Novelties of solid-liquid phase transfer catalyzed synthesis of benzyl diethyl phosphate from the sodium salt of diethyl phosphate

Solid-liquid phase transfer catalysis coupled with mixed solvents, which could be recycled, as a green chemistry procedure, was applied to the synthesis of phosphate from the sodium salt of diethyl phosphate. The benzyl diethyl phosphate was synthesized in good yield via one-pot method from the reaction of the industrial by-product sodium salt of diethyl phosphate with benzyl chloride in solid-liquid phase transfer catalysis and toluene-water mixed solvents. The effects of catalyst structure, the amounts of catalyst, the raw material molar ratio, water loading, and reaction temperature on the conversion of the reaction were investigated. The structure of the benzyl diethyl phosphate generated was confirmed by Elemental Analysis, IR, 1H NMR and GC/MS

Application and progress of nomograms in gastric cancer

Gastric cancer, as one of the malignant tumors with a significant disease burden globally, emphasizes the importance of early diagnosis and personalized treatment for improving patient prognosis. In recent years, clinical prediction models (CPMs) have played a crucial role in predicting disease risks, assisting medical decision-making, and evaluating clinical prognosis and benefits as tools for risk–benefit assessment. Nomograms, as an important visualization form of clinical prediction models, have been increasingly applied in tumor-related research. Numerous studies have constructed multiple nomogram models by integrating clinical, pathological, laboratory, imaging data, and genetic characteristics, providing an accurate and effective tool for predicting the risk of gastric cancer, early diagnosis, treatment response assessment, and prognosis analysis. This article aims to review the current clinical applications and research progress of nomograms in gastric cancer, with the goal of providing robust references and theoretical support for clinical practice

Synthesis and biological evaluation of novel bi-gold mitocans in lung cancer cells

Mitochondria are promising drug target for cancer treatment. We previously demonstrated that a bi-gold compound BGC2a was more potent than the mono-gold drug auranofin in suppressing cancer cells due to increased gold atom number that led to higher drug accumulation in and thereby inhibition of mitochondria. To exploit the potential of this new strategy, we further designed and synthesized a series of bi-gold mitocans, the compounds targeting mitochondria. The results showed that most of the newly synthesized mitocans exhibited obviously lower IC50 than auranofin, an old drug that is repurposed in clinical trials for cancer treatment. The best mitocan C3P4 was nearly 2-fold more potent than BGC2a in human non-small cell lung cancer A549 cells and mantle cell lymphoma Jeko-1 cells, exhibiting substantial colony formation-suppressing and tumor-suppressing effects in A549 cells xenograft model. C3P4 induced apoptosis in a dose-dependent manner and arrested cell cycle at G0/G1 phase. The mechanistic study showed that C3P4 significantly increased the global reactive oxygen species and mitochondrial superoxide level, and reduced the mitochondrial membrane potential. C3P4 preferentially accumulated in mitochondria as measured by the gold content and substantially inhibited oxygen consumption rate and ATP production. These results further validated our hypothesis that targeting mitochondria would be promising to develop more potent anticancer agents. C3P4 may be further evaluated as a drug candidate for lung cancer treatment

Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma

In light of a global rise in the number of patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of hepatocellular carcinoma (HCC), with the annual occurrence of MASLD-driven HCC expected to increase by 45%–130% by 2030. Although MASLD has become a serious major public health threat globally, the exact molecular mechanisms mediating MASLD-driven HCC remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on the utility of bioactive compounds to halt the progression of MASLD to MASLD-driven HCC. In this review, we first briefly review the recent progress of the possible mechanisms of pathogenesis and progression for MASLD-driven HCC. We then discuss the application of bioactive compounds to mitigate MASLD-driven HCC through different modulatory mechanisms encompassing anti-inflammatory, lipid metabolic, and gut microbial pathways, providing valuable information for future treatment and prevention of MASLD-driven HCC. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of MASLD-driven HCC is still warranted

Dendritic Polyglycerol Amine: An Enhanced Substrate to Support Long-Term Neural Cell Culture

Long-term stable cell culture is a critical tool to better understand cell function. Most adherent cell culture models require a polymer substrate coating of poly-lysine or poly-ornithine for the cells to adhere and survive. However, polypeptide-based substrates are degraded by proteolysis and it remains a challenge to maintain healthy cell cultures for extended periods of time. Here, we report the development of an enhanced cell culture substrate based on a coating of dendritic polyglycerol amine (dPGA), a non-protein macromolecular biomimetic of poly-lysine, to promote the adhesion and survival of neurons in cell culture. We show that this new polymer coating provides enhanced survival, differentiation and long-term stability for cultures of primary neurons or neurons derived from human induced pluripotent stem cells (hiPSCs). Atomic force microscopy analysis provides evidence that greater nanoscale roughness contributes to the enhanced capacity of dPGA-coated surfaces to support cells in culture. We conclude that dPGA is a cytocompatible, functionally superior, easy to use, low cost and highly stable alternative to poly-cationic polymer cell culture substrate coatings such as poly-lysine and poly-ornithine. Summary statement Here, we describe a novel dendritic polyglycerol amine-based substrate coating, demonstrating superior performance compared to current polymer coatings for long-term culture of primary neurons and neurons derived from induced pluripotent stem cells

