Immunogenic cuproptosis in cancer immunotherapy via an in situ cuproptosis-inducing system.

Cell death-based therapies combined with immunotherapy have great potential in cancer therapy. To further explore and apply the combined therapies, the immunogenicity of different cell death modes in colorectal cancer (CRC) was evaluated by a cause-and-effect framework encompassing 12 cell death modes. Results show robust correlations among cuproptosis, immunogenic cell death (ICD) and immunity in CRC, as observed in our in-house and other independent cohorts, which are substantiated by in vitro and in vivo experiments.

Peptide-conjugated alginate fiber: A skeletal muscle regenerative scaffold.

Biopolymeric fibers have garnered significant attention in biomedical applications due to their ability to promote tissue regeneration through aligned microstructures. Alginate (Alg) is commonly used to prepare wet-spun fibers through ionic interactions. However, ion-crosslinked Alg fibers present limitations in tissue regeneration due to their rapid degradation under physiological conditions and the absence of binding sites for bioactive molecules.

The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells.

The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that HNRNPU depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size.

BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation.

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells).

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC.

Single-Cell Analysis Reveals Cxcl14 Fibroblast Accumulation in Regenerating Diabetic Wounds Treated by Hydrogel-Delivering Carbon Monoxide.

Nonhealing skin wounds are a problematic complication associated with diabetes. Therapeutic gases delivered by biomaterials have demonstrated powerful wound healing capabilities. However, the cellular responses and heterogeneity in the skin regeneration process after gas therapy remain elusive.

Advances in the use of local anesthetic extended-release systems in pain management.

Pain management remains among the most common and largely unmet clinical problems today. Local anesthetics play an indispensable role in pain management. The main limitation of traditional local anesthetics is the limited duration of a single injection.

Disruption of neuronal RHEB signaling impairs oligodendrocyte differentiation and myelination through mTORC1-DLK1 axis.

How neuronal signaling affects brain myelination remains poorly understood. We show dysregulated neuronal RHEB-mTORC1-DLK1 axis impairs brain myelination. Neuronal Rheb cKO impairs oligodendrocyte differentiation/myelination, with activated neuronal expression of the imprinted gene Dlk1.

Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner.

Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using oncogenic transgenes and discovered transformed cell lines compatible with reprogramming when transfected with Oct4/Sox2/Klf4/Myc.

Photoinhibiting via simultaneous photoabsorption and free-radical reaction for high-fidelity light-based bioprinting.

Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys.

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold . Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation.

Antagonizing apolipoprotein J chaperone promotes proteasomal degradation of mTOR and relieves hepatic lipid deposition.

Background And Aims: Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis.

Locally controlled release of immunosuppressive promotes survival of transplanted adult spinal cord tissue.

Transplantation of adult spinal cord tissue (aSCT) is a promising treatment for spinal cord injury (SCI) basing on various types of neural cells and matrix components inside aSCT. However, long-term systemic administration of immunosuppressors (e.g.

The homeodomain of Oct4 is a dimeric binder of methylated CpG elements.

Oct4 is essential to maintain pluripotency and has a pivotal role in establishing the germline. Its DNA-binding POU domain was recently found to bind motifs with methylated CpG elements normally associated with epigenetic silencing. However, the mode of binding and the consequences of this capability has remained unclear.

Assessment of ELISA-based method for the routine examination of serum indoxyl sulfate in patients with chronic kidney disease.

Introduction: Indoxyl sulfate (IS), a protein-bound uremic toxin, is associated with kidney function and chronic kidney disease (CKD)-related complications. Currently, serum IS levels are primarily quantified using mass spectrometry-based methods, which are not feasible for routine clinical examinations.

Methods: The efficiencies of three commercial ELISA kits in determination of serum IS were validated by comparing with ultra-performance liquid chromatography (UPLC)-MS/MS-based method using Bland-Altman analysis.

Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state.

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity.

Discovery of Novel 7-Azaindole Derivatives as Selective Covalent Fibroblast Growth Factor Receptor 4 Inhibitors for the Treatment of Hepatocellular Carcinoma.

Fibroblast growth factor receptor 4 (FGFR4) has been identified as a potential target for the treatment of hepatocellular carcinoma (HCC) with aberrant FGFR4 signaling because of its important role in HCC progression and development. Several FGFR4 inhibitors are under clinical development. Using a 7-azaindole scaffold, we discovered a series of novel selective and covalent FGFR4 inhibitors by performing a structure-based design approach.

Metal-organic framework-based hydrogel with structurally dynamic properties as a stimuli-responsive localized drug delivery system for cancer therapy.

Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials, the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.

In situ injectable hydrogel-loaded drugs induce anti-tumor immune responses in melanoma immunochemotherapy.

Melanoma is a highly aggressive tumor located in the skin, with limited traditional therapies. In order to reduce the side effects caused by traditional administration method and amplify the killing effect of immune system against tumor cells, an in situ injectable hydrogel drug delivery system is developed for the first time which co-delivers doxorubicin (Dox) and imiquimod (R837) for the synergistic therapy of melanoma. The mechanical properties and stability of the hydrogel are characterized and the optimal doses of hydrogel and drugs are also identified.

Flexible conductive silk-PPy hydrogel toward wearable electronic strain sensors.

Conductive hydrogels have been studied as promising materials for the flexible and wearable bioelectronics, because of their unique electrical and mechanical properties. Addition of conducting polymers in biomaterial-based hydrogel matrix is a simple yet effective way to construct hydrogels with good conductivity and flexibility. In this work, a conductive hydrogel composed by a silk hydrogel and a conducting polymer, polypyrrole (PPy), is developed viapolymerization of pyrrole into the silk fibroin network.

Flexible conductive silk-PPy hydrogel toward wearable electronic strain sensors.

Conductive hydrogels have been studied as promising materials for the flexible and wearable bioelectronics, because of their unique electrical and mechanical properties. Addition of conducting polymers in biomaterial-based hydrogel matrix is a simple yet effective way to construct hydrogels with good conductivity and flexibility. In this work, a conductive hydrogel composed by a silk hydrogel and a conducting polymer, polypyrrole (PPy), is developed via in-situ polymerization of pyrrole into the silk fibroin network.

Bioinspired bimodal micro-nanofibrous scaffolds promote the tenogenic differentiation of tendon stem/progenitor cells for achilles tendon regeneration.

Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties.

Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells.

Transposable elements (TEs) occupy nearly 40% of mammalian genomes and, whilst most are fragmentary and no longer capable of transposition, they can nevertheless contribute to cell function. TEs within genes transcribed by RNA polymerase II can be copied as parts of primary transcripts; however, their full contribution to mature transcript sequences remains unresolved. Here, using long and short read (LR and SR) RNA sequencing data, we show that 26% of coding and 65% of noncoding transcripts in human pluripotent stem cells (hPSCs) contain TE-derived sequences.

An NT-3-releasing bioscaffold supports the formation of -modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury.

The mechanism underlying neurogenesis during embryonic spinal cord development involves a specific ligand/receptor interaction, which may be help guide neuroengineering to boost stem cell-based neural regeneration for the structural and functional repair of spinal cord injury. Herein, we hypothesized that supplying spinal cord defects with an exogenous neural network in the NT-3/fibroin-coated gelatin sponge (NF-GS) scaffold might improve tissue repair efficacy. To test this, we engineered -modified neural stem cell (NSC)-derived neural network tissue with robust viability within an NF-GS scaffold.