Effects of Stress on Biological Characteristics and Metabolism of Periodontal Ligament Stem Cells of Deciduous Teeth.

INTRODUCTION AND AIMS: Periodontal ligament stem cells (PDLSCs) from deciduous teeth (DePDLSCs) can perceive and respond to mechanical signals upon exposure to various environments. The effects of mechanical stress on the biological characteristics and metabolism of DePDLSCs were investigated using in vitro stress loading. METHODS: DePDLSCs were subjected to mechanical stresses of different strengths. Cell proliferation, expression of osteogenic/osteoclastic factors, apoptosis, and oxidative stress levels were evaluated using CCK-8 assays, alkaline phosphatase staining, real-time PCR, flow cytometry, and malondialdehyde and superoxide dismutase assays. Liquid chromatography-mass spectrometry was used to perform nontargeted metabolomic detection and analysis. RESULTS: Under stresses of 75 and 150 kPa, the expression of osteogenesis-related factors OPG, ALP, and RUNX2 decreased, and the ratio of RANKL/OPG significantly increased. A pressure of 150 kPa induced oxidative stress and caused a significant increase in cell apoptosis. Among the differential metabolites screened from the 150 kPa group, spermine, spermidine, ceramide, phosphatidylethanolamine, lysophosphatidylethanolamine, linoleic acid, and docosatrienoic acid were the most significantly upregulated. The metabolites screened from the 75 kPa group were mainly related to glycerophospholipid and sphingolipid metabolism, oxidative phosphorylation, and mineral absorption, which were common pathways affected in both experimental groups. CONCLUSION: A certain degree of mechanical stress can inhibit the proliferative activity and osteogenic differentiation of DePDLSCs, enhance their osteoclast-inducing ability, and cause elevated levels of cell apoptosis and oxidative stress. The metabolic expression profile of DePDLSCs changed significantly under stress. Understanding changes in cellular activity and metabolic reactions may provide an experimental basis for elucidating the role of mechanical stress in root resorption and periodontal tissue remodelling of deciduous teeth. CLINICAL RELEVANCE: Mechanical stress may affect periodontal tissue remodeling and root resorption of DePDLSc.

Research Status and Trends in Periodontal Ligament Stem Cells: A Bibliometric Analysis over the Past Two Decades.

Objective: Currently, the summaries of research on periodontal ligament stem cells (PDLSCs) are mainly reviews, and the systematic evaluation of all relevant studies is lacking. The aim of our study was to reveal the research status and developmental trends of PDLSCs using bibliometric analyses. Methods: Publications on PDLSC from 2004 to 2023 in the PubMed database were searched and then screened according to certain inclusion and exclusion criteria. Two researchers browsed the included papers and recorded information such as the research type and research model. The VOSviewer software was used to analyze the distribution of authors, journals, and institutions. The contents and directions of PDLSC research were summarized by analyzing high-frequency keywords. The CiteSpace software was used to monitor burst words, determine hot factors, and indicate developmental trends. Results: During the past two decades, the number of studies on PDLSCs increased. China published the most related papers. The primary type of article was basic research. Among core journals, the Journal of Periodontal Research had the highest number of publications. The Fourth Military Medical University (China) was leading in the number of articles on PDLSCs. Research topics mainly included mechanism of periodontal diseases, tissue engineering and regeneration, biological characteristics of PDLSCs, and comparison with other stem cells. Infectious inflammation and mechanical stimulation were important pathological conditions and research topics. Conclusion: The research of PDLSCs is still in a rapid development stage. Our study provides new insights into the current research status and future trend in this field.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Potential Predictive of Thoracic CT Value and Bone Mineral Density T-Value in COPD Complicated with Osteoporosis.

Background: COPD, combined with Osteoporosis, has a high incidence and potential for great harm. Choosing an optimal diagnostic method to achieve bone mineral density (BMD) screening is crucial for COPD patients. Studies on COPD patients with BMD reduction are lacking. Purpose: To identify the risk factors of BMD reduction and osteoporosis in COPD patients. Patients and Methods: We included a total of 81 patients with AECOPD, who were admitted to the hospital from July 1, 2019, to January 31, 2020. Patients were grouped into BMD normal group, BMD reduced group and OP group. The areas under ROC curve were used to explore the value of CT values in the diagnosis of bone abnormality, and clinical indicators were collected. Results: The CT value of the vertebral cancellous bone is highly correlated with the T value of BMD (R > 5.5, P < 0.0001). Using multivariate Logistic regression analysis, we showed that COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid were independent factors affecting different BMD levels in COPD patients. No significant difference in bone formation indexes between groups. ß-crossL was negatively correlated with serum IL-6 (r=-0.254, P=0.022), and ALP was positively correlated with serum TNF-α (r=0.284, P=0.023). Conclusion: Thoracolumbar vertebral cancellous bone CT has potential value in the diagnosis of bone abnormality. COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid may contribute to the BMD reduction in COPD patients, and serum IL-6 and TNF-α regulate bone metabolism in COPD patients.

Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Transcription factor WRKY75 maintains auxin homeostasis to promote tomato defense against Pseudomonas syringae.

The hemibiotrophic bacterial pathogen Pseudomonas syringae infects a range of plant species and causes enormous economic losses. Auxin and WRKY transcription factors play crucial roles in plant responses to P. syringae, but their functional relationship in plant immunity remains unclear. Here, we characterized tomato (Solanum lycopersicum) SlWRKY75, which promotes defenses against P. syringae pv. tomato (Pst) DC3000 by regulating plant auxin homeostasis. Overexpressing SlWRKY75 resulted in low free indole-3-acetic acid (IAA) levels, leading to attenuated auxin signaling, decreased expansin transcript levels, upregulated expression of PATHOGENESIS-RELATED GENES (PRs) and NONEXPRESSOR OF PATHOGENESIS-RELATED GENE 1 (NPR1), and enhanced tomato defenses against Pst DC3000. RNA interference-mediated repression of SlWRKY75 increased tomato susceptibility to Pst DC3000. Yeast one-hybrid, electrophoretic mobility shift assays, and luciferase activity assays suggested that SlWRKY75 directly activates the expression of GRETCHEN HAGEN 3.3 (SlGH3.3), which encodes an IAA-amido synthetase. SlGH3.3 enhanced tomato defense against Pst DC3000 by converting free IAA to the aspartic acid (Asp)-conjugated form IAA-Asp. In addition, SlWRKY75 interacted with a tomato valine-glutamine (VQ) motif-containing protein 16 (SlVQ16) in vivo and in vitro. SlVQ16 enhanced SlWRKY75-mediated transcriptional activation of SlGH3.3 and promoted tomato defense responses to Pst DC3000. Our findings illuminate a mechanism in which the SlVQ16-SlWRKY75 complex participates in tomato pathogen defense by positively regulating SlGH3.3-mediated auxin homeostasis.

Synthesizing Benzotriazole Group-Terminated Carbon Dots as Multifunctional Additives of Poly(ethylene glycol).

Long running-in period and corrosion problems have greatly hindered the practical applications of poly(ethylene glycol) (PEG) lubricants. In this work, benzotriazole group-terminated carbon dots (BT-CDs) were specifically synthesized through a facile solvothermal method. The benzotriazole groups on BT-CD surfaces not only imparted them excellent dispersibility in the PEG base oil but also brought in outstanding anticorrosion ability for BT-CDs. With the aid of the coordination effects between benzotriazole groups and metal atoms, the BT-CDs could quickly and solidly adsorb onto the steel surface to form a dense adsorption layer, which resulted in an amazing phenomenon, i.e., the disappearance of the running-in period for the friction test. Adding 5.0 wt % BT-CDs reduced the friction and wear of PEG200 by 49.16 and 49.52%, respectively. When the duration was prolonged from 20 to 120 min, these values were further enlarged to 53.77 and 60.71%. The worn surface characterization demonstrated that the BT-CDs induced the generation of robust lubricating films on the frictional interfaces, accounting for their distinguished tribological performance. Considering the superior anticorrosion ability and the potential possibility of avoiding the running-in period, the BT-CDs are expected to be developed as particularly promising additives toward PEG.

Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD.

