Revolutionizing drug delivery: low-intensity pulsed ultrasound (LIPUS)-driven deep penetration into hypoxic tumor microenvironments of cholangiocarcinoma.

Hypoxia is a major obstacle in the treatment of solid tumors because it causes immune escape and therapeutic resistance. Drug penetration into the hypoxic regions of tumor microenvironment (TME) is extremely limited. This study proposes using the unidirectional fluid flow property of low-intensity pulsed ultrasound (LIPUS) to overcome drug penetration limitations in the TME.

Functional neural substrates of Parkinson's disease and potential underpinnings of acute responses to acupuncture stimulation.

Parkinson's disease is a heterogenous neurodegenerative disorder with a wide variety of motor and non-motor symptoms. This study used resting-state fMRI to identify the neural substrates of PD and explore the acute neural response to acupuncture stimulation in 74 participants (50 patients with PD and 24 healthy controls). All participants with PD were evaluated for the severity of symptoms using the Unified Parkinson's Disease Rating Scale and Balance Master.

Multiscale crack trapping for programmable adhesives.

The precise control of crack propagation at bonded interfaces is crucial for smart adhesives with advanced performance. However, previous studies have primarily concentrated on either microscale or macroscale crack propagation. Here, we present a hybrid adhesive that integrates microarchitectures and macroscopic nonlinear cut architectures for unparalleled adhesion control.

Prediction of the minimum amount of anti-adhesive agent required for entire intra-abdominal cavity using fluorescent dye.

Purpose: Studies on the appropriate amount of anti-adhesive agents for preventing postoperative adhesion are lacking. This animal study aimed to investigate the distribution of an anti-adhesive agent in the abdominal cavity and estimate the necessary amount to cover the entire cavity.

Methods: Fluorescent dye Flamma-552 was conjugated to Guardix-sol to create Guardix-Flamma, which was laparoscopically applied to the abdominal cavity of two 10-kg pigs in different amounts: 15 mL for G1 and 35 mL for G2.

Measurement of human peritoneal surface area using artificial intelligence software in abdominal computed tomography.

Purpose: The calculation of the intraperitoneal organ surface area is important for understanding their anatomical structure and for conducting basic and clinical studies on diseases related to the peritoneum. To measure the intraperitoneal surface area in a living body by applying artificial intelligence (AI) techniques to the abdominal cavity using computed tomography and to prepare clinical indicators for application to the abdominal cavity.

Methods: Computed tomography images of ten adult males and females with a healthy body mass index and ten adults diagnosed with colon cancer were analyzed to determine the peritoneal and intraperitoneal surface areas of the organs.

Entosis: the core mechanism and crosstalk with other cell death programs.

Cell death pathways play critical roles in organism development and homeostasis as well as in the pathogenesis of various diseases. While studies over the last decade have elucidated numerous different forms of cell death that can eliminate cells in various contexts, how certain mechanisms impact physiology is still not well understood. Moreover, recent studies have shown that multiple forms cell death can occur in a cell population, with different forms of death eliminating individual cells.

Pan-cancer mutational signature analysis of 111,711 targeted sequenced tumors using SATS.

Tumor mutational signatures are informative for cancer diagnosis and treatment. However, targeted sequencing, commonly used in clinical settings, lacks specialized analytical tools and a dedicated catalogue of mutational signatures. Here, we introduce SATS, a scalable mutational signature analyzer for targeted sequencing data.

Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors.

Background: Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.

Methods: Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study.

CD20/TNFR1 dual-targeting antibody enhances lysosome rupture-mediated cell death in B cell lymphoma.

Obinutuzumab is a therapeutic antibody for B cell non-Hodgkin's Lymphoma (BNHL), which is a glyco-engineered anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and causes binding-induced direct cell death (DCD) through lysosome membrane permeabilization (LMP). Tumour necrosis factor receptor 1 (TNFR1), a pro-inflammatory death receptor, also evokes cell death, partly through lysosomal rupture. As both obinutuzumab- and TNFR1-induced cell deaths are mediated by LMP and combining TNFR1 and obinutuzumab can amplify LMP-mediated cell death, we made dual-targeting antibody for CD20 and TNFR1 to enhance DCD of obinutuzumab.

Magnetoresponsive Artificial Cilia Self-Assembled with Magnetic Micro/Nanoparticles.

Biological cilia have exquisitely organized dynamic ultrafine structures with submicron diameters and exceptional aspect ratios, which are self-assembled with ciliary proteins. However, the construction of artificial cilia with size and dynamic functions comparable to biological cilia remains highly challenging. Here, we propose a self-assembly technique that generates magnetoresponsive artificial cilia with a highly ordered 3D structural arrangement using vapor-phase magnetic particles of varying sizes and shapes.

Purification and Detection of Ubiquitinated Plant Proteins Using Tandem Ubiquitin Binding Entities.

The timing and amplitude of plant signaling are frequently regulated through posttranslational modification of key signaling sectors, which facilitates rapid and flexible responses. Protein ubiquitination can serve as a degradation marker, influence subcellular localization, alter protein-protein interactions, and affect protein activity. Identification of polyubiquitinated proteins has been challenging due to their rapid degradation by the proteasome or removal of modifications by deubiquitination enzymes (DUBs).

Self-Assembled Artificial Nanocilia Actuators.

