A Neural Network for Segmenting Tumours in Ultrasound Rectal Images.

Ultrasound imaging is the most cost-effective approach for the early detection of rectal cancer, which is a high-risk cancer. Our goal was to design an effective method that can accurately identify and segment rectal tumours in ultrasound images, thereby facilitating rectal cancer diagnoses for physicians. This would allow physicians to devote more time to determining whether the tumour is benign or malignant and whether it has metastasized rather than merely confirming its presence.

RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes.

The leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and their phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the LRRK2-regulated RAB GTPase in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brain through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis.

Targeting Specific Kinase Substrates Rescues Increased Colitis Severity Induced by the Crohn's Disease-Linked LRRK2-N2081D Variant.

LRRK2 contains a kinase domain where both the N2081D Crohn's disease (CD) risk and the G2019S Parkinson's disease (PD)-pathogenic variants are located. The mechanisms by which the N2081D variant increase CD risk, and how these adjacent mutations result in distinct diseases, remain unclear. To investigate the pathophysiology of the CD-linked LRRK2 N2081D variant, we generated a knock-in (KI) mouse model and compared its effects to those of the LRRK2-G2019S mutation.

RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes.

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis.

Adaptive Gait Acquisition through Learning Dynamic Stimulus Instinct of Bipedal Robot.

Standard alternating leg motions serve as the foundation for simple bipedal gaits, and the effectiveness of the fixed stimulus signal has been proved in recent studies. However, in order to address perturbations and imbalances, robots require more dynamic gaits. In this paper, we introduce dynamic stimulus signals together with a bipedal locomotion policy into reinforcement learning (RL).

Ultra-low frequency magnetic energy focusing for highly effective wireless powering of deep-tissue implantable electronic devices.

The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices.

Silencing Parkinson's risk allele Rit2 sex-specifically compromises motor function and dopamine neuron viability.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and arises from dopamine (DA) neuron death selectively in the substantia nigra pars compacta (SNc). Rit2 is a reported PD risk allele, and recent single cell transcriptomic studies identified a major RIT2 cluster in PD DA neurons, potentially linking Rit2 expression loss to a PD patient cohort. However, it is still unknown whether Rit2 loss itself impacts DA neuron function and/or viability.

Coaxially printed magnetic mechanical electrical hybrid structures with actuation and sensing functionalities.

Soft electromagnetic devices have great potential in soft robotics and biomedical applications. However, existing soft-magneto-electrical devices would have limited hybrid functions and suffer from damaging stress concentrations, delamination or material leakage. Here, we report a hybrid magnetic-mechanical-electrical (MME) core-sheath fiber to overcome these challenges.

Rit2 silencing in dopamine neurons drives a Parkinsonian phenotype.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and arises from dopamine (DA) neuron death selectively in the substantia nigra pars compacta (SNc). Rit2 is a reported PD risk allele, and recent single cell transcriptomic studies identified a major RIT2 cluster in PD DA neurons, potentially linking Rit2 expression loss to a PD patient cohort. However, it is still unknown whether Rit2 loss itself is causative for PD or PD-like symptoms.

The Impact of Digital Economy on the Efficiency of Green Financial Investment in China's Provinces.

The global digital operation of finance has accelerated, and the transformation and upgrading of the financial industry has been fully empowered by digital technology, which has promoted the development of traditional financial industry toward green finance. Accelerating the pace of China's entry into the digital economy era has given the green financial industry new opportunities in its digital transformation. Therefore, the research reported in this paper selects provincial panel data and discusses the impact efficiency of the digital economy on green financial investment in China by static panel OLS and the threshold model method, and constructs a threshold model with regional industry scale and green financial audit as threshold variables.

High-throughput fabrication of soft magneto-origami machines.

