Designing Iterative Learning Schemes for Cooperative-Antagonistic Systems With Random Access Communication Protocols.

In this article, the design issue for an iterative learning controller is investigated for the cooperative-antagonistic system under the scheduling effects of random access protocol (RAP). In order to reflect the heterogeneous characteristic of the underlying system, the dynamics of each node in the cooperative-antagonistic system are described by a two-time-scale system. For the purpose of avoiding data collisions in signal transmissions, the so-called RAP is introduced to schedule the data exchanges among nodes, where the transmission opportunities of nodes are modeled by a sequence of random variables with certain transition probabilities.

Canagliflozin Mediates Mitophagy Through the AMPK/PINK1/Parkin Pathway to Alleviate ISO-induced Cardiac Remodeling.

Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects.

USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation.

Construction of Tetrahymena strains with highly active arsenic methyltransferase genes for arsenic detoxification in aquatic environments.

Biomethylation is an effective means of arsenic detoxification by organisms living in aquatic environments. Ciliated protozoa (including Tetrahymena species) play an important role in the biochemical cycles of aquatic ecosystems and have a potential application in arsenic biotransformation. This study compared arsenic tolerance, accumulation, methylation, and efflux in 11 Tetrahymena species.

Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer.

BACKGROUNDThe tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).METHODSThis study involved 2,600 patients with GC from 9 independent cohorts.

Non-invasive CT imaging biomarker to predict immunotherapy response in gastric cancer: a multicenter study.

Background: Despite remarkable benefits have been provided by immune checkpoint inhibitors in gastric cancer (GC), predictions of treatment response and prognosis remain unsatisfactory, making identifying biomarkers desirable. The aim of this study was to develop and validate a CT imaging biomarker to predict the immunotherapy response in patients with GC and investigate the associated immune infiltration patterns.

Methods: This retrospective study included 294 GC patients who received anti-PD-1/PD-L1 immunotherapy from three independent medical centers between January 2017 and April 2022.

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses.

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N-methyladenosine (mA) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood.

CRISPR/Cas-Based Techniques for Live-Cell Imaging and Bioanalysis.

CRISPR/Cas systems have found widespread applications in gene editing due to their high accuracy, high programmability, ease of use, and affordability. Benefiting from the cleavage properties ( or ) of Cas enzymes, the scope of CRISPR/Cas systems has expanded beyond gene editing and they have been utilized in various fields, particularly in live-cell imaging and bioanalysis. In this review, we summarize some fundamental working mechanisms and concepts of the CRISPR/Cas systems, describe the recent advances and design principles of CRISPR/Cas mediated techniques employed in live-cell imaging and bioanalysis, highlight the main applications in the imaging and biosensing of a wide range of molecular targets, and discuss the challenges and prospects of CRISPR/Cas systems in live-cell imaging and biosensing.

Biology-guided deep learning predicts prognosis and cancer immunotherapy response.

Substantial progress has been made in using deep learning for cancer detection and diagnosis in medical images. Yet, there is limited success on prediction of treatment response and outcomes, which has important implications for personalized treatment strategies. A significant hurdle for clinical translation of current data-driven deep learning models is lack of interpretability, often attributable to a disconnect from the underlying pathobiology.

Asymptotic Stability of Delayed Boolean Networks With Random Data Dropouts.

In real networks, communication constraints often prevent the full exchange of information between nodes, which is inevitable. This brief investigates the problem of time delay and randomly missing data in Boolean networks (BNs). A Bernoulli random variable is assigned to each node to characterize the probability of data packet dropout.

Non-invasive tumor microenvironment evaluation and treatment response prediction in gastric cancer using deep learning radiomics.

The tumor microenvironment (TME) plays a critical role in disease progression and is a key determinant of therapeutic response in cancer patients. Here, we propose a noninvasive approach to predict the TME status from radiological images by combining radiomics and deep learning analyses. Using multi-institution cohorts of 2,686 patients with gastric cancer, we show that the radiological model accurately predicted the TME status and is an independent prognostic factor beyond clinicopathologic variables.

