CS12192 Reverses Alopecia Areata by Selectively Targeting JAK3/JAK1/TBK1.

The approval of JAK inhibitors, represented by baricitinib, for the treatment of alopecia areata (AA) has ushered in a new era. However, their excessive immunosuppressive effects have also raised numerous concerns. Therefore, the development of JAK inhibitors with different selectivities may enhance drug safety while maintaining therapeutic efficacy.

Sleep-Associated Traits and Hearing Difficulties in Noise: A Bidirectional Mendelian Randomization Study.

Objectives: The aim of this study was to investigate the causal relationships between sleep-associated traits and hearing difficulties in noise (HDinN) by Mendelian randomization (MR) analysis.

Design: Single nucleotide polymorphisms associated with chronotype, insomnia, sleep duration, daytime dozing or sleeping, and ease of getting up in the morning were extracted from European population genome-wide association study pooled data for bidirectional MR analysis. The MR-Egger regression, the inverse variance weighted technique, and the weighted median method were used for data analysis.

Rapidly synthesized porous alloy heterostructure catalysts for ultra-low energy water splitting under industrial conditions.

RANEY® nickel is extensively applied in industrial settings for its low cost and ease of scale-up. Nevertheless, its poor activity and high energy consumption restrict the progress of large-scale hydrogen production. Here, we used a RANEY® nickel substrate combined with a one-step electrodeposition method to prepare porous NiFe@RN bifunctional catalysts.

Identification of novel drug targets for osteoarthritis by integrating genetics and proteomes from blood.

Background: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis.

Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway.

Unlabelled: Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation, and impedes atherosclerosis progression. However, the regulatory mechanisms of efferocytosis under atherogenic conditions remain poorly understood.

Inhibition of PKC-δ retards kidney fibrosis via inhibiting cGAS-STING signaling pathway in mice.

Kidney fibrosis is considered to be the ultimate aggregation pathway of chronic kidney disease (CKD), but its underlying mechanism remains elusive. Protein kinase C-delta (PKC-δ) plays critical roles in the control of growth, differentiation, and apoptosis. In this study, we found that PKC-δ was highly upregulated in human biopsy samples and mouse kidneys with fibrosis.

CS12192: A novel selective and potent JAK3 inhibitor mitigates acute graft-versus-host disease in bone marrow transplantation.

Background: Despite the significant role of JAK3 in various autoimmune diseases, including graft-versus-host disease (GVHD), there has been a lack of potent and selective JAK3 inhibitors specifically studied for GVHD. In our preclinical investigations, we evaluated a novel JAK3 inhibitor called CS12192, which is already undergoing clinical investigation in autoimmune diseases.

Methods: We evaluated the efficacy of CS12192 in GVHD through mixed lymphocyte reaction (MLR) in both mouse and human cells, as well as allogeneic bone marrow transplantation (BMT) in a murine model.

A Data Compression Method for Wellbore Stability Monitoring Based on Deep Autoencoder.

The compression method for wellbore trajectory data is crucial for monitoring wellbore stability. However, classical methods like methods based on Huffman coding, compressed sensing, and Differential Pulse Code Modulation (DPCM) suffer from low real-time performance, low compression ratios, and large errors between the reconstructed data and the source data. To address these issues, a new compression method is proposed, leveraging a deep autoencoder for the first time to significantly improve the compression ratio.

CS12192, a novel JAK3/JAK1/TBK1 inhibitor, attenuates autoimmune dermatoses in murine models.

Objective: Autoimmune dermatosis (AID) occurs when the body's immune system attacks skin or tissue, leading to various types of skin disorders or injuries. Recent studies show that Janus kinases (JAKs) play critical roles in autoimmune diseases including AID by regulating multiple cytokine signaling pathways. CS12192, a novel JAK3/JAK1/TBK1 inhibitor, has been reported to exert ameliorative effects in rheumatoid arthritis.

Irisin ameliorates UUO-induced renal interstitial fibrosis through TGF-β1/periostin/MMP-2 signaling pathway.

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice.

TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease.

Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood.

Dysbiosis of the Gut Microbiota in Patients with Psoriatic Arthritis is Closely Related to Lymphocyte Subsets and Cytokines.

The purpose of this research was to characterize the microbiota of patients with psoriatic arthritis (PsA) and to compare the relationship between the microbiota and peripheral lymphocyte subsets and cytokines. We collected stool samples from 13 PsA patients and 26 sex- and age-matched healthy controls (HCs) and researched the gut microbiota by sequencing the V3-V4 variable region of the bacterial 16S rRNA gene with the Illumina Miseq PE300 system. Flow cytometry was used to assess the peripheral lymphocyte subsets in these participants.

Genetic association between interleukin-17 and susceptibility to rheumatoid arthritis.

Background: The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown.

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients.

Objective: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.

Research Design And Methods: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group.

Genetically predicted obstructive sleep apnea is causally associated with an increased risk for periodontitis.

Background: Although obstructive sleep apnea (OSA) and periodontitis are associated, whether this association is causative is uncertain.

Methods: We conducted a bidirectional Mendelian randomization (MR) analysis using data from publically accessible genome-wide association studies. The single-nucleotide polymorphisms (SNPs) for OSA were derived from 16,761 cases and 201,194 controls.

Evaluating the effect of body mass index and 25-hydroxy-vitamin D level on basal cell carcinoma using Mendelian randomization.

Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively.

B cell subsets-related biomarkers and molecular pathways for systemic lupus erythematosus by transcriptomics analyses.

Background: Systemic lupus erythematosus (SLE), an autoimmune disease, is characterised by B-cell abnormalities and a loss of tolerance that can produce autoantibody. However, the imperative genes and molecular pathways involved in the change of B cell populations remain unclear.

Methods: The expression of B cell subsets between SLE and healthy controls (HCs) was detected based on micro-array transcriptome data.

Irisin Ameliorates Renal Tubulointerstitial Fibrosis by Regulating the Smad4/β-Catenin Pathway in Diabetic Mice.

Background: The primary pathophysiology of diabetic kidney disease (DKD) is tubulointerstitial fibrosis (TIF), and an essential contributing element is excessive extracellular matrix deposition. Irisin is a polypeptide formed by splitting fibronectin type III domain containing 5 (FNDC5), which participates in a number of physiological and pathological processes.

Methods: The purpose of this article is to examine irisin's function in DKD and analyze both its in vitro and in vivo effects.

NQO1 alleviates renal fibrosis by inhibiting the TLR4/NF-κB and TGF-β/Smad signaling pathways in diabetic nephropathy.

Objective: Diabetic nephropathy (DN) is one of the main complications of diabetes, and inflammation and fibrosis play an important role in its progression. NAD(P)H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and damage caused by toxic quinones. In the present study, we aimed to investigate the protective effects of NQO1 against diabetes-induced renal inflammation and fibrosis and the underlying mechanisms.