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Bone scaffolds offer hope for oral jawbone repair, yet improving their osteogenic performance remains a clinical challenge. This study investigates a novel approach to enhance early bone formation and osteogenic quality by coloading hydroxyapatite (HA)─internalized osteoblasts (OHA) and osteonectin (ON) onto various scaffolds. Our findings demonstrated that the OHA could effectively facilitate the early bone regeneration by providing rapid calcium and phosphorus ion release via lysosome-mediated HA degradation, while the ON protein helps in ion deposition, cell proliferation, and matrix mineralization. When the PHA (PCL+HA) scaffold was incorporated with both the OHA and ON, the scaffold exhibited superior pro-osteogenic performance, driven by synergistic effects of rapid ion release from the OHA, slow ion release from the PHA, and upregulation of osteogenesis-related genes. The analyses of mechanisms revealed that the OHA activated MAPK and PI3K-Akt pathways, while ON stimulated calcium and Wnt signaling, collectively promoting the osteogenic potential. The strategy presented in this study paves a promising way for the development of advanced bone scaffolds to improve the bone regeneration quality.

Species with different genetic backgrounds exhibit distinct metabolic traits. Nine beef cattle were selected for the experiment to study changes in serum metabolic phenotypes, rumen microbiota diversity, and composition in beef cattle from different genetic backgrounds. Three groups were Chinese Simmental (S group), Simmental×Chinese Holstein (SH group), and Simmental × Mongolian (SM group) cattle. We used ELISA to detect serum biochemical indicators. The Short-chain fatty acids (SCFAs) in the rumen were examined, and a significant difference was observed in the acetic acid content of the three experimental groups (p < 0.01). The propionic acid content in the rumen of the S group was significantly higher than that of the SH and SM groups (p < 0.05). The A/P ratios of both the S and SM groups were significantly higher than that of the SH group (p < 0.05). We analyzed rumen microbiota composition and diversity in each group of cattle using 16 S rRNA sequencing and found that their composition was generally similar in the three groups of crossbred fattening cattle; however, the f&#95;Bacteroidales&#95;RF16&#95;group and g&#95;norank&#95;f&#95;Bacteroidales&#95;RF16&#95;group were significantly enriched in the SH group, whereas Treponema and Spirochaetia were significantly enriched in the SM group. Spirochaetia was significantly enriched in the SM group. Differences in rumen bacterial enrichment indicated that starch, protein, and cellulolytic abilities differed among the S, SH, and SM groups. The results of Spearman correlation analysis confirmed the correlation between rumen genera and serum biochemical indices. Overall, differences in rumen microflora play an important role in influencing the serum metabolic phenotype., (© 2024. The Author(s).)

WOXs are a class of plant-specific transcription factors that play key roles in plant growth and stress responses. However, the mechanism by which WOXs influence adventitious root development in Rosa hybrida remains unclear. In this study, RcWOX gene family in rose was identified and phylogenetically analyzed using bioinformatics analysis. A total of 381 RcWOX gene members were localized on seven chromosomes except of nine members. The main cis -acting elements involved in hormonal, light, developmental, and abiotic stress responses were identified in the promoters of RcWOX genes, suggesting their regulation by these signals. Nine RhWOX genes had significant different expression during rooting process of rose. RhWOX331 , RhWOX308 , RhWOX318 were positive with the formation of rose roots. RhWOX331 was positively involved in the formation of adventitious root primordia, which gene coding a transcription factor localized in the nucleus. The HOX conserved domain in the protein contributed to the self-activating activity of RhWOX331. We obtained genetically modified Arabidopsis to validate the function of RhWOX331 . Overexpression of RhWOX331 gene alleviated the inhibition of root length of A. thaliana primary roots by high concentration of IBA and NPA, and significantly increased the number of lateral roots on the primary roots, as well as the height of A. thaliana plants. Additionally, RhWOX331 promoted adventitious root formation in A. thaliana and mitigated hormonal inhibition by exogenous 6-BA, NPA, and GA 3 . The RhWOX331 promoter contained cis-acting elements such as ABRE, Box 4 and CGTCA-motif et.al. GUS activity analysis showed that the gene acted at the cotyledon attachment site. Taken together, these studies identified a significant expansion of the RcWOX gene family, inferred roles of certain branch members in adventitious root formation, elucidated the function of RhWOX331 in adventitious root initiation, and laid the foundation for further research on the function of WOX gene family in roses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Duan, Hou, Zhang, Liang, Huangfu, Zhang, Yang, Dong and Che.)

Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players in various biological processes. Recent research has revealed their significant functions in immune and inflammatory responses. For instance, butyrate reduces the development of interferon-gamma (IFN-γ) generating cells while promoting the development of regulatory T (Treg) cells. Propionate inhibits the initiation of a Th2 immune response by dendritic cells (DCs). Notably, SCFAs have an inhibitory impact on the polarization of M2 macrophages, emphasizing their immunomodulatory properties and potential for therapeutics. In animal models of asthma, both butyrate and propionate suppress the M2 polarization pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis of gut microbiota leading to altered SCFA production has been implicated in prostate cancer progression. SCFAs trigger autophagy in cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. Manipulating microbiota- producing SCFAs holds promise for cancer treatment. Additionally, SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. This highlights the antimicrobial potential of SCFAs and their role in host defense mechanisms. This comprehensive review provides an in-depth analysis of the latest research on the functional aspects and underlying mechanisms of SCFAs in relation to macrophage activities in a wide range of diseases, including infectious diseases and cancers. By elucidating the intricate interplay between SCFAs and macrophage functions, this review aims to contribute to the understanding of their therapeutic potential and pave the way for future interventions targeting SCFAs in disease management., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background & Aims: Excessive autophagy induces cell death and is regarded as the treatment of cancer therapy. We have confirmed that the anti-cancer mechanism of curcumol is related to autophagy induction. As the main target protein of curcumol, RNA binding protein nucleolin (NCL) interacted with many tumor promoters accelerating tumor progression. However, the role of NCL in cancer autophagy and in curcumol's anti-tumor effects haven't elucidated. The purpose of the study is to identify the role of NCL in nasopharyngeal carcinoma autophagy and reveal the immanent mechanisms of NCL played in cell autophagy., Methods & Results: In the current study, we have found that NCL was markedly upregulated in nasopharyngeal carcinoma (NPC) cells. NCL overexpression effectively attenuated the level of autophagy in NPC cells, and NCL silence or curcumol treatment obviously aggravated the autophagy of NPC cells. Moreover, the attenuation of NCL by curcumol lead a significant suppression on PI3K/AKT/mTOR signaling pathway in NPC cells. Mechanistically, NCL was found to be directly interact with AKT and accelerate AKT phosphorylation, which caused the activation of the PI3K/AKT/mTOR pathway. Meanwhile, the RNA Binding Domain (RBD) 2 of NCL interacts with Akt, which was also influenced by curcumol. Notably, the RBDs of NCL delivered AKT expression was related with cell autophagy in the NPC., Conclusion: The results demonstrated that NCL regulated cell autophagy was related with interaction of NCL and Akt in NPC cells. The expression of NCL play an important role in autophagy induction and further found that was associated with its effect on NCL RNA-binding domain 2. This study may provide a new perspective on the target protein studies for natural medicines and confirm the effect of curcumol not only regulating the expression of its target protein, but also influencing the function domain of its target protein., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Beta vulgaris var. cicla is an edible, ornamental and horticultural plant. However, the difference of components and contents of betalain in beets with different leaf color are not well understood. Here, the stress resistance and metabolites of two B. vulgaris var. cicla cultivars were determined. The differences in stress resistance between red leaf-colored chard (RC) and yellow leaf-colored chard (YC) were positively related to betacyanins (BC) and betaxathins (BX) content in the leaves. Furthermore, a total of 3615 distinct metabolites were identified by UPLC-QTOF-MS in two cultivars, including 70 alkaloids and their derivatives, 249 flavonoids, and 264 terpenoids. There were 17 metabolites attributed to betalain biosynthesis pathway, seven of nine BC were up-regulated, and eight BX showed no significant difference in RC compared with YC. The contents of celosianin II and betanin were the highest BC in RC, at approximately 84.38 and 19.97 times that of YC, respectively. The content of portulacaxanthin II was the highest BX in two beets. Additionally, the BvCYP450 genes were identified based on genome, and the members that might be involved in betalain biosynthesis were screened. BvCYP76AD27, a member of the BvCYP76AD subfamily, had a higher expression level in RC than YC under freezing, drought and shading stress. In yeast Saccharomyces cerevisiae, BvCYP76AD5 and BvCYP76AD27 only hydroxylated tyrosine to L-DOPA, which was transformed into portulacaxanthin II by 4,5-DOPA extradiol dioxygenase. The results contribute to illustrating the molecular mechanism of betalain biosynthesis and provide useful information for further investigation of beet chemistry and sufficient utilization of this species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The accurate detection of parathyroid glands (PGs) during surgery is of great significance in thyroidectomy and parathyroidectomy, which protects the function of normal PGs to prevent postoperative hypoparathyroidism and the thorough removal of parathyroid lesions. Existing conventional imaging techniques have certain limitations in the real-time exploration of PGs. In recent years, a new, real-time, and non-invasive imaging system known as the near-infrared autofluorescence (NIRAF) imaging system has been developed to detect PGs. Several studies have confirmed that this system has a high parathyroid recognition rate and can reduce the occurrence of transient hypoparathyroidism after surgery. The NIRAF imaging system, like a magic mirror, can monitor the PGs during surgery in real time, thus providing great support for surgeries. In addition, the NIRAF imaging system can evaluate the blood supply of PGs by utilizing indocyanine green (ICG) to guide surgical strategies. The NIRAF imaging system and ICG complement each other to protect normal parathyroid function and reduce postoperative complications. This article reviews the effectiveness of the NIRAF imaging system in thyroidectomies and parathyroidectomies and briefly discusses some existing problems and prospects for the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Li, Bao, Huangfu and Zhang.)

