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1.
Sci Adv ; 10(27): eadn2846, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959310

RESUMEN

High-precision light manipulation is crucial for delivering information through complex media. However, existing spatial light modulation devices face a fundamental speed-fidelity tradeoff. Digital micromirror devices have emerged as a promising candidate for high-speed wavefront shaping but at the cost of compromised fidelity due to the limited control degrees of freedom. Here, we leverage the sparse-to-random transformation through complex media to overcome the dimensionality limitation of spatial light modulation devices. We demonstrate that pattern compression by sparsity-constrained wavefront optimization allows sparse and robust wavefront representations in complex media, improving the projection fidelity without sacrificing frame rate, hardware complexity, or optimization time. Our method is generalizable to different pattern types and complex media, supporting consistent performance with up to 89% and 126% improvements in projection accuracy and speckle suppression, respectively. The proposed optimization framework could enable high-fidelity high-speed wavefront shaping through different scattering media and platforms without changes to the existing holographic setups, facilitating a wide range of physics and real-world applications.

2.
BMC Pediatr ; 24(1): 427, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961420

RESUMEN

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study. CASE PRESENTATION: We report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab. CONCLUSIONS: We summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.


Asunto(s)
Encefalomielitis , Rigidez Muscular , Mioclonía , Humanos , Masculino , Niño , Rigidez Muscular/etiología , Encefalomielitis/diagnóstico , Encefalomielitis/complicaciones , Mioclonía/etiología , Mioclonía/diagnóstico
3.
Artículo en Inglés | MEDLINE | ID: mdl-38970420

RESUMEN

SIGNIFICANCE: Herbal medicines demonstrate clinical promise for cancer treatment. Protein post translational modifications (PTMs) regulate tumorigenesis and cancer progression. While PTMs contributing to cancer are well-studied, the precise mechanisms and defined targets of herbal medicines on PTM-associated carcinogenesis remain unclear. Hence, comprehensively understanding how PTMs regulate cancer hallmarks is crucial to elucidate the pharmacological mechanisms of herbal medicines for cancer treatment. RECENT ADVANCES: Advanced development in highly sensitive mass spectrometry (MS)-based techniques has helped utilize PTM-focused studies on cancers. Accumulating evidence has been achieved in laboratory to ascertain the biological mechanism of herbal medicines in cancer therapy. Implication of the strong association between cancer and PTM makes new perspective to comprehend the intricate dialogues between herbal medicines and cellular contexts. CRITICAL ISSUES: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating PTM implicated in cell signaling, apoptosis and transcriptional regulation function, and the possible cellular signaling, have provided important information about the mechanism of many herbal therapies. Continued optimization of proteomic strategies for PTM analysis in herbal medicines are also discussed. FUTURE DIRECTIONS: Rigorous evaluations of herbal medicines and the chemoproteomic strategies are necessary to explore the aberrant regulation of PTM dynamics contributed to the cancer development and herbal associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

4.
Cell Biol Toxicol ; 40(1): 51, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958792

RESUMEN

The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn2+ they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn2+ played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.


Asunto(s)
Desarrollo Embrionario , Defectos del Tubo Neural , Tubo Neural , Estrés Oxidativo , Especies Reactivas de Oxígeno , Óxido de Zinc , Óxido de Zinc/toxicidad , Animales , Estrés Oxidativo/efectos de los fármacos , Embrión de Pollo , Desarrollo Embrionario/efectos de los fármacos , Ratones , Tubo Neural/efectos de los fármacos , Tubo Neural/embriología , Tubo Neural/metabolismo , Humanos , Defectos del Tubo Neural/inducido químicamente , Defectos del Tubo Neural/metabolismo , Defectos del Tubo Neural/embriología , Defectos del Tubo Neural/patología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Femenino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Nanopartículas del Metal/toxicidad , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/toxicidad
5.
Small ; : e2403176, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949041

RESUMEN

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO2 nanoparticle. With an optimized Ag loading (Ag/TiO2 = 0.5 wt%), the Ag atoms will uniformly disperse on TiO2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO2. These characteristics enable the high efficiency of H2 production to 16 580 µmol h-1 g-1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO2@PF3T), the H2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies.

6.
J Mater Chem B ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949411

RESUMEN

Most existing hydrogels, even recently developed injectable hydrogels that undergo a reversible sol-gel phase transition in response to external stimuli, are designed to gel immediately before or after implantation/injection to prevent the free diffusion of materials and drugs; however, the property of immediate gelation leads to a very weak tumour-targeting ability, limiting their application in anticancer therapy. Therefore, the development of tumour-specific responsive hydrogels for anticancer therapy is imperative because tumour-specific responses improve their tumour-targeting efficacy, increase therapeutic effects, and decrease toxicity and side effects. In this review, we introduce the following three types of tumour-responsive hydrogels: (1) hydrogels that gel specifically at the tumour site; (2) hydrogels that decompose specifically at the tumour site; and (3) hydrogels that react specifically with tumours. For each type, their compositions, the mechanisms of tumour-specific responsiveness and their applications in anticancer treatment are comprehensively discussed.

