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1.
Nano Lett ; 24(23): 6838-6843, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38825784

RESUMO

Moiré superlattices, constituted by two-dimensional materials, demonstrate a variety of strongly correlated and topological phenomena including correlated insulators, superconductivity, and integer/fractional Chern insulators. In the realm of topological nontrivial Chern insulators within specific moiré superlattices, previous studies usually observe a single Chern number at a given filling factor in a device. Here we present the observation of gate-tunable Chern numbers within the Chern insulator state of an ABC-stacked trilayer graphene/hexagonal boron nitride moiré superlattice device. Near quarter filling, the moiré superlattice exhibits spontaneous valley polarization and distinct ferromagnetism associated with the Chern insulator states over a range of the displacement field. Surprisingly we find a transition of the Chern number from C = 3 to 4 as the displacement field is increased. Our observation of gate-tunable correlated Chern insulators suggests new ways to control and manipulate topological states in a moiré superlattice device.

2.
Phytomedicine ; 130: 155788, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38838634

RESUMO

BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, affects a broad spectrum of aging populations. AD is characterized by pathological amyloid-ß (Aß) plaques and neurofibrillary tangles, leading to neural degeneration and cognitive decline. The lack of effective treatments for AD highlights the urgent need for novel therapeutic agents, particularly in the early stages. Dimethylsulfoniopropionate (DMSP) is a natural marine compound with antioxidant and neuroprotective properties. However, studies on the efficacy of DMSP in the treatment of AD and its associated mechanisms are limited. PURPOSE: This study aimed to explore the therapeutic effects and mechanisms of action of DMSP as an AD treatment using a preclinical 3 × Tg-AD mouse model. METHODS: The research involved administering DMSP (7 µg/mL and 11 µg/mL in drinking water) to four-month-old 3 × Tg-AD mice consecutively for three months. The Y-maze test, novel object recognition test, and Morris water maze test were used to assess memory and learning ability. The relative expression levels and distribution of proteins relevant to Aß and tau pathology, synapses, and glial cells were analyzed using western blotting and immunofluorescence assays. Additionally, proteomic and bioinformatics approaches were used to explore the potential targets of DMSP treatment. RESULTS: DMSP-treated AD mice showed significantly enhanced cognitive function, suggesting that DMSP mitigates memory and learning impairments in AD. Moreover, DMSP diminished the abnormal accumulation of Aß and phosphorylated tau in both the cortex and hippocampus, which are crucial hallmarks of AD pathology. In addition to its neuroprotective properties, DMSP restored synaptic density and the expression of synaptic and neuronal proteins, which are essential for proper brain function. DMSP displayed anti-inflammatory properties, as evidenced by its ability to suppress inflammatory astrocytes and maintain microglial homeostasis. Notably, DMSP facilitated the maturation of oligodendrocytes (OLs) from oligodendrocyte progenitor cells (OPCs), a critical process in the development of the brain myelination architecture. Proteomic analysis revealed that DMSP positively influenced biological processes crucial for oligodendrocyte development, myelination, and axonal ensheathment, which are often compromised in patients with AD. Protein validation and brain tissue staining supported the role of DMSP in preserving myelin enrichment and sheath integrity. These therapeutic effects were largely attributed to the enhanced expression of myelin-associated glycoprotein (Mag) and tetraspanin Cd9. CONCLUSION: Overall, our findings highlight DMSP as a promising novel therapeutic candidate for AD, offering multifaceted benefits in cognitive and memory enhancement, reduction of Aß and tau pathology, neuronal synapse protection, anti-inflammatory effects, and myelin sheath restoration as an innovative target compared to other studies. In addition to being a potentially effective treatment for AD, DMSP may also have the potential to address other neurodegenerative diseases that are closely associated with myelin impairment.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Camundongos Transgênicos , Fármacos Neuroprotetores , Compostos de Sulfônio , Animais , Doença de Alzheimer/tratamento farmacológico , Compostos de Sulfônio/farmacologia , Camundongos , Fármacos Neuroprotetores/farmacologia , Peptídeos beta-Amiloides/metabolismo , Masculino , Proteínas tau/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo
3.
Discov Oncol ; 15(1): 237, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904918

RESUMO

BACKGROUND: The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738). METHODS: BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day). The primary endpoint was progression-free survival (PFS) per investigator assessment. Secondary endpoints included PFS per blinded independent review committee (BIRC), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), pharmacokinetics, and safety. RESULTS: A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI 5.5, 9.0). Similar results were observed following assessment by BIRC, with median PFS prolonged by 4.3 months. Treatment with EVE + EXE was also associated with improvements in ORR and CBR. No new safety signals were identified in BOLERO-5, with the incidence of adverse events in Chinese patients consistent with the safety profile of both drugs. CONCLUSION: The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.