Therapeutic implications of cancer-associated fibroblast heterogeneity: insights from single-cell and multi-omics analysis

BackgroundCancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME), contributing to tumorigenesis, progression, and resistance to therapy. However, the functional diversity of CAF subpopulations and their role in tumor progression and patient prognosis remain poorly understood. This study aims to explore CAF heterogeneity and their functional roles in the TME using single-cell RNA sequencing (scRNA-seq) and multi-omics data analysis.MethodsscRNA-seq data were analyzed to cluster CAF subpopulations in the TME, with key genes identified through functional annotation. Differentially expressed genes were analyzed, and prognostic genes were selected via Cox and LASSO regression. A risk score model (RiskScore) was developed for survival prediction and immune therapy sensitivity evaluation. Core CAF genes were examined using siRNA interference, qPCR, and Western blotting. Drug sensitivity was assessed to explore the clinical relevance of these genes.ResultsFour CAF subpopulations (CAF-0, CAF-1, CAF-2, CAF-3) were identified, revealing differences in key tumor-associated signaling pathways (e.g., MYC, WNT, TGF-β). Thirteen core genes related to prognosis were identified, and a RiskScore model was developed, showing significantly worse survival rates for high-risk patients (p < 0.001) and features of immune suppression, including increased M0 macrophage infiltration. Drug sensitivity analysis indicated that core genes (e.g., KLRB1, MAP1B) were linked to drug sensitivity, suggesting potential biomarkers for targeted therapy. Experimental validation showed that knockdown of the HIP1R gene significantly reduced tumor cell expression, confirming its critical role in tumor development.ConclusionThis study offers a comprehensive analysis of CAF heterogeneity and its impact on TME, patient prognosis, and drug sensitivity. The developed RiskScore model provides theoretical support for personalized treatment based on CAF-related genes, offering new insights into CAF-driven tumor progression and potential targets for precision oncology and immunotherapy

The 2023 wearable photoplethysmography roadmap

Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology

Modulation of the Proteostasis Network Promotes Tumor Resistance to Oncogenic KRAS Inhibitors

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response, causing severe proteostasis disturbances. However, IRE1α was selectively reactivated in an ER stress-independent manner in acquired KRASi-resistant tumors, restoring proteostasis. Oncogenic KRAS promoted IRE1α protein stability through extracellular signal-regulated kinase (ERK)-dependent phosphorylation of IRE1α, leading to IRE1α disassociation from 3-hydroxy-3-methylglutaryl reductase degradation (HRD1) E3-ligase. In KRASi-resistant tumors, both reactivated ERK and hyperactivated AKT restored IRE1α phosphorylation and stability. Suppression of IRE1α overcame resistance to KRASi. This study reveals a druggable mechanism that leads to proteostasis reprogramming and facilitates KRASi resistance

Adjustment of Administrative Divisions and Upgrading of Industrial Structure in Hefei Metropolitan Area

Administrative regions are an important environment for the operation of China’s market economy. The relevant economic subjects cannot predict the policy of adjustment of administrative divisions and carry out conscious migration behavior, adjustment of administrative divisions can be regarded as a quasi-natural experiment. The three cities of Hefei, Wuhu, and Ma’anshan, which are directly related to the adjustment of the administrative division of Chaohu, are taken as the treatment group, and the seven adjacent cities of Lu’an, Huainan, Chuzhou, Bengbu, Anqing, Chizhou, and Tongling are taken as the control group. Differences-in-Differences method and relevant control variables affecting the upgrading of industrial structure are used to test. The test results show that "Partitions of Chaohu" has a significant industrial structure upgrading effect by promoting the optimization of spatial layout, the cross-regional flow of production factors and the effective management of Chaohu Lake Basin. At the same time, the increase of total retail sales of consumer goods, urban fixed assets investment, public utility expenses in science, education, culture and health, and population plays a significant positive role in promoting the upgrading of industrial structure, while foreign direct investment plays a certain inhibition role in the upgrading of industrial structure. In order to meet the ever-developing space demands and enhance the impact on surrounding areas, the Hefei metropolitan area should be driven by technological innovation, strengthen the integration of industrial chains, improve the business environment and transportation network, and continuously promote the upgrading of industrial structure and the formation and development of new productive forces