The citrus tatter leaf virus (CTLV) is one of the most destructive citrus viral diseases worldwide. In this study, reverse transcription-recombinase polymerase amplification combined with a lateral flow dipstick (RT-RPA-LFD) assay for rapid visual detection of CTLV was established. The assay was performed at 35 ℃ in 27 min without specialised equipment. The RT-RPA-LFD assay showed high specificity to CTLV, and the sensitivity to CTLV was the same as that of quantitative RT-PCR at 3 × 10 3 copies/μL CTLV RNA transcripts. A total of 45 field tangor samples were tested using RT-RPA-LFD, RT-PCR, and RT-qPCR, and the results were consistent. The results demonstrated that the RT-RPA-LFD assay is a promising tool for rapid on-site CTLV detection., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To study shifts in the intestinal microbiota during estrus synchronization in ruminants, we characterized the intestinal microbiota in grazing Simmental cows and the possible mechanism that mediates this shift. Fourteen postpartum Simmental beef cows were synchronized beginning on day 0 (D0) with a controlled internal release device (CIDR), and cloprostenol was injected on D9 when the CIDR was withdrawn. Synchronization ended with timed artificial insemination on D12. Serum and rectal samples harvested on D0, D9, and D12 were analyzed to assess the reproductive hormones and microbiota. Reproductive hormones in the serum of the host were measured using enzyme-linked immunosorbent assay. The microbiota was characterized using 16S rRNA sequencing of the V3−V4 hypervariable region, alpha diversity and beta diversity analyses (principal coordinate analysis, PCoA), cladogram of the linear discriminant analysis effect size (LEfSe) analysis, and microbiota function analysis. Levels of the reproductive hormones, except gonadotropin-releasing hormone (p > 0.05), shifted among D0, D9, and D12 (p < 0.05). Decreased community diversity (Chao1 and ACE) was observed on D12 compared with D0 (p < 0.05). The beta diversity (PCoA) of the microbiota shifted markedly among D0, D9, and D12 (p < 0.05). The LEfSe analysis revealed shifts in the intestinal microbiota communities among D0, D9, and D12 (p < 0.05 and LDA cutoff >3.0). The KEGG pathway analysis showed that carbohydrate metabolism, genetic information and processing, the excretory system, cellular processes and signaling, immune system diseases, and the metabolism were altered (p < 0.05). Reproductive hormones (especially estradiol) were correlated with the alpha diversity indices, beta diversity indices, and an abundance of biomarkers of the shifting intestinal microbiota (p < 0.05). In conclusion, the structure, composition, and function of the intestinal microbiota were shifted during estrus synchronization in a grazing Simmental cow model, and these shifts were mediated by reproductive hormones.

