Immediate loading in partially edentulous patients with fixed implant-supported restorations cases report.

Objectives: This article reports on four rare cases involving multiple trauma-induced adjacent missing anterior teeth in the maxillary or mandibular region. These cases were successfully treated using a 4-axial implant-based alternative insert and an immediate loading protocol. Material and methods: This series of cases was summarized by retrospective study that 4 patients who received a total of 20 immediately loaded implants. These patients had suffered from trauma-induced loss of 8-9 adjacent anterior teeth. The 4-axial-implants were inserted with the assistance of digital pioneer drill guides. The surgical procedure involved alveolar bone trimming or ultrasonic osteotomy, eliminating the need for traditional large-area bone augmentation. Pre- and post-operative CBCT was matched using DTX Studio Implant software, the deviation of implant between actual position and preoperative design was measured and compared using SPSS software package. Results: The average follow-up duration 48 months after implant prostheses, the cumulative retention rate of the implants was 100%, the marginal bone loss averaged 0.53 mm (SD 0.15 mm), and buccal plate bone loss averaged 0.62 mm (SD 0.41 mm). Conclusions: This retrospective clinical report demonstrates the successful treatment of several patients with multiple adjacent maxillary or mandibular anterior teeth using four implant-supported screws to fix the frame and employing immediate loading. The approach resulted in long-term stable clinical outcomes. Moreover, the method not only shortens the period of edentulism but also facilitates easy disassembly, maintenance, and cleaning. Consequently, it emerges as a highly favorable clinical option for patients suffering from extensive tooth loss.

Atomically Dispersed Metal Catalysts for the Conversion of CO2 into High-Value C2+ Chemicals.

The conversion of carbon dioxide (CO2) into value-added chemicals with two or more carbons (C2+) is a promising strategy that cannot only mitigate anthropogenic CO2 emissions but also reduce the excessive dependence on fossil feedstocks. In recent years, atomically dispersed metal catalysts (ADCs), including single-atom catalysts (SACs), dual-atom catalysts (DACs), and single-cluster catalysts (SCCs), emerged as attractive candidates for CO2 fixation reactions due to their unique properties, such as the maximum utilization of active sites, tunable electronic structure, the efficient elucidation of catalytic mechanism, etc. This review provides an overview of significant progress in the synthesis and characterization of ADCs utilized in photocatalytic, electrocatalytic, and thermocatalytic conversion of CO2 toward high-value C2+ compounds. To provide insights for designing efficient ADCs toward the C2+ chemical synthesis originating from CO2, the key factors that influence the catalytic activity and selectivity are highlighted. Finally, the relevant challenges and opportunities are discussed to inspire new ideas for the generation of CO2-based C2+ products over ADCs.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Effectiveness of immediate implant placement into defective sockets in the esthetic zone: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: A defective socket is common after tooth extraction in the esthetic zone, but whether an implant can be immediately placed in a defective socket is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to summarize relevant studies within the last 20 years on implant survival and changes in soft and hard tissues after immediate implant placement in esthetic areas with socket defects. MATERIAL AND METHODS: A search was conducted for the relevant studies in the PubMed/Medline, the Cochrane Library, Web of Science, and Embase databases from January 2000 to March 2022. The literature review, data retrieval, and judgment whether the included studies had a risk of bias were handled independently by 2 reviewers, and a single-arm meta-analysis was performed using a statistical software program. RESULTS: A total of 23 studies evaluating the immediate implant placement of 630 implants (9 studies without a flap and 14 studies with a flap) were included. A 98.1% implant survival rate (95% confidence interval (CI): 96.2%, 100.0%) was determined. Marginal bone loss (MBL) at 6, 12, and ≥24 months were 1.03 mm (95%CI: 1.02, 1.03), 0.72 mm (0.72, 0.73), and 1.15 mm (1.14, 1.16). Gingival recession at 12 months was 0.25 mm (95%CI: 0.17, 0.33). The pink esthetic score (PES) were 12.34 (95%CI: 12.16, 12.52) at 12 months and 12.58 (12.39, 12.76) at ≥24 months. CONCLUSIONS: Current evidence shows that immediate implant placement into defective sockets in esthetic areas is feasible. Immediate implant placement can have a relatively good therapeutic effect in terms of implant survival rate, MBL, gingival recession, and PES.

The Recent Progresses of Electrodes and Electrolysers for Seawater Electrolysis.

