Biology subjects

zhang, d.

Publications and source records attributed to zhang, d..

3 recordsLinked to original sources

bioRxiv2026

MZF1-mediated GAPDH overexpression drives glycolytic reprogramming and neuroendocrine progression in advanced prostate cancer

Drug resistance to the androgen receptor (AR) antagonist is a critical obstacle in the clinic for advanced prostate cancers. Especially, AR antagonist treatment-induced neuroendocrine progression represents a lethal and therapy-resistant subtype. Although transcriptional and epigenetic lineage plasticity have been extensively implicated in treatment-induced neuroendocrine progression, the contribution of metabolic adaptation remains incompletely understood. Here, we identified a previously unrecognized metabolic reprogramming mechanism induced by AR antagonists in castration-resistant prostate cancer (CRPC) models. AR antagonist treatment markedly enhanced glycolytic activity and induced glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. Genetic depletion of GAPDH suppressed AR antagonist-induced glycolytic activation, altered transcriptomic and metabolic programs, reduced neuroendocrine-associated marker expression, and inhibited xenograft tumor growth. Mechanistically, GAPDH promoter pulldown coupled with mass spectrometry, siRNA screening, and chromatin immunoprecipitation assays identified myeloid zinc finger-1 (MZF1) as a key transcription factor for Enzalutamide-induced GAPDH gene expression. Pharmacological inhibition of GAPDH using koningic acid (KA) or penta-O-galloyl-{beta}-D-glucopyranose (PGG) significantly suppressed tumor growth and attenuated neuroendocrine-associated molecular programs in CRPC cell-derived xenograft and patient-derived t-NEPC xenograft models. Collectively, our findings identify an AR antagonist-induced MZF1-GAPDH signaling axis that promotes glycolytic activation and neuroendocrine-associated metabolic adaptation during treatment resistance. These results support targeting GAPDH-dependent metabolic reprogramming as a potential therapeutic strategy for treatment-resistant prostate cancer. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/729867v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@10480b2org.highwire.dtl.DTLVardef@9d2ed8org.highwire.dtl.DTLVardef@16e8705org.highwire.dtl.DTLVardef@1627ad2_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Boosting Ascomycin Production through n-Butanol Addition in the Fermentation Process of Streptomyces hygroscopicus var. ascomyceticus ATCC 14891

Ascomycin (FK520) is a macrolide antibiotic known for its immunosuppressive activities. In this study, we screened several short-chain alcohols to enhance titer of FK520 in Streptomyces hygroscopicus var. ascomyceticus ATCC 14891, with a particular focus on n-butanol addition. After optimizing the n-butanol addition process, we achieved a FK520 yield of 569.37 mg/L with 0.8% n-butanol addition at 27 h, representing a 1.72-fold increase compared with the control group. We subsequently found that ROS levels of n-butanol addition group reached 1.49x105 RFU/g biomass at 29 h, which was 3.02 times higher than the control group. The 0.8% n-butanol addition also promote the accumulation of biosynthesis precursors for FK520 production. The highest ethylmalonyl-CoA content surged to 93.1 nmol/g DCW at 48 h, marking a 5.3-fold increase. Likewise, the highest methylmalonyl-CoA and malonyl-CoA levels increased remarkable 4.33-fold and 3.33-fold compared with the control group at 72 h and at 120 h, respectively. Then, we explored the effects of oxygen supply on FK520 production with n-butanol addition, and improving oxygen supply caused a significant increase of FK520 in shake flask fermentation. Our research has revealed that addition of short-chain alcohols can regulate carbon flux toward FK520 biosynthesis by supplementing various CoA-esters, including ethylmalonyl-CoA, methylmalonyl-CoA, and malonyl-CoA.

microbiology↗

bioRxiv2018

Risk Factors Associated with Dengue Virus Infection in Guangdong Province: a Community-based Case-control Study

BackgroundDengue fever is a mosquito-borne infectious disease, and it is now still epidemic in China, especially in Guangdong Province. Owing to the absence of dengue vaccination, effective preventive measure is critical for controlling of dengue fever. This study aimed to explore the individual risk factors of dengue virus infection in Guangdong Province, as well as to provide a scientific basis for prevention and supervision of dengue fever in future.\n\nMethodsA case-control study including 237 cases and 237 controls was performed. The data was collected from the epidemiological questionnaires. Univariate analysis was used for preliminary screening of 28 variables potentially related to dengue virus infection, and an unconditioned logistic regression analysis was used for multivariate analysis to analysis those statistically significant variables.\n\nResultsMultivariate analysis of the result showed three independent risk factors: activities in the park (odd ratio [OR]= 1.70, 95%CI 1.03 to 2.83), outdoor sports (OR= 1.67, 95%CI 1.07 to 2.62), and poor indoor daylight quality (OR= 2.27, 95%CI 1.00 to 5.15); and two protective factors: two persons per room (OR=0.43, 95%CI 0.28 to 0.67), three persons and above per room (OR=0.43, 95%CI 0.22 to 0.86), using air-condition (OR=0.43, 95%CI 0.20 to 0.93).\n\nConclusionThese results are conducive to learn the risk factors for dengue virus infection in Guangdong Province. It is crucial to provide effective and efficient strategy to improve environmental protection and anti-mosquito measures. In addition, more systematic studies are needed to explore the other potential risk factors for dengue fever infection.\n\nAuthor summaryDengue fever, one of the mosquito-borne infectious diseases, is mainly transmitted by Aedes aegypti in Asia and Southeast Asia countries. Since 1978, the incidence of dengue fever has markedly increased in China especially in Guangdong province. In order to formulate the effective prevention and control measures, we explored the risk factors of dengue virus infection in Guangdong Province by conducting a case-control study. In this study, 237 patients with dengue virus infection and 237 participants without dengue virus infection were included. Then through these questionnaires and data analysis, we found that activities in the park, outdoor sports, and poor indoor daylight quality significantly contributed to the residents risk of dengue virus infection. On the other hand, we observed that using air-condition and using anti-mosquito measures were effective personal prevention interventions.

scientific communication and education↗