Biomedical subjects

Lin Zhou

Publications and source records attributed to Lin Zhou.

8 recordsLinked to original sources

PubMed2026

Screening, Physiological Characterization, Genomic Analysis and Optimization by Conjugated Linoleic Acid Bioconversion of Two Lactiplantibacillus plantarum Strains.

Conjugated linoleic acid (CLA) comprises a group of C18 fatty acids containing conjugated double bonds and has been associated with potential anti-obesity and antitumor effects. In this study, 116 presumptive lactic acid bacteria (LAB) isolates were recovered from homemade Sichuan pickles. Primary screening identified 28 CLA-producing isolates, among which strains 7# and 31# showed the highest absorbance at 233 nm (A233). CLA production by both strains was subsequently optimized and quantified using gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF). Under the optimized conditions, strain 31# produced 66.50 ± 3.80 μg/mL total CLA, including 52.70 ± 3.29 μg/mL c9,t11-CLA and 13.80 ± 0.51 μg/mL t10,c12-CLA. Strain 7# produced 26.79 ± 1.09 μg/mL total CLA, including 14.05 ± 0.49 μg/mL c9,t11-CLA and 12.74 ± 0.60 μg/mL t10,c12-CLA. Physiological, biochemical, and safety assessments showed that strain 31# outperformed strain 7# overall, supporting its use in further product development and mechanistic studies. Functional annotation using the COG database and pathway mapping with KEGG identified candidate genes encoding an enzyme associated with linoleic acid isomerization in both strains. Potential mechanisms underlying their different CLA-producing capacities were also examined, providing a basis for the selection and development of high-CLA-producing strains.

conjugated linoleic acid↗

PubMed2026

Tracing and characterization of a family outbreak of subtype B2 botulism linked to homemade pickled eggs in Jinan, China.

Foodborne botulism (FB) results from the ingestion of food contaminated with botulinum neurotoxin. Here, we report a family outbreak of foodborne botulism caused by Clostridium botulinum subtype B2 linked to homemade pickled eggs. On August 13, 2024, the Jinan Center for Disease Control and Prevention and the Shanghe County Center for Disease Control and Prevention collaborated to investigate an outbreak of botulism poisoning related to a family gathering in Shanghe County, Jinan City. A total of 4 people attended the family gathering, three of whom developed clinical symptoms of botulism after consuming pickled eggs. The diagnosis of botulism was suspected through collaborative efforts by the Qilu Medical Prevention and Control Innovation Integration Mechanism and multidisciplinary consultations across multiple hospitals. We detected the bont gene using real-time quantitative PCR (qPCR) in Jinan CDC, determined the toxin serotype by mouse bioassay (MBA) in China CDC and performed whole-genome sequencing of bacterial strains isolated from patient feces, the homemade pickled eggs and soil in both laboratories. It was shown that the toxin type and bont gene were subtype B2, belonging to the ha gene cluster. The Clostridium botulinum strains isolated from two patients were closely related to the strains from the homemade pickled eggs through whole-genome single nucleotide polymorphism analysis. We also found that Clostridium botulinum strains from soil clustered into one branch with those from patients and food, suggesting that the source of Clostridium botulinum contamination may be from soil, although the contamination pathway was not clear. Importantly, our findings provided a basis for clinical antitoxin treatment, in which one patient successfully gave birth after recovery. These results underscore the importance of strengthening public education about the health risks associated with consuming homemade fermented or preserved foods and enhancing the laboratory detection capabilities.

Botulism↗

PubMed2026

Biosynthesis and Glycosylation of Antarlides, the Polyene Macrolides Possessing Androgen Receptor Antagonistic Activity.

Antarlides (ATLs) are tetraene macrolides discovered from Streptomyces spp. They demonstrated excellent antagonist activities toward mutated androgen receptors (ARs) related to the drug resistances in AR-targeted prostate cancer treatment. Herein, a biosynthetic gene cluster (BGC) of type I modular polyketide synthases (PKSs) from S. conglobatus ATCC 31005 was verified to be responsible for the biosynthesis of ATLs in the heterologous host S. lividans SBT5. The atl BGC was also activated in situ in S. conglobatus by equipping a strong promoter for the PKS genes operon. Unexpectedly, a new glycosylated product, ATL D1, was produced in the heterologous expression. ATL D1 was also generated in the S. conglobatus mutant bearing activated atl BGC through the introduction of a GT1 family glycosyltransferase gene mgt from S. lividans. Enzymatic analysis showed that the protein MGT catalyzed the glycosylation of ATL D to yield ATL D1 by attaching a β-d-glucose to the C11-hydroxyl position. Moreover, site-directed mutation of MGT resulted in an iterative glycosylation to yield ATL D2 bearing a disaccharide at the C11-hydroxyl. These results offer a platform for constructing efficient biosynthetic pathway of ATLs, and the O-glycosylation could be applied to improve the pharmaceutical properties of ATLs.

Glycosylation↗

PubMed2026

Prime assembly with linear DNA donors enables large genomic insertions.

Targeted insertion of large DNA fragments has promising applications for genome engineering and gene therapy1,2. Twin prime-editing guide RNAs have enabled relatively large insertions, but the efficiency remains low for insertions greater than 400 base pairs3-6. Here we describe a prime assembly (PA) approach for the insertion of large DNA donor fragments, of which the ends are designed to overlap with the flaps generated by twin prime editing (twinPE). We used PA to insert one or multiple overlapping DNA fragments, with total insertion sizes ranging from 0.1 kb to 11 kb. An inhibitor of non-homologous end joining enhanced both the efficiency and precision of insertions. PA relies on DNA templates that are easily produced, does not require co-delivery of exogenous DNA-dependent DNA polymerases and proceeds in non-cycling cells, suggesting independence from canonical homology-directed repair pathways. Our study demonstrates that PA can initiate Gibson-like assembly in cells to generate gene insertions without double-stranded DNA breaks, recombinases or homology-directed repair.