The utilization of renewable energy for hydrogen production presents a promising pathway towards achieving carbon neutrality in energy consumption. Water electrolysis, utilizing pure water, has proven to be a robust technology for clean hydrogen production. Recently, seawater electrolysis has emerged as an attractive alternative due to the limitations of deep-sea regions imposed by the transmission capacity of long-distance undersea cables. However, seawater electrolysis faces several challenges, including the slow kinetics of the oxygen evolution reaction (OER), the competing chlorine evolution reaction (CER) processes, electrode degradation caused by chloride ions, and the formation of precipitates on the cathode. The electrode and catalyst materials are corroded by the Cl- under long-term operations. Numerous efforts have been made to address these issues arising from impurities in the seawater. This review focuses on recent progress in developing high-performance electrodes and electrolyser designs for efficient seawater electrolysis. Its aim is to provide a systematic and insightful introduction and discussion on seawater electrolysers and electrodes with the hope of promoting the utilization of offshore renewable energy sources through seawater electrolysis.

The value of microvascular Doppler ultrasound technique, qualitative or quantitative shear-wave elastography of breast lesions for predicting axillary nodal burden in patients with breast cancer.

Background: The status of the axillary lymph node (ALN) in patients with breast cancer can critically inform clinical decision-making and prognosis. Preoperative evaluation of limited nodal burden (0-2 metastatic ALNs) and high nodal burden (≥3 metastatic ALNs) is vital for individual treatment in patients with breast cancer. Thus, this study aimed to evaluate the value of Angio-PLUS (AP; Aixplorer, SuperSonic Imagine) and the qualitative and quantitative shear-wave elastography (SWE) of breast lesions to predict limited or high axillary nodal burden and to develop a model for predicting limited or high axillary nodal burden. Methods: From March 2020 to November 2022, a total of 232 consecutive patients with breast cancer comprising 232 breast lesions were enrolled retrospectively from Yueyang Central Hospital. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and area under the receiver operating characteristic curve (AUC) of AP, qualitative SWE, quantitative SWE, and the predictive model for evaluating limited or high axillary nodal burden were compared. Results: There was no significant difference in AP patterns between the limited nodal burden group and high nodal burden group. The best cutoff values of Emin (the minimal value of the first Q-box), Emean (the mean value of the first Q-box), Emax (the maximum value of the first Q-box), Eratio (ratio of the first Q-Box and the second Q-Box) and standard deviation for predicting limited or high nodal burden were 80.85 KPa, 133.45 KPa, 153.40 KPa, 9.95, and 19.25 KPa, respectively. The Emax had the highest AUC, and its sensitivity, specificity, PPV, NPV, accuracy, and AUC were 71.64%, 56.36%, 40.00%, 83.04%, 60.78%, and 0.640 [95% confidence interval (CI): 0.575-0.702], respectively. The sensitivity, specificity, PPV, NPV, accuracy, and AUC of seven color patterns for qualitative SWE were 71.64%, 74.55%, 53.33%, 86.62%, 73.71%, and 0.731 (95% CI: 0.669-0.787), respectively, which was significantly higher than all the other quantitative SWE parameters. ALN evaluation in ultrasound and qualitative SWE were independent risk factors for predicting limited or high nodal burden according to a binary logistics regression analysis. The AUC of the predictive model based on independent risk factors was 0.820 (95% CI: 0.765-0.867), which was significantly higher than that of the other independent risk factors. Conclusions: The seven color patterns in the qualitative SWE of breast lesions were valuable for predicting limited or high nodal burden for patients with breast cancer. Compared with quantitative SWE, qualitative SWE exhibited a better diagnostic performance. Breast lesions present no findings, vertical stripes, and spot patterns were important indicators for limited nodal burden. The predictive model developed in this study could be a simple, noninvasive, and convenient method for predicting limited or high nodal burden, which would be beneficial for clinical decision-making and individual treatment to improve prognosis.

DADS Inhibits the Proliferation of MDCC-MSB-1 Cells by Inducing Autophagy via the MEK/ERK Signalling Pathway.

