The pig pangenome provides insights into the roles of coding structural variations in genetic diversity and adaptation.

Structural variations have emerged as an important driving force for genome evolution and phenotypic variation in various organisms, yet their contributions to genetic diversity and adaptation in domesticated animals remain largely unknown. Here we constructed a pangenome based on 250 sequenced individuals from 32 pig breeds in Eurasia and systematically characterized coding sequence presence/absence variations (PAVs) within pigs. We identified 308.3-Mb nonreference sequences and 3438 novel genes absent from the current reference genome. Gene PAV analysis showed that 16.8% of the genes in the pangene catalog undergo PAV. A number of newly identified dispensable genes showed close associations with adaptation. For instance, several novel swine leukocyte antigen (SLA) genes discovered in nonreference sequences potentially participate in immune responses to productive and respiratory syndrome virus (PRRSV) infection. We delineated previously unidentified features of the pig mobilome that contained 490,480 transposable element insertion polymorphisms (TIPs) resulting from recent mobilization of 970 TE families, and investigated their population dynamics along with influences on population differentiation and gene expression. In addition, several candidate adaptive TE insertions were detected to be co-opted into genes responsible for responses to hypoxia, skeletal development, regulation of heart contraction, and neuronal cell development, likely contributing to local adaptation of Tibetan wild boars. These findings enhance our understanding on hidden layers of the genetic diversity in pigs and provide novel insights into the role of SVs in the evolutionary adaptation of mammals.

Photoactivatable CRISPR/Cas12a Sensors for Biomarkers Imaging and Point-of-Care Diagnostics.

In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin, respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo, allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.

Diagnosis and Vulnerability Risk Assessment of Atherosclerotic Plaques Using an Amino Acid-Assembled Near-Infrared Ratiometric Nanoprobe.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Nanoparticle-Coupled Single-Molecule Kinetic Fingerprinting for Enzymatic Activity Detection.

The sensitive and accurate detection of biomarkers plays an important role in clinical diagnosis and drug discovery. Currently, amplification-based methods for biomarker detection are widely explored. However, the key challenges of these methods are limited reproducibility and high background noise. To overcome these limitations, we develop a robust plasmonic nanoparticle-coupled single-molecule kinetic fingerprinting (PNP-SMKF) method to achieve ultrasensitive detection of protein kinase A (PKA). Transient binding of a short fluorescent probe with the genuine target produces a distinct kinetic signature that is completely different from that of the background signal, allowing us to recognize PKA sensitively. Importantly, integrating a plasmonic nanoparticle efficiently breaks the concentration limit of the imager strand for single-molecule imaging, thus achieving a much faster imaging speed. A limit of detection (LOD) of as low as 0.0005 U/mL is readily realized. This method holds great potential as a versatile platform for enzyme detection and inhibitor screening in the future.

Low-Background CRISPR/Cas12a Sensors for Versatile Live-Cell Biosensing.

The trans-cleavage activity of CRISPR/Cas12a has been widely used in biosensing. However, many CRISPR/Cas12a-based biosensors, especially those that work in "on-off-on" mode, usually suffer from high background and thus impossible intracellular application. Herein, this problem is efficiently overcome by elaborately designing the activator strand (AS) of CRISPR/Cas12a using the "RESET" effect found by our group. The activation ability of the as-designed AS to CRISPR/Cas12a can be easily inhibited, thus assuring a low background for subsequent biosensing applications, which not only benefits the detection sensitivity improvement of CRISPR/Cas12a-based biosensors but also promotes their applications in live cells as well as makes it possible to design high-performance biosensors with greatly improved flexibility, thus achieving the analysis of a wide range of targets. As examples, by using different strategies such as strand displacement, strand cleavage, and aptamer-substrate interaction to reactivate the inhibited enzyme activity, several CRISPR/Cas12a-based biosensing systems are developed for the sensitive and specific detection of different targets, including nucleic acid (miR-21), biological small molecules (ATP), and enzymes (hOGG1), giving the detection limits of 0.96 pM, 8.6 µM, and 8.3 × 10-5 U/mL, respectively. Thanks to the low background, these biosensors are demonstrated to work well for the accurate imaging analysis of different biomolecules in live cells. Moreover, we also demonstrate that these sensing systems can be easily combined with lateral flow assay (LFA), thus holding great potential in point-of-care testing, especially in poorly equipped or nonlaboratory environments.