Animals↗

PubMed2026

Intron editing of RISBZ1 confers thermotolerance for grain filling in rice.

RISBZ1 encodes the transcription factor bZIP58, which regulates grain filling; intron editing of RISBZ1 to eliminate aberrant alternatively spliced transcripts increased grain weight without compromising key agronomic traits under normal conditions, and enhanced grain weight and quality under heat stress conditions.

Oryza↗

PubMed2025

MYC and p53 Alterations Cooperate through VEGF Signaling to Repress Cytotoxic T-cell and Immunotherapy Responses in Prostate Cancer.

UNLABELLED: Patients with castration-resistant prostate cancer (CRPC) are generally unresponsive to tumor-targeted treatments and immunotherapies. Genetic alterations acquired during the evolution of CRPC may affect antitumor immunity and immunotherapy responses, which could inform personalized therapeutic strategies. Using our innovative electroporation-based mouse models, we generated distinct genetic subtypes of CRPC found in patients and uncovered unique immune microenvironments. Specifically, mouse and human prostate tumors with MYC amplification and p53 disruption had weak cytotoxic lymphocyte infiltration and an overall dismal prognosis. MYC and p53 cooperated to induce tumor-intrinsic secretion of VEGF, which signaled through VEGFR2 expressed on CD8+ T cells to directly inhibit T-cell migration and effector functions. Targeting VEGF-VEGFR2 signaling in vivo remodeled the immunosuppressive prostate tumor microenvironment, leading to CD8+ T-cell-mediated primary tumor and metastasis growth suppression and significantly increased overall survival in MYC- and p53-altered CRPC. VEGFR2 blockade also led to the induction of PD-L1 in tumors and produced antitumor efficacy in combination with PD-L1 immune checkpoint blockade in multiple preclinical CRPC mouse models. Thus, these results identify a genetic mechanism of immunosuppression through VEGF signaling in prostate cancer that can be targeted to reactivate immune and immunotherapy responses in an aggressive subtype of CRPC. SIGNIFICANCE: VEGFR2 blockade inhibits VEGF-mediated T-cell suppression and potentiates the effects of PD-L1 immune checkpoint blockade to treat castration-resistant prostate cancer driven by MYC and p53 alterations.

Male↗

PubMed2025

PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.

Immunotherapy modalities have revolutionized cancer treatment for a number of metastatic and treatment-refractory tumor types. Still, many malignancies that lack T cell infiltration and are termed immunologically "cold" fail to respond to these modalities. One approach to increase tumor immunogenicity has been to induce stimulator of interferon gene (STING) and downstream interferon signaling that is often dysregulated in cold tumors. Despite some early success of STING agonists in preclinical cancer models, these approaches have not been successful in the clinic due to poor tumor penetrance and systemic toxicities. Here, we performed a genome-wide CRISPR screen to uncover therapeutic targets to activate STING expression in human tumors. We identified the lysosomal hydrolase Palmitoyl Protein Thioesterase1 (PPT1) as a negative regulator of STING highly expressed in cold ovarian and prostate tumors. Genetic or pharmacological PPT1 suppression increased STING protein stability and its downstream activation of interferon and inflammatory cytokine signaling to enhance T cell migration. Treatment of preclinical prostate and ovarian cancer models expressing low levels of STING with the small molecule PPT1 inhibitor GNS561 enhanced STING expression and activation, leading to infiltration and activation of cytotoxic T cells that turned these tumors "hot" and reduced tumor growth, fibrosis, and dissemination without toxicity. Further analysis demonstrated that PPT1 is associated with reduced STING expression, CD8+ T cell numbers, overall survival, and immunotherapy outcomes in ovarian and prostate cancer patients. Thus, PPT1 inhibition may be a promising approach to activate STING and potentiate the effects of immunotherapy in cold tumors.

Membrane Proteins↗

PubMed2024

The AKR1C1-CYP1B1-cAMP signaling axis controls tumorigenicity and ferroptosis susceptibility of extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma (ECC), a highly malignant type of cancer with increasing incidence, has a poor prognosis due to limited treatment options. Based on genomic analysis of ECC patient samples, here we report that aldo-keto reductase family 1 member C1 (AKR1C1) is highly expressed in human ECC tissues and closely associated with ECC progression and poor prognosis. Intriguingly, we show that inducible AKR1C1 knockdown triggers ECC cells to undergo ferroptosis. Mechanistically, AKR1C1 degrades the protein stability of the cytochrome P450 family member CYP1B1, a newly discovered mediator of ferroptosis, via ubiquitin-proteasomal degradation. Additionally, AKR1C1 decreases CYP1B1 mRNA level through the transcriptional factor aryl-hydrocarbon receptor (AHR). Furthermore, the AKR1C1-CYP1B1 axis modulates ferroptosis in ECC cells via the cAMP-PKA signaling pathway. Finally, in a xenograft mouse model of ECC, AKR1C1 depletion sensitizes cancer cells to ferroptosis and synergizes with ferroptosis inducers to suppress tumor growth. Therefore, the AKR1C1-CYP1B1-cAMP signaling axis is a promising therapeutic target for ECC treatment, especially in combination with ferroptosis inducers.

Humans↗