7.
Biochem Pharmacol ; 226: 116412, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38971334

RESUMEN

Increases in de novo lipogenesis that disturbed lipid homeostasis and caused lipid accumulation are a major cause of NAFLD and obesity. SREBP1 is a crucial regulatory factor controlling the expression of rate-limiting enzymes of lipid synthesis. A reduction in SREBP1expression can reduce lipid accumulation. Thus, we utilized an SREBP1-luciferase-KI HEK293 cell line constructed by our lab to screen 200 kinds of epigenetic drugs for their ability to downregulate SREBP1expression. BI-7273, an inhibitor of bromodomain-containing protein 9 (BRD9), was screened and found to decrease SREBP1 expression. What is more, BI-7273 has been confirmed that it could reduce lipid accumulation in HepG2 cells by BODIPY staining, and significantly decrease the protein expression of SREBP1 and FASN. To explore the potential mechanism BI-7273 reducing lipid accumulation, RNA sequencing (RNA-seq) was performed and demonstrated that BI-7273 reduced lipid accumulation by downregulating the AKT/mTOR/SREBP1 pathway in vitro. Finally, these results were verified in NAFLD and obesity mouse model induced by high fat diet (HFD). The results indicated that BI-7273 could decrease mouse body weight and improve insulin sensitivity, but also exhibited a strong negative correlation with serum lipid levels, and also demonstrated that BI-7273 reduced lipid accumulation via AKT/mTOR/SREBP1 pathway in vivo. In conclusion, our results revealed that BI-7273 decreases lipid accumulation by downregulating the AKT/mTOR/SREBP1 pathway in vivo and in vitro. This is the first report demonstrating the protective effect of this BRD9 inhibitor against NAFLD and obesity. BRD9 may be a novel target for the discovery of effective drugs to treat lipid metabolism disorders.

8.
Angew Chem Int Ed Engl ; : e202406140, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981859

RESUMEN

Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6% (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.

9.
J Bone Miner Metab ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981876

RESUMEN

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

10.
Adv Sci (Weinh) ; : e2400586, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984490

RESUMEN

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

11.
Mol Neurobiol ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985257

RESUMEN

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

12.
Genes Dis ; 11(5): 101020, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38988323

RESUMEN

Mutations or abnormal expression of oncogenes and tumor suppressor genes are known to cause cancer. Recent studies have shown that epigenetic modifications are key drivers of cancer development and progression. Nevertheless, the mechanistic role of epigenetic dysregulation in the tumor microenvironment is not fully understood. Here, we reviewed the role of epigenetic modifications of cancer cells and non-cancer cells in the tumor microenvironment and recent research advances in cancer epigenetic drugs. In addition, we discussed the great potential of epigenetic combination therapies in the clinical treatment of cancer. However, there are still some challenges in the field of cancer epigenetics, such as epigenetic tumor heterogeneity, epigenetic drug heterogeneity, and crosstalk between epigenetics, proteomics, metabolomics, and other omics, which may be the focus and difficulty of cancer treatment in the future. In conclusion, epigenetic modifications in the tumor microenvironment are essential for future epigenetic drug development and the comprehensive treatment of cancer. Epigenetic combination therapy may be a novel strategy for the future clinical treatment of cancer.

13.
Front Neurol ; 15: 1363225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988597

RESUMEN

Introduction: Although acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions. Methods: This is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea. Discussion: This randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea. Trial registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

14.
Xenobiotica ; : 1-8, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38994684

RESUMEN

The selection of appropriate starting dose and suitable method to predict an efficacious dose for novel oncology drug in the early clinical development stage poses significant challenges. The traditional methods of using body surface area transformation from toxicology studies to predict the first-in human (FIH) starting dose, or simply selecting the maximum tolerated dose (MTD) or maximum administered dose (MAD) as efficacious dose or recommended phase 2 dose (RP2D), are usually inadequate and risky for novel oncology drugs.Due to the regulatory efforts aimed at improving dose optimization in oncology drug development, clinical dose selection is now shifting away from these traditional methods towards a comprehensive benefit/risk assessment-based approach. Quantitative pharmacology analysis (QPA) plays a crucial role in this new paradigm. This mini-review summarizes the use of QPA in selecting the starting dose for oncology FIH studies and potential efficacious doses for expansion or phase 2 trials. QPA allows for a more rational and scientifically based approach to dose selection by integrating information across studies and development phases.In conclusion, the application of QPA in oncology drug development has the potential to significantly enhance the success rates of clinical trials and ultimately support clinical decision-making, particularly in dose selection.

