Repurposing Mercaptopurine Through Collateral Lethality to Treat Cancers with Somatic Loss.

Somatic retinoblastoma 1 () loss is prevalent across different cancer types and is enriched in treatment-refractory tumors, such as castration-resistant prostate cancer (CRPC) and small-cell lung cancer, but cannot be considered as a direct druggable target. In this study, we revealed that the close proximity of nudix hydrolase 15 () and may result in their common somatic codeletion or epigenomic cosilencing in different cancer types and subsequent significant positive correlations of their expressions at the bulk transcriptional and single-cell levels. With clinical CRPC samples, co-loss of and were commonly observed (14 out of 21).

Single-cell and spatial transcriptomics profile the interaction of macrophages and fibroblasts in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) remains one of the most prevalent malignancies. A series of differentially expressed genes (DEGs) have been identified in tumor samples and play critical roles in modulating the characteristics of tumor cells. However, some DEGs are specifically expressed in the tumor microenvironment (TME) cells.

Robust High-Spin State in One-Dimensional CrX (X = Cl, Br, I) at the Single-Chain Limit.

Low-dimensional magnetic materials have garnered significant interest due to their unique physical properties and potential applications. Nevertheless, the synthesis of one-dimensional (1D) magnetic materials presents challenges, and the properties of these 1D materials at the single-chain limit have not been well investigated. We here explore experimentally and theoretically 1D CrX (X= Cl, Br, I) magnetic single chains residing within carbon nanotubes.

The power spectrum map of gyro-sulcal functional activity dissociation in macaque brains.

Nonhuman primates, particularly rhesus macaques, have served as crucial animal models for investigating complex brain functions. While previous studies have explored neural activity features in macaques, the gyro-sulcal functional dissociation characteristics are largely unknown. In this study, we employ a deep learning model named one-dimensional convolutional neural network to differentiate resting state functional magnetic resonance imaging signals between gyri and sulci in macaque brains, and further investigate the frequency-specific dissociations between gyri and sulci inferred from the power spectral density of resting state functional magnetic resonance imaging.

Prognostic Value of a Serological-Based Clinical Model for Gastric Cancer Patients.

: Surgery remains the cornerstone of diagnosis and treatment for gastric cancer. This study aims to develop and validate a serology-based clinical scoring system to predict and evaluate the prognosis of gastric cancer patients. : Clinicopathological data of primary gastric cancer patients who underwent surgical treatment from 2009 to 2018 were collected and divided into training and validation cohorts.

Comparison among Early-Onset, Late-Onset, and Conventional-Onset Adenocarcinoma of Stomach and Esophagogastric Junction: a Retrospective Study.

Background: The incidence of EOGC has been increasing, while COGC has decreased over the past few decades. The objective of this study was to identify differences in clinical characteristics and prognosis and to verify survival results among early-onset gastric cancer (EOGC), conventional-onset gastric cancer (COGC), late-onset gastric cancer (LOGC), and within the adenocarcinoma of the esophagogastric junction (AEG) group.

Materials And Methods: A retrospective trend analysis was conducted on patients diagnosed with gastric adenocarcinoma between 2002 and 2021.

A modified liver retraction method decreases liver dysfunction after laparoscopic gastrectomy.

Background: In laparoscopic gastrectomy, liver retraction is an important procedure to obtain a sufficient operative view to ensure the quality of surgery. However, postoperative liver dysfunction is frequently encountered after liver retraction. This study aims to explore the effect of a modified liver retraction method (MLR) we designed on the postoperative liver function of patients receiving laparoscopic radical gastrectomy.

Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment.

The gut microbiota crucially regulates the efficacy of immune checkpoint inhibitor (ICI) based immunotherapy, but the underlying mechanisms remain unclear at the single-cell resolution. Using single-cell RNA sequencing and subsequent validations, we investigate gut microbiota-ICI synergy by profiling the tumor microenvironment (TME) and elucidating critical cellular interactions in mouse models. Our findings reveal that intact gut microbiota combined with ICIs may synergistically increase the proportions of CD8, CD4, and γδ T cells, reduce glycolysis metabolism, and reverse exhausted CD8 T cells into memory/effector CD8 T cells, enhancing antitumor response.

Biological Prior Knowledge-Embedded Deep Neural Network for Plant Genomic Prediction.

Genomic prediction is a powerful approach that predicts phenotypic traits from genotypic information, enabling the acceleration of trait improvement in plant breeding. Traditional genomic prediction methods have primarily relied on linear mixed models, such as Genomic Best Linear Unbiased Prediction (GBLUP), and conventional machine learning methods like Support Vector Regression (SVR). Traditional methods are limited in handling high-dimensional data and nonlinear relationships.

Soluble-microneedle enhance three T-cell activation signals as efficient tumor vaccines for melanoma prevention and treatment.

Therapeutic tumor vaccines, which activate self-T cells to eliminate tumors, hold tremendous promise in future cancer immunotherapy with high specificity and low side effects. To effectively activate T cell, dendritic cells (DCs) need simultaneously provide three indispensable signals to naive T cells, including MHC-antigen signal, costimulation signal and cytokine stimulation. However, current marketed therapeutic tumor vaccines still suffer from lacking the ability to activate three stimulation signals at the same time, which resulted to the low response rate and unsatisfied therapeutic efficiency.

