Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.

Th1 cells reduce the osteoblast-like phenotype in valvular interstitial cells by inhibiting NLRP3 inflammasome activation in macrophages.

BACKGROUND AND AIMS: Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. METHODS AND RESULTS: The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow-derived macrophages reduced the osteogenic calcification of valvular interstitial cells. CONCLUSION: Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms.

Mechano-growth factor regulates periodontal ligament stem cell proliferation and differentiation through Fyn-RhoA-YAP signaling.

BACKGROUND: Mechano-growth factor (MGF), which is a growth factor produced specifically in response to mechanical stimuli, with potential of tissue repair and regeneration. Our previous research has shown that MGF plays a crucial role in repair of damaged periodontal ligaments by promoting differentiation of periodontal ligament stem cells (PDLSCs). However, the molecular mechanism is not fully understood. This study aimed to investigated the regulatory effect of MGF on differentiation of PDLSCs and its molecular mechanism. METHODS: Initially, we investigated how MGF impacts cell growth and differentiation, and the relationship with the activation of Fyn-p-YAPY357 and LATS1-p-YAPS127. Then, inhibitors were used to interfere Fyn phosphorylation to verify the role of Fyn-p-YAP Y357 signal after MGF stimulation; moreover, siRNA was used to downregulate YAP expression to clarify the function of YAP in PDLSCs proliferation and differentiation. Finally, after C3 was used to inhibit the RhoA expression, we explored the role of RhoA in the Fyn-p-YAP Y357 signaling pathway in PDLSCs proliferation and differentiation. RESULTS: Our study revealed that MGF plays a regulatory role in promoting PDLSCs proliferation and fibrogenic differentiation by inducing Fyn-YAPY357 phosphorylation but not LATS1-YAP S127 phosphorylation. Moreover, the results indicated that Fyn could not activate YAP directly but rather activated YAP through RhoA in response to MGF stimulation. CONCLUSION: The research findings indicated that the Fyn-RhoA-p-YAPY357 pathway is significant in facilitating the proliferation and fibrogenic differentiation of PDLSCs by MGF. Providing new ideas for the study of MGF in promoting periodontal regenerative repair.

Poorly controlled type 1 diabetes mellitus seriously impairs female reproduction via immune and metabolic disorders.

RESEARCH QUESTION: Does type 1 diabetes mellitus (T1DM) affect reproductive health of female patients? What is the potential mechanism of reproductive dysfunction in female patients caused by T1DM? DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level. RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways. CONCLUSION: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

CD34+ stromal cells/telocytes and their role in mouse lung development: Light microscopy, immunofluorescence, ultrastructural and scanning electron microscopy evidence.

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

Diversity, Variance, and Stability of Root Phenes of Peanut (Arachis hypogaea L.).

Root phenes are associated with the absorptive efficiency of water and fertilizers. However, there are few reports on the genetic variation and stability of peanut (Arachis hypogaea L.) root architecture under different environments. In this study, the diversity, variance and stability of root phenes of 89 peanut varieties were investigated with shovelomics (high throughput phenotyping of root system architecture) for two years in both field and laboratory experiments. The root phenes of these peanut genotypes presented rich diversity; for example, the value of total root length (TRL) ranged from 347.84 cm to 1013.80 cm in the field in 2018, and from 55.14 cm to 206.22 cm in the laboratory tests. The root phenes of different genotypes varied differently; for example, the coefficient of variation (CV) of TRL ranged from 24.0 to 83.5 across the two-year field test. Field and laboratory evaluations were highly correlated, especially on lateral root density (LRD) and root angle (RA), and the quadrant graph analysis of LRD and RA implied that 69.7% of the roots belong to the same type. These not only further reflect root phenes stability through different environment but also demonstrate that some root phenes identified at early stage can indicate their status at later growth stage. In addition, root phenes showed a strong correlation with shoot growth, especially root dry weight (RDW), TRL and（nodule number）NN. Thus, laboratory tests in combination with field shovelomics can efficiently screen and select genotypes with contrasting root phenes to optimize water and nutrient management.