As part of the development of an infectious bursal disease virus (IBDV) subunit vaccine, this study was designed to improve the expression of highly soluble VP2-LS3 (Haemophilus parasuis lumazine synthase 3, LS3) protein by using different tagged vectors in E. coli . IBDV VP2-LS3 gene was designed and synthesized. Fusion tags, GST, NusA, MBP, Ppi, γ-crystallin, ArsC, and Grifin were joined to the N-terminus of VP2-LS3 protein. Seven expression plasmids were constructed, and each plasmid was transformed into E. coli BL21 (DE3) competent cells. After induction by IPTG, the solubility and expression levels of the various VP2-LS3 proteins were analyzed by SDS-PAGE and Western Blot analysis. The fusion tag that significantly promoted soluble expression of the VP2-LS3 protein was selected. Recombinant proteins were purified using Ni-NTA affinity chromatography, then cleaved by using TEV protease and detected by using transmission electron microscopy. Gel electrophoresis and sequencing analysis showed that all seven recombinant vectors were successfully constructed. GST, NusA, MBP, Ppi, γ-crystallin, ArsC, and Grifin enhanced the expression and solubility of VP2 protein; however, MBP was more effective for the high-purity production of VP2-LS3. Western Blot analysis confirmed successful generation of VP2-LS3 fusion protein in E. coli . The result of transmission electron microscopy showed that VP2-LS3 formed nano-sized particles with homogeneous shape and relatively uniform size. This study established a method to generate VP2-LS3 recombinant protein, which may lay a foundation for the development and subsequent study of IBDV subunit vaccines.

Osthole is a natural coumarin which has been proved to inhibit growth of cancer cells by inducing cell death, while its mechanism was considered to be just caused by apoptosis. In our study, we found that osthole activated not just apoptosis, but also pyroptosis which is a form of regulated cell death accompanied by loss of cell membrane integrity and lactate dehydrogenase (LDH) release. Caspase-3 is a key protein of apoptosis as well as pyroptosis. The apoptosis and pyroptosis induced by osthole were all inhibited by irreversible caspase-3 inhibitor Z-DEVD-FMK. Meanwhile, knockdown of gasdermin E (GSDME) only reduced the osthole-induced pyroptosis but did not affect the occurrence of apoptosis. Our proteomic analysis revealed that the expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) was decreased in osthole-treated cells. Moreover, NQO1 inhibition by osthole induced the overproduction of reactive oxygen species (ROS), as well as apoptosis and pyroptosis. ROS inhibitor N-Acetyl-L-cysteine (NAC) not only reduced osthole-induced apoptosis but also reversed its effect on the pyroptosis. Meanwhile, knockdown of NQO1 by si-NQO1 or its inhibitor dicoumarol (DIC) not only enhanced ROS generation but also strengthened the GSDME-mediated pyroptosis. Finally, we demonstrated that osthole inhibited tumor growth and the expression of NQO1 in a HeLa xenograft mode. Similar to the results in vitro , osthole stimulated the activation of caspase-3, PARP, and GSDME in vivo . Taken together, all these data suggested that osthole induced apoptosis and caspase-3/GSDME-mediated pyroptosis via NQO1-mediated ROS accumulation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Juan Wang et al.)

Autophagy is usually considered as a protective mechanism against cell death, and in the meantime, leads to cell injury even apoptosis. Apoptosis and autophagy are very closely connected and may cooperate, coexist, or antagonize each other on progressive occurrence of cell death triggered by natural compounds. Therefore, the interplay between the two modes of death is essential for the overall fate of cancer cells. Our previous study revealed that curcumol induced apoptosis in nasopharyngeal carcinoma (NPC) cells. Recently, curcumol was found to induce autophagy in cancer cells. However, whether curcumol can induce NPC cells autophagy and the effects of autophagy on apoptosis remain elusive. In this study, we found that curcumol induced autophagy through AMPK/mTOR pathway in CNE-2 cells. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine (3-MA) or apoptosis inhibitor z-VAD-fmk significantly increased proliferation while attenuated apoptosis and autophagy compared with the curcumol 212 μM group. In contrast, combining curcumol with autophagy agonist rapamycin and apoptosis inducer MG132 synergized the apoptotic and autophagic effect of curcumol. Taken together, our study demonstrates that curcumol promotes autophagy in NPC via AMPK/mTOR pathway, induces autophagy enhances the activity of curcumol in NPC cells; the combination of autophagy inducer and curcumol can be a new therapeutic strategy for NPC., (© 2021 John Wiley & Sons Ltd.)

