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).

Triglycerides to apolipoprotein A1 ratio: an effective insulin resistance-associated index in identifying metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus.

Background: The triglycerides to Apolipoprotein A1 ratio (TG/APOA1) holds promise to be a more valuable index of insulin resistance for the diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between TG/APOA1 and MAFLD, as well as compare the efficacy of TG/APOA1 with triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-c) and triglyceride-glucose (TyG) index in identifying MAFLD among individuals with T2DM.

Method: This study consecutively recruited 779 individuals with T2DM for the investigation.

Cas12e orthologs evolve variable structural elements to facilitate dsDNA cleavage.

Exceptionally diverse type V CRISPR-Cas systems provide numerous RNA-guided nucleases as powerful tools for DNA manipulation. Two known Cas12e nucleases, DpbCas12e and PlmCas12e, are both effective in genome editing. However, many differences exist in their in vitro dsDNA cleavage activities, reflecting the diversity in Cas12e's enzymatic properties.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Single-Bundle Posterior Cruciate Ligament Reconstruction With Suture Tape Augmentation and Transtibial Tubercle Fixation.

The posterior cruciate ligament (PCL) is the strongest ligament of the knee and plays an important role in stabilizing the knee joint posteriorly. PCL tears are common injuries in sports injuries and traffic accidents; however, clinical outcomes after PCL reconstruction have not yet met clinicians' expectations, with a high postsurgery failure rate reported. Suture tape augmentation and supplementary fixation have shown ideal biomechanical properties in early studies.

Multi-enzyme assemblies both in the cell membrane and cytoplasm boost intracellular lycopene production.

The multi-enzyme assembly system demonstrates remarkable potential in enhancing both intracellular and extracellular enzyme catalysis. In this study, we employed a novel icosahedral protein cage, Mi3, as a protein scaffold and combined it with an ester bond-based peptide tagging system, ReverseTag/ReverseCatcher, to improve the enzymatic catalytic efficiency both in vitro and in vivo. In vitro, we fused ReverseTag to the N-terminal of exo-inulinase (EXINU) from Pseudomonas mucidolens, yielding ReverseTag-EXINU, which effectively bound to the surface of the ReverseCatcher-Mi3 protein cage.

Single-cell RNA sequencing algorithms underestimate changes in transcriptional noise compared to single-molecule RNA imaging.

Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise remains unclear. Here, we utilize a small-molecule perturbation (5'-iodo-2'-deoxyuridine [IdU]) to amplify noise and assess noise quantification from numerous single-cell RNA sequencing (scRNA-seq) algorithms on human and mouse datasets and then compare it to noise quantification from single-molecule RNA fluorescence in situ hybridization (smFISH) for a panel of representative genes.

Integrated self-powered sensors based on cubic nanostructure and cascade amplification strategies.

The advantages of simple structure and easy portability inherent to self-powered biosensors have broad application prospects in clinical diagnosis and implantable medical devices. In light of the limitations of the clinical detection sensitivity, this study devised and fabricated a three-dimensional (3D) cubic structure of MoS₂ that was self-assembled by 2D nanosheets. The multi-dimensional structure design provides a broad binding site for the incubation of biological probes and the loading of biological enzymes, which can accelerate the electron transfer rate and effectively improve the detection sensitivity.

Outcome of Surgery for Hypothalamic Hamartoma-Related Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis.

Background And Objectives: There is a paucity of data directly comparing the outcome of surgical techniques available for the treatment of hypothalamic hamartomas (HHs). This study aims to evaluate the safety and efficacy of commonly used surgical approaches in the treatment of HH-related epilepsy.

Methods: A systematic review and individual participant data (IPD) meta-analysis was conducted.

Ultrasensitive electrochemiluminescencent multivalent aptamer sensor based on energy and electron transfer dual quenching tactics.

An efficient "on-off-on" electrochemiluminescence (ECL) aptasensor utilizing dual-mechanism quenching was constructed for detecting furanyl fentanyl (FuF). The first signal "on" state was achieved by novel dual-ligand zinc metal-organic frameworks (Zn-MOFs), which were synthesized by self-assembly reaction using zinc atom clusters as metal nodes, achieving strong and stable ECL emission. The "off" state was realized by the energy and electron quenching effect of copper-doped WO.

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

Effect of COVID-19 vaccine in adults infected with the Delta variant of SARS-CoV-2: a retrospective cohort study.

Background: Reducing mortality among those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a critical challenge in clinic. The objective of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) vaccine on the prognosis of individuals infected with the Delta variant of SARS-CoV-2.

Methods: In a single-center, retrospective cohort study, all adult patients with COVID-19 from designated hospital in Xi'an, China, during the Delta outbreak from December 2021 to January 2022 were enrolled.

Feasibility and safety of endomyocardial biopsy by lumenless pacing lead sheath-directed method during cardiac implantable electronic device implantation.

Background: Patients with an indication for a cardiovascular implantable electronic device (CIED) are complicated with special cardiomyopathy or other unspecified cardiac abnormalities and may need endomyocardial biopsy (EMB). However, EMB by a bioptome is usually avoided to reduce the risk of lead displacement in the CIED periprocedural period.

Objective: We aimed to assess the safety and feasibility of a novel approach for transvenous right ventricular (RV) EMB using the lead sheath method (L-S-M) during CIED implantation and compared it with the traditional bioptome method (T-B-M).

Enhanced CO Coordinates the Spatial Recruitment of Diazotrophs in Rice Via Root Development.

Understanding the reciprocal interaction between root development and coadapted beneficial microbes in response to elevated CO (eCO) will facilitate the identification of nutrient-efficient cultivars for sustainable agriculture. Here, systematic morphological, anatomical, chemical and gene expression assays performed under low-nitrogen conditions revealed that eCO drove the development of the endodermal barrier with respect to L-/S-shaped lateral roots (LRs) in rice. Next, we applied metabolome and endodermal-cell-specific RNA sequencing and showed that rice adapts to eCO by spatially recruiting diazotrophs via flavonoid secretion in L-shaped LRs.

Development and Evaluation of a Novel Resuscitation Teamwork Model for Out-of-Hospital Cardiac Arrest in the Emergency Department.

Study Objective: Cardiopulmonary resuscitation (CPR) is critical for out-of-hospital cardiac arrest patients but is prone to rapid changes and errors. Effective teamwork and leadership are essential for high-quality CPR. We aimed to introduce the Airway-Circulation-Leadership-Support (A-C-L-S) teamwork model in the emergency department (ED) to address these challenges.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Electron transfer mediated activation of periodate by contaminants to generate O by charge-confined single-atom catalyst.

The electron transfer process (ETP) is able to avoid the redox cycling of catalysts by capturing electrons from contaminants directly. However, the ETP usually leads to the formation of oligomers and the reduction of oxidants to anions. Herein, the charge-confined Fe single-atom catalyst (Fe/SCN) with Fe-NS configuration was designed to achieve ETP-mediated contaminant activation of the oxidant by limiting the number of electrons gained by the oxidant to generate O.

Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential.

The steadily growing number of experimental G-protein-coupled receptor (GPCR) structures has revealed diverse locations of allosteric modulation, and yet few drugs target them. This gap highlights the need for a deeper understanding of allosteric modulation in GPCR drug discovery. The current work introduces a systematic annotation scheme to structurally classify GPCR binding sites based on receptor class, transmembrane helix contacts, and, for membrane-facing sites, membrane sublocation.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

Background: The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients.

Methods: This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm).

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).