CyHV-2 infection triggers mitochondrial-mediated apoptosis in GiCF cells by upregulating the pro-apoptotic gene ccBAX.

Apoptosis is a physiological cell death phenomenon, representing one of the fundamental physiological mechanisms for maintaining homeostasis in living organisms. Previous studies have observed typical apoptotic features in Carassius auratus gibelio caudal fin cell (GiCF) infected with Cyprinid herpesvirus 2 (CyHV-2), and found a significant up-regulation of ccBAX expression in these infected cells. However, the specific apoptotic mechanism involved remains unclear. In this study, we utilized the GiCF cell line to investigate the apoptotic mechanism during CyHV-2 infection. Immunofluorescence staining revealed translocation of ccBAX into mitochondria upon CyHV-2 infection. Flow cytometry analysis demonstrated that overexpression of ccBAX expedited virus-induced apoptosis, characterized by heightened mitochondrial depolarization, increased transcriptional levels of Cytochrome c (Cyto c) in both the cytoplasm and mitochondria, and augmented Caspase 3/7 enzyme activity. Bax inhibitor peptide V5 (BIP-V5), an inhibitor interfering with the function of Bax proteins, inhibited Bax-mediated apoptotic events through the mitochondrial pathway and attenuated apoptosis induced by CyHV-2. In this study, it was identified for the first time that CyHV-2 induces apoptosis via the mitochondrial pathway in GiCF cells, bridging an important gap in our understanding regarding cell death mechanisms induced by herpesvirus infections in fish species. These findings provide a theoretical basis for comprehending viral apoptotic regulation mechanisms and the prevention and control of cellular pathologies caused by CyHV-2 infection.

Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

The impact of the combat method on radiomics feature compensation and analysis of scanners from different manufacturers.

BACKGROUND: This study investigated whether the Combat compensation method can remove the variability of radiomic features extracted from different scanners, while also examining its impact on the subsequent predictive performance of machine learning models. MATERIALS AND METHODS: 135 CT images of Credence Cartridge Radiomic phantoms were collected and screened from three scanners manufactured by Siemens, Philips, and GE. 100 radiomic features were extracted and 20 radiomic features were screened according to the Lasso regression method. The radiomic features extracted from the rubber and resin-filled regions in the cartridges were labeled into different categories for evaluating the performance of the machine learning model. Radiomics features were divided into three groups based on the different scanner manufacturers. The radiomic features were randomly divided into training and test sets with a ratio of 8:2. Five machine learning models (lasso, logistic regression, random forest, support vector machine, neural network) were employed to evaluate the impact of Combat on radiomic features. The variability among radiomic features were assessed using analysis of variance (ANOVA) and principal component analysis (PCA). Accuracy, precision, recall, and area under the receiver curve (AUC) were used as evaluation metrics for model classification. RESULTS: The principal component and ANOVA analysis results show that the variability of different scanner manufacturers in radiomic features was removed (P˃0.05). After harmonization with the Combat algorithm, the distributions of radiomic features were aligned in terms of location and scale. The performance of machine learning models for classification improved, with the Random Forest model showing the most significant enhancement. The AUC value increased from 0.88 to 0.92. CONCLUSIONS: The Combat algorithm has reduced variability in radiomic features from different scanners. In the phantom CT dataset, it appears that the machine learning model's classification performance may have improved after Combat harmonization. However, further investigation and validation are required to fully comprehend Combat's impact on radiomic features in medical imaging.

Series Arc Fault Detection under Vibration Condition Based on N-M-M-B.

Under the conditions of a mechanical fault in a motor, mechanical vibration of a specific frequency can be generated. The electrical contact points directly connected to the motor can vibrate at the same frequency. The electrical contact points with poor contact can easily produce a series arc fault under vibration conditions, which affects the reliability of the power supply. In order to detect the series arc fault under different vibration conditions, the arc fault generator is connected between the back end of the frequency converter and the motor. An arc fault experiment under different vibration conditions was carried out and the fault phase current and arc voltage signals were collected. In this paper, the noise-assisted multivariate empirical mode decomposition and the correlation coefficient between each intrinsic mode function are used to select the fault feature signals. Then, the reconstructed signal is input into the series arc fault model combining a multi-scale convolutional neural network and a bidirectional long short-term memory network for training. The research results show that the series arc fault detection method proposed in this paper can effectively detect the series arc fault and can preliminarily identify the type of motor fault causing the mechanical vibration of the motor; the model has good noise immunity and generalization.