Background: Mogroside V, the main ingredient of Siraitia grosvenorii, has been proved to have therapeutic effects on pulmonary diseases. The specific mechanism still remains to be clarified, which hinders the potence of its medicinal value., Purpose: Serum and lung metabolomics based on LC-MS analysis were applied to explore the mechanism of mogroside V against lung inflammation., Method: In this study, balb/c mice were divided into control, model, mogeoside V and SH groups. We evaluated the protective effects of mogroside V on lung inflammation in asthmatic mice. Suhuang Zhike Jiaonang was used as positive drug. Metabolic profiles of serum and lung samples of mice in control, model and mogroside V groups were analyzed by LC-MS., Results: Administration of mogroside V effectively relieved the expression of biochemical cytokines and lung inflammatory infiltration of asthmatic mice caused by ovalbumin (OVA). And visceral index of mice treated with mogroside V was close to control group. These results indicated that mogroside V ameliorated OVA-induced lung inflammation. LC-MS based metabolomics analysis demonstrated 6 main pathways in asthmatic mice including Vitamin B6 metabolism, Taurine and hypotaurine metabolism, Ascorbate and aldarate metabolism, Histidine metabolism, Pentose and glucuronate interconversions, Citrate cycle (TCA cycle) were regulated after using mogroside V., Conclusion: The study firstly elucidates the metabolic pathways regulated by mogroside V on lung inflammation through metabolomics, providing a theoretical basis for more sufficient utilization and compatibility of mogroside V., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Metastasis is a major cause of recurrence and death in patients with EBV-positive Nasopharyngeal carcinoma (NPC). Previous reports documented that curcumol has both anti-cancer and anti-viral effects, but there is little literature systematically addressing the mechanism of curcumol in EBV-positive tumors. Previously we found that nucelolin (NCL) is a target protein of curcumol in CNE2 cells, an EBV-negative NPC, and in this experiment, we reported a critical role for NCL in promoting migration and invasion of C666-1 cells, an EBV-positive NPC, and found that the expression of NCL determined the level of curcumol's efficacy. Mechanistically, NCL interacted with Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) to activate VEGFA/VEGFR1/PI3K/AKT signaling pathway, which in turn promoted NPC cell invasion and metastasis. Moreover, further study showed that the differential expression of NCL and curcumol intervention only had a regulatory effect on the nuclear accumulation of VEGFR1, which strengthened the anti-cancer effect of curcumol mediated through NCL. Our findings indicated that curcumol exerted anti EBV-positive NPC invasion and metastasis by downregulating EBNA1 and inhibiting VEGFA/VEGFR1/PI3K/AKT signaling by targeting NCL, which provides a novel pharmacological basis for curcumol's clinical use in treating patients with EBV-positive NPC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

MicroRNA-30a-5p (miR-30a-5p), which functions as a tumor suppressor, has been reported to be downregulated in colorectal cancer (CRC) tissues and to be associated with cancer invasion. However, the detailed regulatory mechanism of curcumol in the malignant progression of CRC remains unknown. MTT, Transwell, scratch, western blotting and reverse transcription-quantitative PCR assays were performed to examine how curcumol inhibited CRC cell viability, invasion and migration, and to detect the role of miR-30a-5p and curcumol in the invasion and Hippo signaling pathways of CRC cells. The present study revealed that miR-30a-5p expression was downregulated in human CRC tissues and cells. The results demonstrated that miR-30a-5p downregulation was accompanied by the inactivation of the Hippo signaling pathway, which was demonstrated to promote CRC cell viability, invasion and migration. Curcumol treatment was identified to increase miR-30a-5p expression and to activate the Hippo signaling pathway, which in turn inhibited the invasion and migration of CRC cells. Overexpression of miR-30a-5p enhanced the effects of curcumol on cell invasion and migration, and the Hippo signaling pathway in CRC cells. Furthermore, downregulation of miR-30a-5p reversed the effects of curcumol on cell invasion and migration, and the Hippo signaling pathway in CRC cells. These findings identified novel signaling pathways associated with miR-30a-5p and revealed the effects of curcumol on miR-30a-5p expression. Therefore, curcumol may serve as a potential therapeutic strategy to delay CRC progression., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yu et al.)

