Hybrid Membrane Biomimetic Photothermal Nanorobots for Enhanced Chemodynamic-Chemotherapy-Immunotherapy.

Glioblastoma multiforme (GBM) is a highly invasive and fatal brain tumor with a grim prognosis, where current treatment modalities, including postoperative radiotherapy and temozolomide chemotherapy, yield a median survival of only 15 months. The challenges of tumor heterogeneity, drug resistance, and the blood-brain barrier necessitate innovative therapeutic approaches. This study introduces a strategy employing biomimetic magnetic nanorobots encapsulated with hybrid membranes derived from platelets and M1 macrophages to enhance blood-brain barrier penetration and target GBM.

Precision Control of Cell Type-Specific Behavior via RNA Sensing and Editing.

In the realms of bioengineering and biopharmaceuticals, there exists a critical demand for advanced genetic tools that can interact with specific cell signaling pathways to accurately identify and target various cell types. This research introduces the innovative CRISPR-ADAReader system, which enables precise manipulation of cell activity through sensing target RNA. Featuring both positive and negative feedback loops, the system allows for tailored regulation across different cell types in response to various internal signals, showcasing exceptional programmability, specificity, and sensitivity.

A safe and efficient synthesis of N-Boc-β-amino acid methyl esters from α-amino acids: applications in the formal synthesis of sedum alkaloids.

β-Amino acids are essential components in the synthesis of biologically active compounds. However, obtaining them in enantiomerically pure forms remains challenging. This study investigates a safe and efficient method for synthesizing enantiopure N-Boc-β-amino acid methyl esters, incorporating both natural and unnatural side chains.

RIG-I is an intracellular checkpoint that limits CD8 T-cell antitumour immunity.

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8 T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8 T cells, where it functions as an intracellular checkpoint to negatively regulate CD8 T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8 T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway.

A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation.

The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants.

MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3.

Metastasis poses a huge obstacle to the survival of breast cancer patients. The microRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast cancer and metastasis remain unclear. To elucidate its function in breast cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo.

CYP2E1 mediated advanced oxidation protein products exacerbate acetaminophen induced drug-derived liver injury in vitro and in vivo.

Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD progression and participate in the occurrence and development of liver diseases. However, the mechanisms underlying the regulation of DILI in CKD have not been established.

Recombinant fibroblast growth factor 4 ameliorates axonal regeneration and functional recovery in acute spinal cord injury through altering microglia/macrophage phenotype.

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis.

A Novel Lysosome Targeting Chimera for Targeted Protein Degradation via Split-and-Mix Strategy.

Targeted protein degradation is becoming more and more important in the field of drug development. Compared with proteasomal-based degraders, lysosomal-based degraders have a broader target spectrum of targets, which have been demonstrated to have great potential, especially in degrading undruggable proteins. Recently, we developed a programmable and facile screening PROTAC development platform based on peptide self-assembly termed split-and-mix PROTAC (SM-PROTAC).

The identification of a novel compound heterozygous mutation in hereditary human coagulation factor VII deficiency following a bamboo leaf green snake bite.

Hereditary factor VII (FVII) deficiency is an uncommon autosomal recessive disorder associated with mutations in the F7 gene, and laboratory investigations usually reveal isolated prolongation in prothrombin time (PT)/international normalized ratio (INR). Venom-induced consumptive coagulopathy (VICC) is distinguished by the activation of the coagulation pathway, which is triggered by procoagulant toxins in snake venom. Diagnosing snakebites in patients with hereditary FVII deficiency presents a challenge because prolonged time PT/INR is considered the most valuable diagnostic method for VICC.

Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc.

Background: Disc degeneration is associated with repetitive violent injuries. This study aims to explore the impact of repetitive strikes loading on the biology and biomechanics of intervertebral discs (IVDs) using an organ culture model.

Methods: IVDs from the bovine tail were isolated and cultured in a bioreactor, with exposure to various loading conditions.

Serum calcium is associated with sudden cardiac arrest in stroke patients from ICU: a multicenter retrospective study based on the eICU collaborative research database.

This primary objective of our study was to investigate the relationship between serum calcium levels and the occurrence of sudden cardiac arrest (SCA) in stroke patients. We analyzed the clinical data of 10,423 acute stroke patients admitted to the intensive care unit. The association between serum calcium and SCA following an acute stroke was assessed through multivariate logistic regression.

