen time guideline and meeting sleep duration guideline appeared to be more important on mental outcomes, compared to meeting moderate to vigorous physical activity guideline. Compared with boys, girls were more susceptible to the influences of 24-h movement guidelines on mental health. CONCLUSIONS: Meeting all three components of the 24-h movement guidelines was associated with the most favourable mental health outcomes for both boys and girls. Thus, maintaining a daily balance of sufficient physical activity, limited screen time, and adequate sleep is crucial for enhancing the mental health status of students.


Assuntos
Exercício Físico , Saúde Mental , Tempo de Tela , Estudantes , Humanos , Masculino , Feminino , Estudos Transversais , China , Estudantes/psicologia , Exercício Físico/psicologia , Adolescente , Angústia Psicológica , Sono , Inquéritos e Questionários , Criança , Fatores Sexuais , Estresse Psicológico , Guias como Assunto , População do Leste Asiático
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