Metal-organic frameworks (MOFs), composed of metal ions/clusters and organic ligands and possessing inherent crystallinity, a definite structure, a tunable pore, and multiple functionalizations, have shown potential for numerous applications. Recently, luminescent MOFs (LMOFs) have attracted much attention as sensing materials because their structural and chemical tunability can afford good selectivity through pore-sieving functions with different pore sizes or host framework-guest interactions. Meanwhile, MOFs with high internal surface areas can concentrate analytes to a high density, thereby decreasing detection limits and exhibiting high sensitivity. Numerous LMOFs have been synthesized and employed for sensing applications. Here, the recent advances of LMOFs as chemical sensors based on "mechanism-response" were summarized, including collapse of frameworks, overlap, cation exchange, ligand exchange, reaction- and redox-based mechanisms, electron transfer, energy transfer, hydrogen bonding, linker-analyte interaction, synergistic effects, and multiple interactions. Moreover, in this review, present challenges and future opportunities in this field are discussed. This review could be a valuable reference for the rational construction and sensing applications of LMOFs.

Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG-132. Expression of necroptosis inhibitor caspase-8 was decreased, and levels of necroptosis proteins receptor-interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis-related proteins caspase-3, caspase-7, and caspase-9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis-inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin-1 attenuated both osthole-induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N-acetylcysteine decreased osthole-induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy., (© 2020 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Epigallocatechin‑3‑gallate (EGCG), a polyphenol present in green tea, exhibits anticancer effects in various types of cancer. A number of studies have focused on the effects of EGCG on lung cancer, but not ovarian cancer. Previous reports have implicated that EGCG suppressed ovarian cancer cell proliferation and induced apoptosis, but its potential anticancer mechanisms and signaling pathways remain unclear. Thus, it is necessary to determine the anti‑ovarian cancer effects of EGCG and explore the underlying mechanisms. In the present study, EGCG exerted stronger proliferation inhibition on SKOV3 cells compared with A549 cells and induced apoptosis in SKOV3 cells, as well as upregulated PTEN expression and downregulated the expression of phosphoinositide‑dependent kinase‑1 (PDK1), phosphor (p)‑AKT and p‑mTOR. These effects were reversed by the PTEN inhibitor VO‑Ohpic trihydrate. The results of the mouse xenograft experiment demonstrated that 50 mg/kg EGCG exhibited increased tumor growth inhibition compared with 5 mg/kg paclitaxel. In addition, PTEN expression was upregulated, whereas the expression levels of PDK1, p‑AKT and p‑mTOR were downregulated in the EGCG treatment group compared with those in untreated mice in vivo. In conclusion, the results of the present study provided a new underlying mechanism of the effect of EGCG on ovarian cancer and may lead to the development of EGCG as a candidate drug for ovarian cancer therapy.

Three lanthanide-based metal-organic frameworks, [Tb(HMDIA)(H 2 O) 3 ]·H 2 O ( Tb-MDIA ), [Ho(HMDIA)(H 2 O) 3 ]·(H 2 O) 2 ( Ho-MDIA ), and [Nd(HMDIA)(H 2 O) 3 ]·(H 2 O) 2 ( Nd-MDIA ) from the same V-shaped ligand 5,5'-methylenediisophthalic acid (H 4 MDIA), were prepared by mixing Ln 3+ and H 4 MDIA under solvothermal conditions. The crystal structures of the three complexes were determined by single-crystal X-ray diffraction. The different coordination modes of the organic ligands resulted in different framework structures among the three complexes. The luminescent properties of Ln-MDIA in the ultraviolet-visible region were also studied. Interestingly, the bright-green emitter Tb-MDIA showed high selectivity and sensitivity to allow the naked-eye visualization of Fe 3+ ions and picric acid (PA) explosive, and both sensing mechanisms were revealed. Finally, Ho-MDIA and Nd-MDIA were shown to work as heterogeneous catalysts for the cyanosilylation reaction of aromatic aldehydes, and the catalysts could be recycled at least three times without any decrease in activity.

