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With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines. [ABSTRACT FROM AUTHOR]

Abstract Background Protein palmitoylation, which is catalyzed by palmitoyl-transferase and de-palmitoyl-transferase, plays a crucial role in various biological processes. However, the landscape and dynamics of protein palmitoylation in human cancers are not well understood. Methods We utilized 23 palmitoyl-acyltransferases and seven de-palmitoyl-acyltransferases as palmitoylation-related genes for protein palmitoylation analysis. Multiple publicly available datasets were employed to conduct pan-cancer analysis, examining the transcriptome, genomic alterations, clinical outcomes, and correlation with c-Myc (Myc) for palmitoylation-related genes. Real-time quantitative PCR and immunoblotting were performed to assess the expression of palmitoylation-related genes and global protein palmitoylation levels in cancer cells treated with Myc depletion or small molecule inhibitors. Protein docking and drug sensitivity analyses were employed to predict small molecules that target palmitoylation-related genes. Results We identified associations between palmitoylation and cancer subtype, stage, and patient survival. We discovered that abnormal DNA methylation and oncogenic Myc-driven transcriptional regulation synergistically contribute to the dysregulation of palmitoylation-related genes. This dysregulation of palmitoylation was closely correlated with immune infiltration in the tumor microenvironment and the response to immunotherapy. Importantly, dysregulated palmitoylation was found to modulate canonical cancer-related pathways, thus influencing tumorigenesis. To support our findings, we performed a proof-of-concept experiment showing that depletion of Myc led to reduced expression of most palmitoylation-related genes, resulting in decreased global protein palmitoylation levels. Through mass spectrometry and enrichment analyses, we also identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as significant contributors to mTOR signaling, DNA repair, and immune pathways, highlighting their potential roles in tumorigenesis. Additionally, our study explored the potential of three small molecular (BI-2531, etoposide, and piperlongumine) to modulate palmitoylation by targeting the expression or activity of palmitoylation-related genes or enzymes. Conclusions Overall, our findings underscore the critical role of dysregulated palmitoylation in tumorigenesis and the response to immunotherapy, mediated through classical cancer-related pathways and immune cell infiltration. Additionally, we propose that the aforementioned three small molecule hold promise as potential therapeutics for modulating palmitoylation, thereby offering novel avenues for cancer therapy.

Depression is a common disease that affects physical and mental health and imposes a considerable burden on afflicted individuals and their families worldwide. Depression is associated with a high rate of disability and suicide. It causes a severe decline in productivity and quality of life. Unfortunately, the pathophysiological mechanisms underlying depression have not been fully elucidated, and the risk of its treatment is still presented. Studies have shown that the expression of autophagic markers in the brain and peripheral inflammatory mediators are dysregulated in depression. Autophagy-related genes regulate the level of autophagy and change the inflammatory response in depression. Depression is related to several aspects of immunity. The regulation of the immune system and inflammation by autophagy may lead to the development or deterioration of mental disorders. This review highlights the role of autophagy and neuroinflammation in the pathophysiology of depression, sumaries the autophagy-targeting small moleculars, and discusses a novel therapeutic strategy based on anti-inflammatory mechanisms that target autophagy to treat the disease.

