Optimized gene transduction in human lung organoids: A high-efficiency method for advanced research applications.

Human induced pluripotent stem cell (iPSC)-derived lung organoids, engineered to carry targeted genes, offer a robust platform for investigating mechanistic insights in lung research. Although lentiviral vectors (LVVs) are highly effective for stable expression due to their integrative properties, achieving efficient transduction in human iPSC-derived lung organoids poses a significant technical challenge, likely due to the complex structure of these organoids. In this study, we optimized a method to enhance LVV transduction efficiency by physically disrupting the organoids to increase surface area, followed by spinoculation to apply shear force during cell dissociation.

Magnetic Torque-Driven All-Terrain Microrobots.

All-terrain microrobots possess significant potential in modern medical applications due to their superior maneuverability in complex terrains and confined spaces. However, conventional microrobots often struggle with adaptability and operational difficulties in variable environments. This study introduces a magnetic torque-driven all-terrain multiped microrobot (MTMR) to address these challenges.

A position-enhanced sequential feature encoding model for lung infections and lymphoma classification on CT images.

Purpose: Differentiating pulmonary lymphoma from lung infections using CT images is challenging. Existing deep neural network-based lung CT classification models rely on 2D slices, lacking comprehensive information and requiring manual selection. 3D models that involve chunking compromise image information and struggle with parameter reduction, limiting performance.

Parameter-efficient framework for surgical action triplet recognition.

Purpose: Surgical action triplet recognition is a clinically significant yet challenging task. It provides surgeons with detailed information about surgical scenarios, thereby facilitating clinical decision-making. However, the high similarity among action triplets presents a formidable obstacle to recognition.

SDA-CLIP: surgical visual domain adaptation using video and text labels.

Background: Surgical action recognition is an essential technology in context-aware-based autonomous surgery, whereas the accuracy is limited by clinical dataset scale. Leveraging surgical videos from virtual reality (VR) simulations to research algorithms for the clinical domain application, also known as domain adaptation, can effectively reduce the cost of data acquisition and annotation, and protect patient privacy.

Methods: We introduced a surgical domain adaptation method based on the contrastive language-image pretraining model (SDA-CLIP) to recognize cross-domain surgical action.

Precision Medicine Using Simultaneous Monitoring and Assessment with Imaging and Biomarkers to Manage Mechanical Ventilation in ARDS.

Acute respiratory distress syndrome (ARDS) has a ~ 40% mortality rate with an increasing prevalence exacerbated by the COVID-19 pandemic. Mechanical ventilation is the primary means for life-saving support to buy time for lung healing in ARDS patients, however, it can also lead to ventilator-induced lung injury (VILI). Effective strategies to reduce or prevent VILI are necessary but are not currently delivered.

SARS-CoV-2 virus-like-particles liposomal reconstitution of spike glycoproteins.

The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using its spike glycoprotein through an angiotensin converting enzyme 2 (ACE-2) receptor-mediated pathway. Recent research suggests that spatial distributions of the spike protein may influence viral interactions with target cells and immune systems. The goal of this study has been to develop a liposome-based virus-like particle (VLP) by reconstituting the SARS-CoV-2 spike glycoprotein within a synthetic nanoparticle membrane, aiming to eventually establish tunability in spike protein presentation on the nanoparticle surface.

MT-FiST: A Multi-Task Fine-Grained Spatial-Temporal Framework for Surgical Action Triplet Recognition.

Surgical action triplet recognition plays a significant role in helping surgeons facilitate scene analysis and decision-making in computer-assisted surgeries. Compared to traditional context-aware tasks such as phase recognition, surgical action triplets, comprising the instrument, verb, and target, can offer more comprehensive and detailed information. However, current triplet recognition methods fall short in distinguishing the fine-grained subclasses and disregard temporal correlation in action triplets.

Efficacy and Interpretability Analysis of Noninvasive Imaging Based on Computed Tomography in Patients with Hepatocellular Carcinoma After Initial Transarterial Chemoembolization.

Rationale And Objectives: The objective of this study is to accurately and timely assess the efficacy of patients with hepatocellular carcinoma (HCC) after the initial transarterial chemoembolization (TACE).

Materials And Methods: This retrospective study consisted of 279 patients with HCC in Center 1, who were split into training and validation cohorts in the ratio of 4:1, and 72 patients in Center 2 as an external testing cohort. Radiomics signatures both in the arterial phase and venous phase of contrast-enhanced computed tomography images were selected by univariate analysis, correlation analysis, and least absolute shrinkage and selection operator regression to build the predicting models.

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2.

The Potential Protective Role of GS-441524, a Metabolite of the Prodrug Remdesivir, in Vaccine Breakthrough SARS-CoV-2 Infections.

Unlabelled: Cases of vaccine breakthrough, especially in variants of concern (VOCs) infections, are emerging in coronavirus disease (COVID-19). Due to mutations of structural proteins (SPs) (e.g.

Development and validation of a clinical risk model to predict the hospital mortality in ventilated patients with acute respiratory distress syndrome: a population-based study.

Background: Large variability in mortality exists in patients of acute respiratory distress syndrome (ARDS), especially those with invasive ventilation. The aim of this study was to develop a model to predict risk of in-hospital death in ventilated ARDS patients.