BACKGROUND: Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis. However, the role of emodin in DIC and its molecular targets remain unknown. HYPOTHESIS/PURPOSE: We aimed to clarify the protective role of emodin in mitigating DIC, as well as the mechanisms underlying this effect. METHODS: The model of DIC was established via the intraperitoneal administration of Dox at a dosage of 5 mg/kg per week for a span of 4 weeks. Emodin at two different doses (10 and 20 mg/kg) or a vehicle was intragastrically administered to the mice once per day throughout the Dox treatment period. Cardiac function, myocardial injury markers, pathological morphology of the heart, level of pyroptosis and mitochondrial function were assessed. Protein microarray, biolayer interferometry and pull-down assays were used to confirm the target of emodin. Moreover, GSDMD-overexpressing plasmids were transfected into GSDMD-/- mice and HL-1 cells to further verify whether emodin suppressed GSDMD activation. RESULTS: Emodin therapy markedly enhanced cardiac function and reduced cardiomyocyte pyroptosis in mice induced by Dox. Mechanistically, emodin binds to GSDMD and inhibits the activation of GSDMD by targeting the Trp415 and Leu290 residues. Moreover, emodin was able to mitigate Dox-induced cardiac dysfunction and myocardial injury in GSDMD-/- mice overexpressing GSDMD, as shown by increased EF and FS, decreased serum levels of CK-MB, LDH and IL-1ß and mitigated cell death and cell morphological disorder. Additionally, emodin treatment significantly reduced GSDMD-N expression and plasma membrane disruption in HL-1 cells overexpressing GSDMD induced by Dox. In addition, emodin reduced mitochondrial damage by alleviating Dox-induced GSDMD perforation in the mitochondrial membrane. CONCLUSION: Emodin has the potential to attenuate DIC by directly binding to GSDMD to inhibit pyroptosis. Emodin may become a promising drug for prevention and treatment of DIC.

Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation.

Activation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD. Through structure-based virtual screening, pharmacological screening and subsequent pharmacological validations, we preliminarily identified GSDMD inhibitor Y1 (GI-Y1) as a selective GSDMD inhibitor with cardioprotective effects. Mechanistically, GI-Y1 binds to GSDMD and inhibits lipid- binding and pyroptotic pore formation of GSDMD-N by targeting the Arg7 residue. Importantly, we confirmed the cardioprotective effect of GI-Y1 on myocardial I/R injury and cardiac remodeling by targeting GSDMD. More extensively, GI-Y1 also inhibited the mitochondrial binding of GSDMD-N and its concomitant mitochondrial dysfunction. The findings of this study identified a new drug (GI-Y1) for the treatment of cardiac disorders by targeting GSDMD, and provide a new tool compound for pyroptosis research.

Genetic and cultural adaptations underlie the establishment of dairy pastoralism in the Tibetan Plateau.

BACKGROUND: Domestication and introduction of dairy animals facilitated the permanent human occupation of the Tibetan Plateau. Yet the history of dairy pastoralism in the Tibetan Plateau remains poorly understood. Little is known how Tibetans adapted to milk and dairy products. RESULTS: We integrated archeological evidence and genetic analysis to show the picture that the dairy ruminants, together with dogs, were introduced from West Eurasia into the Tibetan Plateau since ~ 3600 years ago. The genetic admixture between the exotic and indigenous dogs enriched the candidate lactase persistence (LP) allele 10974A > G of West Eurasian origin in Tibetan dogs. In vitro experiments demonstrate that - 13838G > A functions as a LP allele in Tibetans. Unlike multiple LP alleles presenting selective signatures in West Eurasians and South Asians, the de novo origin of Tibetan-specific LP allele - 13838G > A with low frequency (~ 6-7%) and absence of selection corresponds - 13910C > T in pastoralists across eastern Eurasia steppe. CONCLUSIONS: Results depict a novel scenario of genetic and cultural adaptations to diet and expand current understanding of the establishment of dairy pastoralism in the Tibetan Plateau.

Incidence and risk factors of unplanned retreatment following dental general anesthesia in children with severe early childhood caries.

Objective: This study aimed to retrospectively describe the unplanned retreatment of dental general anesthesia (DGA) in children with severe early childhood caries (S-ECC) and explore potential factors that may influence the outcome of DGA treatment. Methods: Medical records of children with S-ECC who received DGA treatment were screened, and necessary data were extracted. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the DGA survival rate and explore the potential factors affecting the success rate of DGA treatment. Results: Medical records of 852 children were included; 509 (59.7%) children with 1,212 (10.7%) teeth underwent unplanned retreatment. Restoration failure (30.12%) and new caries (29.46%) accounted for the most significant proportion of all failures. The median survival times were 510 and 1,911 days at the child and tooth levels, respectively. Unplanned retreatment risk was associated with the age of S-ECC children, frequency of follow-up, and fluoride application (hazard ratio = 0.97, 0.78, 0.69, P < 0.001). Conclusion: The treatment outcome of DGA administered to children with S-ECC was satisfactory at the tooth level from the perspective of the incidence of unplanned retreatment. Restoration failure was the main reason for the high unplanned retreatment rate. Strategies for a better outcome of DGA include improving the professional knowledge and skills of pediatric dentists and enhancing compliance of parents/patients. Health education and regular topical fluoride application may improve the success rate of DGA treatment.