Exogenous Application of Amino Acids Alleviates Toxicity in Two Chinese Cabbage Cultivars by Modulating Cadmium Distribution and Reducing Its Translocation.

Plants communicate underground by secreting multiple amino acids (AAs) through their roots, triggering defense mechanisms against cadmium (Cd) stress. However, the specific roles of the individual AAs in Cd translocation and detoxification remain unclear. This study investigated how exogenous AAs influence Cd movement from the roots to the shoots in Cd-resistant and Cd-sensitive Chinese cabbage cultivars (Jingcui 60 and 16-7 cultivars). The results showed that methionine (Met) and cysteine (Cys) reduced Cd concentrations in the shoots of Jingcui 60 by approximately 44% and 52%, and in 16-7 by approximately 43% and 32%, respectively, compared to plants treated with Cd alone. However, threonine (Thr) and aspartic acid (Asp) did not show similar effects. Subcellular Cd distribution analysis revealed that AA supplementation increased Cd uptake in the roots, with Jingcui 60 preferentially storing more Cd in the cell wall, whereas the 16-7 cultivar exhibited higher Cd concentrations in the organelles. Moreover, Met and Cys promoted the formation of Cd-phosphate in the roots of Jingcui 60 and Cd-oxalate in the 16-7 cultivar, respectively. Further analysis showed that exogenous Cys inhibited Cd transport to the xylem by downregulating the expression of HMA2 in the roots of both cultivars, and HMA4 in the 16-7 cultivar. These findings provide insights into the influence of exogenous AAs on Cd partitioning and detoxification in Chinese cabbage plants.

Effects of straw returning combined with blended controlled-release urea fertilizer on crop yields, greenhouse gas emissions, and net ecosystem economic benefits: A nine-year field trial.

Although straw returning combined with blended controlled-release urea fertilizer (BUFS) has been shown to improve wheat-maize rotation system productivity, their effects on greenhouse gas (GHG) emissions, carbon footprints (CF), and net ecosystem economic benefits (NEEB) are still unknown. Life cycle assessment was used to investigate a long-term (2013-2022) wheat-maize rotation experiment that included straw combined with two N fertilizer types [BUFS and (conventional urea fertilizer) CUFS] and straw-free treatments (BUF and CUF). The results showed that BUFS and CUFS treatments increased the annual yield by 13.8% and 11.5%, respectively, compared to BUF and CUF treatments. The BUFS treatment increased the yearly yield by 13.8% compared to the CUFS treatment. Since BUFS and CUFS treatments increased soil organic carbon (SOC) sink sequestration by 25.0% and 27.0% compared to BUF and CUF treatments, they reduced annual GHG emissions by 7.1% and 4.7% and CF per unit of yield (CFY) by 13.7% and 9.6%, respectively. BUFS treatment also increased SOC sink sequestration by 20.3%, reduced GHG emissions by 10.7% and CFY by 23.0% compared to CUFS treatment. It is worth noting that the BUFS and CUFS treatments increased the annual ecological costs by 41.6%, 26.9%, and health costs by 70.1% and 46.7% compared to the BUF and CUF treatments, but also increased the net yield benefits by 9.8%, 6.8%, and the soil nutrient cycling values by 29.2%, 27.3%, and finally improved the NEEB by 10.1%, 7.3%, respectively. Similar results were obtained for the BUFS treatment compared to the CUFS treatment, ultimately improving the NEEB by 23.1%. Based on assessing yield, GHG emissions, CF, and NEEB indicators, the BUFS treatment is recommended as an ideal agricultural fertilization model to promote sustainable and clean production in the wheat-maize rotation system and to protect the agroecological environment.

Transcriptome analysis of large yellow croaker (Larimichthys crocea) at different growth rates.

