Publications by authors named "Shixin Ma"

Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.

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Article Synopsis
  • Coordination of cellular metabolism is crucial for effective CD8 T cell responses during infections, highlighting the role of cytosolic acetyl-CoA production.
  • The enzyme ATP citrate lyase (ACLY) is responsible for generating acetyl-CoA from citrate, and its absence leads T cells to rely on an alternative pathway involving acyl-CoA synthetase short-chain family member 2 (ACSS2) which uses acetate.
  • Both ACLY and ACSS2 are important for managing acetyl-CoA levels, impacting T cell function through modifications like histone acetylation and chromatin accessibility at key effector gene sites.
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Background: A series of complications will inevitably occur after thoracoscopic pulmonary resection. How to avoid or reduce postoperative complications is an important research area in the perioperative treatment of thoracic surgery. This study analyzed the risk factors for thoracoscopic postoperative complications of non-small cell lung cancer (NSCLC) and established a nomogram prediction model in order to provide help for clinical decision-making.

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Objective: The inflammatory response and the nutritional status are associated with overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but it is unclear which biomarkers are better suited to predict prognosis. This study sought to determine which of the commonly existing inflammatory and nutritional indicators best predicted the OS.

Methods: This study included 15 compound indicators based on inflammation or nutrition, with cutoff points obtained through the receiver operating characteristic (ROC) curve.

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Purpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work.

Patients And Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis.

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Article Synopsis
  • Scientists are trying to figure out why some cancers don't respond well to chemotherapy, which is medicine that fights cancer.
  • They used a special tool called CRISPR to study how different cancer cells react to seven different cancer drugs.
  • The researchers found that even though cancers can develop resistance in different ways, there's a specific target, called PLK4, that could help overcome this resistance and improve treatment.
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Objective: To investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with operable non-small-cell lung carcinoma (NSCLC). By constructing the nomogram model, it can provide a reference for clinical work.

Methods: A total of 899 patients with non-small cell lung cancer who underwent surgery in our hospital between January 2017 and June 2021 were retrospectively included.

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Objective: The purpose of this study was to construct a nomogram model based on the general characteristics, histological features, pathological and immunohistochemical results, and inflammatory and nutritional indicators of patients so as to effectively predict the overall survival (OS) and progression-free survival (PFS) of patients with non-small cell lung cancer (NSCLC) after surgery.

Methods: Patients with NSCLC who received surgical treatment in our hospital from January 2017 to June 2021 were selected as the study subjects. The predictors of OS and PFS were evaluated by univariate and multivariable Cox regression analysis using the Cox proportional risk model.

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Background: The emergence of immune checkpoint inhibitors (ICIs) provides a variety of options for patients with advanced non-small-cell lung cancer (NSCLC). After the application of ICIs, the immune system of patients was highly activated, and immune-related adverse events (irAEs) could occur in some organ systems, and irAEs seemed to be associated with the survival prognosis of patients. Therefore, we evaluated the association between survival outcomes and irAEs in NSCLC patients and conducted a systematic review and meta-analysis.

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Background: Atrial fibrillation (AF) is highly prevalent in the population, yet the factors contributing to AF events in susceptible individuals remain partially understood. The potential relationship between meteorological factors and AF, particularly with abnormal electrocardiograph (ECG) repolarization, has not been adequately studied. This case-crossover study aims to investigate the association between meteorological factors and daily hospital visits for AF with abnormal ECG repolarization in Shanghai, China.

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Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems.