Diallyl disulfide (DADS) is effective at suppressing tumour cell growth and proliferation. This study verified the morphology and growth activity of MDCC-MSB-1 cells by using an MTT assay to detect the effect of DADS on the proliferation of MDCC-MSB-1 cells and a CCK8 assay to detect the effect of DADS on the viability and proliferation of MDCC-MSB-1 cells. We found that the viability and proliferation of MDCC-MSB-1 cells decreased with increasing DADS concentrations. MDC staining and Western blotting were used to analyse autophagy, the associated protein LC3 and the MEK/ERK pathway proteins MEK and ERK and to investigate changes in cellular autophagy based on cell morphology and molecular biology. With increasing concentrations of DADS, MDCC-MSB-1 cell autophagy increased in a gradient manner. Additionally, the conversion of the autophagy marker protein LC3-I increased with increasing drug concentrations, and the relative expression of LC3-II steadily increased, as did the expression of key protein components of the MEK/ERK signalling pathway, including P-MEK1/2 and P-ERK1/2. These results suggest that DADS induces autophagy through the MEK/ERK pathway, thereby inhibiting the proliferation of MDCC-MSB-1 cells.

Exploiting the synergistic antibacterial activity of shikimic acid and ceftiofur against methicillin-resistant Staphylococcus aureus.

Efforts to curtail the escalating health threat posed by methicillin-resistant Staphylococcus aureus (MRSA), a formidable superbug, necessitate the development of innovative treatment strategies. Leveraging potential compounds from natural sources in tandem with antibiotics has emerged as a promising approach against MRSA. These strategies should enhance the antibiotic efficacy, reduce dosage and toxicity, and bypass MRSA resistance. In this study, we used a checkerboard assay to illustrate the significant synergistic anti-MRSA effect of shikimic acid (SA), a naturally occurring compound, and ceftiofur (CF). Time-kill curves further revealed that a combination of 1/4 of the minimum inhibitory concentration (MIC) of SA and 1/8 MIC of the sodium CF eradicated MRSA within 2 h, with no noticeable toxicity observed with these concentrations. In vivo experiments confirmed that this combination therapy demonstrated robust antimicrobial activity against MRSA-induced bacteremia in mice, significantly reducing bacterial loads in the kidneys, liver, and spleen, attenuating inflammatory cell infiltration, and alleviating pathological damage. This study not only offers a compelling strategy, capitalizing on the synergistic potential of SA and CF, to rapidly address antibiotic resistance but also contributes significantly to the refinement of antimicrobial therapeutic strategies.

Self-Supporting Mn-RuO2 Nanoarrays for Stable Oxygen Evolution Reaction in Acid.

Currently, the process of an acidic oxygen evolution reaction (OER) necessitates the use of Iridium dioxygen (IrO2), which is both expensive and incredibly scarce on Earth. Ruthenium dioxygen (RuO2) offers high activity for acidic OERs and presents a potential substitution for IrO2. Nevertheless, its practical application is hindered by its relatively poor stability. In this study, we have developed Mn-doped RuO2 (Mn-RuO2) nanoarrays that are anchored on a titanium (Ti) mesh utilizing a two-step methodology involving the preparation of MnO2 nanoarrays followed by a subsequent Ru exchange and annealing process. By precisely optimizing the annealing temperature, we have managed to attain a remarkably low overpotential of 217 mV at 10 mA cm-2 in a 0.5 M H2SO4 solution. The enhanced catalytic activity of our Mn-RuO2 nanoarrays can be attributed to the electronic modification brought about by the high exposure of active sites, Mn dopant, efficient mass transfer, as well as the efficient transfer of electrons between the Ti mesh and the catalyst arrays. Furthermore, these self-supported Mn-RuO2 nanoarrays demonstrated excellent long-term stability throughout a chronoamperometry test lasting for 100 h, with no discernible changes observed in the Ru chemical states.

Ultrasound radiomics based on axillary lymph nodes images for predicting lymph node metastasis in breast cancer.

Objectives: To determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging. Methods: A total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared. Result: Radiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively. Conclusion: The radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.

