Fusing a Novel Anti-CTLA-4 Nanobody to the IgG1 Fc Region Strengthens Its Ability to Induce CD8 T Cell-Mediated Immune Responses Against Solid Tumors.

Background: Our previously described a nanobody precisely targeting CTLA-4 and demonstrated that it can promote the antitumor response of adoptive T cells. Here we examined whether fusing it to the IgG1 Fc region would induce stronger, longer-lasting T-cell immune responses after exposure to the dendritic-tumor cell fusions.

Methods: The fusion of nanobody to Fc region was overexpressed in .

A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8 T cells in solid tumours.

Background: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions.

Results: The fusion protein enhanced the response of CD8 T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts.

Mechanical Properties and Thermal Decomposition Mechanism of Glycidyl Azide Polyol Energetic Thermoplastic Elastomer Binder with RDX Composite.

To improve the reinforcement effect between a binder and high solid filler in a propellant formula, grafting the bonding group into the binder to form a neutral polymeric is a practically novel approach to improving the interface properties of the propellant. In this work, a glycidyl azide polyol energetic thermoplastic elastomer binder with a -CN bonding group (GAP-ETPE) was synthesized, and the mechanical and thermal decomposition mechanism of GAP-ETPE with Hexogeon (RDX) model propellants were studied. The stress-strain results indicated that the tensile strength and strain of GAP-ETPE/RDX model propellants were 6.

RACGAP1 knockdown synergizes and enhances the effects of chemotherapeutics on ovarian cancer.

Among the three most prevalent cancers affecting the female reproductive system, ovarian cancer (OV) ranks as the second most frequently diagnosed. It is important to investigate the genomic complexity of OV to develop diagnostic and therapeutic strategies. Through the utilization of bioinformatics analysis, it was determined that RacGTPase Activating Protein 1 (RACGAP1) holds significant significance in the field of OV chemotherapeutics, an aspect that has not been thoroughly explored in prior investigations.

Activation of CRF/CRFR1 Signaling in the Central Nucleus of the Amygdala Contributes to Chronic Stress-Induced Exacerbation of Neuropathic Pain by Enhancing GluN2B-NMDA Receptor-Mediated Synaptic Plasticity in Adult Male Rats.

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related disorders such as depression and post-traumatic stress disorder, represent significant clinical challenges. Previously we have documented that chronic forced swim (FS) stress exacerbates neuropathic pain in spared nerve injury (SNI) rats, associated with an up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (GluN2B-NMDARs) in the central nucleus of the amygdala (CeA). However, the molecular mechanisms underlying chronic FS stress (CFSS)-mediated exacerbation of pain sensitivity in SNI rats still remain unclear.

TRPV4 enhances the synthesis of fatty acids to drive the progression of ovarian cancer through the calcium-mTORC1/SREBP1 signaling pathway.

Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel activated by various stimuli, such as heat. A recent study reported that high expression of TRPV4 predicted a poor prognosis in ovarian cancer patients. This study demonstrated that TRPV4 was highly expressed in ovarian cancer and had the ability to promote proliferation and migration.

Recent advances in flame retardant and mechanical properties of polylactic acid: A review.

The large-scale application of ecofriendly polymeric materials has become a key focus of scientific research with the trend toward sustainable development. Mechanical properties and fire safety are two critical considerations of biopolymers for large-scale applications. Polylactic acid (PLA) is a flammable, melt-drop carrying, and strong but brittle polymer.

Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer.

Purpose: Transglutaminases (TGs) are multifunctional enzymes exhibiting transglutaminase crosslinking, as well as atypical GTPase/ATPase and kinase activities. Here, we used an integrated comprehensive analysis to assess the genomic, transcriptomic and immunological landscapes of TGs across cancers.

Methods: Gene expression and immune cell infiltration patterns across cancers were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Enrichment Analysis (GSEA) datasets.

Deficiency Leads to Motor Impairments and Autism-Like Behaviors via Dysfunction of Cerebellar Purkinje Cells in Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with highly heritable heterogeneity. Mutations of CUB and sushi multiple domains 3 () gene have been reported in individuals with ASD. However, the underlying mechanisms of CSMD3 for the onset of ASD remain unexplored.

CCBE1 promotes mitochondrial fusion by inhibiting the TGFβ-DRP1 axis to prevent the progression of hepatocellular carcinoma.

The extracellular matrix (ECM), as an important component of the tumor microenvironment, exerts various roles in tumor formation. Mitochondrial dynamic disorder is closely implicated in tumorigenesis, including hyperfission in HCC. We aimed to determine the influence of the ECM-related protein CCBE1 on mitochondrial dynamics in HCC.

Sodium alginate and Chitosan aided design of form-stable Polyrotaxane based phase change materials with ultra-high latent heat.

We prepared a series of highly porous Polyrotaxane/sodium alginate, and Polyrotaxane/Chitosan foam alloys according to a sustainable pathway by using water as the only solvent. The foam alloys were further used as supporter materials for poly (ethylene glycol) (PEG) encapsulation, to fabricate shape-stable bio-based phase change materials (PCMs). The pore morphology and the internal interface between PEG and foam alloys were characterized by scanning electron microscope (SEM).

Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain.

Bone cancer pain is a common symptom in cancer patients with bone metastases and its underlying mechanisms remain unknown. Here, we report that Runx1 directly upregulates the transcriptional activity of P2X3 receptor (P2X3R) gene promoter in PC12 cells. Knocking down Runx1 in dorsal root ganglion (DRG) neurons suppresses the functional upregulation of P2X3R, attenuates neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats, whereas overexpressing Runx1 promotes P2X3R gene transcription in DRG neurons, induces neuronal hyperexcitability and pain hypersensitivity in naïve rats.

Influence of Nutritional Status on Prognosis of Stroke Patients With Dysphagia.

Context: Stroke is an acute cerebrovascular disease and a neurological disorder that occurs due to a cerebral arterial embolism and rupture. Acute stroke is often accompanied by dysphagia, which reduces patients' intake of food and nutrients, decreases their nutritional status, and affects their quality of life.

Objective: The study intended to identify the demographic and clinical characteristics of stroke patients with dysphagia and to explore the relationship of those characteristics to nutritional status and prognosis.

Soil texture is an important factor determining how microplastics affect soil hydraulic characteristics.

Microplastic pollution and changes to soil hydraulic characteristics affect the physical properties and functions of soil; however, knowledge remains limited on how microplastics influence soil hydraulic properties. Nonetheless, it is important to understand these relationships to maintain soil health and ensure sustainable land use, especially in the current "plastic age." This case study explored how different particle sizes (20, 200, and 500 μm) and concentrations (up to 6%) of polypropylene microplastics affect the hydraulic properties of three soil textures (loam, clay, and sand).

Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein.

Melanin concentrating hormone (MCH), an orexigenic neuropeptide, is primarily secreted by the hypothalamus and acts on its receptor, the melanin-concentrating hormone receptor 1 (MCHR1), to regulate appetite and energy homeostasis. The Melanocortin Receptor Accessory Protein 2 (MRAP2), a small single transmembrane protein broadly expressed in multiple tissues, has been defined as a vital endocrine modulator of five melanocortin receptors (MC1R-MC5R) and several other GPCRs in the regulation of central neuronal activities and peripheral energy balance. Here, we demonstrated the interaction between MRAP2 and MCHR1 by immunoprecipitation and bimolecular fluorescent assay and found that MRAP2 could inhibit MCHR1 signaling .

A low amino acid environment promotes cell macropinocytosis through the YY1-FGD6 axis in Ras-mutant pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), cancer with a high mortality rate and the highest rate of KRAS mutation, reportedly internalizes proteins via macropinocytosis to adapt to low amino acid levels in the tumor microenvironment. Here, we aimed to identify a key regulator of macropinocytosis for the survival of tumor cells in a low amino acid environment in PDAC. FYVE, RhoGEF, and PH domain-containing protein 6 (FGD6) were identified as key regulators of macropinocytosis.

Transcranial Magnetic Stimulation Alleviates Levodopa-Induced Dyskinesia in Parkinson's Disease and the Related Mechanisms: A Mini-Review.

After long-term use of levodopa, Parkinson's patients almost inevitably develop dyskinesia, a kind of drug side effect manifesting as uncontrollable choreic movements and dystonia, which could be crippling yet have limited therapeutic options. Transcranial magnetic stimulation is the most widely studied non-invasive neuromodulation technology to treat levodopa-induced dyskinesia. Many studies have shown that transcranial magnetic stimulation has beneficial effects on levodopa-induced dyskinesia and is patient-tolerable, barely with reported adverse effects.

Effect of p18 on endothelial barrier function by mediating vascular endothelial Rab11a-VE-cadherin recycling.

Endothelial barrier integrity requires recycling of VE-cadherin to adherens junctions. Both p18 and Rab11a play significant roles in VE-cadherin recycling. However, the underlying mechanism and the role of p18 in activating Rab11a have yet to be elucidated.

Overexpression of ARHGAP30 suppresses growth of cervical cancer cells by downregulating ribosome biogenesis.

We aimed to identify whether Rho GTPase activating proteins (RhoGAPs) were downregulated in cervical cancers and might be targeted to reduce the growth of cervical cancer using the GEO database and immunohistochemical analysis to identified changes in transcription and protein levels. We analyzed their proliferation, clone formation ability, and their growth as subcutaneous tumors in mice. To detect ARHGAP30 localization in cells, immunofluorescence assays were conducted.

[Effect of PADI4 on the Expression of Inflammatory Cytokines During NB4 Cells Differentiation].

Objective: To investigate the expression of peptidylarginine deiminase 4 (PADI4) during the process of differentiation into granulocyte of NB4 cells induced by all-trans-retinoic acid (ATRA) and whether PADI4 is involved in the inflammatory cytokines expression.

Methods: Granulocyte differentiation model of NB4 cells induced by ATRA was established. The cell morphology changes were observed by Wright-Giemsa staining.