Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.

Pathological changes in the locus coeruleus-norepinephrine (LC-NE) neurons, the major source of norepinephrine (NE, also known as noradrenaline) in the brain, are evident during the early stages of neurodegenerative diseases (ND). Research on both human and animal models have highlighted the therapeutic potential of targeting the LC-NE system to mitigate the progression of ND and alleviate associated psychiatric symptoms. However, the early and widespread degeneration of the LC-NE system presents a significant challenge for direct intervention in ND.

Nuclear receptor PPARγ targets GPNMB to promote oligodendrocyte development and remyelination.

Myelin injury occurs in brain ageing and in several neurological diseases. Failure of spontaneous remyelination is attributable to insufficient differentiation of oligodendrocyte precursor cells (OPCs) into mature myelin-forming oligodendrocytes in CNS demyelinated lesions. Emerging evidence suggests that peroxisome proliferator-activated receptor γ (PPARγ) is the master gatekeeper of CNS injury and repair and plays an important regulatory role in various neurodegenerative diseases.

Z-Score Experience Replay in Off-Policy Deep Reinforcement Learning.

Reinforcement learning, as a machine learning method that does not require pre-training data, seeks the optimal policy through the continuous interaction between an agent and its environment. It is an important approach to solving sequential decision-making problems. By combining it with deep learning, deep reinforcement learning possesses powerful perception and decision-making capabilities and has been widely applied to various domains to tackle complex decision problems.

Delayed immune-related adverse events profile associated with immune checkpoint inhibitors: a real-world analysis.

Background: Immune-related adverse events (irAEs) typically occur within 3 months of initiating immune-checkpoint inhibitors (ICIs), which has been extensively documented. But the clinical profiles of late-onset irAEs remain inadequately characterized. Therefore, this study aims to quantify the correlation between delayed irAEs and ICIs, and to delineate the profiles of delayed toxicities associated with ICIs using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).

Binary classification from N-Tuple Comparisons data.

Pairwise comparison classification (Pcomp) is a recently thriving weakly-supervised method that generates a binary classifier based on feedback information from comparisons between unlabeled data pairs (one is more likely to be positive than the other). However, this approach turns out challenging in more complex scenarios involving comparisons among more than two instances. To overcome this problem, this paper starts with a comprehensive exploration of the triplet comparisons data (the first instance is more likely to be positive than the second instance, and the second instance is more likely to be positive than the third instance).

Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway.

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties.

Engineering performance of tungsten network reinforced copper matrix composites synthesized by selective laser melting and infiltration.

To solve poor engineering performance of copper-tungsten alloys operated at high temperatures, 3D network tungsten frameworks were prepared using a selective laser melting (SLM) process, and then copper was melted and diffused into these tungsten network structures to form copper matrix composites with different copper contents (i.e. Cu-10vol%W and Cu-30vol%W).

Application of the 'online assessment + FOBT at home' to improve participation and the efficacy of opportunistic screening for colorectal cancer: a retrospective cohort study.

Background: Colorectal cancer (CRC) screening faces two major challenges: insufficient screening coverage and poor adherence. A smartphone applet named "Early Screening Assistant (ESA)" was developed to create an online risk-assessment and fecal occult blood test (FOBT) at home. This retrospective study was designed to evaluate whether the new CRC screening strategy can improve the colonoscopy participation rate (PR) and lesion detection rate (DR).

Fixed-Time Composite Neural Learning Control of Flexible Telerobotic Systems.

This article is devoted to the fixed-time synchronous control for a class of uncertain flexible telerobotic systems. The presence of unknown joint flexible coupling, time-varying system uncertainties, and external disturbances makes the system different from those in the related works. First, the lumped system dynamics uncertainties and external disturbances are estimated successfully by designing a new composite adaptive neural networks (CANNs) learning law skillfully.

Peroxisom proliferator-activated receptor-γ coactivator-1α in neurodegenerative disorders: A promising therapeutic target.

