A therapeutic regimen using neoantigen-specific TCR-T cells for HLA-A*2402-positive solid tumors.

The adoptive transfer of TCR-T cells specific to neoantigens preferentially exhibits potent cytotoxicity to tumor cells and has shown promising efficacy in various preclinical human cancers. In this study, we first identified a functional TCR, Tcr-1, which selectively recognized the SYT-SSX fusion neoantigen shared by most synovial sarcomas. Engineered T-cell expressing Tcr-1 (Tcr-T1) demonstrated HLA-A*2402-restricted, antigen-specific anti-tumoral efficacy against synovial sarcoma cells, both in vitro and in vivo.

Formal analysis of signal protocol based on logic of events theory.

The Signal is an end-to-end encrypted communication protocol composed of a double ratchet (DR) protocol and an extended triple Diffie-Hellman (X3DH) protocol. Its complex ratchet structure and the characteristics of protocol composition make it challenging to realize formal analysis. A formal analysis method based on logic of events theory (LoET) is proposed to conduct a security analysis of the Signal protocol.

Chromodomain Y-like (CDYL) inhibition ameliorates acute kidney injury in mice by regulating tubular pyroptosis.

Acute kidney injury (AKI) is a common disease, but lacking effective drug treatments. Chromodomain Y-like (CDYL) is a kind of chromodomain protein that has been implicated in transcription regulation of autosomal dominant polycystic kidney disease. Benzo[d]oxazol-2(3H)-one derivative (compound D03) is the first potent and selective small-molecule inhibitor of CDYL (K = 0.

Liposome-based in situ antigen-modification strategy for "universal" T-cell-receptor engineered T cell in cancer immunotherapy.

T-cell receptor (TCR) engineered T-cell therapy, unlike chimeric antigen receptor T-cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR-T-cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges.

Tirzepatide attenuates mammary tumor progression in diet-induced obese mice.

We report for the first time an anticancer benefit of tirzepatide-a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist-in a model of obesity and breast cancer in female mice. Long-term tirzepatide treatment induced weight loss, mitigated obesity-driven changes in circulating metabolic hormone levels, and suppressed orthotopic E0771 mammary tumor growth. Relative to tirzepatide, chronic calorie restriction, an established anticancer intervention in preclinical models, promoted even greater weight loss, systemic hormonal regulation, and tumor suppression.

Membrane fusogenic nanoparticle-based HLA-peptide-addressing universal T cell receptor-engineered T (HAUL TCR-T) cell therapy in solid tumor.

T cell receptor-engineered T (TCR-T) cell therapy has demonstrated therapeutic effects in basic research and clinical trials for treating solid tumors. Due to the peptide-dependent recognition and the human leukocyte antigen (HLA)-restriction, TCR-T cell therapy is generally custom designed to target individual antigens. The lack of suitable universal targets for tumor cells significantly limits its clinical applications.

Anisotropic charge transfer and gate tuning for p-SnS/n-MoS vertical van der Waals diodes.

2D-material-based van der Waals heterostructures (vdWhs) have shown great potential in next-generation multi-functional microelectronic devices. Thanks to their sharp interface and ultrathin thickness, 2D p-n junctions with high rectification properties have been established by combining p-type monochalcogenides with n-type transition metal dichalcogenides. However, the anisotropic rectification together with the charge transfer and gate effect has not been clarified.

PINOID and PIN-FORMED Paralogous Genes Are Required for Leaf Morphogenesis in Rice.

Auxin plays an essential role in modulating leaf development. However, its role in leaf development in rice (Oryza sativa L.) remains largely unknown.

LncRNA and its role in gastric cancer immunotherapy.

Gastric cancer (GC) is a potential dominant disease in tumor immunotherapy checkpoint inhibitors, and adoptive cell therapy have brought great hope to GC patients. However, only some patients with GC can benefit from immunotherapy, and some patients develop drug resistance. More and more studies have shown that long non-coding RNAs (lncRNAs) may be important in GC immunotherapy's prognosis and drug resistance.

Nanomodified Switch Induced Precise and Moderate Activation of CAR-T Cells for Solid Tumors.

Chimeric antigen receptor (CAR)-T cell therapy is a transformative treatment against advanced malignancies. Unfortunately, once administrated in vivo, CAR-T cells become out of artificial control, and fierce response to CAR-T therapy may cause severe adverse events, represented by cytokine-release syndrome and on-target/off-tumor effects. Here, a nanomodified switch strategy is developed, leading to sustained and precise "on-tumor only" activation of CAR-T cells.

Engineered Lactococcus lactis secreting Flt3L and OX40 ligand for in situ vaccination-based cancer immunotherapy.

In situ vaccination is a promising strategy to convert the immunosuppressive tumor microenvironment into an immunostimulatory one with limited systemic exposure and side effect. However, sustained clinical benefits require long-term and multidimensional immune activation including innate and adaptive immunity. Here, we develop a probiotic food-grade Lactococcus lactis-based in situ vaccination (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand.

Side channel analysis based on feature fusion network.

Various physical information can be leaked while the encryption algorithm is running in the device. Side-channel analysis exploits these leakages to recover keys. Due to the sensitivity of deep learning to the data features, the efficiency and accuracy of side channel analysis are effectively improved with the application of deep learning algorithms.

Neoantigen-targeted TCR-T cell therapy for solid tumors: How far from clinical application.

T cell receptor-engineered T (TCR-T) cells targeting neoantigens present potential immunotherapy for solid tumors. With the continuous optimization of the entire production procedures, the manufacturing process of TCR-T cells is becoming more efficient and productive. However, clinical-scale manufacturing of TCR-T cells still encounters tremendous challenges.

Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.

