Genome-Wide Identification of Glutathione S-Transferase Genes in Eggplant (Solanum melongena L.) Reveals Their Potential Role in Anthocyanin Accumulation on the Fruit Peel.

Anthocyanins are ubiquitous pigments derived from the phenylpropanoid compound conferring red, purple and blue pigmentations to various organs of horticultural crops. The metabolism of flavonoids in the cytoplasm leads to the biosynthesis of anthocyanin, which is then conveyed to the vacuoles for storage by plant glutathione S-transferases (GST). Although GST is important for transporting anthocyanin in plants, its identification and characterization in eggplant (Solanum melongena L.) remains obscure. In this study, a total of 40 GST genes were obtained in the eggplant genome and classified into seven distinct chief groups based on the evolutionary relationship with Arabidopsis thaliana GST genes. The seven subgroups of eggplant GST genes (SmGST) comprise: dehydroascorbate reductase (DHAR), elongation factor 1Bγ (EF1Bγ), Zeta (Z), Theta(T), Phi(F), Tau(U) and tetra-chlorohydroquinone dehalogenase TCHQD. The 40 GST genes were unevenly distributed throughout the 10 eggplant chromosomes and were predominantly located in the cytoplasm. Structural gene analysis showed similarity in exons and introns within a GST subgroup. Six pairs of both tandem and segmental duplications have been identified, making them the primary factors contributing to the evolution of the SmGST. Light-related cis-regulatory elements were dominant, followed by stress-related and hormone-responsive elements. The syntenic analysis of orthologous genes indicated that eggplant, Arabidopsis and tomato (Solanum lycopersicum L.) counterpart genes seemed to be derived from a common ancestry. RNA-seq data analyses showed high expression of 13 SmGST genes with SmGSTF1 being glaringly upregulated on the peel of purple eggplant but showed no or low expression on eggplant varieties with green or white peel. Subsequently, SmGSTF1 had a strong positive correlation with anthocyanin content and with anthocyanin structural genes like SmUFGT (r = 0.9), SmANS (r = 0.85), SmF3H (r = 0.82) and SmCHI2 (r = 0.7). The suppression of SmGSTF1 through virus-induced gene silencing (VIGs) resulted in a decrease in anthocyanin on the infiltrated fruit surface. In a nutshell, results from this study established that SmGSTF1 has the potential of anthocyanin accumulation in eggplant peel and offers viable candidate genes for the improvement of purple eggplant. The comprehensive studies of the SmGST family genes provide the foundation for deciphering molecular investigations into the functional analysis of SmGST genes in eggplant.

Rhizosphere metabolic cross-talk from plant-soil-microbe tapping into agricultural sustainability: Current advance and perspectives.

Rhizosphere interactions from plant-soil-microbiome occur dynamically all the time in the "black microzone" underground, where we can't see intuitively. Rhizosphere metabolites including root exudates and microbial metabolites act as various chemical signalings involving in rhizosphere interactions, and play vital roles on plant growth, development, disease suppression and resistance to stress conditions as well as proper soil health. Although rhizosphere metabolites are a mixture from plant roots and soil microbes, they often are discussed alone. As a rapid appearance of various omics platforms and analytical methods, it offers possibilities and opportunities for exploring rhizosphere interactions in unprecedented breadth and depth. However, our comprehensive understanding about the fine-tuning mechanisms of rhizosphere interactions mediated by these chemical compounds still remain clear. Thus, this review summarizes recent advances systemically including the features of rhizosphere metabolites and their effects on rhizosphere ecosystem, and looks forward to the future research perspectives, which contributes to facilitating better understanding of biochemical communications belowground and helping identify novel rhizosphere metabolites. We also address challenges for promoting the understanding about the roles of rhizosphere metabolites in different environmental stresses.

RAB10 Facilitates Colorectal Cancer Progression through Activation of the NF-κB Signaling Pathway.