Preosteoclast plays a pathogenic role in syndesmophyte formation of ankylosing spondylitis through the secreted PDGFB - GRB2/ERK/RUNX2 pathway.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joint and spine. However, the real mechanisms of immune cells acting on syndesmophyte formation in AS are not well identified. We aimed to find the key AS-associated cytokine and assess its pathogenic role in AS. METHODS: A protein array with 1000 cytokines was performed in five AS patients with the first diagnosis and five age- and gender-matched healthy controls to discover the differentially expressed cytokines. The candidate differentially expressed cytokines were further quantified by multiplex protein quantitation (3 AS-associated cytokines and 3 PDGF-pathway cytokines) and ELISA (PDGFB) in independent samples (a total of 140 AS patients vs 140 healthy controls). The effects of PDGFB, the candidate cytokine, were examined by using adipose-derived stem cells (ADSCs) and human fetal osteoblast cell line (hFOB1.19) as in vitro mesenchymal cell and preosteoblast models, respectively. Furthermore, whole-transcriptome sequencing and enrichment of phosphorylated peptides were performed by using cell models to explore the underlying mechanisms of PDGFB. The xCELLigence system was applied to examine the proliferation, chemotaxis, and migration abilities of PDGFB-stimulated or PDGFB-unstimulated cells. RESULTS: The PDGF pathway was observed to have abnormal expression in the protein array, and PDGFB expression was further found to be up-regulated in 140 Chinese AS patients. Importantly, PDGFB expression was significantly correlated with BASFI (Pearson coefficient/p value = 0.62/6.70E - 8) and with the variance of the mSASSS score (mSASSS 2 years - baseline, Pearson coefficient/p value = 0.76/8.75E - 10). In AS patients, preosteoclasts secreted more PDGFB than the healthy controls (p value = 1.16E - 2), which could promote ADSCs osteogenesis and enhance collagen synthesis (COLI and COLIII) of osteoblasts (hFOB 1.19). In addition, PDGFB promoted the proliferation, chemotaxis, and migration of ADSCs. Mechanismly, in ADSCs, PDGFB stimulated ERK phosphorylation by upregulating GRB2 expression and then increased the expression of RUNX2 to promote osteoblastogenesis of ADSCs. CONCLUSION: PDGFB stimulates the GRB2/ERK/RUNX2 pathway in ADSCs, promotes osteoblastogenesis of ADSCs, and enhances the extracellular matrix of osteoblasts, which may contribute to pathological bone formation in AS.

MOF-Derived CoSe2@NiFeOOH Arrays for Efficient Oxygen Evolution Reaction.

Water electrolysis is a compelling method for the production of environmentally friendly hydrogen, minimizing carbon emissions. The electrolysis of water heavily relies on an effective and steady oxygen evolution reaction (OER) taking place at the anode. Herein, we introduce a highly promising catalyst for OER called CoSe2@NiFeOOH arrays, which are supported on nickel foam. This catalyst, referred to as CoSe2@NiFeOOH/NF, is fabricated through a two-step process involving the selenidation of a Co-based porous metal organic framework and subsequent electrochemical deposition on nickel foam. The CoSe2@NiFeOOH/NF catalyst demonstrates outstanding activity for the OER in an alkaline electrolyte. It exhibits a low overpotential (η) of 254 mV at 100 mA cm-2, a small Tafel slope of 73 mV dec-1, and excellent high stability. The good performance of CoSe2@NiFeOOH/NF can be attributed to the combination of the high conductivity of the inner layer and the synergistic effect between CoSe2 and NiFeOOH. This study offers an effective method for the fabrication of highly efficient catalysts for an OER.

TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis.

OBJECTIVES: Innate immunity significantly contributes to systemic sclerosis (SSc) pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc. METHODS: The expression of TLR8 was analyzed based on a public dataset and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model. RESULTS: TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1ß, COL I, COL III, and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB, and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo. CONCLUSION: TLR8 might be a promising therapeutic target to improve the treatment strategy for SSc skin inflammation and fibrosis.

An optimal method for quantifying the facial sebum level and characterizing facial sebum features.