Temperature-Sensitive Nano-GOx Combined with Downregulation of Tumor Stemness to Initiate Robust Antitumor Efficacy.

GOx-mediated glucose depletion offers an alternative noninvasive strategy for tumor therapy, but its lower catalytic activity limits its clinical application. Herein, we designed a temperature-sensitive nano-GOx (NG) that was constructed by gold nanorods chemically modified with GOx (AuNRs-GOx) and coated with temperature-sensitive lipids. The chemical linkage could maintain the natural conformation of GOx, ensuring that NG exerted powerful catalytic activity within the tumor and initiated antitumor immune response through moderate starvation and mild photothermal therapy (mPTT) to coregulating dendritic cells (DCs) and tumor-associated macrophages (TAMs).

Discovery of HMPL-306 (Ranosidenib), a New Potent and Selective Dual Inhibitor of Mutant IDH1 and 2 in Clinical Development for Cancer Treatment.

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are identified in various cancers. Accumulated ()-2-hydroxyglutarate (2-HG) caused by mutant IDHs leads to blockage of cell differentiation, thereby inducing malignant transformation. Herein we describe the medicinal chemistry efforts that discovered novel mutant IDH inhibitor HMPL-306 (ranosidenib) via structure-activity relationship studies and pharmacokinetic optimization from internal hit compound .

Single cell immunoprofile of synovial fluid in rheumatoid arthritis with TNF/JAK inhibitor treatment.

Numerous patients with rheumatoid arthritis (RA) manifest severe syndromes, including elevated synovial fluid volumes (SF) with abundant immune cells, which can be controlled by TNF/JAK inhibitors. Here, we apply single-cell RNA sequencing (scRNA-seq) and subsequent validations in SF from RA patients. These analyses of synovial tissue show reduced density of SF-derived pathogenic cells (e.

Versatile Ordering Network: An Attention-Based Neural Network for Ordering Across Scales and Quality Metrics.

Ordering has been extensively studied in many visualization applications, such as axis and matrix reordering, for the simple reason that the order will greatly impact the perceived pattern of data. Many quality metrics concerning data pattern, perception, and aesthetics are proposed, and respective optimization algorithms are developed. However, the optimization problems related to ordering are often difficult to solve (e.

Autosuppression of MdNAC18.1 endowed by a 61-bp promoter fragment duplication delays maturity date in apple.

Maturity date considerably influences fruit marketing period and commercial value and it is of particular importance in apple due to its association with fruit firmness that determines storage and shelf life, but the underlying mechanism remains unclear. In this study, we report a 61-bp fragment duplication in the MdNAC18.1 promoter that underpins maturity date variation in apple.

Regulating tumor cells to awaken T cell antitumor function and enhance melanoma immunotherapy.

Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX).

snRNA-seq of human ovaries reveals heat shock proteins are associated with obesity related cancer risk.

Background: Obesity significantly impacts female reproductive health and increases the risk of gynecological tumors. However, the specific transcriptional changes that occur in the ovarian microenvironment during obesity-induced stress and the relationship between obesity and ovarian cancer remain unclear.

Methods: Our study investigated the single-cell landscape of the ovarian cortex in individuals with varying BMI levels by snRNA-seq, revealing weight-stage related cellular composition deviations and expression profile irregularities.

Transcriptomic data of peach varieties with different chilling requirement levels.

Objectives: Peach is a deciduous tree widely cultivated in temperate and subtropical regions that requires a process of bud endodormancy to produce normal flowering and fruiting. This release requires a certain accumulation of cold, named chilling requirement (CR). CR is genotype dependent and with varies levels among different species and accessions.

Deciphering the genetic mechanisms of chilling requirement for bud endodormancy release in deciduous fruit trees.

Bud endodormancy in deciduous fruit trees is an adaptive trait evolved by selection for the capacity to survive unfavorable environmental conditions. Deciduous trees require a certain amount of winter chill named chilling requirement (CR) to promote bud endodormancy release. In recent decades, global warming has endangered the chill accumulation in deciduous fruit trees.

eradication following endoscopic resection might prevent metachronous gastric cancer: a systematic review and meta-analysis of studies from Japan and Korea.

Objectives: A systematic review and meta-analysis was performed to evaluate the preventive effectiveness of eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia.

Methods: PubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups.

The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the genes have been identified in humans, i.e.

Clinicopathological features of hepatoid adenocarcinoma and non-hepatoid adenocarcinoma of the stomach: A systematic review and meta-analysis.

Background: Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique malignant gastric tumor with a significantly worse prognosis than non-hepatoid adenocarcinoma of the stomach (non-HAS). The present study explored the clinicopathological features of HAS and non-HAS patients to provide insights into HAS treatment strategies.

Methods: From December 26, 2023, we performed a comprehensive search of the PubMed, Web of Science, Cochrane Library, and Embase.

Origins and Genetic Characteristics of Egyptian Peach.

Peach (), a significant economic fruit tree in the Rosaceae family, is extensively cultivated in temperate and subtropical regions due to its abundant genetic diversity, robust adaptability, and high nutritional value. Originating from China over 4000 years ago, peaches were introduced to Persia through the Silk Road during the Han Dynasty and gradually spread to India, Greece, Rome, Egypt, Europe, and America. Currently grown in more than 80 countries worldwide, the expansion of peach cultivation in Egypt is mainly due to the development and utilization of peach varieties with low chilling requirements.