Background: Colorectal cancer (CRC) is the third most prevalent malignancy globally, ranking as the second leading cause of cancer-related mortality. Emerging evidence highlights RAB10's involvement in the progression of various malignant tumors; however, its specific role in CRC remains unclear. Objective: To explore the oncogenic role of RAB10 in colorectal cancer progression by investigating its impact on NF-κB activation, aiming to identify a novel genetic biomarker for enhanced diagnosis and treatment of CRC. Methods: This study collected CRC tissue samples and utilized The Cancer Genome Atlas (TCGA) database for RAB10 expression verification through Western blot (WB). Cellular phenotype experiments were conducted on CRC cell lines, including quantitative real-time-polymerase chain reaction (qRT-PCR), CCK-8, transwell assay, and wound healing assay (HCT116 and SW480). Additionally, the impact of RAB10 on NF-κB signaling was assessed through qRT-PCR and WB. Results: RAB10 exhibited upregulation in CRC tissue samples compared to normal counterparts. Furthermore, RAB10 promoted the proliferation, migration, and invasion of HCT116 and SW480 cells. Notably, RAB10 induced NF-κB activation in CRC in vitro. Conclusion: This study revealed the oncogenic function of RAB10, explaining its role in activating NF-κB in CRC. The findings present RAB10 as a potential genetic biomarker for CRC diagnosis and treatment.

Serum vitamin D is substantially reduced and predicts flares in diabetic retinopathy patients.

AIMS/INTRODUCTION: Research has suggested that vitamin D deficiency is associated with diabetic retinopathy (DR). Our study aimed to determine whether vitamin D deficiency is the cause of diabetic retinopathy or if diabetic retinopathy reduces vitamin D levels. MATERIALS AND METHODS: Participants with type-2 diabetes were recruited for this prospective observational clinical study and were divided into a diabetic group without retinopathy and a diabetic group with retinopathy, with additional healthy volunteers serving as a control group. The differences in clinical characteristics among the three groups were also compared. Patients without retinopathy were then followed for 1 year to monitor the incidence of diabetic retinopathy. After follow-up, participants were divided into subgroups based on whether diabetic retinopathy occurred. The baseline data of the subgroups were compared, and the independent risk factors were analyzed. RESULTS: Vitamin D levels were generally low. Participants with diabetic retinopathy had significantly lower vitamin D levels than did those without retinopathy (P < 0.01). A comparison of the two subgroups revealed lower baseline vitamin D concentrations in the new-DR subgroup than in the non-DR subgroup (P < 0.01). Vitamin D deficiency and elevated HbA1c levels were found to be independent risk factors for diabetic retinopathy (OR = 0.935, 95% CI: 0.867-0.981, P = 0.006; OR = 2.208, 95% CI: 1.764-2.764, P < 0.01). The limit of vitamin D intake according to the receiver-operating characteristic (ROC) curve was 26.01 ng/mL, and the area under the ROC curve was 0.603 (95% CI: 0.559-0.706, P = 0.002). CONCLUSIONS: Vitamin D levels were significantly lower in patients diagnosed with diabetic retinopathy. More importantly, vitamin D deficiency may accelerate the onset of diabetic retinopathy.

Tiam1 regulates proliferation, invasion, and differentiation in neuroblastoma through the Tiam1/Rac1 signaling pathway.

Neuroblastoma is the most common extracranial solid tumor in children. The purpose of the present study is to detect the prognostic role and potential therapeutic efficacy of the T lymphoma invasion and metastasis 1 (Tiam1) in neuroblastoma. The overexpression of Tiam1 protein is frequently observed in neuroblastoma. Tiam1 expression is closely associated with adverse prognosis of neuroblastoma and risk group classification. Knockdown of TIAM1 by lentivirus expressing short hairpin RNA against TIAM1 (sh-TIAM1) inhibited the proliferation, invasion and cell-cycle progression, and promoted apoptosis of the neuroblastoma cell lines SH-SY5Y and SK-N-AS. Additionally, downregulation of the differentiation-related protein expression and decreased Rac1 expression was observed in the sh-TIAM1-transfected SH-SY5Y cells. In vivo, nude mice bearing TIAM1 knockdown SH-SY5Y cells showed improved overall survival and tumor growth suppression. The results demonstrate that inhibition of Tiam1 expression is a potential strategy for targeted therapy in neuroblastoma.