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Article Synopsis
  • * Treatment with αCTLA-4 enhanced survival in a mouse model of glioblastoma, with this effect relying on the presence of CD4 T cells and their interaction with microglia.
  • * CD4 T cells were found to activate microglia through IFNγ, leading to increased tumor suppression, indicating a critical CD4 T cell-microglia interaction for effective anti-tumor immunity.
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  • Hyperglycemia can cause heart problems in people with diabetes, and there's no approved drug to help yet, but metformin might improve this condition.
  • In tests on mice and heart cells, metformin reduced heart damage and stopped heart cells from growing too much when there was high glucose.
  • Researchers found out that metformin works by changing certain proteins in the cells that are involved in heart cell growth and movement, making it a potential treatment for diabetes-related heart issues.
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CD8 T cells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets, but how chromatin is site-specifically remodeled during their differentiation is unclear. Due to its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8 T cells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions (OCRs) at enhancers.

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  • Transcription factors (TFs) play a crucial role in determining different T cell states, particularly in contexts like viral infections and cancer, leading to the creation of a detailed atlas of nine CD8 T cell differentiation states for predicting TF activity.
  • The study highlights the functional contrast between terminally exhausted T cells (TEX), which are dysfunctional, and tissue-resident memory T cells (T), which provide protection, while emphasizing the challenges in selectively promoting the beneficial state without allowing TEX differentiation.
  • Using techniques like CRISPR screening and single-cell RNA sequencing, researchers identified specific TFs linked to TEX state differentiation, discovered new TEX-specific TFs, and established potential targets for enhancing tumor control by improving T cell functionalities.
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This study determined the physical and mechanical characteristics of fresh black fungus during the harvesting season to provide basic data for the development of mechanical equipment for black fungus harvesting and processing. We have conducted a comprehensive test of black fungus cultivars "Heishan". The mono-factor separation force experiments of black fungus and black fungus virgulate medium were conducted.

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Despite the fundamental roles of TGF-β family signaling in cell fate determination in all metazoans, the mechanism by which these signals are spatially and temporally interpreted remains elusive. The cell-context-dependent function of TGF-β signaling largely relies on transcriptional regulation by SMAD proteins. Here, we discover that the DNA repair-related protein, HMCES, contributes to early development by maintaining nodal/activin- or BMP-signaling-regulated transcriptional network.

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The CRISPR-based nucleic acid detection systems have shown great potential for point-of-care testing of viral pathogens, especially in the context of COVID-19 pandemic. Here we optimize several key parameters of reaction chemistry and develop a Chemical Enhanced CRISPR Detection system for nucleic acid (termed CECRID). For the Cas12a/Cas13a-based signal detection phase, we determine buffer conditions and substrate range for optimal detection performance, and reveal a crucial role of bovine serum albumin in enhancing trans-cleavage activity of Cas12a/Cas13a effectors.

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In the direct competition for metabolic resources between cancer cells and tumor-infiltrating CD8 T cells, the latter are bound to lose out. These effector lymphocytes are therefore rendered exhausted or dysfunctional. Emerging insights into the mechanisms of T cell unresponsiveness in the tumor microenvironment (TME) point towards epigenetic mechanisms as crucial regulatory factors.

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RNA viruses are responsible for many zoonotic diseases that post great challenges for public health. Effective therapeutics against these viral infections remain limited. Here, we deployed a computational framework for host-based drug repositioning to predict potential antiviral drugs from 2,352 approved drugs and 1,062 natural compounds embedded in herbs of traditional Chinese medicine.

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The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA in infected and malignant cells and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) production via the STING pathway. Here, we examined the contribution of anion channels to cGAMP transfer and anti-viral defense. A candidate screen revealed that inhibition of volume-regulated anion channels (VRACs) increased propagation of the DNA virus HSV-1 but not the RNA virus VSV.

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Our knowledge of T cell metabolism relies primarily on studies performed in vitro that may not fully recapitulate physiological conditions in vivo. In this issue of Immunity, Ma et al. find that the in vivo environment dictates the metabolic phenotype of effector CD8+ T cells-particularly their glucose utilization.

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Dendritic cells (DCs) play pivotal roles in T-cell homeostasis and activation, and metabolic programing has been recently linked to DC development and function. However, the metabolic underpinnings corresponding to distinct DC functions remain largely unresolved. Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function.

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