TYK2 inhibition enhances Treg differentiation and function while preventing Th1 and Th17 differentiation.

Janus kinase (JAK) inhibitors are widely used to inhibit inflammatory cytokine signaling in autoimmune and inflammatory diseases, but their effect on regulatory T cells (Tregs) is poorly characterized. We investigated the effect of a JAK inhibitor, upadacitinib, on human Treg differentiation and phenotype in comparison to BMS-986202, a selective Tyrosine kinase 2 (TYK2) inhibitor. Both upadacitinib and BMS-986202 blocked naive CD4 T cell differentiation into Th1/17 cells, but only BMS-986202 and a related TYK2 inhibitor, deucravacitinib, spared interleukin-2 (IL-2) signaling and Treg induction.

Multimodal Luminescence in CaInTaO:Pr Phosphors: Applications in Dynamic Anticounterfeiting and Optical Thermometry.

The advancement of phosphors with multiple capabilities has garnered significant interest, especially for applications in optical thermometry and dynamic anticounterfeiting technologies. In this work, we successfully synthesized a series of color-tunable Pr single-doped CaInTaO (CITO:Pr) persistent luminescence (PersL) materials by using a high-temperature solid-state method. The crystal structure of the obtained CITO:Pr phosphor was characterized by X-ray diffraction and Rietveld refinement.

High Coverage Carbon Monoxide Adsorption on a ZnAlO Surface: A DFT Study.

ZnAlO spinel is widely used as a support in various reactions due to its thermal stability. Investigating the interaction between CO and ZnAlO is essential for understanding the surface reaction mechanisms. In the present work, density functional theory (DFT) and atomistic thermodynamics were employed to investigate the adsorption of CO on perfect and O-defective ZnAlO surfaces at varying CO coverages.

Q fever diagnosed using metagenomic next-generation sequencing in Guangdong Province, China.

Q fever is a zoonotic disease caused by infection with (). Due to its atypical symptoms and the absence of specific detection methods, Q fever is underdiagnosed commonly. Herein, we report a case of Q fever confirmed by metagenomic next-generation sequencing (mNGS) in March 2024 in Guangdong Province, China.

Simultaneous profiling of native-state proteomes and transcriptomes of neural cell types using proximity labeling.

Deep molecular phenotyping of cells at transcriptomic and proteomic levels is an essential first step to understanding cellular contributions to development, aging, injury, and disease. Since proteome and transcriptome level abundances only modestly correlate with each other, complementary profiling of both is needed. We report a novel method called simultaneous protein and RNA -omics (SPARO) to capture the cell type-specific transcriptome and proteome simultaneously from both in vitro and in vivo experimental model systems.

Visible to near-infrared emissions of BiMoO: Pr multifunctional phosphors for multi-mode temperature sensing, white LEDs and bioimaging.

Research on multifunctional luminous materials has garnered a lot of interest in the fields of optical sensing, biological imaging, white light-emitting diodes illumination, etc. A novel multifunctional phosphor of Pr-doped BiMoO (BMO: Pr), created via the solid-state method, was investigated in this work. X-ray diffraction, scanning electron microscopy, diffuse reflectance spectroscopy, photoluminescence spectra, and fluorescence decay curves were employed to analyze the produced phosphors.

Preventive effect of Tyr-Pro, a blood-brain barrier transportable dipeptide, on memory impairment in SAMP8 mice.

In a series of studies on blood-brain barrier transportable peptides, a soybean dipeptide, Tyr-Pro, penetrated the mouse brain parenchyma after oral intake and improved short and long memory impairment in acute Alzheimer's model mice. Here, we aimed to clarify the anti-dementia effects of this peptide administered to SAMP8 mice prior to dementia onset. At the end of the 25-week protocol in 16-week-old SAMP8 mice, Tyr-Pro (10 mg/kg/day) significantly improved the reduced spatial learning ability compared with that in the control and amino acid (Tyr + Pro) groups as indicated by the results of Morris water maze tests conducted for five consecutive days.

Impact of Peptide Transport and Memory Function in the Brain.

Recent studies have reported the benefits of food-derived peptides for memory dysfunction. Beyond the physiological effects of peptides, their bioavailability to the brain still remains unclear since the blood-brain barrier (BBB) strictly controls the transportation of compounds to the brain. Here, updated transportation studies on BBB transportable peptides are introduced and evaluated using in vitro BBB models, in situ perfusion, and in vivo mouse experiments.

Complete genome sequence of a novel mitovirus isolated from the phytopathogenic fungus Alternaria alternata causing apple leaf blotch.

In this study, a novel mitovirus, tentatively designated as "Alternaria alternata mitovirus 2" (AaMV2), was isolated from the fungus Alternaria alternata f. sp. mali causing apple leaf blotch disease.

Cross-species transmission of a novel bisegmented orfanplasmovirus in the phytopathogenic fungus .

Mycoviruses have been found in various fungal species across different taxonomic groups, while no viruses have been reported yet in the fungus In this study, a novel orfanplasmovirus, namely Exserohilum rostratum orfanplasmovirus 1 (ErOrfV1), was identified in the strain JZ1 from maize leaf. The complete genome of ErOrfV1 consists of two positive single-stranded RNA segments, encoding an RNA-dependent RNA polymerase and a hypothetical protein with unknown function, respectively. Phylogenetic analysis revealed that ErOrfV1 clusters with other orfanplasmoviruses, forming a distinct phyletic clade.

Unravelling the mechanism of columnar-to-equiaxed transition and grain refinement in ultrasonic vibration assisted laser welding of Ti6Al4V titanium alloy.