The unsynchronized growth of the large yellow croaker (Larimichthys crocea), which impacts growth efficiency, poses a challenge for aquaculture practitioners. In our study, juvenile stocks of large yellow croaker were sorted by size after being cultured in offshore cages for 4 months. Subsequently, individuals from both the fast-growing (FG) and slow-growing (SG) groups were sampled for analysis. High-throughput RNA-Seq was employed to identify genes and pathways that are differentially expressed during varying growth rates, which could suggest potential physiological mechanisms that influence growth rate. Our transcriptome analysis identified 382 differentially expressed genes (DEGs), comprising 145 upregulated and 237 downregulated genes in comparison to the SG group. GO and KEGG enrichment analyses indicated that these DEGs are predominantly involved in signal transduction and biochemical metabolic pathways. Quantitative PCR (qPCR) results demonstrated that cat, fasn, idh1, pgd, fgf19, igf2, and fads2 exhibited higher expression levels, whereas gadd45b and gadd45g showed lower expression compared to the slow-growing group. In conclusion, the differential growth rates of large yellow croaker are intricately associated with cellular proliferation, metabolic rates of the organism, and immune regulation. These findings offer novel insights into the molecular mechanisms and regulatory aspects of growth in large yellow croaker and enhance our understanding of growth-related genes.

Use of 3D printing models for donor tooth extraction in autotransplantation cases.

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.

Analysis and validation of potential ICD-related biomarkers in development of myopia using machine learning.

PURPOSE: We aimed to identify and verify potential biomarkers in the development of myopia associated with immunogenic cell death (ICD). METHODS: We download high myopia (HM) dataset GSE136701 from Gene Expression Omnibus. Differentially expressed genes in HM were identified to overlapped with ICD-related genes. Least absolute shrinkage and selection operator were used to select the Hub genes. Furthermore, the correlation between the hub genes and immune infiltration, immune response activities, and hub genes Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis was investigated using Spearman's rank correlation. Prediction of the miRNAs upstream of the Hub genes was based on the TargetScan database. We used guinea pig lens-induced myopia model's scleral tissues performed quantitative real-time polymerase chain reaction. RESULTS: We identified overlapped with ICD-related genes (LY96, IL1A, IL33, and AGER) and two genes (LY96 and AGER) as hub genes. Single sample gene set enrichment analysis and Spearman's rank correlation revealed that hub gene expression levels in HM were significantly correlated with the infiltration percentages of CD56dim natural killer cells, macrophages, immature B cells, and the immune response activities of APC co-stimulation and Kyoto Encyclopedia of Genes and Genomes pathways, such as terpenoid backbone biosynthesis, aminoacyl-trna biosynthesis, Huntington's disease, oxidative phosphorylation; there were a few additional signaling pathways compared to normal samples. Additionally, several miRNA were predicted as upstream regulators of LY96 and AGER. LY96 was identified as a significantly differentially expressed biomarker in myopia guinea pig's scleral tissues, as verified by qPCR. CONCLUSION: LY96 was identified and verified as a ICD-related potential myopia biomarker. Molecular mechanisms or pathways involved in myopia development by LY96 requires further research.

[Piezo1 Mediates the Regulation of Substrate Stiffness on Primary Cilia in Chondrocytes]. / Piezo1介导基底硬度调控软骨细胞初级纤毛形态.

