Hasil untuk "Organic chemistry"

R. Bergman

M. Ghadiri, J. Granja, R. Milligan et al.

L. Dubois, R. Nuzzo

S. Stahl

B. Holliday, C. Mirkin

K. Klabunde

K. Jähnisch, V. Hessel, H. Löwe et al.

J. Bernstein, Raymond E. Davis, L. Shimoni et al.

R. Handy, F. Kammer, J. Lead et al.

M. Essington

J. Pinson, F. Podvorica

P. Ziemann, R. Atkinson

Tien D. Ho, Cheng Zhang, L. Hantao et al.

Khalid S. Mohammad, Fatimah Hussain Bu Izran

Bone remains one of the most hospitable—and devastating—destinations for metastatic cancer cells. At the center of this unwelcome alliance is transforming growth factor‑β (TGF‑β), a cytokine stored in the mineralized matrix and unleashed during osteoclastic bone resorption. Once activated, TGF‑β fuels a self‑reinforcing “vicious cycle”: it co‑opts tumor cells to undergo epithelial‑to‑mesenchymal transition, recruits and primes osteoclasts, suppresses osteoblast function, and shapes an immunosuppressive niche that shields malignant clones. The result is a micro‑environment exquisitely tuned for tumor survival, skeletal destruction, and therapy resistance. This review traces the molecular choreography of TGF‑β signaling within the bone tumor microenvironment (TME), detailing its crosstalk with osteogenic, immune, and stromal compartments across breast, prostate, and lung cancer metastases. We synthesize pre‑clinical and clinical efforts to interrupt this pathway, ranging from ligand-neutralizing antibodies and activin receptor-like kinase 5 (ALK5) kinase inhibitors to antisense oligonucleotides and tumor-selective ligand traps—and examine why benefits observed in early trials are tempered by dose‑limiting toxicities and adaptive resistance. Beyond TGF‑β itself, we highlight parallel targets in the TME, including receptor activator of nuclear factor kappa-B ligand (RANKL)‑driven osteoclastogenesis, vascular endothelial growth factor/fibroblast growth factor (VEGF/FGF)‑mediated angiogenesis, and immune checkpoints such as PD‑1, TIM‑3, and LAG‑3, arguing that multi‑pronged combinations guided by real‑time TME profiling offer the most promising path forward. We outline pressing research priorities: mapping the spatiotemporal dynamics of TGF‑β activation, identifying predictive biomarkers for patient stratification, and engineering bone‑targeted delivery systems that preserve normal tissue repair. By decoding and disrupting the TGF‑β‑centered circuitry of bone metastasis, we can move closer to therapies that not only palliate skeletal complications but also prolong life for patients with advanced cancer.

Yexuan Pu, Qian Jin, Yuewei Zhang et al.

Abstract Multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are preferred for their high efficiency and high colour purity in organic light-emitting diodes (OLEDs). However, the design strategies of MR-TADF emitters in the red region are very limited. Herein, we propose a concept for a paradigm shift in orange-red/deep-red MR emitters by linking the outer phenyl groups in a classical MR framework through intramolecular sulfur (S) locks. Endowed with the planar architectural feature of the MR mother core, the proof-of-concept S-embedded emitters S-BN and 2S-BN also exhibit considerable flatness, which proves critical in avoiding the direct establishment of potent charge transfer states and inhibiting the non-radiative decay process. The emission maxima of S-BN and 2S-BN are 594 nm and 671 nm, respectively, and both have a high photoluminescence quantum yield of ~100%, a rapid radiative decay rate of around 107 s−1, and a remarkably high reverse intersystem crossing rates of about 105 s−1. Notably, maximum external quantum efficiencies of 39.9% (S-BN, orange-red) and 29.3% (2S-BN, deep-red) were also achieved in typical planar OLED structures with ameliorated efficiency roll-offs.

Aigerim Kantureyeva, Gulbaram Ustenova, Alenka Zvonar Pobirk et al.