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis.

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

Modulation of adipose tissue metabolism by exosomes in obesity.

Obesity and its related metabolic complications represent a significant global health challenge. Central to this is the dysregulation of glucolipid metabolism, with a predominant focus on glucose metabolic dysfunction in the current research, whereas adipose metabolism impairment garners less attention. Exosomes (EXs), small extracellular vesicles (EVs) secreted by various cells, have emerged as important mediators of intercellular communication and have the potential to be biomarkers, targets, and therapeutic tools for diverse diseases. In particular, EXs have been found to play a role in adipose metabolism by transporting cargoes such as noncoding RNAs (ncRNA), proteins, and other factors. This review article summarizes the current understanding of the role of EXs in mediating adipose metabolism disorders in obesity. It highlights their roles in adipogenesis (encompassing adipogenic differentiation and lipid synthesis), lipid catabolism, lipid transport, and white adipose browning. The insights provided by this review offer new avenues for developing exosome-based therapies to treat obesity and its associated comorbidities.

The research landscape of oxidative stress in osteoarthritis from 1998 to 2021: a systematic bibliometric analysis.

OBJECTIVE: A substantial body of literature pertaining to oxidative stress in osteoarthritis (OA) has been published over the past few decades. However, a comprehensive systematic analysis in this field is currently lacking. The objective of this study was to perform a bibliometric analysis to visualize the current research hotspots and evolving trends associated with oxidative stress in OA, in order to contribute to a more comprehensive understanding of this field. METHODS: The raw data pertaining to oxidative stress in OA, published between 1998 and 2021, were obtained from the Web of Science Core Collection database (WoSCC). In order to provide comprehensive results across multiple dimensions, various bibliometric software tools were employed to quantify and analyze the research focuses and trends regarding oxidative stress in OA. RESULTS: A total of 1178 original articles and reviews on oxidative stress in OA were included, with China and the USA emerging as the primary driving forces in this research field. Notably, Wenzhou Medical University stood out as the most prolific institution in terms of publication volume. Blanco FJ was the most prolific author, and the journal with the most publications was Osteoarthritis and Cartilage. The analysis of keyword burst detection revealed that the investigation of chondrocyte senescence induced by oxidative stress was the most frequent. CONCLUSION: The burgeoning body of literature pertaining to oxidative stress in OA has experienced a consistent growth over the past few decades, and this field will garner widespread attention and in-depth investigation. The frontier of chondrocyte senescence, as revealed by bibliometric analyses, represents a special focus of this field, with potential as a vital therapeutic target for OA.

Economic co-production of cellulosic ethanol and microalgal biomass through efficient fixation of fermentation carbon dioxide.

An integrated process for the co-production of cellulosic ethanol and microalgal biomass by fixing CO2 generated from bioethanol fermentation is proposed. Specifically, over one-fifth of the fermentative carbon was converted into high-purity CO2 during ethanol production. The optimal concentration of 4 % CO2 was identified for the growth and metabolism of Chlorella sp. BWY-1. A multiple short-term intermittent CO2 supply system was established to efficiently fix and recycle the waste CO2. Using this system, economical co-production of cellulosic ethanol by Zymomonas mobilis and microalgal biomass in biogas slurry wastewater was achieved, resulting in the production of ethanol at a rate of 0.4 g/L/h and a fixed fermentation CO2 of 3.1 g/L/d. Moreover, the amounts of algal biomass and chlorophyll a increased by over 50 % and two-fold, respectively. Through techno-economic analysis, the integrated process demonstrated its cost-effectiveness for cellulosic ethanol production. This study presents an innovative approach to a low-carbon circular bioeconomy.

Elevated serum CA199 levels in patients suffering type 2 diabetes vs. various types of cancer.