Background: Protein palmitoylation, which is catalyzed by palmitoyl-transferase and de-palmitoyl-transferase, plays a crucial role in various biological processes. However, the landscape and dynamics of protein palmitoylation in human cancers are not well understood. Methods: We utilized 23 palmitoyl-acyltransferases and seven de-palmitoyl-acyltransferases as palmitoylation-related genes for protein palmitoylation analysis. Multiple publicly available datasets were employed to conduct pan-cancer analysis, examining the transcriptome, genomic alterations, clinical outcomes, and correlation with c-Myc (Myc) for palmitoylation-related genes. Real-time quantitative PCR and immunoblotting were performed to assess the expression of palmitoylation-related genes and global protein palmitoylation levels in cancer cells treated with Myc depletion or small molecule inhibitors. Protein docking and drug sensitivity analyses were employed to predict small molecules that target palmitoylation-related genes. Results: We identified associations between palmitoylation and cancer subtype, stage, and patient survival. We discovered that abnormal DNA methylation and oncogenic Myc-driven transcriptional regulation synergistically contribute to the dysregulation of palmitoylation-related genes. This dysregulation of palmitoylation was closely correlated with immune infiltration in the tumor microenvironment and the response to immunotherapy. Importantly, dysregulated palmitoylation was found to modulate canonical cancer-related pathways, thus influencing tumorigenesis. To support our findings, we performed a proof-of-concept experiment showing that depletion of Myc led to reduced expression of most palmitoylation-related genes, resulting in decreased global protein palmitoylation levels. Through mass spectrometry and enrichment analyses, we also identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as significant contributors to mTOR signaling, DNA repair, and immune pathways, highlighting their potential roles in tumorigenesis. Additionally, our study explored the potential of three small molecular (BI-2531, etoposide, and piperlongumine) to modulate palmitoylation by targeting the expression or activity of palmitoylation-related genes or enzymes. Conclusions: Overall, our findings underscore the critical role of dysregulated palmitoylation in tumorigenesis and the response to immunotherapy, mediated through classical cancer-related pathways and immune cell infiltration. Additionally, we propose that the aforementioned three small molecule hold promise as potential therapeutics for modulating palmitoylation, thereby offering novel avenues for cancer therapy. [ABSTRACT FROM AUTHOR]

Reactive sulphur species (RSS) play a vital role in cellular redox homeostasis and signal transduction. The lysosome is a vital organelle in eukaryotic cells involved in phagocytosis, digestion and degradation of proteins or damaged organelles, repair of cell membrane and energy metabolism. Lysosomal RSS are closely associated with normal functions of the lysosome, and abnormal RSS homeostasis may lead to lysosomal dysfunction and some serious diseases. Thus, real‐time visualization of lysosomal RSS is of great significance. Due to the prominent advantages of fluorescence imaging technology, many small molecular fluorescent probes for detecting lysosomal RSS have been developed. Herein, we have systematically summarized the versatile small molecular and lysosome‐targetable fluorescent probes available for detecting RSS, including their chemical structures, response mechanisms and bioapplications. In addition, we have highlighted the current status, challenges and developmental prospects for RSS‐responsive small molecular fluorescent probes. We sincerely hope that this review can instruct researchers interested in constructing new fluorescent probes for RSS and draw attention toward the significance of lysosomal RSS. [ABSTRACT FROM AUTHOR]

Objectives: It is necessary to develop a high-performance and biocompatible contrast agent to accurately diagnose various diseases via in vivo computed tomography (CT) imaging. Here, we synthesized a small molecular Bi-DOTA complex as a high-performance contrast agent for in vitro and in vivo CT bioimaging. Materials and Methods: In our study, Bi-DOTA was fabricated through a facile and one-pot synthesis strategy. The formed Bi-DOTA complex was characterized via different techniques. Furthermore, Bi-DOTA was used for in vitro and in vivo CT bioimaging to verify its X-ray attenuation ability, especially in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging. Results: A small molecular Bi-DOTA complex with a molecular mass of 0.61 kDa was synthesized successfully, which exhibited outstanding dispersion, good biocompatibility, and superior X-ray attenuation ability. Meanwhile, we showed that the obtained contrast agent was quite biocompatible and safe in the given concentration range as confirmed by in vitro and in vivo cytotoxicity assay. Also, the proposed contrast agent can be rapidly excreted from the body via the urinary system, avoiding the potential side effects caused by long-term retention in vivo. Importantly, Bi-DOTA was successfully used in high-quality in vitro CT imaging, in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging. Conclusions: These superiorities allowed Bi-DOTA to be used as an efficient CT contrast agent and laid down a new way of designing high-performance CT contrast agents with great clinical transformation potential. [ABSTRACT FROM AUTHOR]