[Oral health and hygiene behavior in chronic renal failure patients].

Purpose: To investigate the oral health and hygiene behavior of chronic renal failure(CRF) patients in Shenzhen, so as to provide basis for formulating education for them.

Methods: The history of renal failure, oral health status and oral health care behavior of 336 patients with chronic renal failure(CRF) in the hemodialysis center of Shenzhen Second People's Hospital were investigated by questionnaire and oral examinations.

Results: At an average, dialysis was required for 3.

Computational identification of long non-coding RNAs associated with graphene therapy in glioblastoma multiforme.

Glioblastoma multiforme represents the most prevalent primary malignant brain tumour, while long non-coding RNA assumes a pivotal role in the pathogenesis and progression of glioblastoma multiforme. Nonetheless, the successful delivery of long non-coding RNA-based therapeutics to the tumour site has encountered significant obstacles attributable to inadequate biocompatibility and inefficient drug delivery systems. In this context, the use of a biofunctional surface modification of graphene oxide has emerged as a promising strategy to surmount these challenges.

Aberrant expression of multiple glycolytic enzyme genes is significantly associated with disease progression and survival outcomes in prostate cancers.

Prostate cancer is the leading cause of cancer death after lung cancer in men. Recent studies showed that aberrant metabolic pathways are involved in prostate cancer development and progression. In this study, we performed a systemic analysis of glycolytic enzyme gene expression using the TCGA-PRAD RNAseq dataset.

Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics.

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of cells together, single-cell multi-omics enables us to uncover the heterogeneity within tumors and understand the unique molecular characteristics of different cell populations. By doing so, we can identify rare subpopulations of cells that are influential in tumor growth, metastasis, and resistance to therapy.

Covalent PROTAC design method based on a sulfonyl pyridone probe.

Covalent proteolysis-targeting chimeras (PROTACs) offer enhanced selectivity, prolonged action, and increased efficacy against challenging target proteins. The conventional approach relies on covalent ligands, but our study presents an innovative method employing an -sulfonyl pyridone warhead to selectively target tyrosine (Tyr) residues. The von Hippel-Lindau (VHL) moiety is transferred from the warhead to the exposed Tyr, allowing us to design a STING degrader (DC 0.

A ferroptosis-related LncRNAs signature for predicting prognoses and screening potential therapeutic drugs in patients with lung adenocarcinoma: A retrospective study.

Background: Lung adenocarcinoma (LUAD) has a high mortality rate. Ferroptosis is linked to tumor initiation and progression.

Aims: This study aims to develop prognostic models of ferroptosis-related lncRNAs, evaluate the correlation between differentially expressed genes and tumor microenvironment, and identify prospective drugs for managing LUAD.

Pyridinium-Based Strategy for a Bioorthogonal Conjugation-Assisted Purification Method for Profiling Cell Surface Proteome.

Cell surface proteins (CSPs) are valuable targets for therapeutic agents, but achieving highly selective CSP enrichment in cellular physiology remains a technical challenge. To address this challenge, we propose a newly developed sulfo-pyridinium ester (SPE) cross-linking probe, followed by two-step imaging and enrichment. The SPE probe showed higher efficiency in labeling proteins than similar NHS esters at the level of cell lysates and demonstrated specificity for Lys in competitive experiments.

Covalent Peptide LSD1 Inhibitor Specifically Recognizes Cys360 in the Enzyme-Active Region.

Lysine-specific demethylase 1 (LSD1) is a promising therapeutic target, especially in cancer treatment. Despite several LSD1 inhibitors being discovered for the cofactor pocket, none are FDA-approved. We aimed to develop stabilized peptides for irreversible LSD1 binding, focusing on unique cysteine residue Cys360 in LSD1 and SNAIL1.

A novel selective ERK1/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer.

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity.

Why Treg should be the focus of cancer immunotherapy: The latest thought.

Regulatory T cells are a subgroup of T cells with immunomodulatory functions. Different from most cytotoxic T cells and helper T cells, they play a supporting role in the immune system. What's more, regulatory T cells often play an immunosuppressive role, which mainly plays a role in maintaining the stability of the immune system and regulating the immune response in the body.

Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation.

Cyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS.