Iridium-catalyzed asymmetric reductive amination of C2-acylpyridines.

Chiral 1-pyridin-2-yl-ethylamines are significant building blocks for synthetic chemistry and pharmaceutical sciences, while their stereoselective and practical synthesis remains challenging and usually troublesome. Herein, we present a novel iridium-catalyzed direct asymmetric reductive amination of 2-acylpyridines with anilines, affording a series of chiral 1-pyridin-2-yl-ethylamines with up to 97% yield and 95% ee. A 5 mmol scale reaction is also performed to demonstrate the practicality of this method.

Heterologous expression of heat-resistant obscure (Hero) proteins enhances thermotolerance in plants.

Improving plant stress tolerance and crop productivity is critical. Membraneless biomolecular condensates formed via liquid-liquid phase separation (LLPS) have been shown to mediate plant responses to various stresses, including heat. While recent advances have elucidated the LLPS role in stress tolerance mechanisms, translating these findings into practical strategies for enhancing plant resilience remains a formidable challenge.

Asparagine endopeptidase (AEP) inhibitor formulation via zein-based nanoparticle improves the therapeutic efficacy toward Alzheimer's disease.

Asparagine endopeptidase (AEP) plays a critical role in Alzheimer's disease (AD) by cleaving amyloid precursor protein (APP) at N585 and tau protein at N368. Genetic deletion or pharmacological inhibition of AEP using compound 11a ameliorates AD pathology in murine models. To improve the therapeutic potential of 11a, we synthesized structural analogs and developed a zein-based nanoparticle delivery system to enhance pharmacokinetics.

A supramolecular approach to improve the performance and operational stability of all-perovskite tandem solar cells.

Wide-bandgap perovskite is pivotal as a photoactive layer in the top cell of prevailing tandem solar cells. However, the intrinsic instability of wide-bandgap perovskite solar cells is predominantly attributed to the vacancy defects caused by multiple ion migration. Here, we incorporate an ether ring super-molecule into perovskite.

Venus flytraps' metabolome analysis discloses the metabolic fate of prey animal foodstock.

Carnivorous plants such as the Venus flytrap Dionaea muscipula survive in nutrient-poor habitats by attracting and consuming animals. Upon deflection of the touch-sensitive trigger hairs, the trap closes instantly. Panicking prey repeatedly collides with trigger hairs, which activate the endocrine system: mechano- and chemosensors translate the information on the prey's nature, size, and activity into jasmonate-dependent lytic enzyme secretion.

Discovery of novel Cytochrome bd oxidase inhibitors against Mycobacterium tuberculosis.

Drug-resistant Mycobacterium tuberculosis remains a major challenge to effective tuberculosis (TB) control. Cytochrome bd oxidase (Cyt-bd), a critical terminal oxidase within the electron transport chain of M. tuberculosis, maintains bacterial survival under respiratory stress but remains an underexplored therapeutic target.

ShiftKD: Benchmarking knowledge distillation under distribution shift.

Knowledge Distillation (KD) transfers knowledge from large models to small models and has recently achieved remarkable success. However, the reliability of existing KD methods in real-world applications, especially under distribution shift, remains underexplored. Distribution shift refers to the data distribution drifts between the training and testing phases, and this can adversely affect the efficacy of KD.

Attenuation of Ca signaling by overexpression of PMCA2 affects the microglial response to pathological events.

Microglia strongly impact the pathologic course of brain diseases and injuries. Intracellular Ca dynamics serve as central integrators, connecting microglial sensing capacity to their responses. We generated a mouse line with microglial overexpression of plasma membrane Ca-ATPase (PMCA)2, a central regulator of cytoplasmic Ca homeostasis.

Precise knock-in of stress-responsive cis-regulatory elements using gene targeting for improving abiotic stress tolerance in plants.

Plants are subjected to a multitude of biotic and abiotic stresses, which frequently impede growth and may result in economic losses. One of the primary objectives in plant breeding is the development of stress-tolerant varieties. The modification of protein-coding sequences through gene editing and transgenic methods is a widely utilized approach for enhancing stress tolerance in plants.

Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress.

Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation patterns under acute versus chronic social defeat stress. However, differences in physiological impacts and regulatory pathways between these stress conditions remain understudied.

Development of Positron Emission Tomography Radiotracers for Imaging α-Synuclein Aggregates.

Neurodegenerative diseases (NDDs) that are characterized by the accumulation of alpha-synuclein (α-syn) aggregates in both neurons and the non-neuronal cells of the brain are called synucleinopathies. The most common synucleinopathies includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Significant progress has been made in the development of positron emission tomography (PET) radiotracers for synucleinopathies, yielding several α-syn tracers that have entered clinical studies.

Convergent adaptive control based prescribed-time synchronization of switched fuzzy competitive network systems with time-varying delays.

This paper addresses the prescribed-time control problem for discontinuous fuzzy neutral-type competitive neural networks (FNTCNNs) featuring switchings and time-varying delays. Notably, FNTCNNs constitute a generalized class of singularly perturbed Filippov systems. The establishment of a prescribed-time stability lemma for time-varying delay singularly perturbed systems remains a critical yet unresolved challenge.

TORC: Target-Oriented Reference Construction for supervised cell-type identification in scRNA-seq.

Cell-type identification is a crucial step in single cell RNA-seq (scRNA-seq) data analysis, for which supervised methods are preferred due to their accuracy and efficiency. Performance is highly dependent on the quality of the reference data, but there is no method for selecting and constructing reference data. We develop Target-Oriented Reference Construction (TORC), a widely applicable strategy for constructing reference data given a target dataset for scRNA-seq supervised cell-type identification.

Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition.