ETHYLENE-INSENSITIVE 3-LIKE 2 regulates ß-carotene and ascorbic acid accumulation in tomatoes during ripening.

ETHYLENE-INSENSITIVE 3/ETHYLENE-INSENSITIVE 3-LIKEs (EIN3/EILs) are important ethylene response factors during fruit ripening. Here, we discovered that EIL2 controls carotenoid metabolism and ascorbic acid (AsA) biosynthesis in tomato (Solanum lycopersicum). In contrast to the red fruits presented in the wild type (WT) 45 d after pollination, the fruits of CRISPR/Cas9 eil2 mutants and SlEIL2 RNA interference lines (ERIs) showed yellow or orange fruits. Correlation analysis of transcriptome and metabolome data for the ERI and WT ripe fruits revealed that SlEIL2 is involved in ß-carotene and AsA accumulation. ETHYLENE RESPONSE FACTORs (ERFs) are the typical components downstream of EIN3 in the ethylene response pathway. Through a comprehensive screening of ERF family members, we determined that SlEIL2 directly regulates the expression of 4 SlERFs. Two of these, SlERF.H30 and SlERF.G6, encode proteins that participate in the regulation of LYCOPENE-ß-CYCLASE 2 (SlLCYB2), encoding an enzyme that mediates the conversion of lycopene to carotene in fruits. In addition, SlEIL2 transcriptionally repressed L-GALACTOSE 1-PHOSPHATE PHOSPHATASE 3 (SlGPP3) and MYO-INOSITOL OXYGENASE 1 (SlMIOX1) expression, which resulted in a 1.62-fold increase of AsA via both the L-galactose and myoinositol pathways. Overall, we demonstrated that SlEIL2 functions in controlling ß-carotene and AsA levels, providing a potential strategy for genetic engineering to improve the nutritional value and quality of tomato fruit.

Salicylic acid regulates two photosystem II protection pathways in tomato under chilling stress mediated by ETHYLENE INSENSITIVE 3-like proteins.

Chilling stress seriously impairs photosynthesis and activates a series of molecular responses in plants. Previous studies have shown that ETHYLENE INSENSITIVE 3 (EIN3) and EIN3-like (SlEIL) proteins mediate ethylene signaling and reduce plant tolerance to freezing in tomato (Solanum lycopersicum). However, the specific molecular mechanisms underlying an EIN3/EILs-mediated photoprotection pathway under chilling stress are unclear. Here, we discovered that salicylic acid (SA) participates in photosystem II (PSII) protection via SlEIL2 and SlEIL7. Under chilling stress, the phenylalanine ammonia-lyase gene SlPAL5 plays an important role in the production of SA, which also induces WHIRLY1 (SlWHY1) transcription. The resulting accumulation of SlWHY1 activates SlEIL7 expression under chilling stress. SlEIL7 then binds to and blocks the repression domain of the heat shock factor SlHSFB-2B, releasing its inhibition of HEAT SHOCK PROTEIN 21 (HSP21) expression to maintain PSII stability. In addition, SlWHY1 indirectly represses SlEIL2 expression, allowing the expression of l-GALACTOSE-1-PHOSPHATE PHOSPHATASE3 (SlGPP3). The ensuing higher SlGPP3 abundance promotes the accumulation of ascorbic acid (AsA), which scavenges reactive oxygen species produced upon chilling stress and thus protects PSII. Our study demonstrates that SlEIL2 and SlEIL7 protect PSII under chilling stress via two different SA response mechanisms: one involving the antioxidant AsA and the other involving the photoprotective chaperone protein HSP21.

Survival Analysis and Risk Factors of Pulpectomy among Children with Severe Early Childhood Caries Treated under General Anesthesia: A Retrospective Study.

