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Overexpression of the thymidine phosphorylase (TP) enzyme induces angiogenesis, which eventually leads to metastasis and tumor growth. The crucial role of TP in cancer development makes it an important target for anticancer drug discovery. Currently, there is only one US-FDA-approved drug, i.e., Lonsurf, a combination of trifluridine and tipiracil, for the treatment of metastatic colorectal cancer. Unfortunately, numerous adverse effects are associated with its use, such as myelosuppression, anemia, and neutropenia. Since the last few decades, the discovery of new, safe, and effective TP inhibitory agents has been rigorously pursued. In the present study, we evaluated a series of previously synthesized dihydropyrimidone derivatives 1–40 for their TP inhibitory potential. Compounds 1, 12, and 33 showed a good activity with IC50 = 314.0 ± 0.90, 303.5 ± 0.40, and 322.6 ± 1.60 µM, respectively. The results of mechanistic studies revealed that compounds 1, 12, and 33 were the non-competitive inhibitors. These compounds were also evaluated for cytotoxicity against 3T3 (mouse fibroblast) cells and were found to be non-cytotoxic. Finally, the molecular docking suggested the plausible mechanism of non-competitive inhibition of TP. The current study thus identifies some dihydropyrimidone derivatives as potential inhibitors of TP, which can be further optimized as leads for cancer treatment.

Shenkang Injection (SKI) is a traditional Chinese medicine injection commonly used in the clinical treatment of chronic kidney disease. Although it has been confirmed that SKI has anti-kidney fibrosis effects, the underlying mechanism remains unclear. To investigate the effects of SKI on epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway and explore its potential anti-fibrosis mechanism. A unilateral ureteral obstruction (UUO) model was induced by ligating the left ureter of male SD rats. A total of 24 rats were randomly divided into the following four groups: sham group, model group, SKI group, and benazepril group. The rats in each group were treated for 28 days, and renal function was evaluated by blood urea nitrogen (BUN) and serum creatinine (Scr). The degree of renal fibrosis was assessed by hematoxylin and eosin (HE) and Masson staining. Extracellular matrix (ECM) deposition was evaluated by immunohistochemistry. Real-time fluorescent quantitative PCR (RT-qPCR) and western blotting were used to detect the expression of genes and proteins in the Wnt/β-catenin signaling pathway. Further studies were performed in vitro using HK-2 cells treated with TGF-β1. At 28 days postoperation, the levels of BUN and Scr expression were significantly increased in the UUO group. SKI and benazepril reduced the levels of BUN and Scr, which displayed protective renal effects. Pathological staining showed that compared with the sham operation group, the renal parenchymal structure was severely damaged, the number of glomeruli was reduced, and a large amount of collagen was deposited in the kidney tissue of the UUO group. SKI treatment reduced morphological changes. Immunohistochemistry showed that compared with the sham operation group, the content of collagen I and FN in the kidney tissue of the UUO group were significantly increased, whereas the SKI content was decreased. In addition, compared with the UUO group, the levels of Wnt1, active β-catenin, Snail1, and PAI-1 expression were reduced in the SKI group, suggesting that SKI may reduce renal fibrosis by mediating the Wnt/β-catenin pathway. Further in vitro studies showed that collagen I, FN, and α-SMA levels in HK-2 cells were significantly increased following stimulation with TGF-β1. SKI could significantly reduce the expression of collagen I, FN, and α-SMA. A scratch test showed that SKI could reduce HK-2 migration. In addition, by stimulating TGF-β1, the levels of Wnt1, active β-catenin, snail1, and PAI-1 were significantly upregulated. SKI treatment could inhibit the activity of the Wnt/β-catenin signaling pathway in HK-2 cells. SKI improves kidney function by inhibiting renal fibrosis. The anti-fibrotic effects may be mediated by regulation of the Wnt/β-catenin pathway and EMT inhibition.

Chronic kidney disease (CKD) represents a significant global public health burden, affecting over 10% of the world’s population. Its high morbidity, multifactorial complications, and substantial mortality impose significant burdens on healthcare systems and patients, necessitating considerable investment in healthcare resources. Renal fibrosis (RF) is a key pathological feature and driver of CKD progression. Extensive research indicates that autophagy participates in the complete pathogenesis of RF. Under physiological conditions, autophagy is essential for maintaining renal cellular homeostasis. However, under pathological conditions, perhaps aberrant and sustained activation of autophagy contributes to oxidative stress, apoptosis, inflammation, etc. Ultimately, they accelerate the development of RF. The role of autophagy in RF is currently controversial. This review investigates the molecular mechanisms by which intrinsic renal cell autophagy contributes to RF across diverse disease models, suggesting that autophagy and its associated regulatory pathways represent potential diagnostic and therapeutic targets for CKD.

As the population ages, neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD. Tea polyphenols can lower the morbidity of PD and AD by reducing oxidative stress and regulating signaling pathways and metal chelation. Theanine can inhibit the glutamate receptors and regulate the extracellular concentration of glutamine, presenting neuroprotective effects. Additionally, the neuroprotective mechanisms of caffeine and theaflavins may contribute to the ability to antagonize the adenosine receptor A2AR and the antioxidant properties, respectively. Thus, tea bioactive components might be useful for neuronal degeneration treatment in the future. In the present paper, the neuro protection and the mechanisms of tea and its bioactive components are reviewed. Moreover, the potential challenges and future work are also discussed.