Fibroblast-specific knockout of METTL1 attenuates myocardial infarction-induced cardiac fibrosis.

Cardiac fibrosis, a common pathology in inherited and acquired heart diseases, necessitates the identification of diagnostic and therapeutic targets. Methyltransferase Like 1 (METTL1), an enzyme responsible for RNA modification by methylating guanosine to form m7G, is an emerging area of research in understanding cellular processes and disease pathogenesis. Dysregulation of m7G modification has been implicated in various diseases.

Cancer immunotherapy response prediction from multi-modal clinical and image data using semi-supervised deep learning.

Background And Purpose: Immunotherapy is a standard treatment for many tumor types. However, only a small proportion of patients derive clinical benefit and reliable predictive biomarkers of immunotherapy response are lacking. Although deep learning has made substantial progress in improving cancer detection and diagnosis, there is limited success on the prediction of treatment response.

Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration.

Background: Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion.

Methods: AOM/DSS model in Il11 and Apc/Il11 mice were used to detect tumor growth and CD8 T infiltration.

Initial analytical theory of plasma disruption and experimental evidence.

It is a great physical challenge to achieve controlled nuclear fusion in magnetic confinement tokamak and solve energy shortage problem for decades. In tokamak plasma, large-scale plasma instability called disruption will halt power production of reactor and damage key components. Prediction and prevention of plasma disruption is extremely urgent and important.

ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy.

The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1.

Metformin Collaborates with PINK1/Mfn2 Overexpression to Prevent Cardiac Injury by Improving Mitochondrial Function.

Both mitochondrial quality control and energy metabolism are critical in maintaining the physiological function of cardiomyocytes. When damaged mitochondria fail to be repaired, cardiomyocytes initiate a process referred to as mitophagy to clear defective mitochondria, and studies have shown that PTEN-induced putative kinase 1 (PINK1) plays an important role in this process. In addition, previous studies indicated that peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that promotes mitochondrial energy metabolism, and mitofusin 2 (Mfn2) promotes mitochondrial fusion, which is beneficial for cardiomyocytes.

Angiotensin II-induced calcium overload affects mitochondrial functions in cardiac hypertrophy by targeting the USP2/MFN2 axis.

Ubiquitination, a common type of post-translational modification, is known to affect various diseases, including cardiac hypertrophy. Ubiquitin-specific peptidase 2 (USP2) plays a crucial role in regulating cell functions, but its role in cardiac functions remains elusive. The present study aims to investigate the mechanism of USP2 in cardiac hypertrophy.

Hand-sewn esophagojejunostomy in transthoracic single-port assisted laparoscopic esophagogastrectomy for Siewert type II adenocarcinoma of the esophagogastric junction with esophageal invasion > 3 cm.

Background: An optimal method for digestive tract reconstruction (DTR) in laparoscopic radical resection of Siewert type II adenocarcinoma of esophagogastric junction (AEG) has not yet been standardized. The aim of this study was to evaluate the safety and feasibility of a hand-sewn esophagojejunostomy (EJ) technique during transthoracic single-port assisted laparoscopic esophagogastrectomy (TSLE) for Siewert type II AEG with esophageal invasion > 3 cm.

Methods: The perioperative clinical data and short-term outcomes for patients who underwent TSLE using hand-sewn EJ for Siewert type II AEG with esophageal invasion > 3 cm between March 2019 and April 2022 have been retrospectively reviewed.

Nested Group Testing Procedure.

We investigated the false-negative, true-negative, false-positive, and true-positive predictive values from a general group testing procedure for a heterogeneous population. We show that its false (true)-negative predictive value of a specimen is larger (smaller), and the false (true)-positive predictive value is smaller (larger) than that from individual testing procedure, where the former is in aversion. Then we propose a nested group testing procedure, and show that it can keep the sterling characteristics and also improve the false-negative predictive values for a specimen, not larger than that from individual testing.