Downregulation of the splicing regulator NSRP1 confers resistance to CDK4/6 inhibitors via activation of interferon signaling in breast cancer.

The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy is the first-line therapy for ER+/Her2- breast cancer, however, the development of drug resistance limited the efficacy of the agents. Although activation of the IFN signaling pathway has been identified as a critical driver of intrinsic and acquired CDK4/6i resistance, it remains unknown how the IFN signaling pathway was activated in resistant cells. Here, we report that NSRP1, a regulator of alternative mRNA splicing is downregulated in CDK4/6i resistant breast cancer cells and contributes to CDK4/6i resistance by mediating alternative splicing of NSD2 mRNA and activation of the IFN signaling pathway.

Engineering and targeting potential of CAR NK cells in colorectal cancer.

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promise, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors.

Memory Reconsolidation Updating in Substance Addiction: Applications, Mechanisms, and Future Prospects for Clinical Therapeutics.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse.

Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer.

The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy.

Steering the course of CAR T cell therapy with lipid nanoparticles.

Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy.

Utilizing a structure-based virtual screening approach to discover potential LSD1 inhibitors.

Background: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment.

Methods: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database.

Triglyceride-glucose index as a potential predictor for in-hospital mortality in critically ill patients with intracerebral hemorrhage: a multicenter, case-control study.

Background: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH).

Methods: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD).

Intelligent classification of major depressive disorder using rs-fMRI of the posterior cingulate cortex.

Major Depressive Disorder (MDD) is a widespread psychiatric condition that affects a significant portion of the global population. The classification and diagnosis of MDD is crucial for effective treatment. Traditional methods, based on clinical assessment, are subjective and rely on healthcare professionals' expertise.

Multi-strain probiotics ameliorate Alzheimer's-like cognitive impairment and pathological changes through the AKT/GSK-3β pathway in senescence-accelerated mouse prone 8 mice.

Background: Alzheimer's disease (AD), the most prevalent type of dementia, still lacks disease-modifying treatment strategies. Recent evidence indicates that maintaining gut microbiota homeostasis plays a crucial role in AD. Targeted regulation of gut microbiota, including probiotics, is anticipated to emerge as a potential approach for AD treatment.

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders.

The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages.

The gut microbiome modulates the susceptibility to traumatic stress in a sex-dependent manner.

Post-traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats.

Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents.

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients.

Involvement of spinal NADPH oxidase 4 and endoplasmic reticulum stress in morphine-tolerant rats.

Morphine tolerance (MT) is currently a challenging issue related to intractable pain treatment. Studies have shown that reactive oxygen species (ROSs) derived from NADPH oxidase (NOX) and produced in response to endoplasmic reticulum (ER) stress participate in MT development. However, which NOX subtype initiates ER stress during MT development is unclear.

Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma.

Introduction: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development.

Importance of accurate diagnosis of congenital agenesis of the gallbladder from atypical gallbladder stone presentations: A case report.

Background: Congenital agenesis of the gallbladder (CAGB) is a rare condition often misdiagnosed as cholecystolithiasis, leading to unnecessary surgeries. Accurate diagnosis and surgical exploration are crucial in patients with suspected CAGB or atypical gallbladder stone symptoms. Preoperative imaging, such as magnetic resonance cholangiopancreatography (MRCP), plays a vital role in confirming the diagnosis.

Activation of Epac in the BLA disrupts reconsolidation and attenuates heroin-seeking behaviour.

The susceptibility to drug cravings evoked by stimuli poses a formidable hurdle in the treatment of addiction and the prevention of relapse. Pharmacological interventions targeting drug-associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition.

Maximum likelihood synchronization algorithm correction for photon-counting communications with blocking loss.

To realize deep space optical communications with high capacity and sensitivity, synchronization of pulse-position modulation (PPM) signals is crucial. In this study, the maximum likelihood synchronization algorithm based on inter-symbol guard times was generalized to the scenario with strong blockage of single-photon detectors, where higher PPM slot frequency and signal-noise ratio could be adopted. Furthermore, a slot frequency offset compensation method was proposed, and simulations and experiments were performed to verify the performance improvement of the proposed corrected synchronization algorithm under blockage.

RIPK3 promotes hantaviral replication by restricting JAK-STAT signaling without triggering necroptosis.

Hantaan virus (HTNV) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (HFRS), resulting in a high mortality rate of 15%. Interferons (IFNs) play a critical role in the anti-hantaviral immune response, and IFN pretreatment efficiently restricts HTNV infection by triggering the expression of a series of IFN-stimulated genes (ISGs) through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT) pathway. However, the tremendous amount of IFNs produced during late infection could not restrain HTNV replication, and the mechanism remains unclear.

STING strengthens host anti-hantaviral immunity through an interferon-independent pathway.

Hantaan virus (HTNV), the prototype virus of hantavirus, could escape innate immunity by restraining type I interferon (IFN) responses. It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells. Here, we demonstrate that the stimulator of interferon genes (STING) strengthens the host IFN-independent anti-hantaviral immunity.

miR-221/222 Promote Endothelial Differentiation of Adipose-Derived Stem Cells by Regulation of PTEN/PI3K/AKT/mTOR Pathway.

Adipose-derived stem cells (ADSCs) are a type of adult mesenchymal stem cell that show a repair effect on ischemic tissues owing to their capacity for endothelial differentiation. MicroRNA-221/222 (miR-221/222) has been extensively studied in endothelial cells (ECs). However, the mechanism that regulates ADSCs differentiation into ECs remains unknown.

Efficacy and safety of anti-angiogenesis agents combined with chemoradiotherapy in the treatment of locally advanced cervical cancer: a meta-analysis of randomized controlled trials.

Background: Neovascularization is an important factor causing radiotherapy resistance, tumor growth, and metastasis. It may provides a new direction for treatment of cervical cancer.

Objective And Methods: The main objective is to systematically evaluate the clinical efficacy and safety of antiangiogenic therapy combined with CCRT in the treatment of cervical cancer.

Bolt-Loosening Detection Using 1D and 2D Input Data Based on Two-Stream Convolutional Neural Networks.

At present, the detection accuracy of bolt-loosening diagnoses is still not high. In order to improve the detection accuracy, this paper proposes a fault diagnosis model based on the TSCNN model, which can simultaneously extract fault features from vibration signals and time-frequency images and can precisely detect the bolt-loosening states. In this paper, the LeNet-5 network is improved by adjusting the size and number of the convolution kernels, introducing the dropout operation, and building a two-dimensional convolutional neural network (2DCNN) model.