<i>Ceratocarpus arenarius</i> (Chenopodiaceae) is an under-investigated annual plant that occurs in dry areas stretching from eastern and south-eastern Europe to East Asia. This article presents the botanical characterization and examination of proximate parameters, minerals and cytotoxic activity of <i>C. arenarius</i> that grows wild in Kazakhstan. The results of morphological analysis using a light microscope, based on cross-sections of stems, roots and leaves, provide the necessary data to develop a regulatory document for this herbal substance as a raw material for use in the pharmaceutical, cosmetic and food industries. The investigated proximate characteristics included moisture content (6.8 ± 0.28%), ash (5.9 ± 0.40%), fat (12.5 ± 21.28%) and protein (392.85 ± 25.50). The plant is also rich in minerals (mg/100 g dry weight); Na (20.48 ± 0.29), K (302.73 ± 1.15), Zn (4.45 ± 0.35), Fe (1.18 ± 0.03), Cu (0.11 ± 0.02), Mn (0.76 ± 0.01), Ca (131.23 ± 0.09) and Mg (60.69 ± 0.72). The ethanolic extract of <i>C. arenarius</i> showed no acute toxicity against the brine shrimp nauplii.

Shaoming Jin, Yaonan Wang, Xiao Ning et al.

The aim of individuals consuming health supplements is to attain a robust state through nutritional regulation. However, some unscrupulous manufacturers, motivated by profit, fraudulently incorporate drugs or unauthorized components with therapeutic effects into the product for instant product performance enhancement. The long-term use of these products may inadvertently inflict harm on human health and fail to promote nutritive healthcare. The illegal inclusion of these substances is prevalent in kidney-tonifying and sexuality-enhancing products. Developing effective analytical methods to identify these products and screen for illegal added ingredients can effectively prevent such products from reaching and remaining on the market. A target screening method for the detection and quantification of 90 phosphodiesterase type 5 inhibitors (PDE-5is) in 5 kinds of health products was developed and validated. The type of dietary supplements varied from tablets, capsules, and protein powder to wine and beverages. Sample preparation was completed with a one-step liquid phase extraction. The screening process of 90 PDE-5is was done efficiently within 25 min by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using the dynamic multiple reaction monitoring (dMRM) technique. The LODs of 90 PDE-5is were detected at levels ranging from 25 to 85 ng/g or ng/mL. This novel targeting methodology was effective and can be applied to routine market supervision. Among 286 batches of samples, 8 batches were found to be positive. Three kinds of PDE-5is were first detected in healthy products. The screening method demonstrated herein will be a promising and powerful tool for rapid screening of PDE-5is.

Elena Genova, Paola Rispoli, Yue Fengming et al.

Abstract Background Differentiation of patient-specific induced pluripotent stem cells (iPS) helps researchers to study the individual sensibility to drugs. However, differentiation protocols are time-consuming, and not all tissues have been studied. Few works are available regarding pancreatic exocrine differentiation of iPS cells, and little is known on culturing and cryopreserving these cells. Methods We differentiated the iPS cells of two pediatric Crohn’s disease patients into pancreatic progenitors and exocrine cells, adapting and shortening a protocol for differentiating embryonic stem cells. We analyzed the expression of key genes and proteins of the differentiation process by qPCR and immunofluorescence, respectively. We explored the possibility of keeping differentiated cells in culture and freezing and thawing them to shorten the time needed for the differentiation. We analyzed the cell cycle of undifferentiated and differentiated cells by flow cytometry. Results The analysis of mRNA levels of key pancreatic differentiation genes PDX1 and pancreatic amylase indicate that iPS cells were successfully differentiated into pancreatic exocrine cells with expression of PDX1 (one way ANOVA p < 0.0001), and the two isoforms of amylase (one way ANOVA p < 0.05) significantly higher in exocrine cells in comparison to iPS cells. Differentiation efficiency was also confirmed by immunofluorescence analysis of PDX1 and amylase. We confirmed the possibility of shortening the time necessary for obtaining pancreatic cells without losing differentiation efficiency. Pancreatic progenitors and exocrine cells were maintained in culture and cryopreserved. Interestingly, the stemness marker OCT4 resulted significantly lower after subculturing (OCT4 p < 0.001; one-way ANOVA) and after freezing and thawing procedures (p < 0.05, one-way ANOVA) suggesting a reduction of undifferentiated stem cells leading to a purer population of pancreatic progenitor cells. Also, the stemness marker NANOG resulted lower after passaging, corroborating this result. Conclusions In this work, we optimized the generation of patient-specific pancreatic differentiated cells and laid the foundation for creating a bank of patient-specific pancreatic lines exploitable for tailored pharmacological assays. Trial registration The study was approved by the Ethical Committee of the Institute of Maternal and Child Health IRCCS Burlo Garofolo, with approval number 1556 (internal ID RC 44/22).

