Heterogeneous cellular responses to hyperthermia support combined intraperitoneal hyperthermic immunotherapy for ovarian cancer mouse models.

The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment.

Integrated analysis of single-cell and bulk transcriptomics reveals cellular subtypes and molecular features associated with osteosarcoma prognosis.

Background: Osteosarcoma (OS) is the most common primary bone malignancy with variable molecular biology and prognosis. However, our understanding of the association between cell types and OS progression remains poor.

Methods: We generated a human OS cell atlas by integrating over 110,000 single cells from 17 samples.

Clinicopathological significance of deficient DNA mismatch repair and MLH1 promoter methylation in gastric adenosquamous carcinoma.

Primary gastric adenosquamous carcinoma (GASC) is a rare tumor that exhibits aggressive behavior and currently lacks standardized therapeutic recommendations. Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) and positive PD-L1 expression confer sensitivity to immune checkpoint inhibitors; however, their statuses in GASC remain uncertain. In this study, clinical features, MMR/MSI status, MLH1 methylation, two T-cell markers, and PD-L1 expression of 30 GASC cases were collected from three institutions.

Efficient nonlinear function approximation in analog resistive crossbars for recurrent neural networks.

Analog In-memory Computing (IMC) has demonstrated energy-efficient and low latency implementation of convolution and fully-connected layers in deep neural networks (DNN) by using physics for computing in parallel resistive memory arrays. However, recurrent neural networks (RNN) that are widely used for speech-recognition and natural language processing have tasted limited success with this approach. This can be attributed to the significant time and energy penalties incurred in implementing nonlinear activation functions that are abundant in such models.

Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.

Utricle is an important vestibular sensory organ for maintaining balance. 3,3'-iminodipropionitrile (IDPN), a prototype nitrile toxin, has been reported to be neurotoxic and vestibulotoxic, and can be used to establish an damage model of vestibular dysfunction. However, the mechanism of utricular HCs damage caused by IDPN is unclear.

Maternal phthalates exposure promotes neural stem cell differentiation into phagocytic astrocytes and synapse engulfment via IRE1α/XBP1s pathway.

Humans are widely exposed to phthalates, a common chemical plasticizer. Previous cohort studies have revealed that maternal exposure to monobutyl phthalate (MBP), a key metabolite of phthalates, is associated with neurodevelopmental defects. However, the molecular mechanism remains unclear.

Hyperbaric Oxygen Therapy Improves Motor Symptoms, Sleep, and Cognitive Dysfunctions in Parkinson's Disease.

Introduction: The aim of the study was to systematically analyze the therapeutic effectiveness of hyperbaric oxygen therapy compared with conventional drug therapy in patients with Parkinson's disease.

Methods: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database searched to the end of March 2023. Two authors independently screened and abstracted data from each trial.

Clinical efficacy and mechanism of the combination of autologous platelet-rich gel and recombinant human acidic fibroblast growth factor in the management of refractory diabetic foot.

Objective: This study aims to explore the influence of combining autologous platelet-rich gel (APG) with continuous vacuum-sealed drainage (CVSD) and the exogenous recombinant human acidic fibroblast growth factor (rh-aFGF) on the healing processes of diabetic foot ulcers (DFU). The primary objective is to elucidate the complex molecular mechanisms associated with DFU, providing innovative perspectives for its treatment.

Methods: Ninety patients diagnosed with DFU were randomly allocated into three distinct groups.

Integrated single-cell transcriptomic analyses identify a novel lineage plasticity-related cancer cell type involved in prostate cancer progression.

Background: Cancer cell plasticity is the ability of neoplastic cells to alter their identity and acquire new biological properties under microenvironmental pressures. In prostate cancer (PCa), lineage plasticity often results in therapy resistance and trans-differentiation to neuroendocrine (NE) lineage. However, identifying the cancer cells harboring lineage plasticity-related status remains challenging.

Clinical Features and Outcomes of Long-Term Lead Performance by Left Bundle Branch Pacing.

Left bundle branch pacing (LBBP) is an emerging physiological pacing technique that expanded in recent reports. The long-term safety and feasibility of LBBP lack adequate evaluation.The study aimed to evaluate the long-term lead performance and clinical outcomes of LBBP.

Computing high-degree polynomial gradients in memory.

Specialized function gradient computing hardware could greatly improve the performance of state-of-the-art optimization algorithms. Prior work on such hardware, performed in the context of Ising Machines and related concepts, is limited to quadratic polynomials and not scalable to commonly used higher-order functions. Here, we propose an approach for massively parallel gradient calculations of high-degree polynomials, which is conducive to efficient mixed-signal in-memory computing circuit implementations and whose area scales proportionally with the product of the number of variables and terms in the function and, most importantly, independent of its degree.

EGFR-TKIs Combined with Allogeneic CD8+ NKT Cell Immunotherapy to Treat Patients with Advanced EGFR-Mutated Lung Cancer.

To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm.

The expression and biological role of complement C1s in esophageal squamous cell carcinoma.

The present work focused on investigating the role of the altered expression of complement C1s in proliferation and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and explore its biological functions in ESCC, so as to lay a theoretical foundation and provide certain clinical reference for diagnosing and treating ESCC. Complement C1s expression within ESCC was assessed, and its clinical pathological characteristics in ESCC patients were analyzed. Subsequently, experiments were performed to further explore the mechanisms by which complement C1s affected ESCC.

off-target profiling for enhanced drug safety assessment.

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety.

FGFR2 fusion/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma.

Increasing evidence highlights that fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement shows important therapeutic value for patients with intrahepatic cholangiocarcinoma (ICC). This study aims to explore the association of FGFR2 status with the prognosis and immune cell infiltration profiles of patients with ICC. A total of 226 ICC tissue samples from patients who received surgery at the Department of Liver Surgery at Zhongshan Hospital, Fudan University, were collected retrospectively and assigned to a primary cohort (n = 152) and validation cohort (n = 74) group.

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits.

Background: The expression pattern of gamma aminobutyric acid (GABA) receptor subunits are commonly altered in patients with schizophrenia, which may lead to nerve excitation/inhibition problems, affecting cognition, emotion, and behavior.

Aim: To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.

Methods: This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.

Analysis of factors influencing the recurrence of diabetic foot ulcers.

Objective: The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate.

Methods: A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n = 84) and a non-recurrence group (n = 127).

Environmental monobutyl phthalate exposure promotes liver cancer via reprogrammed cholesterol metabolism and activation of the IRE1α-XBP1s pathway.

Humans are widely exposed to phthalates, a major chemical plasticizer that accumulates in the liver. However, little is known about the impact of chronic phthalate exposure on liver cancer development. In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates.

Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a prevalent myocardial microvascular complication of the myocardium with a complex pathogenesis. Investigating the pathogenesis of DCM can significantly contribute to enhancing its prevention and treatment strategies. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels.

DNA sensing of dendritic cells in cancer immunotherapy.

Dendritic cells (DCs) are involved in the initiation and maintenance of immune responses against malignant cells by recognizing conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). According to recent studies, tumor cell-derived DNA molecules act as DAMPs and are recognized by DNA sensors in DCs. Once identified by sensors in DCs, these DNA molecules trigger multiple signaling cascades to promote various cytokines secretion, including type I IFN, and then to induce DCs mediated antitumor immunity.