Soft magneto-active machines capable of magnetically controllable shape-morphing and locomotion have diverse promising applications such as untethered biomedical robots. However, existing soft magneto-active machines often have simple structures with limited functionalities and do not grant high-throughput production due to the convoluted fabrication technology. Here, we propose a facile fabrication strategy that transforms 2D magnetic sheets into 3D soft magneto-active machines with customized geometries by incorporating origami folding.

, a Cornerstone Gene in Insect Life History.

Insect life cycle is coordinated by hormones and their downstream effectors. Krüppel homolog1 (Kr-h1) is one of the crucial effectors which mediates the actions of the two critical hormones of insects, the juvenile hormone (JH) and 20-hydroxyecdysone (20E). It is a transcription factor with a DNA-binding motif of eight CH zinc fingers which is found to be conserved among insect orders.

4D Printing of Magnetoactive Soft Materials for On-Demand Magnetic Actuation Transformation.

Four-dimensional (4D) printed magnetoactive soft material (MASM) with a three-dimensional (3D) patterned magnetization profile possesses programmable shape transformation and controllable locomotion ability, showing promising applications in actuators and soft robotics. However, typical 4D printing strategies for MASM always introduced a printing magnetic field to orient the magneto-sensitive particles in polymers. Such strategies not only increase the cooperative control complexity of a 3D printer but may also induce local agglomeration of magneto-sensitive particles, which disturbs the magnetization of the already-printed structure.

Programmable Transformation and Controllable Locomotion of Magnetoactive Soft Materials with 3D-Patterned Magnetization.

Magnetoactive soft material (MASM) is distinguished for multifunctional shape manipulations under magnetic actuation, thereby holding a great promise in soft robotics, actuators, electronics, and metamaterials. However, the current research of MASM with continuum hard-magnetic profiles focuses little on the transformation mechanism, high dimensional shape transformation, and multistable locomotion. Herein, we developed a systematic methodology for programmable transformation and controllable locomotion of MASM with 3D-patterned continuum magnetization.

Synj1 haploinsufficiency causes dopamine neuron vulnerability and alpha-synuclein accumulation in mice.

Synaptojanin1 (synj1) is a phosphoinositide phosphatase with dual SAC1 and 5'-phosphatase enzymatic activities in regulating phospholipid signaling. The brain-enriched isoform has been shown to participate in synaptic vesicle (SV) recycling. More recently, recessive human mutations were identified in the two phosphatase domains of SYNJ1, including R258Q, R459P and R839C, which are linked to rare forms of early-onset Parkinsonism.

Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration.

Microglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing; however, the precise mechanisms remain poorly understood. Herein, we report a neuroprotective role for microglia in the clearance of neuron-released α-synuclein.

Autophagy protein NRBF2 has reduced expression in Alzheimer's brains and modulates memory and amyloid-beta homeostasis in mice.

Background: Dysfunctional autophagy is implicated in Alzheimer's Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD.

Methods: To further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs.

The landscape of multiscale transcriptomic networks and key regulators in Parkinson's disease.

Genetic and genomic studies have advanced our knowledge of inherited Parkinson's disease (PD), however, the etiology and pathophysiology of idiopathic PD remain unclear. Herein, we perform a meta-analysis of 8 PD postmortem brain transcriptome studies by employing a multiscale network biology approach to delineate the gene-gene regulatory structures in the substantia nigra and determine key regulators of the PD transcriptomic networks. We identify STMN2, which encodes a stathmin family protein and is down-regulated in PD brains, as a key regulator functionally connected to known PD risk genes.

Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons.

Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear.

Nucleoporin Nup358 facilitates nuclear import of Methoprene-tolerant (Met) in an importin β- and Hsp83-dependent manner.

The bHLH-PAS transcription factor, Methoprene-tolerant (Met), functions as a juvenile hormone (JH) receptor and transduces JH signals by directly binding to E-box like motifs in the regulatory regions of JH response genes. Nuclear localization of Met is crucial for its transcriptional activity. Our previous studies have shown that the chaperone protein Hsp83 facilitates JH-induced Met nuclear import in Drosophila melanogaster.