15.
Sci Rep ; 14(1): 15606, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971868

RESUMEN

Coaxial nozzles are widely used to produce fibers with core-shell structures. However, conventional coaxial nozzles cannot adjust the coaxiality of the inner and outer needles in real-time during the fiber production process, resulting in uneven fiber wall thickness and poor quality. Therefore, we proposed an innovative semi-flexible coaxial nozzle with a dynamic self-centering function. This new design addresses the challenge of ensuring the coaxiality of the inner and outer needles of the coaxial nozzle. First, based on the principles of fluid dynamics and fluid-structure interaction, a self-centering model for a coaxial nozzle is established. Second, the influence of external fluid velocity and inner needle elastic modulus on the centering time and coaxiality error is analyzed by finite element simulation. Finally, the self-centering performance of the coaxial nozzle is verified by observing the coaxial extrusion process online and measuring the wall thickness of the formed hollow fiber. The results showed that the coaxiality error increased with the increase of Young's modulus E and decreased with the increase of flow velocity. The centering time required for the inner needle to achieve force balance decreases with the increase of Young's modulus ( E ) and fluid velocity ( v f ). The nozzle exhibits significant self-centering performance, dynamically reducing the initial coaxiality error from 380 to 60 µm within 26 s. Additionally, it can mitigate the coaxiality error caused by manufacturing and assembly precision, effectively controlling them within 8 µm. Our research provides valuable references and solutions for addressing issues such as uneven fiber wall thickness caused by coaxiality errors.

16.
Physiol Mol Biol Plants ; 30(6): 909-919, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974351

RESUMEN

Bud mutation is a common technique for plant breeding and can provide a large number of breeding materials. Through traditional breeding methods, we obtained a plum plant with bud mutations (named "By") from an original plum variety (named "B"). The ripening period of "By" fruit was longer than that of "B" fruit, and its taste was better. In order to understand the characteristics of these plum varieties, we used transcriptome analysis and compared the gene expression patterns in fruits from the two cultivars. Subsequently, we identified the biological processes regulated by the differentially expressed genes (DEGs). Gene ontology (GO) analysis revealed that these DEGs were highly enriched for "single-organism cellular process" and "transferase activity". KEGG analysis demonstrated that the main pathways affected by the bud mutations were plant hormone signal transduction, starch and sucrose metabolism. The IAA, CKX, ARF, and SnRK2 genes were identified as the key regulators of plant hormone signal transduction. Meanwhile, TPP, the beta-glucosidase (EC3.2.1.21) gene, and UGT72E were identified as candidate DEGs affecting secondary metabolite synthesis. The transcriptome sequencing (RNA-seq) data were also validated using RT-qPCR experiments. The transcriptome analysis demonstrated that plant hormones play a significant role in extending the maturity period of plum fruit, with IAA, CKX, ARF, and SnRK2 serving as the key regulators of this process. Further, TPP, beta-glucosidase (EC3.2.1.21), and UGT72E appeared to mediate the synthesis of various soluble secondary metabolites, contributing to the aroma of plum fruits. The expression of BAG6 was upregulated in "B" as the fruit matured, but it was downregulated in "By". This indicated that "B" may have stronger resistance, especially fungal resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01472-3.

18.
Int J Pharm ; 661: 124457, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992736

RESUMEN

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

19.
World J Gastrointest Oncol ; 16(6): 2504-2519, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994160

RESUMEN

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

20.
J Colloid Interface Sci ; 675: 806-814, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39002231

RESUMEN

Metal-organic compounds have attracted significant attention for lithium-ion battery (LIB) anodes. However, their practical application is severely hindered by the poor structural stability and sluggish Li+ reaction kinetics. Herein, we proposed a new type of metal-organic compound, metal alkoxides, for high-performance LIBs. A series of metal-alkoxide/graphene composites with different transition metal centers and alkoxide anions are prepared to investigate the structural stability, Li-storage ability, and Li+ diffusion kinetics. The results reveal that the metal centers and alkoxide anions have significant influence on the structural stability, molar mass, and electronic structures, which are highly related to the Li-storage performance. Among them, Co-EG/rGO (EG represents the ethylene glycol anion) delivers the best performance involving high specific capacity (975 mAh g-1 at 0.2 A g-1), excellent rate capability (400.8 mAh g-1 at 10 A g-1), and stable cycling performance (86.8 % capacity retention after 600 cycles) due to its stable structure, smaller molar mass, and favorable electronic structure. Moreover, the Li-storage mechanism and solid electrolyte interphase (SEI) evolution of the Co-EG/rGO electrode are studied in detail through multiple ex-situ/in-situ characterizations. This work provides a new type of metal alkoxide anode material for high-rate and long-life LIBs toward practical energy applications.

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