High-Voltage Cable Buffer Layer Ablation Fault Identification Based on Artificial Intelligence and Frequency Domain Impedance Spectroscopy.

In recent years, the occurrence of high-voltage cable buffer layer ablation faults has become frequent, posing a serious threat to the safe and stable operation of cables. Failure to promptly detect and address such faults may lead to cable breakdowns, impacting the normal operation of the power system. To overcome the limitations of existing methods for identifying buffer layer ablation faults in high-voltage cables, a method for identifying buffer layer ablation faults based on frequency domain impedance spectroscopy and artificial intelligence is proposed. Firstly, based on the cable distributed parameter model and frequency domain impedance spectroscopy, a mathematical model of the input impedance of a cable containing buffer layer ablation faults is derived. Through a simulation, the input impedance spectroscopy at the first end of the cables under normal conditions, buffer layer ablation, local aging, and inductive faults is performed, enabling the identification of inductive and capacitive faults through a comparative analysis. Secondly, the frequency domain amplitude spectroscopy of the buffer layer ablation and local aging faults are used as datasets and are input into a neural network model for training and validation to identify buffer layer ablation and local aging faults. Finally, using multiple evaluation metrics to assess the neural network model validates the superiority of the MLP neural network in cable fault identification models and experimentally confirms the effectiveness of the proposed method.

Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration.

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.

[Analysis of hydroxylation and O-glycosylation on lysine sites in deer-hide gelatin].

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.

The effect of 3D-printed plastic teeth on scores in a tooth morphology course in a Chinese university.

BACKGROUND: The tooth morphology course is an important basic dental course. However, it is difficult to fully reflect the three-dimensional (3D) morphological characteristics of tooth structure in two-dimensional pictures in traditional textbooks. The aim of this study was to assess the effect of 3D-printed plastic model teeth in the teaching of tooth morphology. METHODS: Twenty-two undergraduate students who matriculated at the School of Stomatology, the Fourth Medical University, in 2014 and 23 who matriculated in 2016 participated in the study. Each student who matriculated in 2016 was given a full set of fourteen standard 3D-printed plastic model teeth for use during the learning process, and an anonymous questionnaire was used to evaluate the usefulness of the 3D-printed plastic model teeth from the perspective of the students. RESULTS: There was no significant difference between the two groups in the scores of the theoretical examination or the total score. However, for the score of the sculpted gypsum teeth, the students who used the 3D-printed plastic model teeth in their studies scored significantly higher (P = 0.002). More than 90% of the students thought that the 3D-printed plastic model teeth were of great help or were very helpful for mastering the anatomy of teeth and for carving the gypsum teeth. CONCLUSION: Standard 3D-printed plastic teeth can effectively assist students in learning tooth morphology by transforming two-dimensional pictures and descriptions in the textbook into a 3D conformation, effectively promoting students' learning and mastery of tooth morphology and structure. Additionally, the results suggest that 3D-printed plastic model teeth are of great help to the students in mastering and improving their carving skills.

[Herbalogical study on Cervi Colla].

Cervi Colla, deer's gelatin, had two kinds of original sources historically, including the skin and antler of deer, known as Cervi Corii Colla(Lupijiao, LPJ) and Cervi Cornus Colla(Lujiaojiao, LJJ) respectively.LJJ is the mainstream of the market, while LPJ is only used by common people in Guizhou and Jilin etc. This article sorted out the ancient and modern literature(since Rites of the Zhou in Zhou Dynasty) on Cervi Colla and conducted the herbalogical study. The results of the study include:① In ancient China, there were six types of commonly-used Colla derived from six animals, including deer, horse, cow, rat, fish and rhinoceros. Cervi Colla was ranked the most top among them, and it was often used as adhesive to make bow and Chinese inksticks and more commonly used as a medicine.Cervi Cornus Colla was first described as a medicinal by the name "Bai Jiao"(white gelatin)in The Divine Husbandman's Classic of Material Medica(Shen Nong Ben Cao Jing).② Initially, both the skin and antler were used as raw materials to make Cervi Colla, but antler became the only raw material, and deer skin disappeared from the mainstream of raw materials for Cervi Colla. This can be attributed to other diverse and luxurious uses of the skin, such as making dress and hats, etc., and the easy accessibility of deer antlers. ③ The sources of Cervi Colla were not limited to Cervus elaphus(red deer) or C. nippon(sika deer), and it also included animal from the family Cervidae, such as Elaphurus davidianus(elk) and C. unicolor(sambar). ④ The processing method was passed down from ancient times to the present, and no significant changes had occurred. ⑤ LPJ and LJJ had many similar effects, and their nature was both warm. The effect of LJJ was to warm the liver and kidney, replenish vital essence and blood, and to reinforce Yang. While the effect of LPJ was to reinforce both Yin and Yang, replenish blood, and stop bleeding. It has a unique advantage for both reinforcing Yin and Yang. The findings of this paper can provide support for the promotion of LPJ and the development of its medicinal value.