ObjectivesIt is necessary to develop a high-performance and biocompatible contrast agent to accurately diagnose various diseases via in vivo computed tomography (CT) imaging. Here, we synthesized a small molecular Bi-DOTA complex as a high-performance contrast agent for in vitro and in vivo CT bioimaging.Materials and MethodsIn our study, Bi-DOTA was fabricated through a facile and one-pot synthesis strategy. The formed Bi-DOTA complex was characterized via different techniques. Furthermore, Bi-DOTA was used for in vitro and in vivo CT bioimaging to verify its X-ray attenuation ability, especially in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.ResultsA small molecular Bi-DOTA complex with a molecular mass of 0.61 kDa was synthesized successfully, which exhibited outstanding dispersion, good biocompatibility, and superior X-ray attenuation ability. Meanwhile, we showed that the obtained contrast agent was quite biocompatible and safe in the given concentration range as confirmed by in vitro and in vivo cytotoxicity assay. Also, the proposed contrast agent can be rapidly excreted from the body via the urinary system, avoiding the potential side effects caused by long-term retention in vivo. Importantly, Bi-DOTA was successfully used in high-quality in vitro CT imaging, in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.ConclusionsThese superiorities allowed Bi-DOTA to be used as an efficient CT contrast agent and laid down a new way of designing high-performance CT contrast agents with great clinical transformation potential.

With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zheng, Coghi, Chen, Dong and Fan.)

Acidic nucleoplasmic DNA-binding protein 1 (And-1), an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues. Although multiple independent studies have elucidated And-1 as a promising target gene for cancer therapy, an And-1 inhibitor has yet to be identified. Using an And-1 luciferase reporter assay to screen the Library of Pharmacologically Active Compounds (LOPAC) in a high throughput screening (HTS) platform, and then further screen the compound analog collection, we identified two potent And-1 inhibitors, bazedoxifene acetate (BZA) and an uncharacterized compound [(E)-5-(3,4-dichlorostyryl)benzo[c][1,2]oxaborol-1(3H)-ol] (CH3), which specifically inhibit And-1 by promoting its degradation. Specifically, through direct interaction with And-1 WD40 domain, CH3 interrupts the polymerization of And-1. Depolymerization of And-1 promotes its interaction with E3 ligase Cullin 4B (CUL4B), resulting in its ubiquitination and subsequent degradation. Furthermore, CH3 suppresses the growth of a broad range of cancers. Moreover, And-1 inhibitors resensitize platinum-resistant ovarian cancer cells to platinum drugs in vitro and in vivo. Since BZA is an FDA approved drug, we expect a clinical trial of BZAmediated cancer therapy in the near future. Taken together, our findings suggest that targeting And-1 by its inhibitors is a potential broad-spectrum anti-cancer chemotherapy regimen. [ABSTRACT FROM AUTHOR]

Depression is a common disease that affects physical and mental health and imposes a considerable burden on afflicted individuals and their families worldwide. Depression is associated with a high rate of disability and suicide. It causes a severe decline in productivity and quality of life. Unfortunately, the pathophysiological mechanisms underlying depression have not been fully elucidated, and the risk of its treatment is still presented. Studies have shown that the expression of autophagic markers in the brain and peripheral inflammatory mediators are dysregulated in depression. Autophagy-related genes regulate the level of autophagy and change the inflammatory response in depression. Depression is related to several aspects of immunity. The regulation of the immune system and inflammation by autophagy may lead to the development or deterioration of mental disorders. This review highlights the role of autophagy and neuroinflammation in the pathophysiology of depression, sumaries the autophagy-targeting small moleculars, and discusses a novel therapeutic strategy based on anti-inflammatory mechanisms that target autophagy to treat the disease. [Display omitted] • The role of autophagy and neuroinflammation in the pathophysiology of depression. • The latest findings of anti-depressants small moleculars through regulating neuroinflammation and autophagy. • A novel therapeutic strategy based on anti-inflammatory mechanisms that target autophagy to treat depression. [ABSTRACT FROM AUTHOR]

Proteolysis targeting chimera (PROTAC) is a protein degradation technique that has been increasingly used in the development of new drugs in recent years. Akt is a classical serine/threonine kinase, and its role outside of the kinase has gradually gained attention in recent years, making it one of the proteins targeted by PROTACs. Currently, there are many methods used for the evaluation of intracellular protein degradation, but each has its own advantages or disadvantages. This study aimed to investigate the feasibility of evaluating the degradation of pan-Akt proteins in cells by PROTACs (MS21 and MS170) using the NanoLuc luciferase method. After conducting a thorough comparison between this method and the classical western blot assay in various cells, as well as testing the stability of the experiments between multiple batches, we found that NanoLuc luciferase is a highly accurate, stable, low-cost and easy-to-operate method for the evaluation of intracellular pan-Akt degradation by PROTACs with a short cycle time and high cellular expandability. Given the numerous advantages of this method, it is hypothesized that it could be extended to evaluate the degradation of more target proteins of PROTACs. In summary, the NanoLuc luciferase is a suitable method for early protein degradation screening of PROTAC compounds., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press.)