Background: Asparagine endopeptidase (AEP) is implicated in the pathogenesis of Alzheimer's disease (AD) by cleaving Tau at residue N368, accelerating its hyperphosphorylation and aggregation. The Tau N368/t-Tau ratio in cerebrospinal fluid (CSF) serves as a superior biomarker compared to established biomarkers (p-Tau 181/217) for correlating with tau pathology and synaptic dysfunction in patients with AD, highlighting its diagnostic and therapeutic potential.

Methods: We evaluated the therapeutic efficacy of a Tau N368-specific antibody in two mouse models: Tau P301S (tauopathy) and 3xTg (AD with Aβ/tau pathology).

Transcranial direct current stimulation alleviates chronic pain in knee osteoarthritis by modulating microglial and astrocytic polarization and neuroinflammation.

Aims: Knee osteoarthritis (KOA) chronic pain is linked to neuroinflammation mediated by reactive astrocytes in the primary somatosensory cortex (S1). Reactive astrocytes are classified into neurotoxic A1 and neuroprotective A2 phenotypes, with activated microglia promoting A1 astrocyte formation during chronic pain progression. This study aimed to investigate whether transcranial direct current stimulation (tDCS) can alleviate KOA chronic pain by modulating glial phenotype conversion and neuroinflammatory processes.

Asparagine endopeptidase cleaves apolipoprotein A1 and accelerates pathogenesis of atherosclerosis.

Atherosclerosis is a slowly progressing inflammatory disease characterized with cholesterol disorder and intimal plaques. Asparagine endopeptidase (AEP) is an endolysosomal protease that is activated under acidic conditions and is elevated substantially in both plasma and plaques of patients with atherosclerosis. However, how AEP accelerates atherosclerosis development remains incompletely understood, especially from the view of cholesterol metabolism.

Neuronal C/EBPβ Shortens the Lifespan via Inactivating NAMPT.

The brain plays a central role in aging and longevity in diverse model organisms. Morphological and functional alteration in the aging brain elicits age-associated neuronal dysfunctions. However, the primary mechanism deteriorating the brain functions to regulate the aging process remains incompletely understood.

The Mechanism of Ranunculus ternatus Thunb. against Esophageal Squamous Cell Carcinoma Based on Network Pharmacology and Experimental Verification.

Background: Esophageal Squamous Cell Carcinoma (ESCC) remains a significant global health challenge, underscoring the urgent need for the development of innovative therapeutic approaches. Ranunculus ternatus Thunb., a traditional herbal medicine, has shown potential anticancer properties, but its pharmacological mechanisms against ESCC remain poorly understood.

TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages. TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming.

Identification of NMT1/MA/VPS15 signal pathway as potential therapeutic target in rat cerebral ischemia injury.

Fatty acids play a critical role in cerebral ischemia injury through the regulation of lipid metabolism and inflammatory signaling. Myristic acid (MA), a 14‑carbon saturated fatty acid, serves as a substrate of N-myristoyltransferase 1 (NMT1) and modulates protein function and subcellular localization via myristoylation. We show here that intraperitoneal injection of MA has no effect on the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury.

One nanoparticle delivers two different neuroprotective amino acids into ischemic brain and protects against neuronal death in rat cerebral ischemia injury.

Previous studies have proven that glycine and proline are neuroprotective but have very low permeability through the blood-brain barrier (BBB), which is a major barrier to the application of these neuroprotective amino acids in the therapy of brain injury. In this study, we aimed to develop a therapeutic strategy by which one chitosan nanoparticle could deliver two different neuroprotective amino acids, glycine and proline, into the rat ischemic brain to confer neuroprotection in a rat model of cerebral ischemia-reperfusion (I/R) injury. Using the ion cross-linking method, we developed a preparation in which one chitosan nanoparticle was simultaneously loaded with glycine and proline (AA-NPs).

Neuritin-specific antibody impedes the Treg-mediated suppression of anti-tumor immunity and enhances response to anti-PD1.

Regulatory T cells (Tregs) and effector T cells play critical roles in tumor immunity, with Tregs suppressing immune responses and contributing to an immunosuppressive tumor microenvironment (TME). Neuritin-1 (Nrn), a neuropeptide, has been identified to enhance Treg expansion. However, its role in T cell biology and tumor development remains unclear.

Single-cell transcriptome analyses of PBMCs reveal the immunological characteristics of individuals with phlegm-dampness constitution.

Ancient traditional Chinese medicine (TCM) doctrine says "The superior doctor prevents illnesses," pointing out preventative medicine as the ultimate goal for medical care. TCM recognizes that genetic predisposition and environmental and lifestyle influences contribute to diseases. It divides people into eight constitutions in addition to one normal/healthy kind.

Robotic-based Experimental Procedure for Colorimetric Gas Sensing Development.

This paper presents a robot-based experimental program aimed at developing an efficient and fast colorimetric gas sensor. The program employs an automated Design-Build-Test-learning (DBTL) approach, which optimizes the search process iteratively while optimizing multiple recipes for different concentration intervals of the gas. In each iteration, the algorithm generates a batch of recipe suggestions based on various acquisition functions, and with the increase in the number of iterations, the values of weighted objective function for each concentration interval significantly improve.

CXCL1-CXCR1 pathway mediates hyperthermia-induced microglial processes retraction.

In infants, high fever is associated with robust microglial morphological changes, including process retraction and soma enlargement, which contribute to fever-induced seizures. The molecular mechanisms underlying dynamic process retraction during hyperthermia remain poorly understood. Using a hyperthermia-induced microglial activation model in postnatal day 8 mice, we identified the CXCL1-CXCR1 interaction as a key regulator of process retraction.