Publications by authors named "Huimin Lei"

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs).

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RAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRAS inhibitor breaks the "undruggable" curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers.

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Drought and heatwave are the primary climate extremes for vegetation productivity loss in the global temperate semi-arid grassland, challenging the ecosystem productivity stability in these areas. Previous studies have indicated a significant decline in the resistance of global grassland productivity to drought, but we still lack a systematic understanding of the mechanisms determining the spatiotemporal variations in grassland resistance to drought and heatwave. In this study, we focused on temperate semi-arid grasslands of China (TSGC) to assess the spatiotemporal variations of grassland productivity resistance to different climate extremes: compound dry-hot events, individual drought events, and individual heatwave events that occurred during 2000-2019.

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Despite significantly improved clinical outcomes in EGFR-mutant lung adenocarcinoma, all patients develop acquired resistance and malignancy on the treatment of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Understanding the resistance mechanisms is crucial to uncover novel therapeutic targets to improve the efficacy of EGFR-TKI treatment. Here, integrated analysis using RNA-Seq and shRNAs metabolic screening reveals glutathione S-transferase omega 1 (GSTO1) as one of the key metabolic enzymes that is required for EGFR-TKIs resistance in lung adenocarcinoma cells.

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Article Synopsis
  • - The cGAS-STING pathway is important for immune response and tumor suppression, but when it's activated within cancer cells, it can lead to resistance against chemotherapy drugs.
  • - Chemotherapy causes cancer cells to accumulate cytosolic DNA, triggering the cGAS-STING pathway and related signaling, which helps the cells resist the effects of the drugs.
  • - Blocking STING signaling has been shown to delay and reduce this drug resistance in lab models, suggesting that combining STING activation with chemotherapy might not be effective and could require reevaluation in clinical trials.
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Resistance to epidermal growth factor receptor (EGFR) inhibitors, from the first-generation erlotinib to the third generation osimertinib, is a clinical challenge in the treatment of patients with EGFR-mutant lung adenocarcinoma. Our previous work found that a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1), HKB99, restrains erlotinib resistance in lung adenocarcinoma cells. However, the role of HKB99 in osimertinib resistance and its underlying molecular mechanism remains to be elucidated.

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Reconstruction of natural streamflow is fundamental to the sustainable management of water resources. In China, previous reconstructions from sparse and poor-quality gauge measurements have led to large biases in simulation of the interannual and seasonal variability of natural flows. Here we use a well-trained and tested land surface model coupled to a routing model with flow direction correction to reconstruct the first high-quality gauge-based natural streamflow dataset for China, covering all its 330 catchments during the period from 1961 to 2018.

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Cells experience both endogenous and exogenous DNA damage daily. To maintain genome integrity and suppress tumorigenesis, individuals have evolutionarily acquired a series of repair functions, termed DNA damage response (DDR), to repair DNA damage and ensure the accurate transmission of genetic information. Defects in DNA damage repair pathways may lead to various diseases, including tumors.

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Objective: This study aimed to determine the incidence and clinicopathological patterns of metastatic carcinoma of the parotid gland.

Method: Ninety patients with parotid gland metastases admitted to our hospital between January 2003 and December 2018 were included in this study. Clinical and pathological data were obtained from the medical records and follow-ups.

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Article Synopsis
  • * Overexpression of PSAT1 was found to promote cancer cell survival against the drug erlotinib and enhance tumor spread; however, removing PSAT1 restored drug sensitivity and helped kill cancer cells more effectively.
  • * The research indicates that targeting PSAT1 may be a viable strategy to improve treatment outcomes for lung adenocarcinoma by addressing both its metabolic and nonmetabolic roles in tumor growth and spread.*
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Solar radiation is the external driving force of the Earth's climate system. In different spatial and temporal scales, meteorological elements have different responses and lag periods to solar activity (SA), climatic oscillation (CO), geographic factors (GF) and other influencing factors. However, such studies are not abundant and in-depth in the world.

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Acquired resistance represents a bottleneck to molecularly targeted therapies such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. A deeper understanding of resistance mechanisms can provide insights into this phenomenon and help to develop additional therapeutic strategies to overcome or delay resistance. Here, we identified a pharmacologically targetable metabolic mechanism that drives resistance to EGFR TKIs in lung cancer cell lines and patient-derived xenograft mice.

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Aβ42 peptides can form helix and sheet structure under different conditions. The conformational conversion is closely associated with Aβ peptides aggregation and their neurotoxicity. But the transition from helix to sheet is not be clearly understood.

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The characteristics of soil respiration (R) in semiarid regions are important with regard to the carbon cycle of complex underlying surfaces and estimation of carbon emissions from regional ecosystems. During the growing season (May-September 2016), in situ observations of R were obtained concurrently with measurements of soil bacteria (B), soil moisture (M), and soil temperature (T) at depths of 0-10 cm, in a dune-meadow cascade ecosystem. Results showed that R differences among the various ecosystems were significant (P < 0.

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Accurately estimating evapotranspiration (ET) for meadow wetland ecosystems is of great significance for water management in semiarid regions. Taking a meadow wetland ecosystem in the Horqin Sandy Land as an example, this study coupled the Ball-Berry canopy stomatal conductance model to Penman-Monteith (P-M) model and Shuttleworth-Wallace (S-W) model, and the improved P-M model and SWH model were calibrated and validated by long-term (2013-2018 growing seasons) eddy covariance (EC) measurements. The results indicated that the improved P-M model and SWH model performed well either at half-hourly or daily timescales, with high coefficient of determination (R) and index of agreement (IA) and low root mean square error (RMSE).

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Soil respiration (R) is affected by many factors and shows significant diurnal and seasonal changes at different spatial and temporal scales. However, in a semi-arid steppe, the mechanism of the dynamic influence of environmental factors on R is not clear, and the effect of subtle changes of soil water on R under drought stress is yet to be explored. Therefore, Xilin River Basin, was the study area and a hydrological gradient on the four ecosystems for R and hydrometeorological monitoring was selected.

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved satisfactory clinical effects in the therapy of non-small cell lung cancer (NSCLC), but acquired resistance limits their clinical application. NRF2 has been shown to enhance the resistance to apoptosis induced by radiotherapy and some chemotherapy. In this study, we investigated the role of NRF2 in resistance to EGFR-TKIs.

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Changes in cellular metabolism accompany tumor therapeutic resistance. Metabolite concentrations specifically reflect the cellular state. Glutathione (GSH) metabolism maintains the redox homeostasis while also confers therapeutic resistance to cancer cells.

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Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of non-small cell lung cancer (NSCLC). HKB99 is a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1) that preferentially suppresses cell proliferation and induces more apoptosis in acquired erlotinib-resistant HCC827ER cells compared with its parental HCC827 cells. In this study we identified the molecular biomarkers for HKB99 response in erlotinib-resistant HCC827ER cells.

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Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as erlotinib is a major challenge to achieve an overall clinical benefit of the targeted therapy. Recently, aldehyde dehydrogenase 1 (ALDH1) induction has been found to render lung adenocarcinomas resistant to EGFR-TKIs, and targeting ALDH1A1 becomes a novel strategy to overcome resistance. However, the molecular mechanism underlying such effect remains poorly understood.

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Phosphoglycerate mutase 1 (PGAM1) plays a pivotal role in cancer metabolism and tumor progression via its metabolic activity and interaction with other proteins like α-smooth muscle actin (ACTA2). Allosteric regulation is considered to be an innovative strategy to discover a highly selective and potent inhibitor targeting PGAM1. Here, we identified a novel PGAM1 allosteric inhibitor, HKB99, via structure-based optimization.

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