BACKGROUND: Evidence suggests that sebum content is important in skin disorders such as acne. However, sebum levels change depending on the external environment, and quantifying skin sebum levels is challenging. Here, we propose an optimal method for quantifying the facial sebum level. MATERIALS AND METHODS: Four hundred and sixty participants (160 males and 300 females) aged 20-40 were enrolled in this study. A Sebumeter SM 810 was used to measure the sebum level at five facial locations: the forehead, the chin, the left cheek, the right cheek, and the nose. The participants were divided into two groups; one group underwent a one-time measurement (n = 390, male: female = 120: 270), and the other underwent three consecutive measurements (n = 70, male: female = 40: 30). The casual sebum level (CSL) was measured in all patients after a 30-min acclimatization; subsequently, the sebum removal process was conducted, followed by a resting period of 1 h to determine the sebum excretion rate (SER). Spearman's correlation analysis and the Wilcoxon signed-rank test were used to compare the sebum level consistency and differences between the groups. RESULTS: Although three consecutive measurements better reflected the sebum content, the one-time measurement also represented the relative sebum level. One hour after sebum removal, the sebum level recovered to 70%-90%; thus, this method was applicable for use in SER quantification. Of the five testing points, the sebum content was highest in the nose and lowest in the cheeks (both left and right). In addition, the cheeks were the most stable sites in terms of testing points, testing times, and CSL/SER values. A one-time measurement of the CSL could represent the SER 1 h after the sebum removal. In our cohort, the sebum level of males with oily skin was decreased at age 32-35, and that of males with non-oily skin increased at 28-35. The opposite trend was observed in female participants. CONCLUSION: Sebum measurement methods were assessed, including testing times, indices (interval of time) and sites in a conditioned external environment. A one-time measurement of the CSL 1 h after sebum removal was sufficient to determine the sebum level and SER, and the cheeks are recommended as the testing site. Sex and skin type differences were observed in sebum level changes with age.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

Gut microbiota bridges dietary nutrients and host immunity.

Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other, and thus affect host health and immune-mediated diseases. Here, we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions, emphasizing how this axis might influence host immunity in health and diseases. Of relevance, we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.

Does first-hand evidence undermine young children's initial trust in positive gossip? Evidence from 5- to 6-year-old children.

What happens when children have formed an impression of a peer based on prior gossip, but later learn from direct observation that the gossip is untrue? We interviewed seventy 5- and 6-year-old children in Zhejiang, China. They first heard conflicting positive and negative gossip about an absent third party, and subsequently learned which piece of gossip was true. Initially, both 5- and 6-year-old children tended to endorse the positive rather than the negative gossip. However, when they learned about the inaccuracy of the positive gossip based on their own direct observation, 6-year-old children subsequently doubted it, whereas 5-year-old children showed no such shift. Taken together, the results show that when children decide what gossip to believe, they are initially swayed by its valence but with age they increasingly weigh gossip in relation to their own direct observation.

CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function.

Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins KCNJ4 and KCNJ12, inducing cell cycle arrest, disruption of DNA replication and base excision repair. Overexpression of KCNJ4 and KCNJ12 was involved in ZEA resistance by regulating cell cycle to neutralize toxicity, sustaining mitochondrial morphology and function via attenuating the damage from oxidative stress in the KCNJ4-mitoKATP pathway. In vivo experiments showed that AAV-KCNJ4 delivery significantly improved ZEA-induced renal impairment and increased antioxidative enzyme activity by improving mitochondrial function. Our findings suggest that increasing potassium channel levels may be a putative therapeutic target for mycotoxin-induced damage.

Enhancement of Zyxin Promotes Skin Fibrosis by Regulating FAK/PI3K/AKT and TGF-ß Signaling Pathways via Integrins.

Skin fibrosis is a common pathological manifestation in systemic sclerosis (SSc), keloid, and localized scleroderma (LS) characterized by fibroblast activation and excessive extracellular matrix (ECM) deposition. However, few effective drugs are available to treat skin fibrosis due to its unclear mechanisms. In our study, we reanalyzed skin RNA-sequencing data of Caucasian, African, and Hispanic SSc patients from the Gene Expression Omnibus (GEO) database. We found that the focal adhesion pathway was up-regulated and Zyxin appeared to be the primary focal adhesion protein involved in skin fibrosis, and we further verified its expression in Chinese skin tissues of several fibrotic diseases, including SSc, keloid, and LS. Moreover, we found Zyxin inhibition could significantly alleviate skin fibrosis using Zyxin knock-down and knock-out mice, nude mouse model and skin explants of human keloid. Double immunofluorescence staining showed that Zyxin was highly expressed in fibroblasts. Further analysis revealed pro-fibrotic gene expression and collagen production increased in Zyxin over-expressed fibroblasts, and decreased in Zyxin interfered SSc fibroblasts. In addition, transcriptome and cell culture analyses revealed Zyxin inhibition could effectively attenuate skin fibrosis by regulating the FAK/PI3K/AKT and TGF-ß signaling pathways via integrins. These results suggest Zyxin appears a potential new therapeutic target for skin fibrosis.