Methods: Ventilated patients with ARDS from two public databases (MIMIC-III and eICU-CRD) were randomly divided as training cohort and internal validation cohort.

Non-invasive ventilation versus invasive weaning in critically ill adults: a systematic review and meta-analysis.

Background: Extubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications.

Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data.

Emerging SARS-CoV-2 variants of concern and potential intervention approaches.

The major variant of concerns (VOCs) have shared mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, mostly on the S1 unit and resulted in higher transmissibility rate and affect viral virulence and clinical outcome. The spike protein mutations and other non-structural protein mutations in the VOCs may lead to escape approved vaccinations in certain extend. We will discuss these VOC mutations and discuss the need for combination therapeutic strategies targeting viral cycle and immune host responses.

Ligand modulation of the conformational dynamics of the A adenosine receptor revealed by single-molecule fluorescence.

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Activation of these receptors is modulated by orthosteric ligands, which stabilize one or several states within a complex conformational ensemble. The intra- and inter-state dynamics, however, is not well documented.

Molecular mechanisms of sex bias differences in COVID-19 mortality.

More men than women have died from COVID-19. Genes encoded on X chromosomes, and sex hormones may explain the decreased fatality of COVID-19 in women. The angiotensin-converting enzyme 2 gene is located on X chromosomes.

The association between neutrophil-to-lymphocyte count ratio and mortality in septic patients: a retrospective analysis of the MIMIC-III database.

Background: Neutrophil-to-lymphocyte count ratio (NLCR) has been shown as a feasible parameter associated with outcomes of tumor patients and an accessible predictor of bacteremia. However, only a handful of research shed the light on the association between NLCR and outcomes of septic patients. This study is aimed to evaluate the association between NLCR and all-cause mortality in a population of adult septic patients.

Bayesian counting of photobleaching steps with physical priors.

Counting fluorescence photobleaching steps is commonly used to infer the number n of monomeric units of individual oligomeric protein complexes or misfolded protein aggregates. We present a principled Bayesian approach for counting that incorporates the statistics of photobleaching. Our physics-based prior leads to a simple and efficient numerical scheme for maximum a posteriori probability (MAP) estimates of the initial fluorophore number n^.

Publisher Correction: Exocyst dynamics during vesicle tethering and fusion.

The original version of this Article contained errors in the author affiliations. Affiliation 2 incorrectly read 'Department of Biochemistry and Molecular Genetics and Breast Surgery, Ehime University Graduate School of Medicine, 7910295, Japan' and affiliation 3 incorrectly read 'Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Matsuyama 7910295, Japan.' These errors have now been corrected in both the PDF and HTML versions of the Article.

Exocyst dynamics during vesicle tethering and fusion.

The exocyst is a conserved octameric complex that tethers exocytic vesicles to the plasma membrane prior to fusion. Exocyst assembly and delivery mechanisms remain unclear, especially in mammalian cells. Here we tagged multiple endogenous exocyst subunits with sfGFP or Halo using Cas9 gene-editing, to create single and double knock-in lines of mammary epithelial cells, and interrogated exocyst dynamics by high-speed imaging and correlation spectroscopy.

Ligand-Induced Coupling between Oligomers of the M Receptor and the G Protein in Live Cells.

Uncertainty over the mechanism of signaling via G protein-coupled receptors (GPCRs) relates in part to questions regarding their supramolecular structure. GPCRs and heterotrimeric G proteins are known to couple as monomers under various conditions. Many GPCRs form oligomers under many of the same conditions, however, and the biological role of those complexes is unclear.

Characterization of Fluorescein Arsenical Hairpin (FlAsH) as a Probe for Single-Molecule Fluorescence Spectroscopy.

In recent years, new labelling strategies have been developed that involve the genetic insertion of small amino-acid sequences for specific attachment of small organic fluorophores. Here, we focus on the tetracysteine FCM motif (FLNCCPGCCMEP), which binds to fluorescein arsenical hairpin (FlAsH), and the ybbR motif (TVLDSLEFIASKLA) which binds fluorophores conjugated to Coenzyme A (CoA) via a phosphoryl transfer reaction. We designed a peptide containing both motifs for orthogonal labelling with FlAsH and Alexa647 (AF647).

Synthesis of Stable Multifunctional Perfluorocarbon Nanoemulsions for Cancer Therapy and Imaging.

Nanotechnology provides a promising platform for drug-delivery in medicine. Nanostructured materials can be designed with desired superparamagnetic or fluorescent properties in conjunction with biochemically functionalized moieties (i.e.

Single-Molecule Analysis of the Supramolecular Organization of the M2 Muscarinic Receptor and the Gαi1 Protein.

G protein-coupled receptors constitute the largest family of transmembrane signaling proteins and the largest pool of drug targets, yet their mechanism of action remains obscure. That uncertainty relates to unresolved questions regarding the supramolecular nature of the signaling complex formed by receptor and G protein. We therefore have characterized the oligomeric status of eGFP-tagged M2 muscarinic receptor (M2R) and Gi1 by single-particle photobleaching of immobilized complexes.