A Senescence-Associated Secretory Phenotype of Bone Marrow Mesenchymal Stem Cells Inhibits the Viability of Breast Cancer Cells.

Breast cancer, the most prevalent malignancy in women, often progresses to bone metastases, especially in older individuals. Dormancy, a critical aspect of bone-metastasized breast cancer cells (BCCs), enables them to evade treatment and recur. This dormant state is regulated by bone marrow mesenchymal stem cells (BMMSCs) through the secretion of various factors, including those associated with senescence. However, the specific mechanisms by which BMMSCs induce dormancy in BCCs remain unclear. To address this gap, a bone-specific senescence-accelerated murine model, SAMP6, was utilized to minimize confounding systemic age-related factors. Confirming senescence-accelerated osteoporosis, distinct BMMSC phenotypes were observed in SAMP6 mice compared to SAMR1 counterparts. Notably, SAMP6-BMMSCs exhibited premature senescence primarily due to telomerase activity loss and activation of the p21 signaling pathway. Furthermore, the effects of conditioned medium (CM) derived from SAMP6-BMMSCs versus SAMR1-BMMSCs on BCC proliferation were examined. Intriguingly, only CM from SAMP6-BMMSCs inhibited BCC proliferation by upregulating p21 expression in both MCF-7 and MDA-MB-231 cells. These findings suggest that the senescence-associated secretory phenotype (SASP) of BMMSCs suppresses BCC viability by inducing p21, a pivotal cell cycle inhibitor and tumor suppressor. This highlights a heightened susceptibility of BCCs to dormancy in a senescent microenvironment, potentially contributing to the increased incidence of breast cancer bone metastasis and recurrence observed with aging.

[Comparative study on four major active compounds of Sanvitalia procumbens and Chrysanthemum morifolium cv 'Hangju' and 'Gongju'].

The contents of chlorogenic acid, 3,5-O-caffeoylquinic acid, galuteolin and quercitrin in Sanvitalia procumbens and Chrysanthemum morifolium cv. 'Hangju' and 'Gongju' were determined by RP-HPLC. The main active ingredient of S. procumbens was similar to C. morifolium cv. 'Hangju' and 'Gongju'. The content varied significantly. The contents of chlorogenic acid, quercitrin and galuteolin in S. procumbens were 7.46, 46.58, 26.01 mg x g(-1), respectively, and they were the highest among the samples. The content of 3,5-O-caffeoylquinic acid in C. morifolium cv. 'Hangju' was 14.70 mg x g(-1), it was the highest among the samples. The data of the study provide a basis for further research and development of S. procumbens.

Humoral regulation of iron metabolism by extracellular vesicles drives antibacterial response.

