Polymeric nanocarrier via metabolism regulation mediates immunogenic cell death with spatiotemporal orchestration for cancer immunotherapy.

The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis.

Role of auxin and gibberellin under low light in enhancing saffron corm starch degradation during sprouting.

The mechanisms by which low light accelerates starch macromolecules degradation by auxin and gibberellin (GA) in geophytes during sprouting remain largely unknown. This study investigated these mechanisms in saffron, grown under low light (50 μmol m s) and optimal light (200 μmol m s) during the sprouting phase. Low light reduced starch concentration in corms by 34.

The relationship between school bullying victimization and social mindfulness in middle school students: a chain mediating model of self-concept clarity and cognition reappraisal.

Objective: To determine the relationship between school bullying victimization and social mindfulness and its mechanism in light of the interdependence and schema theories.

Method: The Chinese version of the Delaware Bullying Victimization Scale-student, Emotion Regulation Questionnaire, Self-Concept Clarity Scale and The Social Mindfulness Self-report Scale (SMSRS) were distributed to 553 middle school students.

Results: (1) The correlations of school bullying victimization with social mindfulness, self-concept clarity, and cognition reappraisal were statistically significant.

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment.

The progression of cancer involves mutations in normal cells, leading to uncontrolled division and tissue destruction, highlighting the complexity of tumor microenvironments (TMEs). Immunotherapy has emerged as a transformative approach, yet the balance between efficacy and safety remains a challenge. Nanoparticles such as polymersomes offer the possibility to precisely target tumors, deliver drugs in a controlled way, effectively modulate the antitumor immunity, and notably reduce side effects.

A polymeric nanoplatform enhances the cGAS-STING pathway in macrophages to potentiate phagocytosis for cancer immunotherapy.

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2', 3'-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression.

RPLP1 restricts HIV-1 transcription by disrupting C/EBPβ binding to the LTR.

Long-term non-progressors (LTNPs) of HIV-1 infection may provide important insights into mechanisms involved in viral control and pathogenesis. Here, our results suggest that the ribosomal protein lateral stalk subunit P1 (RPLP1) is expressed at higher levels in LTNPs compared to regular progressors (RPs). Functionally, RPLP1 inhibits transcription of clade B HIV-1 strains by occupying the C/EBPβ binding sites in the viral long terminal repeat (LTR).

Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years.

A Triple-Responsive Polymeric Prodrug Nanoplatform with Extracellular ROS Consumption and Intracellular HO Self-Generation for Imaging-Guided Tumor Chemo-Ferroptosis-Immunotherapy.

High reactive oxygen species (ROS) levels in tumor microenvironment (TME) impair both immunogenic cell death (ICD) efficacy and T cell activity. Furthermore, tumor escapes immunosurveillance via programmed death-1/programmed death ligand-1 (PD-L1) signal, and the insufficient intracellular hydrogen peroxide weakens ferroptosis efficacy. To tackle the above issues, a glutathione (GSH)/ROS/pH triple-responsive prodrug nanomedicine that encapsulates FeO nanoparticle via electrostatic interaction is constructed for magnetic resonance imaging (MRI)-guided multi-mode theranostics with chemotherapy/ferroptosis/immunotherapy.

Cell Death Pathway Regulation by Functional Nanomedicines for Robust Antitumor Immunity.

Cancer immunotherapy has become a mainstream cancer treatment over traditional therapeutic modes. Cancer cells can undergo programmed cell death including ferroptosis, pyroptosis, autophagy, necroptosis, apoptosis and cuproptosis which are find to have intrinsic relationships with host antitumor immune response. However, direct use of cell death inducers or regulators may bring about severe side effects that can also be rapidly excreted and degraded with low therapeutic efficacy.

Nanotechnology-Assisted Immunogenic Cell Death for Effective Cancer Immunotherapy.

Tumor vaccines have been used to treat cancer. How to efficiently induce tumor-associated antigens (TAAs) secretion with host immune system activation is a key issue in achieving high antitumor immunity. Immunogenic cell death (ICD) is a process in which tumor cells upon an external stimulus change from non-immunogenic to immunogenic, leading to enhanced antitumor immune responses.

Carbapenem-resistant gram-negative bacterial prevention practice in nosocomial infection and molecular epidemiological characteristics in a pediatric intensive care unit.

Introduction: The increasing prevalence of carbapenem-resistant gram-negative bacilli infection has emerged as a substantial threat to human health.

Methodology: In January 2017, a screening program for carbapenem-resistant gram-negative bacilli colonization was performed in a pediatric intensive care unit (PICU). Subsequently, different strategies for carbapenem-resistant gram-negative bacilli cohorting and patient placements were introduced in January 2018.

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers.

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug.

Active constituents of saffron ( L.) and their prospects in treating neurodegenerative diseases (Review).

