Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold.

Schnurri-3 inhibition rescues skeletal fragility and vascular skeletal stem cell niche pathology in the OIM model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis.

Tumor-Associated Myeloid Cells Selective Delivery of a Therapeutic Tumor Nano-Vaccine for Overcoming Immune Barriers for Effective and Long-Term Cancer Immunotherapy.

Therapeutic cancer vaccines have the potential to induce regression of established tumors, eradicate microscopic residual lesions, and prevent metastasis and recurrence, but their efficacy is limited by the low antigenicity of soluble antigens and the immunosuppressive tumor-associated macrophages (TAMs) that promote tumor growth. In this study, a novel strategy is reported for overcoming these defenses: a dual-targeting nano-vaccine (NV) based on hepatitis B core antigen (HBcAg) derived virus-like particles (VLPs), N-M2T-gp100 HBc NV, equipped with both SIGNR dendritic cells (DCs)/TAMs-targeting ability and high-density display of tumor-associated antigen (TAA). N-M2T-gp100 HBc NVs-based immunotherapy has demonstrated an optimal interaction between tumor-associated antigens (TAAs) and the immune composition of the tumor microenvironment.

Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis.

Objectives: (1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls.

Methods: This cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded.

Establishing a carcinoembryonic antigen-associated competitive endogenous RNA network and forecasting an important regulatory axis in colon adenocarcinoma patients.

Background: Colorectal cancer is one of the top five malignant tumors in the world in terms of morbidity and mortality. Numerous long non-coding RNAs (lncRNAs) are specifically expressed in tumours and can affect various types of human cancer by participating in competitive endogenous RNA (ceRNA) regulatory networks. However, the specific mechanisms and complex networks of ceRNA regulatory patterns in colon adenocarcinoma (COAD) remain unclear.

Nomogram for Predicting Postoperative Pulmonary Metastasis in Hepatocellular Carcinoma Based on Inflammatory Markers.

Background: Uncertainty surrounds the usefulness of inflammatory markers in hepatocellular carcinoma (HCC) patients for predicting postoperative pulmonary metastasis (PM). The purpose of this study was to assess the predictive value of inflammatory markers as well as to create a new nomogram model for predicting PM.

Methods: Cox regression was utilized to identify independent prognostic variables and to create a nomogram that predicted PM for comparison with a validation cohort and other prediction systems.

SHP-1 Regulates CD8+ T Cell Effector Function but Plays a Subtle Role with SHP-2 in T Cell Exhaustion Due to a Stage-Specific Nonredundant Functional Relay.

SHP-1 (Src homology region 2 domain-containing phosphatase 1) is a well-known negative regulator of T cells, whereas its close homolog SHP-2 is the long-recognized main signaling mediator of the PD-1 inhibitory pathway. However, recent studies have challenged the requirement of SHP-2 in PD-1 signaling, and follow-up studies further questioned the alternative idea that SHP-1 may replace SHP-2 in its absence. In this study, we systematically investigate the role of SHP-1 alone or jointly with SHP-2 in CD8+ T cells in a series of gene knockout mice.

Hyaluronic Acid-Based Reactive Oxygen Species-Responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing.

Diabetic wounds are more likely to develop into complex and severe chronic wounds. The objective of this study is to develop and assess a reactive oxygen species (ROS)-responsive multifunctional injectable hydrogel for the purpose of diabetic wound healing. A multifunctional hydrogel (HA@Cur@Ag) is successfully synthesized with dual antioxidant, antibacterial, and anti-inflammatory properties by crosslinking thiol hyaluronic acid (SH-HA) and disulfide-bonded hyperbranched polyethylene glycol (HB-PBHE) through Michael addition; while, incorporating curcumin liposomes and silver nanoparticles (AgNPs).

Schnurri-3 inhibition rescues skeletal fragility and vascular skeletal stem cell niche pathology in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis.

Microglia dysfunction drives disrupted hippocampal amplitude of low frequency after acute kidney injury.

Aims: Acute kidney injury (AKI) has been associated with a variety of neurological problems, while the neurobiological mechanism remains unclear. In the present study, we utilized resting-state functional magnetic resonance imaging (rs-fMRI) to detect brain injury at an early stage and investigated the impact of microglia on the neuropathological mechanism of AKI.

Methods: Rs-fMRI data were collected from AKI rats and the control group with a 9.

High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma.

Background: To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD.

Objective: In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation.

Binary classification of non-specific low back pain condition based on the combination of B-mode ultrasound and shear wave elastography at multiple sites.

