Biology subjects

Shu, F.

Publications and source records attributed to Shu, F..

5 recordsLinked to original sources

bioRxiv2025

Enhancing HIPEC for Ovarian Cancer using Adjunctive Biomaterials

Ovarian cancer is one of the most lethal gynecological malignancies, with high mortality rates primarily due to late-stage diagnoses and extensive peritoneal metastases. Despite improvements in surgical and chemotherapeutic treatments, the prognosis for advanced ovarian cancer remains poor, highlighting the urgent need for innovative therapeutic approaches. Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a promising treatment, delivering heated chemotherapeutic agents directly into the peritoneal cavity post-cytoreductive surgery. However, HIPEC adoption is limited by three critical complications: suboptimal therapeutic efficacy in resistant tumors; abdominal adhesion formation; and systemic toxicity, including cisplatin-induced nephrotoxicity. This study investigates carbon monoxide gas- entrapping materials (CO-GEMs) as a novel multifunctional adjunctive therapy to address the three HIPEC limitations simultaneously. CO-GEMs effectively encapsulate and deliver carbon monoxide, leveraging the differential effects of CO in cancerous where it has been shown to reduce tumor burden. In ovarian cancer models, CO-GEMs significantly enhanced cisplatin efficacy, reducing the metastatic tumor burden by 46.6% through the downregulation of drug resistance pathways, including the IL-17, TNF, and NF-{kappa}B pathways; ECM receptor interaction, and VEGF signaling. CO-GEMs also prevented peritoneal adhesion formation by suppressing inflammatory cell infiltration and collagen deposition, with a significant reduction in adhesion severity scores. Additionally, enteral CO-GEMs provided significant nephroprotection against cisplatin-induced acute kidney injury, as demonstrated by reduced blood urea nitrogen levels. CO-GEMs represent a promising innovation that simultaneously improves HIPEC therapeutic efficacy, prevents surgical complications, and reduces systemic toxicity. This multifunctional approach addresses multiple clinical limitations of HIPEC, potentially transforming treatment outcomes for patients with advanced ovarian cancer through an enhanced therapeutic index and improved safety profile.

bioengineering↗

bioRxiv2025

Development and Application of a Filamentous Phage-Based Rapid Detection Tool for Ralstonia pseudosolanacearum

Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is a devastating plant disease with a broad host range. Early detection is critical for disease management, yet conventional methods lack speed and specificity. This study developed a rapid detection system using engineered filamentous phages (RSCq) expressing bioluminescence genes (luxAB, nanoluc, and luxSit-i). Among the constructs, RSCqluxAB demonstrated optimal performance, detecting R. pseudosolanacearum at 1.58x103 CFU/mL within 12 hours, with minimal background noise. The phage retained stability for six months at 4{degrees}C, proving suitable for field applications. These findings highlight its potential for early pathogen monitoring, quarantine enforcement, and precision agriculture, though further validation in soil/plant samples is needed.

microbiology↗

bioRxiv2023

Trojan horse virus delivering CRISPR-AsCas12f1 controls plant bacterial wilt caused by Ralstonia solanacearum

Plant bacterial wilt caused by the Ralstonia solanacearum species complex results in huge food and economic losses. Accordingly, the development of an effective control method for this disease is urgently required. Traditional lytic phage biocontrol methods have inherent limitations. However, filamentous phages, which do not lyse host bacteria and exert minimal burden, offer a potential solution. A filamentous phage RSCq that infects R. solanacearum was isolated in this study through genome mining. We constructed engineered filamentous phages based on RSCq by employing our proposed approach with a wide applicability to non-model phages, enabling the infection of R. solanacearum in medium and soil and delivering exogenous genes into bacterial cells. Similar to the Greek soldiers hidden within the Trojan horse, CRISPR-AsCas12f1 gene editing system that targets the key virulence regulator gene hrpB was implanted into the engineered phage, generating the engineered phage RSCqCRISPR-Cas. Our findings demonstrated that RSCqCRISPR-Cas could disarm the key "weapon", hrpB, of R. solanacearum, in medium and in plants. Remarkably, pretreatment with RSCqCRISPR-Cas significantly controlled tobacco bacterial wilt, highlighting the potential of engineered filamentous phages as promising biocontrol agents against plant bacterial wilt and other bacterial diseases.

microbiology↗

bioRxiv2022

TRAF6 modulates PD-L1 expression through YAP1-TFCP2 signaling in melanoma

BackgroundImmunotherapy represented by the programmed death-1 (PD-1)/ligand 1 (PD-L1) monoclonal antibodies has led tumor treatment into a new era. However, the low overall response rate and high incidence of drug resistance largely damage the clinical benefits of existing immune checkpoint therapies. Recent studies correlate the response to PD-1/PD-L1 blockade with PD-L1 expression levels in tumor cells. Hence, identifying molecular targets and pathways controlling PD-L1 protein expression and stability in tumor cells is a major priority. MethodsIn this study, we first performed a Stress and Proteostasis CRISPR interference library-based screening to identify PD-L1 positive modulators. We then used in vitro and in vivo assays to investigate the biological function and mechanism of TRAF6 and its downstream YAP1/TFCP2 signaling in malignant melanoma. ResultsHere, we identified TRAF6 as a critical regulator of PD-L1 in melanoma cells. Suppression of TRAF6 expression down-regulates PD-L1 expression on the membrane surface of melanoma cells. We also found that PD-L1 protein abundance is regulated by YAP1/TFCP2 transcriptional complex. TRAF6 stabilizes YAP1 by K63 poly-ubiquitination modification, subsequently promoting the formation of YAP1/TFCP2 and PD-L1 transcription. Furthermore, inhibition of TRAF6 by Bortezomib enhanced cytolytic activity of CD8+ T cells by reduction of endogenous PD-L1. Notably, Bortezomib enhances anti-tumor immunity to an extent that is comparable to anti-PD-1 mAb therapies with no obvious toxicity. ConclusionsThese findings uncover a novel molecular mechanism for regulating PD-L1 protein abundance by a E3 ligase in cancer cells and reveal the potential of using TRAF6 inhibitors to stimulate internal anti-tumor immunological effect for TRAF6-PD-L1 overexpressing cancers.

cancer biology↗

bioRxiv2020

Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins

The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.

microbiology↗