Objective: To investigate how substrate stiffness regulates the morphology of primary cilia in chondrocytes and to illustrate how Piezo1 mediates the morphology regulation of primary cilia by substrate stiffness. Methods: Polydimethylsiloxane (PDMS) curing agent and the main agent (Dow Corning, Beijing, China) were mixed at the ratio of 1∶10 (stiff), 1∶50 (medium stiffness), and 1∶70 (soft), respectively, to prepare substrate films with the thickness of 1 mm at different levels of stiffness, including stiff substrate of (2.21±0.12) MPa, medium-stiffness substrate of (54.47±6.06) kPa, and soft substrate of (2.13±0.10) kPa. Chondrocytes were cultured with the substrates of three different levels of stiffness. Then, the cells were treated with Tubastatin A (Tub A) to inhibit histone deacetylase 6 (HDAC6), Piezo1 activator Yoda1, and inhibitor GsMTx4, respectively. The effects of HDAC6, Yoda1, and GsMTx4 on chondrocyte morphology and the length of primary cilia were analyzed through immunofluorescence staining. Results: The stiff substrate increased the spread area of the chondrocytes. Immunofluorescence assays showed that the cytoskeleton and the nuclear area of the cells on the stiff substrate were significantly increased (P<0.05) and the primary cilia were significantly extended (P<0.05) compared with those on the medium-stiffness and soft substrates. However, the presence rate of primary cilia was not affected. The HDAC6 activity of chondrocytes increased with the decrease in substrate stiffness. When the activity of HDAC6 was inhibited, the cytoskeletal area, the nuclei area, and the primary cilium length were increased more significantly on the stiff substrate (P<0.05). Further testing showed that Piezo1 activator and inhibitor could regulate the activity of HDAC6 in chondrocytes, and that the length of primary cilia was significantly increased after treatment with the activator Yoda1 (P<0.05). On the other hand, the length of primary cilia was significantly shortened on the stiff substrate after treatment with the inhibitor GsMTx4 (P<0.05). Conclusion: Both substrate stiffness and Piezo1 may affect the morphology of chondrocyte primary cilia by regulating HDAC6 activity.

Research Advances in Targeted Therapy for Heart Failure.

Cardiovascular disease is one of the major diseases threatening the health of Chinese residents, and the death rate has long been the highest on the disease spectrum in China. With the progress of population aging, the prevalence and mortality of cardiovascular diseases remain on the rise, and the current treatment effect on and prognosis of heart failure (HF) are not satisfactory. It is particularly important to explore the potential pathogenic mechanisms of HF and identify new therapeutic targets.

Effects of short-term exposure to gaseous pollutants on metabolic health indicators of patients with metabolic syndrome in Northwest China.

Currently few studies have explored the relationship between exposure to gaseous pollutants and metabolic health indicators in patients, especially in patients with metabolic syndrome (Mets). This study collected 15,520 patients with Mets in a prospective cohort of nearly 50,000 people with 7 years of follow-up from 2011 to 2017, and matched air pollutants and meteorological data during the same period. The mixed effects model was used to analyze the relationship between different short exposure windows (1-week, 1-month, 2-month, and 3-month) of gaseous pollutants (SO2, NO2, and O3) and the metabolic health indicators of patients after controlled the confounding factors. Stratified analysis was performed by demographic characteristics and behavioral factors. The effects of gaseous pollutants on patients with different Met components were also analyzed. The results showed that the short-term exposure to SO2, NO2, and O3 had a certain effect on the metabolic health indicators of patients with Mets in different exposure windows, and with the extension of the exposure window period, the effects increased. The stratified analysis showed that gender, age, and life behaviors might modify these detrimental effects. In addition, the effects of gaseous pollutants on metabolic health indicators in G4 and G7 were more obvious than other Met components, and the effects of gaseous pollutants on the level of LDL-C were found to be statistically significant in most components. Therefore, patients with Mets should pay more attention to the influence of gaseous pollutants to take appropriate protection to reduce potential health risk.

Accurate Monocular SLAM Initialization via Structural Line Tracking.

In this paper, we present a novel monocular simultaneous localization and mapping (SLAM) initialization algorithm that relies on structural features by tracking structural lines. This approach addresses the limitations of the traditional method, which can fail to account for a lack of features or their uneven distribution. Our proposed method utilizes a sliding window approach to guarantee the quality and stability of the initial pose estimation. We incorporate multiple geometric constraints, orthogonal dominant directions, and coplanar structural lines to construct an efficient pose optimization strategy. Experimental evaluations conducted on both the collected chessboard datasets and real scene datasets show that our approach provides superior results in terms of accuracy and real-time performance compared to the well-tuned baseline methods. Notably, our algorithm achieves these improvements while being computationally lightweight, without the need for matrix decomposition.