OBJECTIVES: This study aims to retrospectively evaluate the survival rate of pulpectomy performed under dental general anesthesia (DGA) through long-term follow-up and to explore the risk factors associated with treatment failure. METHODS: The medical records of the children who were diagnosed with S-ECC and received pulpectomy treatment under general anesthesia (GA) from 1 August 2014 to 1 December 2019, in the Stomatological Hospital of Xi'an Jiaotong University, were collected. Two dentistry postgraduates extracted the necessary information and filled in a predesigned excel form. Survival analysis was performed using the Kaplan-Meier method. The shared frailty model was used to explore possible factors affecting the success rate of pulpectomy in primary teeth. RESULTS: A total of 381 children (mean age 3.49 ± 0.90) with S-ECC and 1220 teeth were included in the study, including 590 primary anterior teeth and 630 primary molars. The overall 35-month survival rate was 38.5%, which was 52.9% for anterior teeth and 31.1% for molars. The overall median survival time was 31 months, in which anterior teeth were 35 months and molars were 26 months. The older the children were, the greater the risk of treatment failure (HR 1.56, 95% CI 1.09, 2.24). The risk of pulpectomy failure of primary molars was 1.9 times that of primary anterior teeth (95% CI 1.36, 2.65) and the teeth with abnormal radiological findings before treatment was 1.41 times higher than that of teeth without imaging abnormalities (95% CI 1.74, 3.36). CONCLUSION: The survival rate of primary tooth pulpectomy is acceptable but decreased gradually with time. The failure rate of pulpectomy in primary molars is higher than that of primary anterior teeth. When the primary caries has extended to the pulp and resulted in a nonvital lesion, pulpectomy could be an option for maximum retention of the primary tooth.

Corrosion inhibition mechanism of imidazole ionic liquids with high temperature in 20% HCl solution.

BACKGROUND: This paper focuses on the chemical and physical adsorption of 1-hexyl-2,3-dimethyl imidazolium bromide (HDMIMBr), 1-decyl-2,3-dimethyl imidazolium bromide (DDMIMBr), and 1-hexadecyl-2,3-dimethyl imidazolium bromide (C16DMIMBr) on the surface of mild steel at high temperature in order to explore the mechanism of a corrosion inhibitor in a complex environment. METHODS: Gravimetric, scanning electron microscope, X-ray photoelectron spectroscopy, and electrochemical tests explored the corrosion inhibition performance from the experimental level. Quantum chemical calculations and molecular dynamics simulations reveal the corrosion inhibition mechanism from the molecular scale. RESULTS: The results show that the longer the alkyl chain of the three corrosion inhibitors studied, the better the corrosion inhibition performance. This is due to the hydrophobic effect of the long alkyl chain, which has its own synergistic effect and then self-assembles to form an adsorption film with a multilayer structure. CONCLUSION: This dense adsorption film makes corrosion inhibitors a good application prospect in complex corrosive environments.

A new method for screening acute/chronic lymphocytic leukemia: dual-label time-resolved fluorescence immunoassay.

BACKGROUND: Lymphocytic leukemia (LL) is a primary malignant tumor of hematopoietic tissue, which seriously affects the health of children and the elderly. The study aims to establish a new detection method for screening acute/chronic LL using time-resolved fluorescence immunoassay (TRFIA) via quantitative detection of S100 calcium binding protein A8 (S100A8) and leucine-rich alpha-2-glycoprotein 1 (LRG1) in serum. METHODS: Here a sandwich TRFIA was optimized and established: Anti-S100A8/LRG1 caputre antibodies immobilized on 96-well plates captured S100A8/LRG1, and then banded together with the anti-S100A8/LRG1 detection antibodies labeled with Europium(III) (Eu3+)/samarium(III) (Sm3+) chelates. Finally time resolved fluorometry measured the fluorescence intensity. RESULTS: The sensitivity of S100A8 was 1.15 ng/mL(LogY = 3.4027 + 0.4091 × LogX, R2 = 0.9828, P < 0.001, dynamic range: 2.1-10,000 ng/mL), and 3.2 ng/mL for LRG1 (LogY = 3.3009 + 0.4082 × LogX, R2 = 0.9748, P < 0.001, dynamic range: 4.0-10,000 ng/mL). The intra-assay and inter-assay CVs were low, ranging from 5.75% to 8.23% for S100A8 and 5.30% to 9.45% for LRG1 with high specificity and affinity in serum samples. Bland-Altman plots indicated TRFIA and ELISA kits have good agreement in clinical serum samples. Additionally, the cutoff values for S100A8 and LRG1 were 1849.18 ng/mL and 588.08 ng/mL, respectively. CONCLUSION: The present TRFIA method could be used for the quantitative detection of S100A8 and LRG1 in serum, and it has high sensitivity, accuracy and specificity. Clinically, this TRFIA method could be suitable for screening of LL via the quantitative detection of S100A8 and LRG1.