Naringenin inhibits autophagy and epithelial-mesenchymal transition of human lens epithelial cells by regulating the Smad2/3 pathway.

Cataract is the number one cause of blindness in the world. Fibrosis of the lens is the main cause of cataract. Pathological epithelial-mesenchymal transition (EMT) plays an important role in the development of fibrotic cataract. Inhibition of EMT may be an effective treatment for fibrosis of lens epithelial cells. Naringin (NRG) is one of the major citrus flavonoids, which has many pharmacological properties, including anti-inflammatory and cardioprotective. However, the effect of NRG on cataract induced by abnormal fibrosis of LECs is not clear. Herein, we found NRG inhibited transforming growth factor ß2 (TGFß2)-induced SRA01/04 cell viability. Additionally, NRG inhibited TGFß2-induced cell migration and EMT. We further noticed that NRG inhibited autophagy and Smad2/3 phosphorylation in LECs. We therefore thought Naringenin inhibited autophagy and EMT of human LECs by regulating the Smad2/3 pathway. NRG could therefore serve as a promising drug for cataract treatment.

Identification of Specific N6-Methyladenosine RNA Demethylase FTO Inhibitors by Single-Quantum-Dot-Based FRET Nanosensors.

The fat mass and obesity-associated enzyme (FTO) can catalyze the demethylation of N6-methyladenosine (m6A) residues in mRNA, regulates the cellular level of m6A modification, and plays a critical role in human obesity and cancers. Herein, we develop a single-quantum-dot (QD)-based fluorescence resonance energy transfer (FRET) sensor for the identification of specific FTO demethylase inhibitors. The FTO-mediated demethylation of m6A can induce the cleavage of demethylated DNA to generate the biotinylated DNA fragments, which may function as capture probes to assemble the Cy5-labeled reporter probes onto the QD surface, enabling the occurrence of FRET between the QD and Cy5. The presence of inhibitors can inhibit the FTO demethylation and consequently abolish FRET between the QD and Cy5. The inhibition effect of inhibitors upon FTO demethylation can be simply evaluated by monitoring the decrease of Cy5 counts. We use this nanosensor to screen several small-molecule inhibitors and identify diacerein as a highly selective inhibitor of FTO. Diacerein can inhibit the demethylation activity of endogenous FTO in HeLa cells. Interestingly, diacerein is neither a structural mimic of 2-oxoglutarate (2-OG) nor a chelator of metal ions, and it can selectively inhibit FTO demethylation by competitively binding the m6A-containing substrate.

Preventative effects of metformin on glucocorticoid-induced osteoporosis in rats.

This study evaluated the preventative effects of metformin (Met) on glucocorticoid (GC)-induced osteoporosis in a rat model, compared with alendronate (Aln). Twenty-eight 3-month-old female Sprague-Dawley rats were randomly assigned into four groups: normal control (Ctr), methylprednisolone (MP, 13 mg/kg/day, sc, 5 days per week), MP plus Aln orally (1 mg/kg/day), and MP plus Met orally (200 mg/kg/day). After 9 weeks, serum bone metabolic biochemistry, bone densitometry and histomorphometry were performed. The GC-induced osteoporosis model was characterized by decreased osteocalcin, increased tartrate-resistant acid phosphatase-5b (TRAP-5b), and decreased bone mineral density (BMD) in the femur and fifth lumbar vertebra (L5). Histomorphometrically, MP significantly decreased trabecular bone volume, decreased bone formation and increased bone resorption in proximal metaphysis, compared with the controls. Aln and Met increased the BMDs of femur (0.305 ± 0.011 vs. 0.280 ± 0.012, P < 0.05; 0.304 ± 0.019 vs. 0.280 ± 0.012, P < 0.05) and L5 (0.399 ± 0.029 vs. 0.358 ± 0.022, P < 0.05; 0.397 ± 0.022 vs. 0.358 ± 0.022, P < 0.05), compared with the model group. Met increased osteocalcin and decreased TRAP-5b, but Aln only decreased TRAP-5b, compared with model group. In histomorphometry of tibial proximal metaphysis, Aln and Met increased trabecular bone volume (39.21 ± 2.46 vs. 30.98 ± 5.83, P < 0.05; 38.97 ± 5.56 vs. 30.98 ± 5.83, P < 0.05), while Met increased the bone formation dynamic parameters and decreased bone resorption dynamic parameters, but Aln just decreased bone resorption dynamic parameters, compared with model group significantly. These findings suggest that metformin prevents GC-induced bone loss by suppressing bone resorption and stimulating bone formation in trabecular bone. The action mode of metformin was different from alendronate, which only suppressed bone resorption.

Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling.

Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose-dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up-regulation of downstream osteoclast-related target genes expression. The baicalin-induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p-ERK (U0126) and the Mitf-specific siRNA, respectively. Protein-ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p-ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p-ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.

Ferulic acid induces proliferation and differentiation of rat osteoblasts in vitro through cGMP/PKGII/ENaC signaling.

Ferulic acid (FA) is an active component of the traditional Chinese herb Angelica sinensis. Numerous health benefits have been attributed to FA, but few studies have investigated the effects of FA on osteoblasts (Obs). Our work studied the effects of FA on proliferation, differentiation, and mineralization of rat calvarial Obs and examined the signaling pathways involved. Cell proliferation and differentiation were evaluated by Cell Counting Kit-8 (CCK-8) and alkaline phosphatase (ALP) assay kit, respectively. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKGII) expression was silenced by small interfering RNA (siRNA). The mRNA expression was investigated by semi-quantitative PCR. FA (40-2560 µM) promoted Ob proliferation and differentiation; at 40-640 µM, FA stimulated calcified nodule formation and increased the expression of osteogenic genes encoding osteopontin and collagen-l. FA (40-2560 µM) increased cGMP levels in Obs and upregulated the expression of PKGII, EnaCα, and ENaCγ mRNAs. Downregulated ENaCα mRNA expression in Obs transfected with the siRNA for PKGII was reversed when FA was introduced into Obs. These results demonstrated that FA promoted proliferation, differentiation, and mineralization of Obs in vitro, and enhanced osteogenic genes expression partly through the cGMP-PKGII-ENaC signaling pathway.

[Optimize aqueous extract protocol for Yugubao formula by orthogonal experiment design].

To determine the optimum aqueous extract protocol for Yugubao traditional Chinese medicines formula by using orthogonal experiment design. Through serum pharmacology research, L9(34) orthogonal design with single factor investigation was used to optimize the aqueous extract protocol for Yugubao formula. The effect of water extraction on activity of alkaline phosphatase (ALP) in osteoblast was referred as the evaluation index for investigating four factors: water consumption (A), heating time (B), soaking time (C), and number of decocting (D), analyzing the optimum extraction conditions, and verifying the effectiveness of this process. The optimum aqueous extract protocol for Yugubao was as follows: adding 8 times water into Chinese medical materials, heating for 60 min, soaking for 30 min, and decocting for 1 time. The drug serum of this aqueous extract of Yugubao could significantly up-regulate the osteogenic genes expression. The optimum aqueous extract protocol for Yugubao formula was established in this experiment, providing evidence for the development and utilization of Yugubao traditional Chinese medicines formula.

Epithelial sodium channel enhanced osteogenesis via cGMP/PKGII/ENaC signaling in rat osteoblast.

The amiloride-sensitive epithelial sodium channel (ENaC) is a major contributor to intracellular sodium homeostasis. In addition to epithelial cells, osteoblasts (Obs) express functional ENaCs. Moreover, a correlation between bone Na content and bone disease has been reported, suggesting that ENaC-mediated Na(+) regulation may influence osteogenesis. Obs were isolated and cultured by enzyme digestion. Cell proliferation and differentiation were evaluated by WST-8 assay kit and AKP assay kit respectively. PKGII expression was silenced by siRNA. The mRNA expression was investigated by semi-quantitative PCR and the protein expression was determined by Western-blot. The cell-permeable cGMP analog 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP) increased α-ENaC channel expression in primary rat Obs as indicated by RT-PCR. In addition, 8-pCPT-cGMP stimulation enhanced expression of the mRNA encoding cGMP-dependent protein kinases II (PKGII). The cGMP analog also promoted osteoblast proliferation, differentiation and induced the expression of several osteogenic genes, including core binding factor al, osteocalcin, alkaline phosphatase, collagen type I, and osteopontin. Furthermore, the expression of α-ENaC, the main functional subunit of ENaC, was reduced when a small interfering RNA specific for PKGII was introduced into Obs. Treatment with 8-pCPT-cGMP in cells transfected with the siRNA for PKGII partially reversed downregulated α-ENaC mRNA expression. Our results suggest that 8-pCPT-cGMP stimulates proliferation, differentiation, and osteogenic gene expression in Obs through cGMP/PKGII-dependent regulation of ENaC channel expression. The cGMP/PKGII signaling pathway is a potential target for pharmaceutical interventions to treat metabolic bone diseases.

Vehicle Behavior Discovery and Three-Dimensional Object Detection and Tracking Based on Spatio-Temporal Dependency Knowledge and Artificial Fish Swarm Algorithm.

In complex traffic environments, 3D target tracking and detection are often occluded by various stationary and moving objects. When the target is occluded, its apparent characteristics change, resulting in a decrease in the accuracy of tracking and detection. In order to solve this problem, we propose to learn the vehicle behavior from the driving data, predict and calibrate the vehicle trajectory, and finally use the artificial fish swarm algorithm to optimize the tracking results. The experiments show that compared with the CenterTrack method, the proposed method improves the key indicators of MOTA (Multi-Object Tracking Accuracy) in 3D object detection and tracking on the nuScenes dataset, and the frame rate is 26 fps.

Plasmonic nanoparticle-assisted single-molecule dynamic binding for protein kinase activity digital counting.

In this work, we design a new approach for digital counting-based protein kinase activity assay by using plasmonic nanoparticle-assisted single-molecule dynamic binding. This method breaks the concentration-dependent limitation in single-molecule detection and displays good selectivity and sensitivity with a detection limit as low as 0.0001 U mL-1 for the protein kinase A (PKA) assay, which would find broad applications in drug screening and medical investigations.

Metal-Induced Energy Transfer (MIET) Imaging of Cell Surface Engineering with Multivalent DNA Nanobrushes.

The spacing between cells has a significant impact on cell-cell interactions, which are critical to the fate and function of both individual cells and multicellular organisms. However, accurately measuring the distance between cell membranes and the variations between different membranes has proven to be a challenging task. In this study, we employ metal-induced energy transfer (MIET) imaging/spectroscopy to determine and track the intermembrane distance and variations with nanometer precision. We have developed a DNA-based molecular adhesive called the DNA nanobrush, which serves as a cellular adhesive for connecting the plasma membranes of different cells. By manipulating the number of base pairs within the DNA nanobrush, we can modify various aspects of membrane-membrane interactions such as adhesive directionality, distance, and forces. We demonstrate that such nanometer-level changes can be detected with MIET imaging/spectroscopy. Moreover, we successfully employed MIET to measure distance variations between a cellular plasma membrane and a model membrane. This experiment not only showcases the effectiveness of MIET as a powerful tool for accurately quantifying membrane-membrane interactions but also validates the potential of DNA nanobrushes as cellular adhesives. This innovative method holds significant implications for advancing the study of multicellular interactions.

Desulfovibrio vulgaris caused gut inflammation and aggravated DSS-induced colitis in C57BL/6 mice model.

BACKGROUND: Sulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis. RESULTS: In this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1ß, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo. CONCLUSIONS: Collectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.

Long-term distress throughout one's life: health-related quality of life, economic and caregiver burden of patients with neurofibromatosis type 1 in China.