(−)-Epigallocatechin gallate (EGCG) has attracted significant research interest due to its health-promoting effects such as antioxidation, anti-inflammation and anti-cancer activities. However, its instability and poor bioavailability have largely limited its efficacy and application. Food-grade materials such as proteins, carbohydrates and lipids show biodegradability, biocompatibility and biofunctionality properties. Food-grade encapsulation systems are usually used to improve the bioavailability of EGCG. In the present paper, we provide an overview of materials and techniques used in encapsulating EGCG, in which the adsorption mechanisms of food-grade systems during in vitro digestion are reviewed. Moreover, the potential challenges and future work using food-grade encapsulates for delivering EGCG are also discussed.

Soil microorganisms are essential for sustaining ecosystem functions, driving biogeochemical cycles, and modulating carbon storage. However, the nutrient-mediated mechanisms by which different land-use types shape soil microbial communities remain unclear. This study investigated three typical land-use types—plantation, grassland, and high-standard cropland—in Xinyang City, China, to evaluate their effects on soil microbial community. Results showed that soil nutrient contents—including total nitrogen, total phosphorus, alkaline-hydrolyzable nitrogen, and available phosphorus—as well as microbial alpha diversity indices, were consistently higher in topsoil than in subsoil and more pronounced in plantation than in grassland and cropland. Acidobacteriota, Pseudomonadota, Ascomycota, and Basidiomycota dominated across all land uses, though community composition varied significantly among them. Network analysis revealed strongest microbial connectivity in plantation, intermediate in grassland, and weakest in cropland. Our findings demonstrate that land-use type and soil depth directly affect soil available nutrients, thereby influencing microbial diversity. This study clarifies the nutrient-driven pathways through which land use affects soil ecosystems, providing important insights for sustainable land management and ecological conservation.

Background: the credit scoring model is an effective tool for banks and other financial institutions to distinguish potential default borrowers. The credit scoring model represented by machine learning methods such as deep learning performs well in terms of the accuracy of default discrimination, but the model itself also has many shortcomings such as many hyperparameters and large dependence on big data. There is still a lot of room to improve its interpretability and robustness. Methods: the deep forest or multi-Grained Cascade Forest (gcForest) is a decision tree depth model based on the random forest algorithm. Using multidimensional scanning and cascading processing, gcForest can effectively identify and process high-dimensional feature information. At the same time, gcForest has fewer hyperparameters and has strong robustness. So, this paper constructs a two-stage hybrid default discrimination model based on multiple feature selection methods and gcForest algorithm, and at the same time, it optimizes the parameters for the lowest type II error as the first principle, and the highest AUC and accuracy as the second and third principles. GcForest can not only reflect the advantages of traditional statistical models in terms of interpretability and robustness but also take into account the advantages of deep learning models in terms of accuracy. Results: the validity of the hybrid default discrimination model is verified by three real open credit data sets of Australian, Japanese, and German in the UCI database. Conclusions: the performance of the gcForest is better than the current popular single classifiers such as ANN, and the common ensemble classifiers such as LightGBM, and CNNs in type II error, AUC, and accuracy. Besides, in comparison with other similar research results, the robustness and effectiveness of this model are further verified.

Green tea catechins (GTCs) are a group of bioactive polyphenolic compounds found in fresh tea leaves (Camellia sinensis (L.) O. Kuntze). They have garnered significant attention due to their diverse health benefits and potential therapeutic applications, including as antioxidant and sunscreen agents. Human skin serves as the primary barrier against various external aggressors, including pathogens, pollutants, and harmful ultraviolet radiation (UVR). Skin aging is a complex biological process influenced by intrinsic factors such as genetics and hormonal changes, as well as extrinsic factors like environmental stressors, among which UVR plays a pivotal role in accelerating skin aging and contributing to various dermatological conditions. Research has demonstrated that GTCs possess potent antioxidant properties that help neutralize free radicals generated by oxidative stress. This action not only mitigates cellular damage but also supports the repair mechanisms inherent in human skin. Furthermore, GTCs exhibit anti-carcinogenic effects by inhibiting pathways involved in tumor promotion and progression. GTCs have been shown to exert anti-inflammatory effects through modulation of inflammatory signaling pathways. Chronic inflammation is known to contribute significantly to both premature aging and various dermatological diseases such as psoriasis or eczema. By regulating these pathways effectively, GTCs may alleviate symptoms associated with inflammatory conditions. GTCs can enhance wound healing processes by stimulating angiogenesis. They also facilitate DNA repair mechanisms within dermal fibroblasts exposed to damaging agents. The photoprotective properties attributed to GTCs further underscore their relevance in skincare formulations aimed at preventing sun-induced damage. Their ability to screen UV light helps shield underlying tissues from harmful rays. This review paper aims to comprehensively examine the beneficial effects of GTCs on skin health through an analysis encompassing in vivo and in vitro studies alongside insights into molecular mechanisms underpinning these effects. Such knowledge could pave the way for the development of innovative strategies focused on harnessing natural compounds like GTCs for improved skincare solutions tailored to combat environmental stresses faced by the human epidermis.

Neurodegenerative disease Alzheimer’s disease (AD) is attracting growing concern because of an increasing patient population among the elderly. Tea consumption is considered a natural complementary therapy for neurodegenerative diseases. In this paper, epidemiological studies on the association between tea consumption and the reduced risk of AD are reviewed and the anti-amyloid effects of related bioactivities in tea are summarized. Future challenges regarding the role of tea in preventing AD are also discussed.

Background Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. Method A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. Result Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001 ). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33–6.16)]. Conclusion We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.