Ion channels are expressed in almost all living cells, controlling the in-and-out communications, making them ideal drug targets, especially for central nervous system diseases. However, owing to their dynamic nature and the presence of a membrane environment, ion channels remain difficult targets for the past decades. Recent advancement in cryo-electron microscopy and computational methods has shed light on this issue.

[Modified QuEChERS method based on multi-walled carbon nanotubes coupled with gas chromatography-tandem mass spectrometry for the detection of 10 pyrethroid pesticide residues in tea].

A modified QuEChERS method, based on multi-walled carbon nanotubes (MWCNTs), was established for the detection of 10 pyrethroid pesticides (cyfluthrin, flucythrinate, fenpropathrin, bifenthrin, cyhalothrin, permethrin, cypermethrin, etofenprox, fenvalerate, deltamethrin) in tea, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS). The purification effects and dosages of four carbon nanomaterials, viz. single-walled carbon nanotubes (SWCNTs), MWCNTs, amino-modified MWCNTs, and graphene, were compared.

In situ antigen modification-based target-redirected universal chimeric antigen receptor T (TRUE CAR-T) cell therapy in solid tumors.

Background: Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable success in the treatment of hematologic malignancies, while the success has not yet been replicated in solid tumors. To some extent, the disappointing results can be attributed to the paucity and heterogeneity of target antigens in solid tumors since adequate antigens are the cornerstone for CAR-T cells to recognize and attack tumor cells.

Methods: We established a target-redirected universal CAR-T (TRUE CAR-T) cell therapeutic modality, in which exogenous antigens are loaded onto fusogenic nanoparticles to achieve in situ modification of cell membrane in solid tumors, providing targets for subsequent CAR-T cell therapy.

Band Gap Engineering in Vinylene-Linked Covalent Organic Frameworks for Enhanced Photocatalytic Degradation of Organic Contaminants and Disinfection of Bacteria.

Photocatalysis is regarded as one of the most promising technologies to remove organic contaminants. At present, most of the covalent organic frameworks (COFs) used as photocatalysts are connected by imine or borate bonds, which have relatively low stability and relatively poor π-delocalization. Herein, we report, for the first time, vinylene-linked COFs constructed by various diacetylene and triazine moieties for photocatalytic degradation of organic contaminants and disinfection of bacteria.

Molecular evidence for farnesoic acid O-methyltransferase (FAMeT) involved in the biosynthesis of vitellogenin in the Chinese mitten crab Eriocheir sinensis.

Sesquiterpenoid methyl farnesoate (MF), a crustacean equivalent of insect juvenile hormone (JH III), has essential functions in regulating physiological processes in crustaceans, including reproduction and vitellogenesis. Farnesoic acid O-methyltransferase (FAMeT) is a key rate-limiting enzyme catalyzing the conversion of farnesoic acid (FA) to JH/MF in insects and crustaceans. In this study, a full-length cDNA of EsFAMeT from Eriocheir sinensis was isolated and characterized.

Tumor eradicated by combination of imiquimod and OX40 agonist for in situ vaccination.

Various cancer vaccines have been developed to generate and amplify antigen-specific T cell responses against malignancy. Among them, in situ vaccination is one of the most practical types as it can trigger immune responses without previous antigen identification. Here we reported a novel in situ vaccine by intratumoral injection of imiquimod and OX40 agonist.

RNAi silencing of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) gene inhibits vitellogenesis in Chinese mitten crab Eriocheir sinensis.

The sesquiterpenoid methyl farnesoate (MF), a de-epoxide form of insect juvenile hormone III (JH III), plays an essential role in regulating many crucial physiological processes in crustaceans including vitellogenesis and reproduction. 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is an important rate-limiting enzyme in the mevalonate pathway, which is critical for the synthesis of JH III and MF. In the present study, a full-length cDNA encoding HMGR (EsHMGR) in Eriocheir sinensis was isolated and characterised.

Identification, characterization and mRNA transcript abundance profiles of the carboxylesterase (CXE5) gene in Eriocheir sinensis suggest that it may play a role in methyl farnesoate degradation.

The sesquiterpenoid methyl farnesoate (MF) is a de-epoxidized form of insect juvenile hormone (JH) III in crustaceans, and its precise titer plays important roles in regulating many critical physiological processes, including reproduction and ovarian maturation. Understanding the synthetic and degradation pathways of MF is equally important for determining how to maintain MF titers at appropriate levels and thus for potential applications in crab aquaculture. Although the synthetic pathway of MF has been well established, little is known about MF degradation.

Start-up stage with improved resolution for an electric field-assisted fused deposition.

Electric field-assisted fused deposition modeling (E-FDM) is a promising technique in the field of 3D printing. This paper studies the start-up stage of the printing, which is a process of liquid gradually deforming and making an initial contact with the substrate under the action of electric stress. Polycaprolactone, a popular material for biomedicine, is selected as the printing material.

Low Band Gap Benzoxazole-Linked Covalent Organic Frameworks for Photo-Enhanced Targeted Uranium Recovery.

The inherent features of covalent organic frameworks (COFs) make them highly attractive for uranium recovery applications. A key aspect yet to be explored is how to improve the selectivity and efficiency of COFs for recovering uranium from seawater. To achieve this goal, a series of robust and hydrophilic benzoxazole-based COFs is developed (denoted as Tp-DBD, Bd-DBD, and Hb-DBD) as efficient adsorbents for photo-enhanced targeted uranium recovery.

OsmiR164-targeted OsNAM, a boundary gene, plays important roles in rice leaf and panicle development.

The CUP-SHAPED COTYLEDON (CUC) genes (CUC1, CUC2 and CUC3) regulate organ boundary formation in Arabidopsis. However, the functions of their homologous genes in rice (Oryza sativa) are still unknown. Here, we have identified an orthologous gene of CUC1 and CUC2 in rice, named OsNAM.