Self-assembly of nanoparticles (NPs) is a powerful route to constructing higher-order structures. However, the programmed self-assembly of NPs into non-close-packed, 3D, shape-morphing nanocilia arrays remains elusive, whereas dynamically actuated nanometer cilia are universal in living systems. Here, a programmable self-assembly strategy is presented that can direct magnetic NPs into a highly ordered responsive artificial nanocilia actuator with exquisite nanometer 3D structural arrangements.

SUITOR: Selecting the number of mutational signatures through cross-validation.

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requires little assumptions and no numerical approximations to select the optimal number of signatures without overfitting the data.

Comparison of somatic mutation landscapes in Chinese versus European breast cancer patients.

Recent genomic studies suggest that Asian breast cancer (BC) may have distinct somatic features; however, most comparisons of BC genomic features across populations did not account for differences in age, subtype, and sequencing methods. In this study, we analyzed whole-exome sequencing (WES) data to characterize omatic copy number alterations (SCNAs) and mutation profiles in 98 Hong Kong BC (HKBC) patients and compared with those from The Cancer Genome Atlas of European ancestry (TCGA-EA, N = 686), which had similar distributions of age at diagnosis and PAM50 subtypes as in HKBC. We developed a two-sample Poisson model to compare driver gene selection pressure, which reflects the effect sizes of cancer driver genes, while accounting for differences in sample size, sequencing platforms, depths, and mutation calling methods.

Plasma Membrane Localized GCaMP-MS4A12 by Orai1 Co-Expression Shows Thapsigargin- and Ca-Dependent Fluorescence Increases.

Uniquely expressed in the colon, MS4A12 exhibits store-operated Ca entry (SOCE) activity. However, compared to MS4A1 (CD20), a Ca channel and ideal target for successful leukaemia immunotherapy, MS4A12 has rarely been studied. In this study, we investigated the involvement of MS4A12 in Ca influx and expression changes in MS4A12 in human colonic malignancy.

Targeted Deep Sequencing of Bladder Tumors Reveals Novel Associations between Cancer Gene Mutations and Mutational Signatures with Major Risk Factors.

Purpose: Exome- and whole-genome sequencing of muscle-invasive bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non-muscle-invasive bladder cancer with detailed risk factor information.

Experimental Design: We examined the relationship between smoking and other bladder cancer risk factors and somatic mutations and mutational signatures in bladder tumors. Targeted sequencing of frequently mutated genes in bladder cancer was conducted in 322 formalin-fixed paraffin-embedded bladder tumors from a population-based case-control study.

A semiparametric kernel independence test with application to mutational signatures.

Cancers arise owing to somatic mutations, and the characteristic combinations of somatic mutations form mutational signatures. Despite many mutational signatures being identified, mutational processes underlying a number of mutational signatures remain unknown, which hinders the identification of interventions that may reduce somatic mutation burdens and prevent the development of cancer. We demonstrate that the unknown cause of a mutational signature can be inferred by the associated signatures with known etiology.

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes.

Background & Aims: Gallbladder cancer (GBC) is the most common type of biliary tract cancer, but the molecular mechanisms involved in gallbladder carcinogenesis remain poorly understood. In this study, we applied integrative genomics approaches to characterise GBC and explore molecular subtypes associated with patient survival.

Methods: We profiled the mutational landscape of GBC tumours (whole-exome sequencing on 92, targeted sequencing on 98, in total 190 patients).

Efficacy of Acupuncture Treatment to Prevent Cerebral Vasospasm After Subarachnoid Hemorrhage: A Double-Blind, Randomized Placebo-Controlled Trial.

To investigate the efficacy of acupuncture in preventing cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) and explore its underlying mechanism. A randomized, double-blinded, and placebo-controlled trial. Subjects were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea A total of 50 patients admitted with acute SAH.

Evaluation of a Novel Trocar-Site Closure Device in Laparoscopic Surgery.

Background And Objectives: We evaluated the effectiveness and safety of EZ-Close compared to those of hand suture for trocar-site closure according to obesity.

Methods: Fifty-four cases of laparoscopic colorectal surgery were enrolled. For the same patient, the right port site was closed using EZ-Close and left port site was closed by hand suture among cases with port-site diameter ≥10 mm.

Regulation of reactive oxygen species during plant immunity through phosphorylation and ubiquitination of RBOHD.

Production of reactive oxygen species (ROS) is critical for successful activation of immune responses against pathogen infection. The plant NADPH oxidase RBOHD is a primary player in ROS production during innate immunity. However, how RBOHD is negatively regulated remains elusive.

Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance.

HPV16 causes half of cervical cancers worldwide; for unknown reasons, most infections resolve within two years. Here, we analyze the viral genomes of 5,328 HPV16-positive case-control samples to investigate mutational signatures and the role of human APOBEC3-induced mutations in viral clearance and cervical carcinogenesis. We identify four de novo mutational signatures, one of which matches the COSMIC APOBEC-associated signature 2.

A test of homogeneity of distributions when observations are subject to measurement errors.

When the observed data are contaminated with errors, the standard two-sample testing approaches that ignore measurement errors may produce misleading results, including a higher type-I error rate than the nominal level. To tackle this inconsistency, a nonparametric test is proposed for testing equality of two distributions when the observed contaminated data follow the classical additive measurement error model. The proposed test takes into account the presence of errors in the observed data, and the test statistic is defined in terms of the (deconvoluted) characteristic functions of the latent variables.