Immediate restriction of iron initiated by the host is a critical process to protect against bacterial infections and has been described in the liver and spleen, but it remains unclear whether this response also entails a humoral mechanism that would enable systemic sequestering of iron upon infection. Here we show that upon bacterial invasion, host macrophages immediately release extracellular vesicles (EVs) that capture circulating iron-containing proteins. Mechanistically, in a sepsis model in female mice, Salmonella enterica subsp. enterica serovar Typhimurium induces endoplasmic reticulum stress in macrophages and activates inositol-requiring enzyme 1α signaling, triggering lysosomal dysfunction and thereby promoting the release of EVs, which bear multiple receptors required for iron uptake. By binding to circulating iron-containing proteins, these EVs prevent bacteria from iron acquisition, which inhibits their growth and ultimately protects against infection and related tissue damage. Our findings reveal a humoral mechanism that can promptly regulate systemic iron metabolism during bacterial infection.

Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration.

Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. In vitro experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.

Apoptotic extracellular vesicles alleviate Pg-LPS induced inflammatory responses of macrophages via AMPK/SIRT1/NF-κB pathway and inhibit osteoclast formation.

BACKGROUND: Periodontitis is caused by the imbalance of anti-bacteria immune response and excessive inflammation whereas macrophages play an important role in inflammation. Thus, it is critical for finding efficient anti-inflammatory strategies to alleviate periodontal inflammation and prevent bone destruction. Apoptosis of mesenchymal stem cells (MSCs) exerts immune silencing effects, however, using these effects to develop anti-inflammatory strategies remains unknown. In our study, we extracted apoptotic extracellular vesicles (ApoEVs) from bone marrow MSCs (BMMSCs) and found ApoEVs inhibited macrophages polarizing into proinflammatory condition via AMPK/SIRT1/NF-κB pathway. Besides that, we also found ApoEVs inhibited adjacent osteoclast formation by suppressing the secretion of TNF-α of proinflammatory macrophages. METHODS: BMMSCs derived ApoEVs were extracted by gradient centrifugation. Protein expression level and secreted cytokines of ApoEVs treated macrophages were examined by western blot and ELISA, respectively. Besides, the change of NF-κB pathway and related molecules were examined by immunofluorescence and western blot. The osteoclast formation under the different conditioned mediums from macrophages was measured by TRAP staining, MMP-9 expression, and pit assay. RESULTS: ApoEVs were extracted from staurosporine-induced apoptotic BMMSCs and were in sphere shapes whose diameters are between 100 and 1000 nm. ApoEVs could be phagocyted by macrophages and in turn reduce the expression of COX2 in proinflammatory macrophages. Besides that, ApoEVs suppressed the secretions of TNF-α and IL-6 while elevating the secretion of IL-10 in a dose-dependent manner. Further studies revealed that ApoEVs inhibited macrophages polarizing into proinflammatory phenotypes via AMPK/SIRT1/NF-κB pathway. In addition, ApoEVs inhibited osteoclasts differentiation and bone resorption measured by TRAP staining, MMP-9 expression, and pit resorption area by downregulating the secretion of TNF-α of proinflammatory macrophages. CONCLUSIONS: The results suggest that ApoEVs inhibited macrophages to skew into proinflammatory phenotypes via AMPK/SIRT1/NF-κB pathway and suppress adjacent osteoclasts formation by reducing the secretion of TNF-α. Our findings shed a light on the treatment for periodontitis based on EVs therapy.

Response boosting-based approach for absolute quantification of gelatin peptides using LC-MS/MS.

Response-boosting of MS signal was observed in gelatin samples due to abundant Glycine residues produced by collagen enzymolysis. In this work, a new strategy utilizing response-boosting to enhance detection sensitivity was developed for absolute quantification of Asini Corii Colla, a kind of gelatin commonly used as food therapy products in Asia, by high performance liquid chromatography coupled to tandem mass spectrometry. Peptidomics analysis was used to evaluate the similarity between eight different protein matrices, and deer-hide gelatin was selected as the appropriate simulated matrix. Isotope-labelled internal standard was used to compensate the matrix effect and construct matrix-matched calibration curves. The established method showed reliability in absolute quantification of three species-specific gelatin peptides with good linearity (r2 > 0.997), precision (RSD < 8.5%), repeatability (RSD < 8.9%), accuracy (recovery 89.4%∼106.5%) and sensitivity (LOD 0.02 âˆ¼ 0.98 ng/mL). Thus, the present response-boosting based protocol provides a promising application in quality control of food rich in gelatins.