Low back pain (LBP) is a prevalent and complex condition that poses significant medical, social, and economic burdens worldwide. The accurate and timely assessment and diagnosis of LBP, particularly non-specific LBP (NSLBP), are crucial to developing effective interventions and treatments for LBP patients. In this study, we aimed to investigate the potential of combining B-mode ultrasound image features with shear wave elastography (SWE) features to improve the classification of NSLBP patients.

Tumor-Derived PD-L1 Exosomes with Natural Inflammation Tropism for Psoriasis-Targeted Treatment.

Psoriasis is a chronic inflammatory disease whose etiology is directly related to the dysregulation of cutaneous immune homeostasis. However, how to finely modulate the skin immune microenvironment to restore homeostasis remains an important challenge. Inspired by the natural attribute of tumor exosomes in the immune escape, the tumor-derived exosomes as an active targeting nanoplatform for the effective treatment of inflammatory skin disorder were first reported.

Protective effects of histone deacetylase 6 specific inhibitor tubastatin A on subarachnoid hemorrhage in rats and the underlying mechanisms.

Objectives: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases.

Themis suppresses the effector function of CD8 T cells in acute viral infection.

CD8 T cells play a central role in antiviral immune responses. Upon infection, naive CD8 T cells differentiate into effector cells to eliminate virus-infected cells, and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved. Although extensively investigated, the underlying mechanisms of CD8 T-cell differentiation remain incompletely understood.

A nanoformulation for immunosuppression reversal and broad-spectrum self-amplifying antitumor ferroptosis-immunotherapy.

The efficacy of immunotherapy combined with other therapeutic modalities in the management of cancer has been extensively studied. However, no effective strategy to improve the antitumor effects of immunotherapy at the tumor site has been developed. In this study, we describe a nanoformulation (CP) that integrates ferroptosis-inducing cannabinoid nanoparticles with immunostimulatory Poly(I:C) to enhance antitumor immune responses by activating ferroptosis-immunotherapy pathways.

UBIAD1 protects against oxygen-glucose deprivation/reoxygenation injury via nNOS/NO pathway.

Objectives: Cerebral infarction is a subtype of stroke with high incidence and disability rate. Ischemia reperfusion injury (IRI) is the key point of cerebral infarction treatment. UbiA prenyltransferase domain containing 1 (UBIAD1) is a kind of enzyme with various biological functions including electron transport in mitochondrial respiratory chain, lipid metabolism, and oxidative stress which are related to IRI.

Themis is indispensable for IL-2 and IL-15 signaling in T cells.

To perform their antiviral and antitumor functions, T cells must integrate signals both from the T cell receptor (TCR), which instruct the cell to remain quiescent or become activated, and from cytokines that guide cellular proliferation and differentiation. In mature CD8 T cells, Themis has been implicated in integrating TCR and cytokine signals. We investigated whether Themis plays a direct role in cytokine signaling in mature T cells.

Glycogen synthase kinase 3 drives thymocyte egress by suppressing β-catenin activation of Akt.

Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell–specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, β-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P expression, thereby preventing emigration of thymocytes.

Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury.

Radiation-induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic cancer radiotherapy. However, effective therapeutic agents for this condition are limited. Here, we describe a novel strategy to exert additive effects of a non-erythropoietic EPO derivative (ARA290), along with a free radical scavenger, superoxide dismutase (SOD), using a bioengineered nanoreactor (SOD@ARA290-HBc).

In Situ biomimetic Nanoformulation for metastatic cancer immunotherapy.

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1).

Tubule-specific protein nanocages potentiate targeted renal fibrosis therapy.

Background: Despite the dramatic advances in modern medicine, efficient therapeutic measures for renal fibrosis remain limited. Celastrol (CLT) is effective in treating renal fibrosis in rat models, while causing severe systemic toxicity. Thus, we designed a tubule-specific nanocage (K3-HBc NCs) that effectively deliver CLT to tubular epithelial cell in a virus-like manner.

Berberine Prolongs Mouse Heart Allograft Survival by Activating T Cell Apoptosis the Mitochondrial Pathway.

Berberine, which is a traditional Chinese medicine can inhibit tumorigenesis by inducing tumor cell apoptosis. However, the immunoregulatory of effects berberine on T cells remains poorly understood. Here, we first examined whether berberine can prolong allograft survival by regulating the recruitment and function of T cells.

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study.

The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal-fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion.

Genomic Mutations of Primary and Metastatic Lung Adenocarcinoma in Chinese Patients.

Lung cancer is still the leading cause of cancer-related death worldwide. Of lung cancer, lung adenocarcinoma (LUAD) is the most common subtype. Most patients with LUAD would develop into metastasis, which limits the available treatment.