Publications by authors named "MingRu Wu"

Background: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival.

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Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy.

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One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues.

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Chondrosarcomas represent the second most common primary bone malignancy. Despite the vulnerability of chondrosarcoma cells to nicotinamide adenine dinucleotide (NAD) depletion, targeting the NAD synthesis pathway remains challenging due to broad implications in biological processes. Here, we establish SIRT1 as a central mediator reinforcing the dependency of chondrosarcoma cells on NAD metabolism via HIF-2α-mediated transcriptional reprogramming.

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Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner.

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  • - The properties of face-centered-cubic chromium nitride (CrN) films, such as surface plasmonic resonance, surface wettability, and mechanical nanohardness, were altered by adjusting the nitrogen-to-argon gas ratios during their deposition, with specific ratios being N35, N40, and N45.
  • - The films exhibited hydrophilic characteristics, and their structural properties were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM), revealing a transition in crystal orientation from (111) to (200) as the nitrogen levels varied.
  • - Coupled photon and electron oscillations at the interface between CrN and gold (Au) in these materials were observed, indicating significant interactions in
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  • * Researchers evaluated five different machine learning models and found similar predictive performance among them, significantly outperforming existing clinical prediction tools like the HIAT, THRIVE score, and NADE nomogram.
  • * Out of 1,735 AIS patients studied, 31.2% experienced unfavorable outcomes, and incorporating specific patient data helped improve prediction accuracy, particularly with the Random Forest Classifier (RFC) model.
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  • Cell state-specific promoters are crucial for research as they enable gene expression under specific biological conditions.
  • The study employs next-generation sequencing and machine learning to analyze over 6,100 synthetic promoter designs to create high-performance synthetic promoters with enhanced specificity for various cell states.
  • The researchers successfully identified several synthetic promoters that show unique activity patterns during the differentiation of induced pluripotent stem cells and for specific cancer stem cells, suggesting potential applications in gene therapy and transcriptional studies.
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  • Engineered immune-cell therapies are effective against B cell cancers, but face challenges like insufficient targetable antigens, immune suppression by tumors, and severe side effects.
  • Synthetic biology offers potential solutions to enhance these therapies by allowing targeted attack on cancer cells while protecting healthy cells.
  • This article reviews recent advancements in gene circuit therapies utilizing immune cells and discusses the future hurdles and directions for clinical implementation.
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  • Current limitations in on-demand drug manufacturing can be overcome by using new technologies to streamline processes, especially through the simultaneous production of multiple drugs.
  • The proposed strategies focus on producing various biologics from yeast in one batch, including techniques for controlled expression of drugs, consolidated processing, and co-purification of antibodies.
  • These methods provide flexible, cost-effective solutions for decentralized drug manufacturing without needing specialized equipment, making it easier to fulfill urgent therapeutic demands or resource-limited situations.
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  • Cancer immunotherapy has shown promise in clinical trials but faces challenges like the scarcity of targetable antigens and immune suppression by tumors.
  • The study introduces a new gene circuit platform that targets tumors specifically by using synthetic promoters and an RNA-based AND gate to deliver customized immunostimulatory signals only in the presence of cancer cells.
  • Results demonstrated that this approach selectively killed cancer cells while sparing normal cells in the lab, and in mouse models, it significantly reduced tumors and improved survival, indicating potential for broader applications in immunotherapy.
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  • The study examines how cell-free spaces and surface patterns influence collective cell migration.
  • It finds that micropatterned substrates significantly reduce path variance and improve coordination of migrating cells compared to unpatterned surfaces, indicating that mechanical cues are important for guiding cell movement.
  • The findings have potential implications for understanding tissue repair and regeneration by highlighting the role of surface properties in cellular behavior.
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  • CAR T cell therapy using chimeric antigen receptors (CARs) shows promise in eliminating tumors but can cause severe toxicity due to targeting normal cells.
  • Modified NKG2D CAR T cells are effective against various tumors, operating through direct cell killing and cytokine release; however, their ligands can unintentionally affect non-tumor cells.
  • High doses of activated NKG2D CAR T cells can lead to acute toxicity akin to cytokine release syndrome, primarily driven by perforin and GM-CSF, with host immune cells also playing a significant role in this adverse reaction.
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Substantial evidence showed that T cells are the key effectors in immune-mediated tumor eradication; however, most T cells do not exhibit antitumor specificity. In this study, a bispecific T cell engager (BiTE) approach was used to direct T cells to recognize B7H6(+) tumor cells. B7H6 is a specific ligand for the NK cell-activating receptor NKp30.

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Genome-wide expression profiling in systemic sclerosis (SSc) has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks.

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  • Chimeric antigen receptor (CAR) T cell therapies are promising for cancer treatment, but there's a need for new CARs that can target various tumor types, including non-blood cancers.
  • This study focused on using the DNAM-1 receptor, which can recognize certain tumors, to create CARs aimed at several cancer types such as leukemia, ovarian cancer, and melanoma.
  • The DNAM-1 CARs showed strong effectiveness against tumor cells in the lab, decreased tumor size in a melanoma mouse model, and may offer new treatment options for a range of blood and solid tumors expressing PVR and nectin-2.
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Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy. Actively targeting IONPs to tumor cells can further increase therapeutic efficacy and decrease off-target side effects. To target tumor cells, a natural killer (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting IONPs.

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The Natural Killer Group 2D (NKG2D) receptor plays an important role in protecting the host from infections and cancer. By recognizing ligands induced on infected or tumor cells, NKG2D modulates lymphocyte activation and promotes immunity to eliminate ligand-expressing cells. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present a useful target for immunotherapeutic approaches in cancer.

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  • * Researchers developed chimeric antigen receptors (CARs) based on NKp30 that enhanced T cell responses against B7-H6+ tumor cells by triggering immune signaling pathways, resulting in effective tumor cell killing and IFN-γ production.
  • * The study showed that T cells with these NKp30 CARs not only suppressed the growth of B7-H6-expressing tumors in living mice but also resulted in long-lasting immunity against other types of tumors, indicating a promising therapeutic strategy for cancer treatment.
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Forkhead-associated (FHA) domains recognize phosphothreonines, and SQ/TQ cluster domains (SCDs) contain concentrated phosphorylation sites for ATM/ATR-like DNA-damage-response kinases. The Rad53-SCD1 has dual functions in regulating the activation of the Rad53-Dun1 checkpoint kinase cascade but with unknown molecular mechanisms. Here we present structural, biochemical, and genetic evidence that Dun1-FHA possesses an unprecedented diphosphothreonine-binding specificity.

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