4.
J Robot Surg ; 18(1): 248, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856862

RESUMO

The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.


Assuntos
Tempo de Internação , Obesidade , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Obesidade/complicações , Neoplasias da Próstata/cirurgia , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Laparoscopia/métodos , Duração da Cirurgia , Transfusão de Sangue/estatística & dados numéricos
5.
J Robot Surg ; 18(1): 261, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904929

RESUMO

This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.


Assuntos
Períneo , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Períneo/cirurgia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento , Incontinência Urinária/etiologia , Complicações Pós-Operatórias/etiologia
6.
Medicine (Baltimore) ; 103(18): e37524, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701298

RESUMO

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.


Assuntos
Terapia a Laser , Uretra , Estreitamento Uretral , Estreitamento Uretral/cirurgia , Humanos , Terapia a Laser/métodos , Terapia a Laser/efeitos adversos , Uretra/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Masculino , Recidiva , Duração da Cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
7.
Biomaterials ; 309: 122622, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38797119

RESUMO

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.


Assuntos
Antioxidantes , Barreira Hematoencefálica , Carbono , Ferro , Óxido Nítrico , Doença de Parkinson , Animais , Óxido Nítrico/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Carbono/química , Ferro/metabolismo , Ferro/química , Antioxidantes/química , Antioxidantes/metabolismo , Camundongos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Masculino , Lactoferrina/química , Lactoferrina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Polietilenoglicóis/química , Pontos Quânticos/química , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas/química , Íons , Humanos , Camundongos Endogâmicos C57BL
8.
IEEE Trans Med Imaging ; PP2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781067

RESUMO

Deep convolution neural networks have been widely used in medical image analysis, such as lesion identification in whole-slide images, cancer detection, and cell segmentation, etc. However, it is often inevitable that researchers try their best to refine annotations so as to enhance the model performance, especially for cell segmentation task. Weakly supervised learning can greatly reduce the workload of annotations, while there is still a huge performance gap between the weakly and fully supervised learning approaches. In this work, we propose a weakly-supervised cell segmentation method, namely Multi-Task Cell Segmentation Network (MTCSNet), for multi-modal medical images, including pathological, brightfield, fluorescent, phase-contrast and differential interference contrast images. MTCSNet is learnt in a single-stage training manner, where only two annotated points for each cell provide supervision information, and the first one is the centroid, the second one is its boundary. Additionally, five auxiliary tasks are elaborately designed to train the network, including two pixel-level classifications, a pixel-level regression, a local temperature scaling and an instance-level distance regression task, which is proposed to regress the distances between the cell centroid and its boundaries in eight orientations. The experimental results indicate that our method outperforms all state-of-the-art weakly-supervised cell segmentation approaches on public multi-modal medical image datasets. The promising performance also shows that a single-stage learning with two-point labeling approach are sufficient for cell segmentation, instead of fine contour delineation. The codes are available at: https://github.com/binging512/MTCSNet.

9.
Phytomedicine ; 129: 155598, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38608596

RESUMO

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.


Assuntos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Metanálise em Rede , Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/tratamento farmacológico , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Antígeno Prostático Específico/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Produtos Biológicos/farmacologia
10.
J Med Chem ; 67(8): 6705-6725, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38596897

RESUMO

Cefiderocol is the first approved catechol-conjugated cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against Klebsiella pneumoniae and Acinetobacter baumannii, intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized, and evaluated. Extensive structure-activity relationships and structure-metabolism relationships (SMR) were conducted, leading to the discovery of a promising compound 86b (Code no. YFJ-36) with a new thioether linker. 86b exhibited superior and broad-spectrum in vitro antibacterial activity, especially against A. baumannii and K. pneumoniae, compared with cefiderocol. Potent in vivo efficacy was observed in a murine systemic infection model. Furthermore, the physicochemical stability of 86b in fluid medium at pH 6-8 was enhanced. 86b also reduced potential the risk of allergy owing to the quaternary ammonium linker. The improved properties of 86b supported its further research and development.


