Optimized circular RNA vaccines for superior cancer immunotherapy.

Circular RNA (circRNA) has gained attention as a promising platform for mRNA vaccines due to its stability, sustained protein expression, and intrinsic immunostimulatory properties. This study aimed to design and optimize a circRNA cancer vaccine platform by screening for efficient internal ribosome entry sites (IRES) and enhancing circRNA translation efficiency for improved cancer immunotherapy. We screened 29 IRES elements to identify the most efficient one for immune cell translation, ultimately discovering the A (EV-A) IRES.

CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

Heat-Killed subsp. 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study.

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed subsp. 557 (LDL557) could significantly decrease OA progression.

SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations.

Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.

Optimized Adsorption of H and OH over Amorphous SrRuPtOH Nanobelts towards Efficient Alkaline Fuel Cell Catalysis.

PtRu-based catalysts toward hydrogen oxidation reaction (HOR) suffer from low efficiency, CO poisoning and over-oxidation at high potentials. In this work, an amorphization strategy is adopted for preparation of amorphous SrRuPtOH nanobelts (a-SrRuPtOH NBs). The a-SrRuPtOH NBs has optimized adsorption of intermediates (H and OH), increased number of active sites, highly weakened CO poisoning and enhanced anti-oxidation ability owing to the special amorphous structure.

Feasibility of Sub-milliSievert Low-dose Computed Tomography with Deep Learning Image Reconstruction in Evaluating Pulmonary Subsolid Nodules: A Prospective Intra-individual Comparison Study.

Rationale And Objectives: To comprehensively assess the feasibility of low-dose computed tomography (LDCT) using deep learning image reconstruction (DLIR) for evaluating pulmonary subsolid nodules, which are challenging due to their susceptibility to noise.

Materials And Methods: Patients undergoing both standard-dose CT (SDCT) and LDCT between March and June 2023 were prospectively enrolled. LDCT images were reconstructed with high-strength DLIR (DLIR-H), medium-strength DLIR (DLIR-M), adaptive statistical iterative reconstruction-V level 50% (ASIR-V-50%), and filtered back projection (FBP); SDCT with FBP as the reference standard.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Local CpG- siRNA treatment improves antitumor effects of immune checkpoint inhibitors.

Immune checkpoint blockade (ICB) therapy has significantly benefited patients with several types of solid tumors and some lymphomas. However, many of the treated patients do not have a durable clinical response. It has been demonstrated that rescuing exhausted CD8 T cells is required for ICB-mediated antitumor effects.

Care to Explain? AI Explanation Types Differentially Impact Chest Radiograph Diagnostic Performance and Physician Trust in AI.

Background It is unclear whether artificial intelligence (AI) explanations help or hurt radiologists and other physicians in AI-assisted radiologic diagnostic decision-making. Purpose To test whether the type of AI explanation and the correctness and confidence level of AI advice impact physician diagnostic performance, perception of AI advice usefulness, and trust in AI advice for chest radiograph diagnosis. Materials and Methods A multicenter, prospective randomized study was conducted from April 2022 to September 2022.

Coordinated inheritance of extrachromosomal DNAs in cancer cells.

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells.

Design of customized coronavirus receptors.

Although coronaviruses use diverse receptors, the characterization of coronaviruses with unknown receptors has been impeded by a lack of infection models. Here we introduce a strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building artificial receptor scaffolds comprising various modules and generating specific virus-binding domains.

Tailoring smart hydrogels through manipulation of heterogeneous subdomains.

The mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film.

Circulating Tumor DNA in Conjunctival Melanoma: Landscape and Surveillance Value.

Purpose: To evaluate the surveillance value of circulating tumor DNA (ctDNA) for detecting distant metastasis and indicating systemic therapeutic efficacy in conjunctival melanoma (CoM).

Design: Retrospective, observational case series.

Methods: From July 2021 to June 2023, 30 CoM patients in our center underwent plasma ctDNA assessment, out of which 12 individuals presented with distant metastases.

Novel immunotherapeutic approaches in gastric cancer.

Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory.

Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability .

What happens to macromolecules ? What drives the structure-activity relationship and stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC stability. Complex macromolecules, such as ADCs, may undergo changes due to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule.

Quantum Chemical Approaches for Manipulation and Evaluation of Intracage Microelectric Field Strength of Molecular Containers in Y@C and Y@CX (X = Cl, F, and H, Y = NHCl, HO-Cl, and 2HO).

The effect of an oriented external electric field (EEF) on materials has led to the ongoing development, which stimulates us to consider whether intracage microelectric fields (IMEFs) can be used to substitute for the EEF. Focusing on the manipulation and evaluation of the IMEF of asymmetric molecular containers, the host-guest compounds of interesting pineapple-shaped Y@CX (X = vacant, Cl, F, and H; Y = NHCl, HO-Cl, and 2HO) are theoretically constructed and the strength of the IMEF was evaluated by the intrapotential energy surface analysis by using the point charge ( = +1) scanning method. Interestingly, the left and right halves of each cage are like two IMEFs connected in reverse series.

Sulfur filling activates vacancy-induced C-C bond cleavage in polyol electrooxidation.

Using the electrochemical polyol oxidation reaction (POR) to produce formic acid over nickel-based oxides/hydroxides (NiO H ) is an attractive strategy for the electrochemical upgrading of biomass-derived polyols. The key step in the POR, i.e.

Digestion-Free Middle-Down Mass Spectrometry Method for Absolute Quantification of Conjugated Payload from Antibody-Drug Conjugates.

Antibody-drug conjugate (ADC) is a therapeutic modality that aims to improve payload delivery specificity and reduce systemic toxicity. Considering the complex structure of ADCs, various bioanalytical methods by liquid chromatography coupled with mass spectrometry (LC-MS), ligand binding assay (LBA) and hybrid LBA-LC-MS approaches have been established for ADC characterization and quantification. LCMS-based assays enable drug-antibody ratio (DAR) sensitive quantification of the conjugated payload.

Robust Magnetic-Field-Free Perpendicular Magnetization Switching by Manipulating Spin Polarization Direction in RuO/[Pt/Co/Pt] Heterojunctions.

Perpendicular magnetization switching by a magnetic-field-free, energy-efficient electrical approach has remained a great challenge. Here, we demonstrate the realization of robust magnetic-field-free perpendicular magnetization switching in the (101)RuO/[Pt/Co/Pt] heterojunction by manipulating the spin polarization direction. We proposed that the relative strength of out-of-plane spin currents with out-of-plane spin polarization and in-plane spin polarization can be effectively manipulated by tuning the nominal thickness of [Pt/Co/Pt] multilayers and the direction of applied electric current with respect to the RuO crystal orientation.

Molecular Regulation of Shoot Architecture in Soybean.

Soybean (Glycine max [L.] Merr.) serves as a major source of protein and oil for humans and animals.

Entangling gates on degenerate spin qubits dressed by a global field.

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements.

The Oral Administration of subsp. 557 (LDL557) Ameliorates the Progression of Monosodium Iodoacetate-Induced Osteoarthritis.

Low-grade body inflammation is a major cause of osteoarthritis (OA), a common joint disease. Gut dysbiosis may lead to systemic inflammation which can be prevented by probiotic administration. The subsp.