Abstract Clinically used iodinated computer tomography (CT) contrast agents suffer from low sensitivity, and the emerging lanthanide-chelates and CT imaging nanoagents raise great safety concerns. The fusion of high sensitivity and good biocompatibility is highly desired for the development of CT contrast agents. Herein, we propose a facile and green one-pot synthesis strategy for the fabrication of a small molecular CT contrast agent, Bi-diethylene triamine pentaacetate acid (DTPA) complex, for high-performance CT and spectral CT imaging. The Bi-DTPA exhibits yield of near 100%, outstanding water solubility, favorable biocompatibility, large-scale production capability, and superior X-ray attenuation ability, and is successfully applied in high-quality in vivo kidney imaging and gastrointestinal tract CT imaging and appealing spectral CT imaging. The proposed contrast agent can be rapidly excreted from body, avoiding the potential side effects caused by the long-term retention in vivo. Furthermore, our design shows great potential in developing diverse multifunctional contrast agents via chemical modification. The proposed Bi-DTPA with unique superiorities shows a bright prospect in clinic CT imaging, especially spectral CT imaging, and lays down a new way for the design of high-performance CT contrast agents with great clinical transformation potential. [ABSTRACT FROM AUTHOR]

[Display omitted] Transient receptor potential vanilloid 3 (TRPV3) channel is a temperature-sensitive and Ca2+-permeable nonselective cation channel, which is abundantly expressed in skin keratinocyte and plays an important role in skin homeostasis and repair. However, only a few TRPV3 inhibitors were reported. Few selective and potent modulators of the TRPV3 channel have hindered the progress of the investigation and clinical application. TRPV3 channel research still faces challenges and requires the new inhibitors. Flavonoids are a kind of natural compounds with various biological and pharmacological activities including anti-inflammatory and anti allergic effects, which is associated with some physiological effects mediated by TRPV3 channel. Herein, our group designed and synthesized a range of flavone derivatives, and investigated their inhibitory properties on the human TRPV3 channel by electrophysiology technique. Then, we identified a new potent TRPV3 antagonist 2d with IC 50 of 0.62 μM. It also showed good selectivity on TRPV1, TRPV4, TRPA1 and TRPM8. [ABSTRACT FROM AUTHOR]

Recent decade, small molecule organic solar cells have attracted lots of interests. Especially, the synthesis of novel p-conjugated small donor-acceptor molecules and optimization of small molecule organic solar cells processing conditions have been investigated in detail. Although some important progress have been reached, it was still a challenge for further improving their power conversion efficiency, durability and cost effectiveness. This review provided the scientific community with both general and in depth information on the relationships between structure and property depended on processing conditions, for example, donor/acceptor (D/A) weight ratios, solvent and treatment. These drew some rules for process of small molecule organic solar cells, which were very important for further improving the performance of small-molecule organic solar cells. [ABSTRACT FROM AUTHOR]

Cutaneous wounding in late-gestational fetal or postnatal humans results in scar formation without any skin appendages. Early or mid- gestational skin healing in humans is characterized by the absence of scaring in a process resembling regeneration. Tremendous cellular and molecular mechanisms contribute to this distinction, and fibroblasts play critical roles in scar or scarless wound healing. This review discussed the different repair mechanisms involved in wound healing of fibroblasts at different developmental stages and further confirmed that fetal fibroblast transplantation resulted in reduced scar healing in vivo . We also discussed the possible problem in fetal fibroblast transplantation for wound repair. We proposed the use of small molecules to improve the regenerative potential of repairing cells in the wound given that remodeling of the wound microenvironment into a regenerative microenvironment in adults might improve skin regeneration. [ABSTRACT FROM AUTHOR]

CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced. [ABSTRACT FROM AUTHOR]

Line printing offers a feasible approach to remove the pixel well structure which is widely used to confine the ink-jet printed solution. In the study, a uniform line is printed by an ink-jet printer. To achieve a uniform surface profile of the printed line, 10 vol% low-volatile solvent DMA (3,4-Dimethylanisole) is mixed with high-volatile solvent Pxy (p-xylene) as the solvent. After a solution-processable small molecule is dissolved, the surface tension of DMA solution becomes lower than that of Pxy solution, which creates an inward Marangoni flow during the solvent evaporation. The inward Marangoni flow balances out the outward capillary flow, thereby forming a flat film surface. The line width of the printed line depends on the contact angle of the solution on the hole injection layer. [ABSTRACT FROM AUTHOR]

The dodecyl benzene sulfonic iron and p-toluenesulfonic iron were prepared and used in catalytic aquathermolysis of Xinjiang extra-heavy oil (8.5 × 104mPa·s at 50°C). The same and different influences on the aquathermolysis of heavy oil catalyzed by them were studied in depth and compared. The compositions and structure of oil sample before and after reaction were analyzed by element analysis instrument,1H nuclear magnetic resonance and gas chromatography-mass spectrometry. The results showed that the p-toluenesulfonic iron exhibit better viscosity reduction effect and more significant changes for the oil sample than the dodecyl benzene sulfonic iron. [ABSTRACT FROM PUBLISHER]

Protein lysine methylation is a significant protein post-translational modification (PTMs) and has a key function in epigenetic regulation. Protein lysine methyltransferase (PKMTs) mainly catalyzes the lysine methylation of various core histones and a few non-histone proteins. It has been observed that aberrant activity of PKMTs has been found in many cancers and other diseases, and some PKMT inhibitors have been discovered and progressed to clinical trials. This field developed rapidly and has aroused great interest. In this paper, we reviewed the biochemical and biological activities of PKMTs and their association with various cancers. Selective small-molecule inhibitors, including their chemical structure, structure-activity relationship, and in vitro/vivo studies, are also described to provide ideas for the discovery of highly potent, selective PKMT inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Tea is one of the most consumed beverages worldwide. The healthy effects of tea are attributed to a wealthy of different chemical components from tea. Thousands of studies on the chemical constituents of tea had been reported. However, data from these individual reports have not been collected into a single database. The lack of a curated database of related information limits research in this field, and thus a cohesive database system should necessarily be constructed for data deposit and further application. Description The Tea Metabolome database (TMDB), a manually curated and web-accessible database, was developed to provide detailed, searchable descriptions of small molecular compounds found in Camellia spp. esp. in the plant Camellia sinensis and compounds in its manufactured products (different kinds of tea infusion). TMDB is currently the most complete and comprehensive curated collection of tea compounds data in the world. It contains records for more than 1393 constituents found in tea with information gathered from 364 published books, journal articles, and electronic databases. It also contains experimental 1H NMR and 13C NMR data collected from the purified reference compounds or collected from other database resources such as HMDB. TMDB interface allows users to retrieve tea compounds entries by keyword search using compound name, formula, occurrence, and CAS register number. Each entry in the TMDB contains an average of 24 separate data fields including its original plant species, compound structure, formula, molecular weight, name, CAS registry number, compound types, compound uses including healthy benefits, reference literatures, NMR, MS data, and the corresponding ID from databases such as HMDB and Pubmed. Users can also contribute novel regulatory entries by using a web-based submission page. The TMDB database is freely accessible from the URL of http://pcsb.ahau.edu.cn:8080/TCDB/index.jsp. The TMDB is designed to address the broad needs of tea biochemists, natural products chemists, nutritionists, and members of tea related research community. Conclusion The TMDB database provides a solid platform for collection, standardization, and searching of compounds information found in tea. As such this database will be a comprehensive repository for tea biochemistry and tea health research community. [ABSTRACT FROM AUTHOR]