GSDMD (Gasdermin D) Mediates Pathological Cardiac Hypertrophy and Generates a Feed-Forward Amplification Cascade via Mitochondria-STING (Stimulator of Interferon Genes) Axis.

BACKGROUND: Cardiac hypertrophy is initially an adaptive response of cardiomyocytes to neurohumoral or hemodynamic stimuli. Evidence indicates that Ang II (angiotensin II) or pressure overload causes GSDMD (gasdermin D) activation in cardiomyocytes and myocardial tissues. However, the direct impact of GSDMD on cardiac hypertrophy and its underlying mechanisms are not fully understood. METHODS AND RESULTS: In this study, we examined the aberrant activation of GSDMD in mouse and human hypertrophic myocardia, and the results showed that GSDMD deficiency reduced Ang II or pressure overload-induced cardiac hypertrophy, dysfunction, and associated cardiomyocyte pyroptosis in mice. Mechanistically, Ang II-mediated GSDMD cleavage caused mitochondrial dysfunction upstream of STING (stimulator of interferon genes) activation in vivo and in vitro. Activation of STING, in turn, potentiated GSDMD-mediated cardiac hypertrophy. Moreover, deficiency of both GSDMD and STING suppressed cardiac hypertrophy in cardiac-specific GSDMD-overexpressing mice. CONCLUSIONS: Based on these findings, we propose a mechanism by which GSDMD generates a self-amplifying, positive feed-forward loop with the mitochondria-STING axis. This finding points to the prospects of GSDMD as a key therapeutic target for hypertrophy-associated heart diseases.

The Genetic Echo of the Tarim Mummies in Modern Central Asians.

The diversity of Central Asians has been shaped by multiple migrations and cultural diffusion. Although ancient DNA studies have revealed the demographic changes of the Central Asian since the Bronze Age, the contribution of the ancient populations to the modern Central Asian remains opaque. Herein, we performed high-coverage sequencing of 131 whole genomes of Indo-European-speaking Tajik and Turkic-speaking Kyrgyz populations to explore their genomic diversity and admixture history. By integrating the ancient DNA data, we revealed more details of the origins and admixture history of Central Asians. We found that the major ancestry of present-day Tajik populations can be traced back to the admixture of the Bronze Age Bactria-Margiana Archaeological Complex and Andronovo-related populations. Highland Tajik populations further received additional gene flow from the Tarim mummies, an isolated ancient North Eurasian-related population. The West Eurasian ancestry of Kyrgyz is mainly derived from Historical Era populations in Xinjiang of China. Furthermore, the recent admixture signals detected in both Tajik and Kyrgyz are ascribed to the expansions of Eastern Steppe nomadic pastoralists during the Historical Era.

Carboxylate Group-Based Phase-Selective Organogelators with a pH-Triggered Recyclable Property.

Phase-selective organogelators (PSOGs) have recently attracted more attention because of their advantages in handling oil spills and leaked organic solvents. However, it is difficult to separate and recover the organic phase and PSOGs from organic gels due to the strong interaction between them. Aiming to enhance the separation and recovery performance of the organic phase and PSOGs, we synthesized a series of pH-responsive PSOGs by using itaconic anhydride and fatty amines with carbon chain lengths of C12-C18. Here, PSOGs have an excellent gelation ability in that amounts of organic solvents and fuel oil can be solidified at a low concentration (<3 wt %). It is worth noting that these gels are stronger, which is more convenient for removal by a salvage operation. More importantly, compared with traditional organogelators, pH-responsive PSOGs can easily recover the organic phase and fuel oil with an adjustment of the pH without extraction or distillation. Because of the transformation between the hydrophilicity and hydrophobicity of PSOGs by pH stimulation, 83.15% PSOGs are recovered in three-cycle experiments. In addition, the recycled PSOGs can be used to realize the removal of the organic phase again. Herein, we find that pH-responsive PSOGs could be used as promising and sustainable materials for separating and recovering organic solvents/oils and PSOGs.