Neurodegenerative disorders (NDDs) are characterized by progressive loss of selectively vulnerable neuronal populations and myelin sheath, leading to behavioral and cognitive dysfunction that adversely affect the quality of life. Identifying novel therapies that attenuate the progression of NDDs would be of significance. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a widely expressed transcriptional regulator, modulates the expression of genes engaged in mitochondrial biosynthesis, metabolic regulation, and oxidative stress (OS).

A Tiny Model for Fast and Precise Ship Detection via Feature Channel Pruning.

It is of great significance to accurately detect ships on the ocean. To obtain higher detection performance, many researchers use deep learning to identify ships from images instead of traditional detection methods. Nevertheless, the marine environment is relatively complex, making it quite difficult to determine features of ship targets.

2', 4'-Dihydroxy-2,3-dimethoxychalcone: A pharmacological inverse agonist of RORγt ameliorating Th17-driven inflammatory diseases by regulating Th17/Treg.

Multiple sclerosis, inflammatory bowel disease and organ transplant rejection are related to Th17 cell development and inflammatory respond. RORγt, a specific transcription factor regulating Th17 cell differentiation, is a pivotal target for the treatment of diseases. However, the clinical application of RORγt inverse agonists reported so far has been hindered due to limited efficacy and toxic side effects.

Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway.

Background And Objectives: Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair.

Composite Adaptive Guaranteed Performances Synchronization Control for Bilateral Teleoperation System With Asymmetrical Time-Varying Delays.

This article studies the guaranteed performance synchronization control problem for networked bilateral teleoperation systems with system uncertainties. The communication channel connecting the master and the slave is subject to asymmetrical varying time delays with unknown upper bounds. The first result on prescribed performance synchronization control for the bilateral teleoperation system under such a weak assumption on the communication time delays is provided.

Discrete Sliding Mode Control Design for Bilateral Teleoperation System via Adaptive Extended State Observer.

The goal of this paper is to improve the synchronization control performance of nonlinear teleoperation systems with system uncertainties in the presence of time delays. In view of the nonlinear discrete states of the teleoperation system in packet-switched communication networks, a new discrete sliding mode control (DSMC) strategy is performed via a new reaching law in task space. The new reaching law is designed to reduce the chattering and improve control performance.

AIM2 promotes the development of non-small cell lung cancer by modulating mitochondrial dynamics.

Mitochondrial fusion and fission dynamics fine-tune cellular calcium homeostasis, ATP production capacity and ROS production and play important roles in cell proliferation and migration. Dysregulated mitochondrial dynamics is closely related to tumor development, but the mechanism of mitochondrial dynamics dysregulation and its role in the development of lung cancer remains unclear. Here, we demonstrate that the DNA sensor protein absent in melanoma 2 (AIM2) is highly expressed in non-small cell lung cancer (NSCLC) cells and that high AIM2 expression is associated with poor prognosis in patients with NSCLC.

Finite Time Control Design for Bilateral Teleoperation System With Position Synchronization Error Constrained.

Due to the cognitive limitations of the human operator and lack of complete information about the remote environment, the work performance of such teleoperation systems cannot be guaranteed in most cases. However, some practical tasks conducted by the teleoperation system require high performances, such as tele-surgery needs satisfactory high speed and more precision control results to guarantee patient' health status. To obtain some satisfactory performances, the error constrained control is employed by applying the barrier Lyapunov function (BLF).

A Disaster Response and Management Competency Mapping of Community Nurses in China.

Background: It is widely accepted in many parts of the world thatcommunity nurses are of vital importance in various phases of disaster response and management. In China, however, it is not clear whether the Chinese community nurses are able to assume disaster-related duties due to the lack of a systematic assessment.

Methods: A pre-designed and well-tested questionnaire was employed to evaluate the competency in disaster response and management among 205 valid registered Chinese community nurses between September and October 2009.