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1.
Neural Regen Res ; 20(2): 518-532, 2025 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-38819064

RÉSUMÉ

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

2.
Food Chem ; 460(Pt 2): 140628, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39089021

RÉSUMÉ

The study elucidates that the pH shifting treatment unfolds the conformation of soybean protein isolate (SPI), enabling it to intertwine with bacterial cellulose (BC) and form SPI/BC co-assemblies. Results from intrinsic fluorescence spectroscopy and surface hydrophobicity indicate that the SPI with pH shifting treatment shows a notable blue shift in maximum emission wavelength and increased surface hydrophobicity. It demonstrates that pH shifting treatment facilitates the unfolding of SPI's molecular conformation, promoting its entanglement with high aspect ratio BC. Particle size distribution and microstructural analysis further demonstrate that the pH shifting treatment facilitates the formation of SPI/BC co-assemblies. Evaluation of processing properties reveals that the SPI/BC co-assemblies exhibited exceptional gel and emulsification properties, with gel strength and emulsifying activity respectively six and two times higher than natural SPI. This enhancement is attributed to the thickening properties of BC with a high aspect ratio and the superior hydrophobicity of SPI in its molten globule state.

3.
NPJ Precis Oncol ; 8(1): 169, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39090304

RÉSUMÉ

Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, with many patients facing poor prognosis, particularly those with metastatic or drug-resistant tumors. Homologous recombination genes (HRGs) are crucial in tumor progression and therapy resistance, but their clinical significance in LUAD is not well understood. In this study, we systematically characterize key HRGs in LUAD patients, identifying two distinct HR subtypes associated with different outcomes and biological functions. We establish a 5-gene scoring system (XRCC2, RAD51, BRCA1, FANCA, and CHEK1) that reliably predicts patient outcomes and immunotherapy responses in LUAD. Bioinformatics analysis and clinical validation highlight XRCC2 as a crucial biomarker in LUAD. Functional investigations through in vivo and in vitro experiments reveal the role of XRCC2 in promoting lung cancer migration and invasion. Mechanistically, XRCC2 stabilizes vimentin (VIM) protein expression through deubiquitylation. We predict c-MYC as a potential regulator of XRCC2 and demonstrate that inhibiting c-MYC with compound 10058-F4 reduces XRCC2 and VIM expression. Preclinical studies show the synergistic inhibition of metastasis in vivo when combining 10058-F4 with doxorubicin (Dox). Our findings present a potential personalized predictive tool for LUAD prognosis, identifying XRCC2 as a critical biomarker. The c-Myc-XRCC2-VIM axis emerges as a promising therapeutic target for overcoming lung metastasis. This study provides valuable insights into LUAD, proposing a prognostic tool for further clinical validation and unveiling a potential therapeutic strategy for combating lung metastasis by targeting c-Myc-XRCC2-VIM.

4.
Biomed Pharmacother ; 179: 117315, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39153434

RÉSUMÉ

Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.

5.
Magn Reson Med ; 2024 Aug 13.
Article de Anglais | MEDLINE | ID: mdl-39136245

RÉSUMÉ

PURPOSE: To compare the performance of multi-echo (ME) and time-division multiplexing (TDM) sequences for accelerated relaxation-diffusion MRI (rdMRI) acquisition and to examine their reliability in estimating accurate rdMRI microstructure measures. METHOD: The ME, TDM, and the reference single-echo (SE) sequences with six TEs were implemented using Pulseq with single-band (SB) and multi-band 2 (MB2) acceleration factors. On a diffusion phantom, the image intensities of the three sequences were compared, and the differences were quantified using the normalized RMS error (NRMSE). Shinnar-Le Roux (SLR) pulses were implemented for the SB-ME and SB-SE sequences to investigate the impact of slice profiles on ME sequences. For the in-vivo brain scan, besides the image intensity comparison and T2-estimates, different methods were used to assess sequence-related effects on microstructure estimation, including the relaxation diffusion imaging moment (REDIM) and the maximum-entropy relaxation diffusion distribution (MaxEnt-RDD). RESULTS: TDM performance was similar to the gold standard SE acquisition, whereas ME showed greater biases (3-4× larger NRMSEs for phantom, 2× for in-vivo). T2 values obtained from TDM closely matched SE, whereas ME sequences underestimated the T2 relaxation time. TDM provided similar diffusion and relaxation parameters as SE using REDIM, whereas SB-ME exhibited a 60% larger bias in the map and on average 3.5× larger bias in the covariance between relaxation-diffusion coefficients. CONCLUSION: Our analysis demonstrates that TDM provides a more accurate estimation of relaxation-diffusion measurements while accelerating the acquisitions by a factor of 2 to 3.

