Liver-specific gene PGRMC1 blocks c-Myc-induced hepatocarcinogenesis through ER stress-independent PERK activation.

Roles of liver-specific genes (LSGs) in tumor initiation and progression are rarely explored in hepatocellular carcinoma (HCC). Here we show that LSGs are generally downregulated in HCC tumor tissues compared to non-HCC liver tissues, and low-LSG HCCs show poor prognosis and the activated c-Myc pathway. Among the c-Myc- and patient prognosis-associated LSGs, PGRMC1 significantly blocks c-Myc-induced orthotopic HCC formation.

Stromal immune cells expression of Siglec-15 is associated with lower T stage and better prognosis of urinary bladder cancer.

Introduction: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is a novel immune checkpoint, similar to programmed death-ligand (PD-L1), and has emerged as a potential target for cancer immunotherapy. Until recently, little was known about the expression and role of Siglec-15 in bladder cancer (BC).

Methods: In this study, we used immunohistochemical staining to assess the expression of Siglec-15 and PD-L1 in 69 primary BC samples and analyzed their relationship with clinicopathologic characters and prognosis.

Brain derived β-interferon is a potential player in Alzheimer's disease pathogenesis and cognitive impairment.

Background: Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise types of interferons and related cytokines, both from the brain and periphery, responsible for cognitive impairment in patients with AD remain unclear.

Methods: A total of 131 participants (78 [59.

Clinical and Multimodal Imaging Features of Hepatic Inflammatory Pseudotumors: A Two-Center Retrospective Study.

Objectives: Current literature on imaging characteristics of hepatic inflammatory pseudotumor (HIPT) is limited. This study aimed to analyze the contrast-enhanced ultrasound (CEUS) features in HIPT and compare them with contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI).

Methods: A total of 83 patients with histologically proven HIPT from two medical institutions were included in this study.

Cyclophilin A facilitates HIV-1 integration.

Unlabelled: Cyclophilin A (CypA) binds to the HIV-1 capsid to facilitate reverse transcription and nuclear entry and counter the antiviral activity of TRIM5α. Interestingly, recent studies suggest that the capsid enters the nucleus of an infected cell and uncoats prior to integration. We have previously reported that the capsid protein regulates HIV-1 integration.

Now and future: Strategies for diagnosis, prevention and therapies for Alzheimer's disease.

After a number of failed drug studies on Alzheimer's disease (AD) over the past decade, clinical trials of AD started to show encouraging results and were approved or pending approval for clinical use. However, controversies on the clinically meaningful benefits and risks of brain edema and microhemorrhages have reminded us to think further about monitoring treatment and developing new drug targets. The goal of this review is to find insights from clinical trials that aimed at two key pathological features of AD, i.

Elasticity of the HIV-1 core facilitates nuclear entry and infection.

HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid. Recent studies have shown that HIV-1 cores enter the nucleus prior to capsid disassembly. Interactions of the viral capsid with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown.

The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6).

Cyclophilin A Facilitates HIV-1 DNA Integration.

Unlabelled: Cyclophilin A (CypA) promotes HIV-1 infection by facilitating reverse transcription, nuclear entry and by countering the antiviral activity of TRIM5α. These multifunctional roles of CypA are driven by its binding to the viral capsid. Interestingly, recent studies suggest that the HIV-1 capsid lattice enters the nucleus of an infected cell and uncoats just before integration.

The value of apparent diffusion coefficient values in predicting Gleason grading of low to intermediate-risk prostate cancer.

Objectives: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) for low to intermediate-risk prostate cancer (PCa), as well as its correlation with the prognostic Gleason score (GS).

Materials And Methods: Retrospective analysis of MRI images and relevant clinical data from patients with prostate disease. The differences in ADC between different GS groups were compared, and the efficacy of ADC in PCa diagnosis were analyzed.

Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors.

Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma-2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non-tumor liver.

Highly accurate and effective deep neural networks in pathological diagnosis of prostate cancer.

Purpose: To established an AI system to make the pathological diagnosis of prostate cancer.

Methods: Prostate histopathological whole mount (WM) sections from patients underwent robot-assisted laparoscopic prostatectomy were prepared. All the prostate WM pathological sections were converted to digital image data and marked with different colors on the basis of the ISUP Gleason grade group.

The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6).

High burdens of phosphorylated tau protein and distinct precuneus atrophy in sporadic early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare devastating subclassification of Alzheimer's disease (AD). EOAD affects individuals <65 years old, and accounts for 5%-10% of all AD cases. Previous studies on EOAD primarily focused on familial forms, whereas research on sporadic EOAD (sEOAD), which represents 85%-90% of EOAD cases, is limited.

PACAP-Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer's disease.

Background: Autophagy is vital in the pathogenesis of neurodegeneration. Thus far, no studies have specifically investigated the relationship between pituitary adenylate cyclase-activating polypeptide (PACAP) and autophagy, particularly in the context of Alzheimer's disease (AD). This study used in vitro and in vivo models, along with clinical samples, to explore interactions between PACAP and autophagy in AD.

Elasticity of the HIV-1 Core Facilitates Nuclear Entry and Infection.

HIV-1 infection requires passage of the viral core through the nuclear pore of the cell, a process that depends on functions of the viral capsid . Recent studies have shown that HIV- 1 cores enter the nucleus prior to capsid disassembly . Interactions with the nuclear pore complex are necessary but not sufficient for nuclear entry, and the mechanism by which the viral core traverses the comparably sized nuclear pore is unknown.

Multidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization.

HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity.

HIV-1 binds dynein directly to hijack microtubule transport machinery.

Viruses exploit host cytoskeletal elements and motor proteins for trafficking through the dense cytoplasm. Yet the molecular mechanism that describes how viruses connect to the motor machinery is unknown. Here, we demonstrate the first example of viral microtubule trafficking from purified components: HIV-1 hijacking microtubule transport machinery.

Glymphatic system impairment in Alzheimer's disease: associations with perivascular space volume and cognitive function.

Objectives: To investigate glymphatic function in Alzheimer's disease (AD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and to explore the associations between DTI-ALPS index and perivascular space (PVS) volume, as well as between DTI-ALPS index and cognitive function.

Methods: Thirty patients with PET-CT-confirmed AD (15 AD dementia; 15 mild cognitive impairment due to AD) and 26 age- and sex-matched cognitively normal controls (NCs) were included in this study. All participants underwent neurological MRI and cognitive assessments.