Jang-Woon Kim, Juryun Kim, Soon Min Lee et al.

Abstract Background Spinal cord injury (SCI) is a disease that causes permanent impairment of motor, sensory, and autonomic nervous system functions. Stem cell transplantation for neuron regeneration is a promising strategic treatment for SCI. However, selecting stem cell sources and cell transplantation based on experimental evidence is required. Therefore, this study aimed to investigate the efficacy of combination cell transplantation using the brain-derived neurotrophic factor (BDNF) over-expressing engineered mesenchymal stem cell (BDNF-eMSC) and induced pluripotent stem cell-derived motor neuron progenitor cell (iMNP) in a chronic SCI rat model. Method A contusive chronic SCI was induced in Sprague-Dawley rats. At 6 weeks post-injury, BDNF-eMSC and iMNP were transplanted into the lesion site via the intralesional route. At 12 weeks post-injury, differentiation and growth factors were evaluated through immunofluorescence staining and western blot analysis. Motor neuron differentiation and neurite outgrowth were evaluated by co-culturing BDNF-eMSC and iMNP in vitro in 2-dimensional and 3-dimensional. Results Combination cell transplantation in the chronic SCI model improved behavioral recovery more than single-cell transplantation. Additionally, combination cell transplantation enhanced mature motor neuron differentiation and axonal regeneration at the injured spinal cord. Both BDNF-eMSC and iMNP played a critical role in neurite outgrowth and motor neuron maturation via BDNF expression. Conclusions Our results suggest that the combined transplantation of BDNF- eMSC and iMNP in chronic SCI results in a significant clinical recovery. The transplanted iMNP cells predominantly differentiated into mature motor neurons. Additionally, BDNF-eMSC exerts a paracrine effect on neuron regeneration through BDNF expression in the injured spinal cord. Graphical Abstract

Ji Young Park, Hyun-Ji Song, Thanh Cuong Nguyen et al.

Predicting photolithography performance in silico for a given materials combination is essential for developing better patterning processes. However, it is still an extremely daunting task because of the entangled chemistry with multiple reactions among many material components. Herein, we investigated the EUV-induced photochemical reaction mechanism of a model photoacid generator (PAG), triphenylsulfonium cation, using atomiC–Scale materials modeling to elucidate that the acid generation yield strongly depends on two main factors: the lowest unoccupied molecular orbital (LUMO) of PAG cation associated with the electron-trap efficiency ‘before C–S bond dissociation’ and the overall oxidation energy change of rearranged PAG associated with the proton-generation efficiency ‘after C–S bond dissociation’. Furthermore, by considering stepwise reactions accordingly, we developed a two-parameter-based prediction model predicting the exposure dose of the resist, which outperformed the traditional LUMO-based prediction model. Our model suggests that one should not focus only on the LUMO energies but also on the energy change during the rearrangement process of the activated triphenylsulfonium (TPS) species. We also believe that the model is well suited for computational materials screening and/or inverse design of novel PAG materials with high lithographic performances.