Hybrid Biomaterial Initiates Refractory Wound Healing via Inducing Transiently Heightened Inflammatory Responses.

Inflammation plays a crucial role in triggering regeneration, while inadequate or chronic inflammation hinders the regenerative process, resulting in refractory wounds. Inspired by the ideal regeneration mode in lower vertebrates and the human oral mucosa, realigning dysregulated inflammation to a heightened and acute response provides a promising option for refractory wound therapy. Neutrophils play important roles in inflammation initiation and resolution. Here, a hybrid biomaterial is used to stimulate transiently heightened inflammatory responses by precise tempospatial regulation of neutrophil recruitment and apoptosis. The hybrid biomaterial (Gel@fMLP/SiO2 -FasL) is constructed by loading of formyl-met-leu-phe (fMLP) and FasL-conjugated silica nanoparticles (SiO2 -FasL) into a pH-responsive hydrogel matrix. This composition enables burst release of fMLP to rapidly recruit neutrophils for heightened inflammation initiation. After neutrophils act to produce acids, the pH-responsive hydrogel degrades to expose SiO2 -FasL, which induces activated neutrophils apoptosis via FasL-Fas signaling triggering timely inflammation resolution. Apoptotic neutrophils are subsequently cleared by macrophages, and this efferocytosis activates key signalings to promote macrophage anti-inflammatory phenotypic transformation to drive regeneration. Ultimately, Gel@fMLP/SiO2 -FasL successfully promotes tissue regeneration by manipulating inflammation in critical-sized calvarial bone defects and diabetic cutaneous wound models. This work provides a new strategy for refractory wound therapy via inducing transiently heightened inflammatory responses.

NDRG2 ablation reprograms metastatic cancer cells towards glutamine dependence via the induction of ASCT2.

Background: Metastasis is the most common cause of lethal outcome in various types of cancers. Although the cell proliferation related metabolism rewiring has been well characterized, less is known about the association of metabolic changes with tumor metastasis. Herein, we demonstrate that metastatic tumor obtained a mesenchymal phenotype, which is obtained by the loss of tumor suppressor NDRG2 triggered metabolic switch to glutamine metabolism. Methods: mRNA-seq and gene expression profile analysis were performed to define the differential gene expressions in primary MEC1 and metastatic MC3 cells and the downstream pathways of NDRG2. NDRG2 regulation of Fbw7-dependent c-Myc stability were determined by immunoprecipitation and protein half-life assay. Luciferase reporter and ChIP assays were used to determine the roles of Akt and c-Myc in mediating NDRG2-dependent regulation of ASCT2 in in both tumor and NDRG2-knockout MEF cells. Finally, the effect of the NDRG2/Akt/c-Myc/ASCT2 signaling on glutaminolysis and tumor metastasis were evaluated by functional experiments and clinical samples. Results: Based on the gene expression profile analysis, we identified metastatic tumor cells acquired the mesenchymal-like characteristics and displayed the increased dependency on glutamine utilization. Further, the gain of NDRG2 function blocked epithelial-mesenchymal transition (EMT) and glutaminolysis, potentially through suppression of glutamine transporter ASCT2 expression. The ASCT2 restoration reversed NDRG2 inhibitory effect on EMT program and tumor metastasis. Mechanistic study indicates that NDRG2 promoted Fbw7-dependent c-Myc degradation by inhibiting Akt activation, and subsequently decreased c-Myc-mediated ASCT2 transcription, in both tumor and NDRG2-knockout MEF cells. Supporting the biological significance, the reciprocal relationship between NDRG2 and ASCT2 were observed in multiple types of tumor tissues, and associated with tumor malignancy. Conclusions: NDRG2-dependent repression of ASCT2 presumably is the predominant route by which NDRG2 rewires glutaminolysis and blocks metastatic tumor survival. Targeting glutaminolytic pathway may provide a new strategy for the treatment of metastatic tumors.