6.
Sci Prog ; 107(3): 368504241275414, 2024.
Article de Anglais | MEDLINE | ID: mdl-39150376

RÉSUMÉ

BACKGROUND: The pressure fluctuation in the volute can be effectively reduced when the impeller of the double-suction pump is staggered, but the mechanism of this reduction is still unclear. At the same time, the traditional analysis method cannot realize the visualization of pressure fluctuation. OBJECTIVE: The purpose of this article is to explore the spatial distribution, propagation, and attenuation law of pressure fluctuation, and on this basis, to research the reason why staggered impeller reduce pressure fluctuation. METHODS: A new method called Pulse tracking network (PTN) was used in this article. Compared with the traditional method, which only analyzes the pressure fluctuation at scattered points, this method greatly improves the spatial resolution of the pressure fluctuation. In particular, the phase analysis is a major highlight of the method. RESULTS: Staggered impeller significantly reduced the pressure fluctuation intensity dominated by blade passing frequency. At the same time, the propagation of the pressure fluctuation in the volute changed from radial to circumferential in the volute cross-section. CONCLUSIONS: Staggered impeller can effectively reduce pressure fluctuation, and the circumferential propagation caused by it is considered to be the main reason for it.

7.
Adv Sci (Weinh) ; : e2406095, 2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39099408

RÉSUMÉ

Catalytic activation of Caryl-O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4-O-5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light-induced bifunctional N-heterocyclic carbene (NHC)-catalyzed one-electron reduction of diaryl ether 4-O-5 linkage models for the synthesis of trivalent phosphines. The H-bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one-electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model.

10.
CNS Neurosci Ther ; 30(8): e14902, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39138637

RÉSUMÉ

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.


Sujet(s)
Délire avec confusion , microARN , Neurones , Complications postopératoires , ARN circulaire , Sirtuine-3 , Animaux , Sirtuine-3/métabolisme , Sirtuine-3/génétique , Délire avec confusion/métabolisme , Souris , microARN/métabolisme , microARN/génétique , ARN circulaire/métabolisme , Neurones/métabolisme , Neurones/effets des médicaments et des substances chimiques , Mâle , Complications postopératoires/métabolisme , Région CA1 de l'hippocampe/métabolisme , Région CA1 de l'hippocampe/effets des médicaments et des substances chimiques , Souris de lignée C57BL , Fractures du tibia/chirurgie , Potentiel de membrane mitochondriale/effets des médicaments et des substances chimiques , Potentiel de membrane mitochondriale/physiologie
11.
Front Oncol ; 14: 1439209, 2024.
Article de Anglais | MEDLINE | ID: mdl-39165682

RÉSUMÉ

Background: Bone metastases of lung cancer (BMLC) severely diminish patients' quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent. Methods: A comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and Microsoft Office Excel Professional Plus 2016 software. 936 papers related to BMLC were extracted from the Web of Science Core Collection (WoSCC). The number of publications, countries, institutions, global collaborations, authors, journals, keywords, thematic trends, and cited references were then visualized. Finally, the research status and development direction in the last 20 years were analyzed. Results: This study included a total of 936 papers on BMLC from 2004 to 2023. There has been a steady increase in global publications each year, peaking in 2021. China had the highest number of publications, followed by Japan and the United States. Additionally, China had the most citations with an H-index of 35, while the US followed with an H-index of 34, highlighting their significant contributions to the field. "Frontiers in Oncology" had the highest number of publications. CiteSpace analysis identified "lung cancer," "bone metastasis," and "survival" as the top high-frequency keywords, encapsulating the core research focus. Keyword clustering analysis revealed six main clusters representing the primary research directions. Burst analysis of keywords showed that "skeletal complications" had the highest burst intensity from 2005 to 2013, while recent research trends include "immunotherapy" and "denosumab," with bursts from 2021 to 2023. Trend topic analysis indicated that "non-small cell lung cancer," "immunotherapy," and "immune checkpoint inhibitors" represent the cutting-edge research directions in this field. Conclusion: This article reveals the current status and trend of research on BMLC, which is increasing worldwide. China and the United States have contributed the most, but international cooperative research on BMLC should be strengthened. The pathogenesis, early prevention, and individualized treatment of BMLC need to be strengthened for further study, and immunotherapy is the next hotspot of lung cancer bone metastasis research.