AIMS: Carbohydrate antigen 199 (CA199) is a standard tumor marker, and recent studies have found elevated in CA199 levels in patients with diabetes. However, there is no systematic measurement and comparison of serum CA199 levels in patients with diabetes and cancer. Here, a detailed description of the changes in serum CA199 levels in patients with type 2 diabetes and various cancers was explored. METHODS: A total of 5,641 participants were screened for clinical laboratory test results of serum CA199 levels over the past three years (2020-2023). This study included 2,464 healthy controls, 688 patients with type 2 diabetes, and 2,489 patients with 16 different types of cancer. Each type of cancer had more than 30 independent serum CA199 level test results. The serum CA199 levels were compared between cancer groups, type 2 diabetes patients, and healthy controls. Additionally, the CA199 levels of cancer patients were compared with those of patients with type 2 diabetes. RESULTS: The serum CA199 levels of esophagus cancer, lung cancer, pancreatic cancer, ovarian cancer, breast cancer, rectum cancer, prostate cancer, bladder cancer, liver cancer, gastric cancer, cervical cancer, colon cancer, lymphoma, thyroid cancer, intracranial tumors, and nasopharyngeal laryngeal cancer were found to be elevated compared to healthy controls (P < 0.01). In addition, the serum CA199 levels of patients with type 2 diabetes were also significantly elevated compared to healthy controls (P < 0.01). Moreover, the degree of elevation in serum CA199 levels in patients with type 2 diabetes was not significantly different from that observed in some types of cancer, such as esophagus cancer (P = 0.163), breast cancer (P = 0.927), prostate cancer (P = 1.000), bladder cancer (P = 0.406), Lymphoma (P = 0.975), thyroid cancer (P = 1.000), intracranial tumors (P = 0.161), nasopharyngeal and laryngeal cancer (P = 1.000). CONCLUSIONS: Serum CA199 levels also increase in type 2 diabetes, and the magnitude of the increase is similar to that seen in some cancers.

Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc.

Background: The N6-methyladenosine (m6A) dynamics in the progression of intervertebral disc (IVD) aging remain largely unknown. This study aimed to explore the distribution and pattern of m6A modification in nucleus pulpous (NP) tissues of rats at different ages. Methods: Histological staining and MRI were performed to evaluate the degeneration of IVD. The expression of m6A modifiers was analyzed using qRT-PCR and western blot. Subsequently, methylated RNA immunoprecipitation next generation sequencing and RNA-seq were conducted to identify differences in m6A methylome and transcriptome of NP tissues. Results: Compared to 2-month-old rats, we found significant changes in the global m6A level and the expression of Mettl3 and FTO in NP tissues from 20-month-old rats. During the progression of NP aging, there were 1126 persistently differentially m6A peaks within 931 genes, and 51 persistently differentially expressed genes. GO and KEGG analyses showed that these m6A peaks and m6A modified genes were mainly engaged in the biological processes and pathways of intervertebral disc degermation (IDD), such as extracellular matrix metabolism, angiogenesis, inflammatory response, mTOR and AMPK signaling pathways. Meanwhile, conjoint analyses and Venn diagram revealed a total of 405 aging related genes contained significant methylation and expression levels in 20-month-old rats in contrast to 2-month-old and 10-month-old rats. Moreover, it was found that four aging related genes with hypermethylated modification including BUB1, CA12, Adamts1, and Adamts4 depicted differentially expressed at protein level, of which BUB1 and CA12 were decreased, while Adamts1 and Adamts4 were increased during the progression of NP aging. Conclusion: Collectively, this study elucidated the distribution and pattern of m6A modification during the aging of IVD. Furthermore, the m6A modified genes were involved in the IDD related biological processes and pathways. These findings may provide novel insights into the mechanisms and therapies of IDD from the perspective of aging.

Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

Establishment and validation of a prognostic nomogram for patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Colorectal neuroendocrine carcinoma is a relatively rare tumor, for which a prognosis prediction model is lacking. Based on the data from Surveillance, Epidemiology, and End Results (SEER) database and Fujian Cancer Hospital, the study constructed and validated a prognostic nomogram to assess overall survival of patients with colorectal neuroendocrine carcinoma(CRNEC). METHODS: We extracted data of patients diagnosed with CRNEC from the SEER database. These patients were randomly divided into a training cohort(N = 1425) and an internal validation cohort(N = 612). Data of patients diagnosed with CRNEC in Fujian Cancer Hospital was collected as an external validation cohort(N = 54). A prognostic nomogram was established. The performance of the nomogram was assessed with ROC curve, C-index and calibration curve. Decision curve analysis(DCA) and ROC curve were used to compare the prediction efficacy of nomogram with the seventh edition of the TNM classification of the American Joint Commission of Cancer. RESULTS: Nine variables were identified as independent predictors. Nomogram were established by the nine variables. AUC of the nomogram in predicting 1-, 3- and 5-year OS were 0.900, 0.912 and 0.915 in training cohort, 0.900, 0.925 and 0.919 in internal validation cohort, 0.900, 0.903 and 0.928 in external validation cohort. C-index were 0.845, 0.854 and 0.837. Calibration curves overlapped well with reference lines. Compared with the AJCC TNM staging system, the nomogram performed more effectively. Patients classified into low-risk and high-risk groups by the nomogram scores and performed well in stratification. CONCLUSION: The prognostic nomogram established and validated in our study can accurately and effectively predict the prognosis of patients with CRNEC.

Evaluating polygenic risk scores for predicting cardiometabolic traits and disease risks in the Taiwan Biobank.

Type 2 diabetes (T2D) and hypertension are common comorbidities and, along with hyperlipidemia, serve as risk factors for cardiovascular diseases. This study aimed to evaluate the predictive value of polygenic risk scores (PRSs) on cardiometabolic traits related to T2D, hypertension, and hyperlipidemia and the incidence of these three diseases in Taiwan Biobank samples. Using publicly available, large-scale genome-wide association studies summary statistics, we constructed cross-ethnic PRSs for T2D, hypertension, body mass index, and nine quantitative traits typically used to define the three diseases. A composite PRS (cPRS) for each of the nine traits was constructed by aggregating the significant PRSs of its genetically correlated traits. The associations of each of the nine traits at baseline as well as the change of trait values during a 3- to 6-year follow-up period with its cPRS were evaluated. The predictive performances of cPRSs in predicting future incidences of T2D, hypertension, and hyperlipidemia were assessed. The cPRSs had significant associations with baseline and changes of trait values in 3-6 years and explained a higher proportion of variance for all traits than individual PRSs. Furthermore, models incorporating disease-related cPRSs, along with clinical features and relevant trait measurements achieved area under the curve values of 87.8%, 83.7%, and 75.9% for predicting future T2D, hypertension, and hyperlipidemia in 3-6 years, respectively.

The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4.

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated glutathione peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD.

Comparative Analysis of Metabolic Variation in Eggplant Fruit of Different Varieties Reveals Metabolites Important for Quality Traits.

Eggplant is one of the most important vegetable crops worldwide and has been considered to have great antioxidant activity. However, little information is available about the primary metabolic composition of the nutritional values of eggplant. Using a widely targeted metabolome approach, the current study investigated primary metabolic variation in 13 eggplant varieties with different morphologies. A total of 503 primary metabolites (amino acids, lipids, nucleotides, organic acids, vitamin, saccharides, and alcohols) and 170 phenolic acids were detected, among which 211 metabolites were differently accumulated. Metabolic pathway analysis of the differential metabolites revealed the significant enrichment of phenylpropanoid biosynthesis, arginine biosynthesis, alpha-linolenic acid metabolism, and linoleic acid metabolism. The higher levels of amino acids and lipids were related to the umami, soft, and waxy taste of eggplant fruit. The present work substantially contributes to the knowledge of primary metabolite compositions regarding fruit-eating quality and provides useful information for the future breeding of eggplant.

Association of altered fibrinogen indexes levels as a potential biomarker in determining the possible onset of diabetic retinopathy.