Introduction: Neurofibromatosis type 1 (NF1) is a rare genetic disorder, with lack of evidence of disease burden in China. We aimed to describe the economic burden, health-related quality of life (HRQL), and caregiver burden of NF1 patients in China. Methods: We conducted an online cross-sectional survey employing the China Cloud Platform for Rare Diseases, with 223 caregivers of NF1 pediatric patients (patients under 18), and 226 adult patients. Economic burden was estimated using direct and indirect costs related to NF1 in 2021, and the Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI-GH). HRQL measures included EQ-5D-Y proxy version and PedsQL™ 4.0 Generic Core Scales (PedsQL GCS) proxy version for pediatric patients, and EQ-5D-5L and PedsQL™ 3.0 Neurofibromatosis Module (PedsQL NFM) for adult patients. Caregiver burden was estimated by Zarit Burden Interview (ZBI). Results: For pediatric patients, the average direct cost in 2021 was CNY 33,614 (USD 4,879), and employed caregivers' annual productivity loss was 81 days. EQ-5D-Y utility was 0.880 ± 0.13 and VAS score was 75.38 ± 20.67, with 52.6% patients reporting having problems in "pain/discomfort" and 42.9% in "anxiety/depression." PedsQL GCS total score was 68.47 ± 19.42. ZBI score demonstrated that 39.5% of caregivers had moderate-to-severe or severe burden. For adult patients, average direct cost in 2021 was CNY 24,531 (USD 3,560). Patients in employment reported an absenteeism of 8.5% and presenteeism of 21.6% according to the results of WPAI-GH. EQ-5D-5L utility was 0.843 ± 0.17 and VAS score was 72.32 ± 23.49, with more than half of patients reporting having problems in "pain/discomfort" and "anxiety/depression" dimensions. PedsQL NFM total score was 68.40 ± 15.57. Conclusion: Both pediatric and adult NF1 patients in China had a wide-ranging economic burden and low HRQL, especially in the psychological dimension. Caregivers for NF1 pediatric patients experienced considerable caregiver burden. More attention and support from policymakers and stakeholders are required to relieve NF1 patients' and caregivers' distress.

The synthesis and evaluation of novel hydroxyl substituted chalcone analogs with in vitro anti-free radicals pharmacological activity and in vivo anti-oxidation activity in a free radical-injury Alzheimer's model.

Alzheimer's disease (AD) pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radical activity tests. Further research revealed that C7 could elevate glutathione peroxidase (GSH-PX) and super oxide dismutase (SOD) levels and lower malonaldehyde (MDA) level in vivo in the Alzheimer's model. The indication of C7's effect on AD needs further study.

Lysine Demethylase 1B Promotes Tear Secretion Disorder in Sjogren's Syndrome by Regulating the PAX6/CLU Axis.

The impacts of lysine demethylase 1B (KDM1B) have been probed in multiple diseases, but the effects of KDM1B on SS remained obscure. The study aimed to unravel the efficiency of KDM1B on SS progression via the paired box 6 (PAX6)/clusterin (CLU) axis. NODB10. H2b mice were selected to establish the SS model. KDM1B, Pax6, and CLU expression in SS mice was assessed. Adeno-associated viruses carrying KDM1B, Pax6, and CLU were injected into the SS mice to detect tear secretion, epithelium corneal fluorescein staining scores, and levels of specific markers of lacrimal gland epithelial cells, neurotransmitter receptors that induce secretion from the lacrimal gland, and genes encoding normal tear components. The relation among KDM1B, Pax6, and CLU was examined. The rescue experiments were conducted for verifying the interaction among KDM1B, Pax6, and CLU. KDM1B expression was elevated, while Pax6 and CLU levels were decreased in the lacrimal gland tissues of SS mouse models. KDM1B decrement and Pax6 augmentation improved tear secretion, reduced corneal fluorescein staining score, decreased levels of specific markers of lacrimal gland epithelial cells, and increased levels of neurotransmitter receptors that induce secretion from the lacrimal gland and genes encoding normal tear components. KDM1D suppressed Pax6 expression by mediating H3K4me2 demethylation. Pax6 promoted the expression of CLU at the transcriptional level by binding to the CLU promoter. Silencing of Pax6 or CLU could reverse the effects of KDM1B reduction on improving the tear secretion disorder of SS mice. Silencing KDM1B mitigates the tear secretion disorder of SS mice via modulating the Pax6/CLU axis.