12.
PLoS One ; 19(8): e0308354, 2024.
Article de Anglais | MEDLINE | ID: mdl-39146275

RÉSUMÉ

BACKGROUND: Rotator cuff tears are a common shoulder injury that significantly impacts patients' daily lives and work abilities. Although surgical treatment methods for rotator cuff tears have been continuously improved with advances in medical technology, postoperative rehabilitation remains challenging. Therefore, finding effective rehabilitation treatments is crucial for improving patient prognosis and enhancing quality of life. This study will aim to systematically evaluate the impact of low-intensity pulsed ultrasound (LIPUS) on postoperative rehabilitation of rotator cuff tears, comprehensively assessing the efficacy and safety of LIPUS in postoperative recovery. METHODS: This protocol will search multiple databases including PubMed/MEDLINE, Embase, Cochrane Library, CNKI, Scopus, and Web of Science to identify randomized controlled trials related to LIPUS for postoperative rehabilitation of rotator cuff tears. The search will encompass literature published from the inception of the databases up to April 2024. Methodological quality assessment and data extraction will be conducted using the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analysis will be performed on appropriate studies using either random-effects or fixed-effects models, and subgroup analyses will be conducted to explore potential heterogeneity. Studies meeting the inclusion criteria will be included in the analysis. All analyses will be performed using Stata version 16.0. RESULTS: The incidence of rotator cuff tear rates will be assessed by imaging techniques such as MRI or ultrasound. Pain intensity will be scored using standardized pain assessment scales, such as the Visual Analog Scale (VAS). Improved range of motion (ROM) in shoulder flexion, abduction, and rotation. Functional outcomes will be evaluated using effective measures such as Constant-Murley scores (CMS) and shoulder joint scores by American Shoulder and Elbow Surgeons (ASES). Adverse events associated with LIPUS therapy, including skin irritation, increased pain, or any other complications. Subgroup analysis will also be carried out if possible. DISCUSSION AND CONCLUSION: Following the meta-analysis, we will assess the overall effect of LIPUS on postoperative rehabilitation of rotator cuff tears, and further explore its impact on aspects such as pain relief, functional improvement, and postoperative complications. It is anticipated that this study will provide comprehensive evidence regarding the role of LIPUS in postoperative rehabilitation of rotator cuff tears, guiding clinical practice and future research. The resultant manuscript will be submitted for publication in a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: CRD42024530798.


Sujet(s)
Méta-analyse comme sujet , Lésions de la coiffe des rotateurs , Revues systématiques comme sujet , Humains , Lésions de la coiffe des rotateurs/chirurgie , Lésions de la coiffe des rotateurs/rééducation et réadaptation , Ondes ultrasonores , Ultrasonothérapie/méthodes , Coiffe des rotateurs/chirurgie , Coiffe des rotateurs/imagerie diagnostique , Amplitude articulaire , Qualité de vie
13.
Cell Host Microbe ; 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39106870