Assuntos
Antibacterianos , Catecóis , Desenho de Fármacos , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Catecóis/química , Catecóis/farmacologia , Catecóis/síntese química , Animais , Relação Estrutura-Atividade , Camundongos , Bactérias Gram-Negativas/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , beta-Lactamas/farmacologia , beta-Lactamas/síntese química , beta-Lactamas/química , Cefalosporinas/farmacologia , Cefalosporinas/síntese química , Cefalosporinas/química , Descoberta de Drogas
11.
J Med Chem ; 67(8): 6585-6609, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38598362

RESUMO

G0775, an arylomycin-type SPase I inhibitor that is being evaluated in a preclinical study, exhibited potent antibacterial activities against some Gram-negative bacteria but meanwhile suffered defects such as a narrow antibacterial spectrum and poor pharmacokinetic properties. Herein, systematic structural modifications were carried out, including optimization of the macrocyclic skeleton, warheads, and lipophilic regions. The optimization culminated in the discovery of 138f, which showed more potent activity and a broader spectrum against clinically isolated carbapenem-resistant Gram-negative bacteria, especially against Acinetobacter baumannii and Pseudomonas aeruginosa. 162, the free amine of 138f, exhibited an excellent pharmacokinetic profile in rats. In a neutropenic mouse thigh model of infection with multidrug-resistant P. aeruginosa, the potent in vivo antibacterial efficacy of 162 was confirmed and superior to that of G0775 (3.5-log decrease vs 1.1-log decrease in colony-forming unit (CFU)). These results support 162 as a potential antimicrobial agent for further research.


Assuntos
Antibacterianos , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Animais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Relação Estrutura-Atividade , Pseudomonas aeruginosa/efeitos dos fármacos , Ratos , Acinetobacter baumannii/efeitos dos fármacos , Masculino
12.
Opt Express ; 32(7): 11665-11672, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571008

RESUMO

We demonstrated a 978 nm laser diode (LD) side-pumped YSGG/Er:YSGG/YSGG composite crystal with a size of Ф 3 mm × 65 mm and continuous-wave (CW) mode. By optimizing resonator length and output mirror transmittance, a maximum output power of 28.02 W is generated, corresponding to slope efficiency of 17.55% and optical-optical efficiency of 12.29%, respectively. The thermal focal lengths are obtained by resonator stability condition. The laser wavelength is centered near 2.8 µm. Moreover, the beam quality factors M x2/M y2 are fitted to be 8.14 and 7.35, respectively. The above results indicate that a high-performance 2.8 µm CW laser can be achieved by LD side-pumped YSGG/Er:YSGG/YSGG composite crystal with excellent heat dissipation ability, which promotes effectively the development and applications of the mid-infrared solid-state lasers.

13.
Med Res Rev ; 44(4): 1904-1922, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38483176

RESUMO

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5'-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.


Assuntos
Envelhecimento Saudável , Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Animais , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Envelhecimento
14.
ACS Appl Mater Interfaces ; 16(13): 16973-16982, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38502909

RESUMO

Superhydrophobic surfaces (SHS) offer versatile applications by trapping an air layer within microstructures, while water jet impact can destabilize this air layer and deactivate the functions of the SHS. The current work presents for the first time that introducing parallel hydrophilic strips to SHS (SHS-s) can simultaneously improve both water impalement resistance and drag reduction (DR). Compared with SHS, SHS-s demonstrates a 125% increase in the enduring time against the impact of water jet with velocity of 11.9 m/s and a 97% improvement in DR at a Reynolds number of 1.4 × 104. The key mechanism lies in the enhanced stability of the air layer due to air confinement by the adjacent three-phase contact lines. These lines not only impede air drainage through the surface microstructures during water jet impact, entrapping the air layer to resist water impalement, but also prevent air floating up due to buoyancy in Taylor-Couette flow, ensuring an even spread of the air layer all over the rotor, boosting DR. Moreover, failure modes of SHS under water jet impact are revealed to be related to air layer decay and surface structure destruction. This mass-producible structured surface holds the potential for widespread use in DR for hulls, autonomous underwater vehicles, and submarines.

15.
Mol Psychiatry ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302560

RESUMO

Drug addiction is a chronic and debilitating disease that is considered a global health problem. Various cell types in the brain are involved in the progression of drug addiction. Recently, the xenobiotic hypothesis has been proposed, which frames substances of abuse as exogenous molecules that are responded to by the immune system as foreign "invaders", thus triggering protective inflammatory responses. An emerging body of literature reveals that microglia, the primary resident immune cells in the brain, play an important role in the progression of addiction. Repeated cycles of drug administration cause a progressive, persistent induction of neuroinflammation by releasing microglial proinflammatory cytokines and their metabolic products. This contributes to drug addiction via modulation of neuronal function. In this review, we focus on the role of microglia in the etiology of drug addiction. Then, we discuss the dynamic states of microglia and the correlative and causal evidence linking microglia to drug addiction. Finally, possible mechanisms of how microglia sense drug-related stimuli and modulate the addiction state and how microglia-targeted anti-inflammation therapies affect addiction are reviewed. Understanding the role of microglia in drug addiction may help develop new treatment strategies to fight this devastating societal challenge.

16.
BMC Cancer ; 24(1): 261, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402385

RESUMO

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.