Research suggests that fibrinogen was related to diabetic retinopathy (DR). Then, the relationship between functional indices of fibrinogen and detailed staging of DR has not been explored. Type 2 diabetic and healthy control subjects (n = 960) were recruited in a cross-sectional study. Participants with type 2 diabetes mellitus were categorized into five stages according to their fundus lesions, and fibrinogen (Fib) and its functional indices (angle α and k value) were measured. The angle α levels increased in diabetic subjects with retinopathy compared with those without, and it was significantly elevated early in retinopathy. In contrast, the k value levels slightly decreased. Despite observing an increase in angle α levels and a decrease in k value levels during the later stages of retinopathy compared to the earlier stages, there was no statistically significant difference in the later stages. The association of the angle α and k value with DR was independent of the hyperglycaemic state and other potential confounders (OR = 1.672, 95% CI 1.489-1.876, P < 0.01; OR = 0.013, 95% CI 0.004-0.041, P < 0.01). The angle α levels and k value levels were closely correlated with retinopathy (r = 0.593, P < 0.00; r = - 0.646, P < 0.01). The ROC curve indicated that the diagnostic value of angle α and k value were (AUC = 0.897, P < 0.001; AUC = 0.859, P < 0.001). Fibrinogen function indexes, such as angle α and k value, may be valuable for the early diagnosis of DR but do not directly assess the severity of DR.

Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics, in vivo, and in vitro study.

Objective: The mechanisms of chondrocytes ferroptosis in osteoarthritis (OA) have not yet been fully elucidated. This study aimed to identify key ferroptosis related genes (FRGs) involved in chondrocytes ferroptosis. Methods: LASSO, SVM-RFE, and receiver operating characteristic curve (ROC) were performed to screen key differentially expressed FRGs (DEFRGs). Functional analyses were conducted using GO, and KEGG analyses. Unsupervised clustering analysis was used to identify ferroptosis related patterns. The CeRNA network was constructed to predict the upstream miRNAs and lncRNAs. Finally, we validated the role of EGFR in chondrocytes ferroptosis using in vivo and in vitro experiments. Results: A total of 42 DEFRGs were identified between OA and normal cartilages. GO and KEGG analyses indicated that these DEFRGs were significantly engaged in ferroptosis related biological processes and pathways, such as cellular response to oxidative stress, positive regulation of programmed cell death, MAPK and PI3K-Akt signaling pathways. Moreover, four key DEFRGs, including ACSF2, AURKA, EGFR, and KLHL24, were considered as potential biomarkers of OA. Moreover, two distinct ferroptosis related patterns were determined, and a total of 882 differentially expressed genes were identified which might participate in extracellular matrix degradation and inflammatory response. In addition, the CeRNA network showed that EGFR could be competitively regulated by 3 lncRNAs and 4 miRNAs. Significantly, the expression of EGFR was downregulated in human OA cartilages, OA mouse model, and erastin induced chondrocytes. EGFR inhibition could induce the occurrence of chondrocytes ferroptosis and ECM degradation which could be reversed by the addition of Ferrostatin-1. Conclusion: Our study has identified ACSF2, AURKA, EGFR, and KLHL24 as ferroptosis-related biomarkers in OA. Furthermore, we have conducted a preliminary investigation into the role of EGFR in regulating chondrocytes ferroptosis. These findings offer novel insights into the molecular mechanisms underlying OA.

ChecMatE: A workflow package to automatically generate machine learning potentials and phase diagrams for semiconductor alloys.

Semiconductor alloy materials are highly versatile due to their adjustable properties; however, exploring their structural space is a challenging task that affects the control of their properties. Traditional methods rely on ad hoc design based on the understanding of known chemistry and crystallography, which have limitations in computational efficiency and search space. In this work, we present ChecMatE (Chemical Material Explorer), a software package that automatically generates machine learning potentials (MLPs) and uses global search algorithms to screen semiconductor alloy materials. Taking advantage of MLPs, ChecMatE enables a more efficient and cost-effective exploration of the structural space of materials and predicts their energy and relative stability with ab initio accuracy. We demonstrate the efficacy of ChecMatE through a case study of the InxGa1-xN system, where it accelerates structural exploration at reduced costs. Our automatic framework offers a promising solution to the challenging task of exploring the structural space of semiconductor alloy materials.