Chondrocyte apoptosis in rat mandibular condyles induced by dental occlusion due to mitochondrial damage caused by nitric oxide.

OBJECTIVE: Chondrocyte apoptosis is a pathological manifestation of osteoarthritis. The goal of this report was to explore the role of nitric oxide in chondrocyte apoptosis in osteoarthritic mandibular condylar cartilage. DESIGN: This study used our reported experimental unilateral anterior crossbite in vivo rat model and chondrocyte fluid flow shear stress in vitro model. In the in vivo model, apoptosis in the mandibular condylar cartilage was assessed by detection of the TUNEL-positive cells, the expression levels of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3. In the in vitro model, mitochondrial injury was evaluated, the nitric oxide and superoxide dismutase (SOD) production levels were measured, and the cytochrome C (Cyt C) expression level was detected. The expression levels of apoptosis-related proteins B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and poly-ADP-ribose polymerase 1 (PARP1) were analyzed in both in vivo and in vitro models. The effects of iNOS inhibitor on chondrocyte apoptosis were also investigated. RESULTS: The data indicated that the unilateral anterior crossbite induced cartilage degeneration with enhanced cell apoptosis and stimulated the expression of caspase-3/-9 and iNOS. The fluid flow shear stress upregulated the expression of iNOS, SOD, and nitric oxide, reduced mitochondrial membrane potential, and promoted Cyt C to enter the cytoplasm. All of these changes were reversed by iNOS inhibitors. CONCLUSION: The abnormal occlusion stimulated mitochondrial damage and apoptosis of the chondrocytes in the mandibular condylar cartilage mediated by nitric oxide. Inhibiting nitric oxide production could be a therapeutic strategy.

A strategy for identifying species-specific peptide biomarkers in deer-hide gelatin using untargeted and targeted mass spectrometry approaches.

Deer-hide gelatin (DHG) is an important animal-derived traditional Chinese medicine (TCM), which has been applied in TCM for over 400 years. However, it is extremely difficult to distinguish DHG with adulteration or made with other animal skins due to the highly processing procedure. Therefore, a simple strategy for identifying species-specific peptide biomarkers in deer-hide gelatin (DHG) is needed. In the present study, untargeted and targeted mass spectrometry approaches were implemented to analyze comprehensive peptidomic profiles of trypsin-digested animal gelatins. Mathematics set theory was then used to interrogate the relationship between different samples and peptides in the target species set, while the peptides were not considered as species-specific biomarkers in other sets. Two peptides were identified as DHG-specific peptides. Targeted mass spectrometry approach was then used to verify these two peptides. It showed that these two peptides could be used for distinguishing DHG from other animal hide gelatins. The present strategy provides a simple method for peptide biomarker discovery, which can be applied in the identification of specific peptides in some highly processed animal derived traditional Chinese medicines (TCMs). Thus, the present work provides an effective strategy for rapid, simple discovery and application of species-specific peptide biomarkers to ensure animal derived TCMs quality and make them authenticable and traceable.

A rapid and low-cost approach to evaluate the allergenicity of herbal injection using HPLC analysis.

Herbal medicines have ever been thought harmless, but it is obviously not true. Many adverse reports emerged with the development of their popular application in the world. Allergic reactions, especially serious immediate hypersensitivity, frequently occurred when herbal injections were used in clinic and made this ever prevailing agent nearly disappear in China. The aim of this study is to establish a rapid and economical method for the prediction of the allergenicity of herbal injections. Ovalbumin (OVA) and four other herbal injections, in which two of them were well known for their allergenicity, were selected to sensitize and stimulate the animals. Serotonin in the animal serum was detected with HPLC to reflect the anaphylactic response and compared with the other cytokines which could mediate the anaphylaxis, including histamine, IgE and ß-hexosaminidase. The results suggest that serotonin can be detected quickly and has good correlation with the other allergy-related cytokines. It is a promising way for predicting the allergenicity of the herbal injections and those complicated natural products.