RÉSUMÉ

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

14.
Head Neck ; 2024 Aug 13.
Article de Anglais | MEDLINE | ID: mdl-39138647

RÉSUMÉ

PURPOSE: Head and neck cancer cells commonly express programmed death ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR), both of which play pivotal roles in the antitumor cellular immune response. Pembrolizumab, a PD-1 inhibitor, and cetuximab, an EGFR inhibitor, are typically effective agents combined with neoadjuvant platinum-based chemotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy in patients with HNSCC. METHODS: Patients with HNSCC underwent radical surgery and complete cervical lymph node dissection following neoadjuvant immunochemotherapy at RenJi Hospital from January 2021 to June 2024 were retrospectively analyzed. The primary endpoint was major pathological response (MPR). We further explored the relationship between the efficacy and immune estimators. FINDINGS: Twenty-one patients were enrolled in this retrospective study. The MPR was 66.7%, including 11 patients who achieved a pathological complete response (pCR). The overall response rate (ORR) was 90.5%, and the complete response (CR) rate was 28.6%. The oropharynx, as the primary site, was the sensitive tumor type to neoadjuvant immunochemotherapy. The most common adverse event (AEs) was anemia (61.9%). No grade 4 AE or delayed surgery was reported. Laryngeal preservation rates were 90.9% (10/11), and pathological findings confirmed negative surgical margins for all patients. Moreover, pre-treatment peripheral lymphocyte count, monocyte count, and platelet to lymphocyte ratio (PLR) displayed a significant correlation with the treatment response. CONCLUSION: Pembrolizumab plus cetuximab with chemotherapy for patients with HNSCC is a feasible and safe clinical protocol fulfilling organ preservation and life quality improvement. Pre-treatment peripheral immune estimators could help to screen patients who may respond to the neoadjuvant immunochemotherapy.

15.
Nanomaterials (Basel) ; 14(15)2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39120423

RÉSUMÉ

Optical logic devices are essential functional devices for achieving optical signal processing. In this study, we design an ultra-compact (4.92 × 2.52 µm2) reconfigurable optical logic gate by using inverse design method with DBS algorithm based on Sb2Se3-SOI integrated platform. By selecting different amorphous/crystalline distributions of Sb2Se3 via programmable electrical triggers, the designed structure can switch between OR, XOR, NOT or AND logic gate. This structure works well for all four logic functions in the wavelength range of 1540-1560 nm. Especially at the wavelength of 1550 nm, the Contrast Ratios for XOR, NOT and AND logic gate are 13.77 dB, 11.69 dB and 3.01 dB, respectively, indicating good logical judgment ability of the device. Our design is robust to a certain range of fabrication imperfections. Even if performance weakens due to deviations, improvements can be obtained by rearranging the configurations of Sb2Se3 without reproducing the whole device.

16.
J Vis ; 24(8): 5, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39110583

RÉSUMÉ

Contextual cueing is a phenomenon of visual statistical learning observed in visual search tasks. Previous research has found that the degree of deviation of items from its centroid, known as variability, determines the extent of generalization for that repeated scene. Introducing variability increases dissimilarity between multiple occurrences of the same repeated layout significantly. However, current theories do not explain the mechanisms that help to overcome this dissimilarity during contextual cue learning. We propose that the cognitive system initially abstracts specific scenes into scene layouts through an automatic clustering unrelated to specific repeated scenes, and subsequently uses these abstracted scene layouts for contextual cue learning. Experiment 1 indicates that introducing greater variability in search scenes leads to a hindering in the contextual cue learning. Experiment 2 further establishes that conducting extensive visual searches involving spatial variability in entirely novel scenes facilitates subsequent contextual cue learning involving corresponding scene variability, confirming that learning clustering knowledge precedes the contextual cue learning and is independent of specific repeated scenes. Overall, this study demonstrates the existence of multiple levels of learning in visual statistical learning, where item-level learning can serve as material for layout-level learning, and the generalization reflects the constraining role of item-level knowledge on layout-level knowledge.


Sujet(s)
Signaux , Humains , Stimulation lumineuse/méthodes , Apprentissage/physiologie , Jeune adulte , Mâle , Femelle , Reconnaissance visuelle des formes/physiologie , Perception visuelle/physiologie , Adulte , Analyse de regroupements , Attention/physiologie
17.
Int J Pharm ; : 124584, 2024 Aug 12.
Article de Anglais | MEDLINE | ID: mdl-39142465

RÉSUMÉ

Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and ß-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and ß-arbutin interacted with keratin or SC lipids, further demonstrating the relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than ß-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, ß-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with ß-arbutin, as confirmed by molecular simulation and 13Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor affecting the intermolecular force between arbutin and the SC, thereby resulting in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than ß-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration.