In this study, the microstructural evolution and mechanical properties of Ti6Al4V titanium alloy welded joints subjected to ultrasonic assisted laser welding were scrutinized, while numerical simulations were employed to explicate the grain refinement mechanism. The simulations indicate that the ultrasonic vibration significantly improves the overall fluidity and temperature of the molten pool. Under the identical condition of laser power and welding speed (1500 W, 1.

Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology.

Dysfunction in fast-spiking parvalbumin interneurons (PV-INs) may represent an early pathophysiological perturbation in Alzheimer's Disease (AD). Defining early proteomic alterations in PV-INs can provide key biological and translationally-relevant insights. We used cell-type-specific in-vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state PV-IN proteomes.

Adiponectin-Receptor Agonistic Dipeptide Tyr-Pro Stimulates the Acetylcholine Nervous System in NE-4C Cells.

The dipeptide Tyr-Pro has physiological potential for intact transportability into the brain parenchyma, prevention of cognitive impairment, and an adiponectin receptor 1 (AdipoR1) agonistic effect. The present study aimed to understand the effect of Tyr-Pro on the acetylcholine (ACh) nervous system and its underlying mechanism in NE-4C nerve cells. Concentration-dependent ACh production was induced by stimulation with Tyr-Pro and AdipoRon (an AdipoR1 agonist), along with the expression of AdipoR1 and choline acetyltransferase (ChAT) in NE-4C cells.

Near infrared emissions from both high efficient quantum cutting (173%) and nearly-pure-color upconversion in NaY(WO):Er/Yb with thermal management capability for silicon-based solar cells.

Raising photoelectric conversion efficiency and enhancing heat management are two critical concerns for silicon-based solar cells. In this work, efficient Yb infrared emissions from both quantum cutting and upconversion were demonstrated by adjusting Er and Yb concentrations, and thermo-manage-applicable temperature sensing based on the luminescence intensity ratio of two super-low thermal quenching levels was discovered in an Er/Yb co-doped tungstate system. The quantum cutting mechanism was clearly decrypted as a two-step energy transfer process from Er to Yb.

The Combination of Upconversion Nanoparticles and Perovskite Quantum Dots with Temperature-Dependent Emission Colors for Dual-Mode Anti-Counterfeiting Applications.

Novel and high-security anti-counterfeiting technology has always been the focus of attention and research. This work proposes a nanocomposite combination of upconversion nanoparticles (UCNPs) and perovskite quantum dots (PeQDs) to achieve color-adjustable dual-mode luminescence anti-counterfeiting. Firstly, a series of NaGdF: Yb/Tm UCNPs with different sizes were synthesized, and their thermal-enhanced upconversion luminescence performances were investigated.

A memory-improving dipeptide, Tyr-Pro, can reach the mouse brain after oral administration.

The transport and accumulation of orally administered functional food-derived peptides in the brain was not fully explored. Thus, in the present study, we aimed to provide critical evidence regarding brain accumulation of a memory-improving soy dipeptide, Tyr-Pro, following oral administration. Stable isotope-labeled Tyr-Pro (Tyr-[C,N]Pro) was orally administered to male ICR mice at 10 or 100 mg/kg.

Structure-activity relationship study of central pyridine-derived TYK2 JH2 inhibitors: Optimization of the PK profile through C4' and C6 variations.

Efforts directed at improving potency and preparing structurally different TYK2 JH2 inhibitors from the first generation of compounds such as 1a led to the SAR study of new central pyridyl based analogs 2-4. The current SAR study resulted in the identification of 4h as a potent and selective TYK2 JH2 inhibitor with distinct structural differences from 1a. In this manuscript, the in vitro and in vivo profiles of 4h are described.

Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology.

One of the earliest pathophysiological perturbations in Alzheimer's Disease (AD) may arise from dysfunction of fast-spiking parvalbumin (PV) interneurons (PV-INs). Defining early protein-level (proteomic) alterations in PV-INs can provide key biological and translationally relevant insights. Here, we use cell-type-specific in vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state proteomes of PV interneurons.

Efficacy of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) on the amygdala-HPA axis in rats with kidney-deficiency symptom pattern induced by hydrocortisone.

Objective: To investigated the effects of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney- deficiency symptom pattern (KYDS).

Methods: Sixty male Sprague Dawley rats were randomly divided into a control group ( 12) and an experimental group ( 48). Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

Purpose: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway.

Methods: The rat SCI models were established by the impact method.

[Effect of moxibustion on Nogo/neurotrophin receptor signaling pathway in rats with cerebral ischemia/reperfusion injury].

Objective: To observe the effect of moxibustion treatment on the expression of Nogo-A, Nogo receptor (NgR), neurotrophin receptor p75 (p75NTR) and leucine rich repeat and Ig domain containing 1 (Lingo-1) in brain tissue of rats with cerebral ischemia/reperfusion injury (CI/RI), so as to analyze its mechanism underlying improvement of CI/RI.

Methods: Male SD rats were randomly divided into sham operation group (16 rats), model group (17 rats), NEP1-40 (extracellular peptide residues 1-40, a blocker targeting NgR) group (model+blocker, 17 rats) and moxibustion group (model+moxibustion, 17 rats). The CI/RI model was established by occlusion of the left middle cerebral artery (MCAO).

Cell type-specific biotin labeling in vivo resolves regional neuronal and astrocyte proteomic differences in mouse brain.

Proteomic profiling of brain cell types using isolation-based strategies pose limitations in resolving cellular phenotypes representative of their native state. We describe a mouse line for cell type-specific expression of biotin ligase TurboID, for in vivo biotinylation of proteins. Using adenoviral and transgenic approaches to label neurons, we show robust protein biotinylation in neuronal soma and axons throughout the brain, allowing quantitation of over 2000 neuron-derived proteins spanning synaptic proteins, transporters, ion channels and disease-relevant druggable targets.