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Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED in vivo and in vitro. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells via downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth in vitro and in vivo via suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

The most common types of renal carcinoma is kidney renal clear cell carcinoma (KIRC). ESM1 is a secreted protein, which involved in, lipids and glucose metabolism, but their role in angiogenesis is contradictory in different disease, especially in KIRC. Bioinformatic analysis confirmed the ESM1 expression and prognosis in KIRC. IHC staining revealed protein expression of ESM1 in KIRC samples. The role of ESM1 in KIRC proliferation and migration were tested by MTT, EdU, transwell analysis. The role of its paracrine function in KIRC angiogenesis was tested by functional experiments. The downstream molecular mechanism of ESM1 were further elucidated by WB and functional experiments. ESM1 was significantly increased in KIRC with prognostic significance. ESM1 knockdown inhibited the invasiveness capability and viability of KIRC cell. The paracrine of ESM1 enhanced HUVECs proliferation and migration to format tube in KIRC cell conditional medium. ESM1 knockdown induced the inactivation of Akt/mTOR and Ras pathway to attenuate proliferation, migration, invasion and angiogenesis in KIRC. ESM1 was a key role in the tumor microenvironment (TME) of KIRC, which promoted the proliferation, migration, invasion, and angiogenesis by activating Akt/mTOR and Ras pathway. It is a potential therapeutic target for KIRC patients. [ABSTRACT FROM AUTHOR]

The computational efficiency of the discrete element simulation process is often a limiting factor. However, the use of the coarse-grained method, which employs dimensional analysis to amplify particles, significantly improves computational efficiency. This research utilizes the coarse-grained method to amplify particles and examines the impact of linear models on the mechanical of fly ash. By examining parameters such as magnification, stiffness, sliding friction coefficient, and rolling friction coefficient, we establish the relationship between fly ash cohesion, internal friction angle, and microscopic parameters in discrete element method (DEM) simulation. The simulation results demonstrate that the shear strength of fly ash increases as magnification, stiffness, and sliding friction coefficient increase. The rolling friction coefficient, on the other hand, has minimal effect on shear strength. The elastic potential energy of the system is unaffected by magnification, with stiffness inversely proportional to adaptable potential power. However, sliding and rolling friction coefficients positively impact adaptable potential power. Furthermore, this study proposes a practical simplification method for amplification of materials with small particle sizes. The comparison between numerical simulation and experimental data yields consistent results. As a result, this study provides a foundation for the application of large-scale fly ash transportation, storage, and other engineering purposes. [ABSTRACT FROM AUTHOR]

Hematologic measures such as hematocrit and white blood cell (WBC) count are heritable and clinically relevant. We analyzed erythrocyte and WBC phenotypes in 52,531 individuals (37,775 of European ancestry, 11,589 African Americans, and 3,167 Hispanic Americans) from 16 population-based cohorts with Illumina HumanExome BeadChip genotypes. We then performed replication analyses of new discoveries in 18,018 European-American women and 5,261 Han Chinese. We identified and replicated four new erythrocyte trait-locus associations (CEP89, SHROOM3, FADS2, and APOE) and six new WBC loci for neutrophil count (S1PR4), monocyte count (BTBD8, NLRP12, and IL17RA), eosinophil count (IRF1), and total WBC count (MYB). The association of a rare missense variant in S1PR4 supports the role of sphingosine-1-phosphate signaling in leukocyte trafficking and circulating neutrophil counts. Loss-of-function experiments for S1pr4 in mouse and s1pr4 in zebrafish demonstrated phenotypes consistent with the association observed in humans and altered kinetics of neutrophil recruitment and resolution in response to tissue injury.

N6-methyladenosine (m6A) modification is the most common, abundant and conservative posttranscriptional modification. More and more evidence suggest that via various mechanisms, it has a certain impact on tumors, such as liver cancer, gastric cancer, lung cancer, bladder cancer and melanoma. It has been found that YTHDF1, as a kind of m6A-modification binding protein, plays an important role in tumor transcription, translation, protein synthesis, immune escape, EMT, chemotherapy resistance and so on. It is expected to find new methods for the diagnosis and treatment of cancer by revealing the mechanism of YTHDF1. This article reviews the research progress in this field.