Assuntos
Microbioma Gastrointestinal , Neoplasias da Próstata , Masculino , Humanos , Bactérias , Disbiose/microbiologia
17.
Nat Nanotechnol ; 19(5): 618-623, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286875

RESUMO

Transition metal dichalcogenide-based moiré superlattices exhibit strong electron-electron correlations, thus giving rise to strongly correlated quantum phenomena such as generalized Wigner crystal states. Evidence of Wigner crystals in transition metal dichalcogenide moire superlattices has been widely reported from various optical spectroscopy and electrical conductivity measurements, while their microscopic nature has been limited to the basic lattice structure. Theoretical studies predict that unusual quasiparticle excitations across the correlated gap between upper and lower Hubbard bands can arise due to long-range Coulomb interactions in generalized Wigner crystal states. However, the microscopic proof of such quasiparticle excitations is challenging because of the low excitation energy of the Wigner crystal. Here we describe a scanning single-electron charging spectroscopy technique with nanometre spatial resolution and single-electron charge resolution that enables us to directly image electron and hole wavefunctions and to determine the thermodynamic gap of generalized Wigner crystal states in twisted WS2 moiré heterostructures. High-resolution scanning single-electron charging spectroscopy combines scanning tunnelling microscopy with a monolayer graphene sensing layer, thus enabling the generation of individual electron and hole quasiparticles in generalized Wigner crystals. We show that electron and hole quasiparticles have complementary wavefunction distributions and that thermodynamic gaps of ∼50 meV exist for the 1/3 and 2/3 generalized Wigner crystal states in twisted WS2.

18.
Nat Mater ; 23(5): 633-638, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38172545

RESUMO

Moiré superlattices provide a highly tuneable and versatile platform to explore novel quantum phases and exotic excited states ranging from correlated insulators to moiré excitons. Scanning tunnelling microscopy has played a key role in probing microscopic behaviours of the moiré correlated ground states at the atomic scale. However, imaging of quantum excited states in moiré heterostructures remains an outstanding challenge. Here we develop a photocurrent tunnelling microscopy technique that combines laser excitation and scanning tunnelling spectroscopy to directly visualize the electron and hole distribution within the photoexcited moiré exciton in twisted bilayer WS2. The tunnelling photocurrent alternates between positive and negative polarities at different locations within a single moiré unit cell. This alternating photocurrent originates from the in-plane charge transfer moiré exciton in twisted bilayer WS2, predicted by our GW-Bethe-Salpeter equation calculations, that emerges from the competition between the electron-hole Coulomb interaction and the moiré potential landscape. Our technique enables the exploration of photoexcited non-equilibrium moiré phenomena at the atomic scale.

19.
Sci Total Environ ; 912: 169275, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38086482

RESUMO

The increase in alien plant invasions poses a major threat to global biodiversity and ecosystem stability. However, the presence of microplastics (MPs) as an environmental stressor could impact the interactions between invasive and native species in an invasive plant community. Nevertheless, the community alterations and underlying mechanisms resulting from these interactions remain unclear. Herein, we systematically investigated the impacts of polyethylene (PE) and polypropylene (PP) on invasive plant communities invaded by Amaranthus palmeri through soil seed bank. The results illustrated that MPs markedly declined community height and biomass, and altered community structure, low-dose MPs could prominently increase community invasion resistance, but reduced community stability. The niche width and niche overlap of A. palmeri and S. viridis declined when exposed to high-dose MPs, but MPs elicited a significant rise in the niche width of S. salsa. PP had the potential to reduce the diversity of invasive plant community. Structural equation model revealed that PP addition could change soil total phosphorus content, thereby leading to a reduction of the community stability. Our study helps to fill the knowledge gap regarding the effects of MPs on invasive plant communities and provide new perspectives for invasive plant management.


Assuntos
Amaranthus , Microplásticos , Plásticos , Ecossistema , Plantas , Solo/química , Polipropilenos
20.
Opt Express ; 31(22): 36429-36438, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017796

RESUMO

We demonstrate the thermal, spectroscopy and laser properties of Ho,Pr doped YAP crystal grown successfully by Cz method. The thermal expansion coefficient, thermal conductivity, absorption and emission spectra of Ho,Pr:YAP crystal are investigated in detail. Additionally, the level lifetimes suggest that Pr3+ is a suitable deactivating ion for Ho:YAP crystal. Particularly, the actual laser performance is optimized by doping active ion Ho with high concentrations and introducing deactivated Pr3+, resulting in decreased laser threshold, increased laser output power and slope efficiency. A 3.01 µm laser with output power of 502 mW, slope efficiency of 6.3% and beam quality factors of 1.42/1.43 is achieved in the Ho,Pr:YAP crystal, as far as we know this is the highest ∼3 µm CW laser power realized in Ho3+ doped oxide crystals.

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