18.
Cancer Med ; 13(15): e7408, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39136200

RÉSUMÉ

BACKGROUND: The MONALEESA­7 and ­2 phase 3 randomized trials demonstrated a statistically significant progression­free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre­ and postmenopausal patients with hormone receptor­positive (HR+)/human epidermal growth factor receptor 2­negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre­ and postmenopausal patients with HR+/HER2­ ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA­7 and ­2 studies. METHODS: Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator­assessed PFS. RESULTS: As of April 25, 2022, the median follow­up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. CONCLUSIONS: These data demonstrate a favorable benefit­risk profile for ribociclib + ET in Chinese patients.


Sujet(s)
Aminopyridines , Protocoles de polychimiothérapie antinéoplasique , Tumeurs du sein , Létrozole , Post-ménopause , Purines , Récepteur ErbB-2 , Récepteurs des oestrogènes , Humains , Aminopyridines/administration et posologie , Aminopyridines/usage thérapeutique , Aminopyridines/effets indésirables , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Purines/administration et posologie , Purines/effets indésirables , Adulte d'âge moyen , Récepteur ErbB-2/métabolisme , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Récepteurs des oestrogènes/métabolisme , Létrozole/administration et posologie , Létrozole/usage thérapeutique , Adulte , Chine , Sujet âgé , Récepteurs à la progestérone/métabolisme , Préménopause , Survie sans progression , Goséréline/administration et posologie , Goséréline/usage thérapeutique , Inhibiteurs de l'aromatase/administration et posologie , Inhibiteurs de l'aromatase/usage thérapeutique , Peuples d'Asie de l'Est
19.
ACS Appl Mater Interfaces ; 16(33): 43806-43815, 2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39105741

RÉSUMÉ

Due to the large volume of exposed atoms and electrons at the surface of two-dimensional materials, interfacial charge coupling has been proven as an efficient strategy to engineer the electronic structures of two-dimensional materials assembled in van der Waals heterostructures. Recently, heterostructures formed by graphene stacked with CrOCl have demonstrated intriguing quantum states, including a distorted quantum Hall phase in the monolayer graphene and the unconventional correlated insulator in the bilayer graphene. Yet, the understanding of the interlayer charge coupling in the heterostructure remains challenging. Here, we demonstrate clear evidences of efficient hole doping in the interfacial-coupled graphene/CrOCl heterostructure by detailed Raman spectroscopy and electrical transport measurements. The observation of significant blue shifts and stiffness of graphene Raman modes quantitatively determines the concentration of hole injection of about 1.2 × 1013 cm-2 from CrOCl to graphene, which is highly consistent with the enhanced conductivity of graphene. First-principles calculations based on density functional theory reveal that due to the large work function difference and the electronegativity of Cl atoms in CrOCl, the electrons are efficiently transferred from graphene to CrOCl, leading to hole doping in graphene. Our findings provide clues for understanding the exotic physical properties of graphene/CrOCl heterostructures, paving the way for further engineering of quantum electronic states by efficient interfacial charge coupling in van der Waals heterostructures.

20.
IEEE Trans Med Imaging ; PP2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39167522

RÉSUMÉ

Microwave-induced thermoacoustic imaging (M-TAI) allows the visualization of macroscopic and microscopic structures of bio-tissues. However, it suffers from severe inherent artifacts that might misguide the subsequent diagnostics and treatments of diseases. To overcome this limitation, we propose an optimized excitation strategy. In detail, the strategy integrates dynamically compound specific absorption rate (SAR) and co-planar configuration of polarization state, incident wave vector and imaging plane. Starting from the theoretical analysis, we interpret the underlying mechanism supporting the superiority of the optimized excitation strategy to achieve an effect equivalent to homogenizing the deposited electromagnetic energy in bio-tissues. The following numerical simulations demonstrate that the strategy enables better preservation of the conductivity weighting of samples while increasing Pearson correlation coefficient. Furthermore, the in vitro and in vivo M-TAI experiments validate the effectiveness and robustness of this optimized excitation strategy in artifact suppression, allowing the simultaneous identification of both boundary and inside fine structures within bio-tissues. All the results suggest that the optimized excitation strategy can be expanded to diverse scenarios, inspiring more suitable strategies that remarkably suppress the inherent artifacts in M-TAI.

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