Pegylated NIR Fluorophore-Conjugated OBHSA Prodrug for ERα-Targeted Theranostics with Enhanced Imaging and Long-Term Retention.

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system's applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach.

MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity.

HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.

HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.

Characteristics of the First Italian Older Adults Vaccinated with an Adjuvanted Respiratory Syncytial Virus (RSV) Vaccine.

: Three respiratory syncytial virus (RSV) vaccines have been recently made available for older adults. Understanding the principal characteristics of the first vaccine-takers can pave the way for a successful vaccination campaign. The objective of this study was to explore the sociodemographic and clinical characteristics of the first Italian users of an adjuvanted RSV vaccine and their attitudes towards RSV and vaccination.

Reduced Presence of SARS-CoV-2 microRNA-like Small RNA in the Serum of Patients with Post-Acute Sequelae SARS-CoV-2 Infection.

The mechanisms underlying post-acute sequelae of SARS-CoV-2 infection (PASC) are a topic of debate. This study examined the presence of SARS-CoV-2 microRNA (miRNA)-like small RNAs in extracellular fluids and their potential link to PASC by using a quantitative stem-loop RT-PCR MiRNA assay. Initially, it was demonstrated that three previously identified SARS-CoV-2 miRNA-like small RNAs, specifically svRNA 1 and 2 and miR-07a, were significantly expressed in infected cells in vitro and released into the supernatant following infection by different SARS-CoV-2 variants.

Studying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .

Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.

HERVs Endophenotype in Autism Spectrum Disorder: Human Endogenous Retroviruses, Specific Immunoreactivity, and Disease Association in Different Family Members.

Increasing evidence indicates that human endogenous retroviruses (HERVs) are important to human health and are an underexplored component of many diseases. Certain HERV families show unique expression patterns and immune responses in autism spectrum disorder (ASD) patients compared to healthy controls, suggesting their potential as biomarkers. Despite these interesting findings, the role of HERVs in ASD needs to be further investigated.

22q11.21 Deletions: A Review on the Interval Mediated by Low-Copy Repeats C and D.

22q11.2 is a region prone to chromosomal rearrangements due to the presence of eight large blocks of low-copy repeats (LCR22s). The 3 Mb 22q11.

Intrathecal Immunoglobulin A Synthesis in Multiple Sclerosis: From Biological Aspects to Clinical Relevance.

Intrathecal immunoglobulin A (IgA) synthesis in multiple sclerosis (MS) has long earned little attention, despite a potential significance in disease pathogenesis and prognosis. The presence of IgA-positive plasma cells in MS lesions and along damaged axons suggests a role in disease pathogenesis. Available clinical evidence about a potential positive or negative prognostic role is scarce and inconclusive.

Comprehensive Analysis of TSPAN32 Regulatory Networks and Their Role in Immune Cell Biology.

Tetraspanin 32 (TSPAN32), a member of the tetraspanin superfamily, is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of chromosome 11p15.5, a critical tumor-suppressor gene region. Although the biology of TSPAN32 remains largely unexplored, accumulating evidence suggests its involvement in hematopoietic functions.

The Passage of Chaperonins to Extracellular Locations in Requires a Functional Dot/Icm System.

HtpB, the chaperonin of the bacterial pathogen , is found in extracellular locations, even the cytoplasm of host cells. Although chaperonins have an essential cytoplasmic function in protein folding, HtpB exits the cytoplasm to perform extracellular virulence-related functions that support 's lifestyle. The mechanism by which HtpB reaches extracellular locations is not currently understood.

The Appearance of Antiphage Antibodies in Sera of Patients Treated with Phages.

: Bacteriophages are neutralized by the sera of patients undergoing phage therapy (PT), particularly during local or concomitant local and oral phage administration in bone infections, soft tissue infections, or upper respiratory tract infections. The antiphage activity of the sera (AAS) level of 27 patients with bacterial infections such as bone infections, soft tissue infections, or upper respiratory tract infections undergoing PT was performed using the plate phage neutralization test. Our preliminary results suggest that high levels of antiphage antibodies appear late in the treatment period, at the earliest in the 3rd-8th week of PT.

Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death.

Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated.

Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry.

MicroRNAs Expression Profile in MN1-Altered Astroblastoma.

Background/objectives: Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 () gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes.

Neuroprotective Effect of the Combination of Citicoline and CoQ10 in a Mouse Model of Ocular Hypertension.

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs), with intraocular pressure (IOP) being its primary risk factor. Despite controlling IOP, the neurodegenerative process often continues. Therefore, substances with neuroprotective, antioxidant, and anti-inflammatory properties could protect against RGC death.

Swimmer's Shoulder: Ultrasound Anatomical Description of Shoulder Tendons in Elite Swimmers and Water Polo Players.

This study aimed to examine the differences in shoulder ultrasonographic parameters between overhead aquatic athletes and their relationship with shoulder pain. Sixty-four healthy junior subjects ( = 128 shoulders) participated in the study, including 17 healthy controls, 25 elite junior swimmers, and 22 elite junior water polo players. An ultrasonographic study of the shoulder was carried out to measure the thickness of the rotator cuff structures in sex- and age-paired groups.

LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells.

Background: The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved.

Automated AI-based image analysis for quantification and prediction of interstitial lung disease in systemic sclerosis patients.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapidly evolving interstitial lung disease (ILD), driving its mortality. Specific imaging-based biomarkers associated with the evolution of lung disease are needed to help predict and quantify ILD.

Methods: We evaluated the potential of an automated ILD quantification system (icolung) from chest CT scans, to help in quantification and prediction of ILD progression in SSc-ILD.

Targeting NF-kappaB-inducing kinase shapes B-cell homeostasis in myasthenia gravis.

Background: B cell immune dysregulation plays a critical role in myasthenia gravis (MG). However, targeted B-cell therapy such as rituximab may result in long-term peripheral B cell clearance and allow for the survival of plasma cells, contributing to frequent infections and relapses. Therefore, we aimed to identify potential novel therapeutic targets that preserve part of B cell function while inhibiting antibody-secreting cells (ASCs).

Study on the response mechanism of MicroRNA novel-13 and novel-44 to Vibrio parahaemolyticus infection in Pinctada fucata martensii.

Pinctada fucata martensii (P. f. martensii) is one of the main pearl oysters cultured in artificial seawater in China.

Glucocorticoids on bone remodeling in systemic lupus erythematosus mice.

Background: Systemic lupus erythematosus requires glucocorticoids for management. This study investigates how glucocorticoids influence bone in a SLE mouse model, focusing on bone mineral density (BMD), microstructure, and remodeling markers.

Methods: MRL/lpr and C57BL/6 mice were administered dexamethasone or saline as a control for 4-weeks.

Specific types of male infertility are correlated with T cell exhaustion or senescence signatures.

The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men.

A quasi-experimental study of general practices' referral to mammography in the post-trials treatment era.

Background: Improvements in breast cancer therapy since the randomized controlled trials of mammography screening might have reduced the screening benefit. Most observational studies of mammography effectiveness would be confounded by these improvements and other factors. Using a design resistant to this confounding, we evaluated whether mammography in asymptomatic women reduces breast cancer mortality during the treatment era succeeding the trials.

Low regulatory T-cells frequency is associated with graft rejection after small bowel transplantation: Clinical and experimental evidence.

Background: Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.