Abstract: Utilization of 2,2-dimethyl-2H-benzimidazole has received strong attention as the electron-deficient unit for the generation of electron donor material for organic photovoltaic cells (OPVs). This paper reports the first small organic molecules based on dimethyl-2H-benzimidazole, which can produce intramolecular charge transfer. Two soluble small organic molecules, MMM and OMO, with dimethyl-2H-benzimidazole unit were synthesized by Suzuki coupling reaction with Pd(0)-catalyst. The spectra of MMM and OMO in the solid thin films show absorption bands with maximum peaks at 374, 598 and 373, 588nm, and the absorption onsets at 678 and 673nm, corresponding to band gaps of 1.83 and 1.84eV, respectively. The devices comprising MMM with PC61BM (1:3) showed a V OC of 0.66V, a J SC of 2.03mA/cm2, and a fill factor (FF) of 0.27, giving a power-conversion efficiency of 0.37%. [Copyright &y& Elsevier]

Abstract: This work presents a modified architecture for conventional pentacene/fullerene (C60) solar cells by inserting alternately deposited C60/pentacene interlayers (~1–2nm per layer). The cell parameters, the incident photon-to-current efficiency spectra and the atomic force microscopy were used to characterize devices that had different numbers of inserting layers. The power conversion efficiency (PCE) increased markedly from 0.77 to 1.60% as the number of the inserted pairs increased from zero to three. The PCE further increased to 1.73% after post-annealing. The interlayers formed an interpenetrating network, enlarging the area over which excitons dissociate. When the number of interlayers and post-annealing conditions were optimized, the resistance and the surface roughness were minimized. When the number of pairs was increased to five, cell performance was degraded. The mechanism by which the properties of the solar cells are related to the inserted layers is presented. [Copyright &y& Elsevier]

The peripheral washout sign was first described in delayed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a small molecular contrast medium in solid lesions of the human breast and liver. It was found to be 100% specific for malignant lesions and could therefore potentially be used as an additional noninvasive diagnostic tool differentiating malignant from benign lesions. The origin of this phenomenon has not yet been explained. The objective of this study was to translate the peripheral washout sign as seen in solid tumours in delayed DCE-MRI in human onto an animal model for further assessment of DCE-MRI characteristics and histological analysis. Small molecular contrast medium DCE-MRI was performed over 42 min in experimental colon carcinoma grown subcutaneously in rats. Qualitative and quantitative analyses for evaluation of presence and characteristics of the peripheral washout sign were accomplished, defining four centripetally distributed tumour zones (central, intermediate, peripheral and marginal). One hundred per cent of the carcinomas demonstrated a peripheral washout sign in DCE-MRI starting at 20 min after bolus injection. Histomorphological analysis was performed for tissue classification and evaluation of microvasculature. Quantitative analysis revealed different enhancement profiles of the four tumour zones. Histology indicated centripetally asymmetric vascularization and vascular endothelial growth factor VEGF/VEGF receptor 2 expression within the tumour tissue. Thus, peripheral washout sign can be translated to an animal model. However, comparison of small molecular contrast medium DCE-MRI with histology revealed that histology alone does not explain the occurrence of the peripheral washout. [ABSTRACT FROM AUTHOR]

Abstract: Small molecular organic light-emitting diodes (MOLED) and polymer organic light-emitting diodes (POLED) were fabricated with yellow light emission phosphorescent dye bis[2-(4-tert-butylphenyl)benzothiazolato-N,C2′] iridium (III) (acetylacetonate) doped in different hosts. The electroluminescent (EL) spectra of both devices shown two peaks generated from iridium dye but the position of main peak changed and became broader for POLED. The maximum luminance of 10,500cd/m2 achieved at 12.5V for MOLED is higher than maximum luminance of 9996cd/m2 at 20V for POLED. The maximum power efficiency of small molecular device is 6.4lm/W, which is higher than 2.3lm/W of polymer device, but the efficiency of both devices will roll off at large current density. [Copyright &y& Elsevier]