L. (saffron) is widely used as a traditional spice for flavoring, coloring and medicinal purposes. As a traditional Chinese herb, saffron promotes blood circulation, removes blood stasis, cools and detoxifies the blood, relieves depression and calms the mind.

Transformable prodrug nanoplatform tumor microenvironment modulation and immune checkpoint blockade potentiates immunogenic cell death mediated cancer immunotherapy.

Chemoimmunotherapy is a promising approach in cancer immunotherapy. However, its therapeutic efficacy is restricted by high reactive oxygen species (ROS) levels, an abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME) as well as immune checkpoints for escaping immunosurveillance. Herein, a new type of TME and reduction dual-responsive polymersomal prodrug (TRPP) nanoplatform was constructed when the D-peptide antagonist (PPA-1) of programmed death ligand-1 was conjugated onto the surface, and talabostat mesylate (Tab, a fibroblast activation protein inhibitor) was encapsulated in the watery core (PPA-TRPP/Tab).

Recent Progress in Multiple Sclerosis Treatment Using Immune Cells as Targets.

Multiple sclerosis (MS) is an autoimmune-mediated demyelinating disease of the central nervous system. The main pathological features are inflammatory reaction, demyelination, axonal disintegration, reactive gliosis, etc. The etiology and pathogenesis of the disease have not been clarified.

Nanoparticle-Mediated STING Activation for Cancer Immunotherapy.

As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway has attracted much attention because of the secretion of various proinflammatory cytokines and chemokines. Many STING agonists have been identified and applied into preclinical or clinical trials for cancer immunotherapy.

Application of 3D reconstruction technology based on an improved MC algorithm in a shotcreting robot.

A shotcreting robot needs to reconstruct the arch surface in three dimensions (3D) during the process of spraying a tunnel. To solve this problem, we propose an improved marching cube (MC) reconstruction method based on a point cloud splice and normal re-orient. First, we use the explosion-proof LIDAR to acquire the point cloud data of the tunnel arch, followed by the use of the iterative closest point algorithm, a PassThrough filter, and a StatisticalOutlierRemoval filter for point cloud splicing, data segmentation, and simplification, respectively.

Improved A* Path Planning Method Based on the Grid Map.

In obstacle spatial path planning, the traditional A* algorithm has the problem of too many turning points and slow search speed. With this in mind, a path planning method that improves the A* (A-Star) algorithm is proposed. The mobile robot platform was equipped with a lidar and inertial measurement unit (IMU).

A Novel Chemical-Electrochemical Hydrogen Production from Coal Slurry by a Two-Step Process: Oxidation of Coal by Ferric Ions and Electroreduction of Hydrogen Ions.

Hydrogen production from the electrolysis of coal slurry is a promising approach under the condition of low voltage (0.8-1.2 V) and medium temperature.

Hybrid-Membrane-Decorated Prussian Blue for Effective Cancer Immunotherapy via Tumor-Associated Macrophages Polarization and Hypoxia Relief.

Both tumor-associated macrophages (TAMs) and hypoxia condition severely restrict the antitumor potency during cancer immunotherapy. It is essential to overcome the two issues for improving therapeutic efficacy. In this study, a hollow mesoporous Prussian blue (HMPB) nanosystem with mannose decoration and hydroxychloroquine (HCQ) adsorption is built, to form Man-HMPB/HCQ.

Oral insulin delivery by epithelium microenvironment-adaptive nanoparticles.

Oral protein drug delivery using nano-based systems remains challenging, as contradictory surface properties are required for efficient navigation through the intestinal mucus and epithelium barriers. Therefore, new nanoplatforms with tunable surface properties in vivo are urgently needed. Inspired by the slightly acidic microclimate of the jejunal epithelial surface, we report a novel epithelium microenvironment-adaptive nanoplatform that undergoes a hydrophilicity-hydrophobicity transition at the epithelial surface.

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy.

Although Fraxinellone (Frax) isolated from L. possessed excellent anti-hepatic fibrosis activity, oral administration of Frax suffered from the inefficient therapeutic outcome due to negligible oral absorption. At present, the oral formulation of Frax is rarely exploited.

Photodynamic-Chemodynamic Cascade Reactions for Efficient Drug Delivery and Enhanced Combination Therapy.

Nanomedicines with photodynamic therapy and reactive oxygen species (ROS)-triggered drug release capabilities are promising for cancer therapy. However, most of the nanomedicines based on ROS-responsive nanocarriers still suffer from serious ROS consumption during the triggered drug release process. Herein, a photodynamic-chemodynamic cascade strategy for the design of drug delivery nanosystem is proposed.

Size-transformable antigen-presenting cell-mimicking nanovesicles potentiate effective cancer immunotherapy.

Artificial antigen-presenting cells (aAPCs) can stimulate CD8 T cell activation. While nanosized aAPCs (naAPCs) have a better safety profile than microsized (maAPCs), they generally induce a weaker T cell response. Treatment with aAPCs alone is insufficient due to the lack of autologous antigen-specific CD8 T cells.