[Display omitted] • A series of 23 compounds with novel skeleton were designed, synthesized and evaluated. • 7c and 8c exhibited potent TRPV3 inhibitory activity which IC 50 values were 1.05 μM and 86 nM, respectively. • 7c and 8c were tested have a good selectivity to TRPV1 and TRPV4. Transient receptor potential vanilloid 3 (TRPV3) channel as a member of thermo TRPV subfamily is primarily expressed in the keratinocytes of the skin and sensory neurons, and plays critical roles in various physiological and pathological processes such as inflammation, pain sensation and skin disorders. However, TRPV3 studies have been challenging, in part due to a lack of research tools such as selective antagonists. Recently, we synthesized a series of cinnamate ester derivatives and evaluated their inhibitory activities on human TRPV3 channels expressed in HEK293 cells using whole-cell patch clamp recordings. And, we identified two potent TRPV3 antagonists 7c and 8c which IC 50 values were 1.05 μM and 86 nM, respectively. It also showed good selectivity to other subfamily members of TRPV, such as TRPV1 and TRPV4. [ABSTRACT FROM AUTHOR]

Acidic nucleoplasmic DNA-binding protein 1 (And-1), an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues. Although multiple independent studies have elucidated And-1 as a promising target gene for cancer therapy, an And-1 inhibitor has yet to be identified. Using an And-1 luciferase reporter assay to screen the Library of Pharmacologically Active Compounds (LOPAC) in a high throughput screening (HTS) platform, and then further screen the compound analog collection, we identified two potent And-1 inhibitors, bazedoxifene acetate (BZA) and an uncharacterized compound [(E)-5-(3,4-dichlorostyryl)benzo[c][1,2]oxaborol-1(3H)-ol] (CH3), which specifically inhibit And-1 by promoting its degradation. Specifically, through direct interaction with And-1 WD40 domain, CH3 interrupts the polymerization of And-1. Depolymerization of And-1 promotes its interaction with E3 ligase Cullin 4B (CUL4B), resulting in its ubiquitination and subsequent degradation. Furthermore, CH3 suppresses the growth of a broad range of cancers. Moreover, And-1 inhibitors re-sensitize platinum-resistant ovarian cancer cells to platinum drugs in vitro and in vivo. Since BZA is an FDA approved drug, we expect a clinical trial of BZA-mediated cancer therapy in the near future. Taken together, our findings suggest that targeting And-1 by its inhibitors is a potential broad-spectrum anti-cancer chemotherapy regimen., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The β-amyloid (Aβ) plaques presented within the brain parenchyma have been widely proved to be one of the hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, the accumulation of Aβ plaques in the brain is intrinsic and fundamental for disease onset, and much research about the early diagnosis of AD is based on this. A recent development in Aβ detection has focused on the mapping of the molecule events in the brain using an exquisite, noninvasive, and inexpensive optical imaging technique, which has stimulated the rapid development of Aβ-specific fluorescent probes. Among them, nearinfrared (NIR) fluorophores have gained adequate attention due to the weak light attenuation in tissues and avoidance from auto-fluorescence of biological matter. In this review, we showcase the current developments of fluorescent probes that are subject to in vitro or in vivo detection of Aβ plaques in the brain, and give an emphasis on the probes used for in vivo twophoton microscopy and NIR imaging by highlighting their biological and photochemical properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Alternative low-temperature solution-processed hole-transporting materials (HTMs) without dopant are critical for highly efficient perovskite solar cells (PSCs). Here, two novel small molecule HTMs with linear π-conjugated structure, 4,4'-bis(4-(di-p-toyl)aminostyryl)biphenyl (TPASBP) and 1,4'-bis(4-(di-p-toyl)aminostyryl)benzene (TPASB), are applied as hole-transporting layer (HTL) by low-temperature (sub-100 °C) solution-processed method in p-i-n PSCs. Compared with standard poly(3,4-ethylenedioxythiophene): poly(styrenesulfonic acid) (PEDOT:PSS) HTL, both TPASBP and TPASB HTLs can promote the growth of perovskite (CH 3 NH 3 PbI 3 ) film consisting of large grains and less grain boundaries. Furthermore, the hole extraction at HTL/CH 3 NH 3 PbI 3 interface and the hole transport in HTL are also more efficient under the conditions of using TPASBP or TPASB as HTL. Hence, the photovoltaic performance of the PSCs is dramatically enhanced, leading to the high efficiencies of 17.4% and 17.6% for the PSCs using TPASBP and TPASB as HTL, respectively, which are ≈40% higher than that of the standard PSC using PEDOT:PSS HTL., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)