A novel aldehyde- and amino-functionalized luminescent metal-organic framework, Cd-TCHO, was constructed through the solvothermal reaction of 4,4',4''-tricarboxytriphenylamine, 2-amino-3-pyridinecarboxaldehyde and cadmium nitrate and was characterized. Post-synthetically oxidizing the aldehyde groups into carboxylate groups afforded a new complex, Cd-TCOOH, and this successful conversion process was confirmed by FT-IR and 1 H NMR studies. With the Brønsted acidic sites inside the cavities of Cd-TCOOH, it could be used as a luminescent sensor for Al 3+ detection with a high selectivity and sensitivity (LOD = 0.54 ppb), which could be attributed to the coordination between free Brønsted acidic sites and Al 3+ . Importantly, it could also detect Lys among 20 kinds of natural amino acids; the selectivity, sensitivity and the sensing mechanism are discussed in detail. Also, both of the sensing processes were carried out in the HEPES buffer.

Background: Tumor-associated antigen overexpression, which has been reported in many types of cancers, may trigger autoantibody secretion. The present study was designed to test whether levels of circulating autoantibodies to survivin protein-derived antigens is altered in liver, esophageal, breast, and lung cancers., Methods: Patients with liver (144), esophageal (159), breast (124), and lung cancers (267), and healthy volunteers (362) were recruited for the study, and serum samples were collected for ELISA autoantibody analysis., Results: Compared with the control group, survivin autoantibody levels were significantly higher in serum from patients with breast cancer and lung cancer, but were significantly lower in serum from patients with liver cancer (p < 0.05). In stage I and II lung cancer, the best-fit areas under the receiver operating characteristic curve was 0.731 (standard error [SE] = 0.023; 95% confidence interval [CI] 0.687-0.776) and the sensitivity, with 90% specificity, was 23.7%., Conclusion: Analysis across four types of malignancies revealed that the survivin autoantibody had good specificity and sensitivity in lung cancer. Circulating autoantibodies to survivin could be a potential biomarker for the early lung cancer diagnosis.

Although existing nanomedicines have focused on the tumor microenvironment with the goal of improving the effectiveness of conventional chemotherapy, the penetration of a tumor's core still represents a formidable barrier for existing drug delivery systems. Therefore, a novel multifunctional hypoxia-induced size-shrinkable nanoparticle has been designed to increase the penetration of drugs, nucleic acids, or probes into tumors. This cooperative strategy relies on three aspects: (i) the responsiveness of nanoparticles to hypoxia, which shrink when triggered by low oxygen concentrations; (ii) the core of a nanoparticle involves an internal cavity and strong positive charges on the surface to deliver both doxorubicin and siRNA; and (iii) a reactive oxygen species (ROS) probe is incorporated in the nanoparticle to monitor its preliminary therapeutic response in real time, which is expected to realize the enhanced efficacy together with the ability to self-monitor the anticancer activity. A more effective inhibition of tumor growth was observed in tumor-bearing zebrafish, demonstrating the feasibility of this cooperative strategy for in vivo applications. This research highlights a promising value in delivering drugs, nucleic acids, or probes to a tumor's core for cancer imaging and treatment., Statement of Significance: Hypoxia-induced chemoresistance of tumor cells still represents a formidable barrier, as it is difficult for existing drug delivery systems to penetrate the tumor hypoxia core. This study involves the hypoxia-responsive size-shrinkable nanoparticle co-delivery of DOX and siRNA to enhance the penetration of DOX deep within tumors and subsequently disturb crucial pathways of cancer development induced by hypoxia and to improve sensitization to DOX chemotherapy. Furthermore, the nanopreparation can combine the ROS probe as a self-reporting nanopreparation to realize the function of real-time feedback efficacy, which has a good application prospect in the diagnosis and treatment of cancer., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Specific circulating autoantibodies are produced by host immune systems to respond to antigens that arise during tumorigenesis. To achieve auxiliary diagnosis, the present study was designed to test whether circulating autoantibodies against tumor-associated antigens (TAAs) were altered in early breast cancer., Methods: A total of 102 breast cancer patients and 146 age-matched healthy volunteers were recruited to participate in this study. Autoantibody expression was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs., Results: Student's t tests showed that expression of autoantibodies against the panel (p16, c-myc, TP53, and ANXA-1) was significantly higher in the breast cancer group, stage I and II breast cancer group, and stage III and IV breast cancer group than in the healthy control group (p < 0.001, p < 0.001, p < 0.001). The sensitivities of detection of the panel (90% specificity) in these groups were 33.3%, 31.7%, and 33.3%, respectively, significantly higher than that of any single autoantibody., Conclusion: The panel of autoantibodies is more sensitive than single TAA autoantibody detection and may be used as biomarkers for early diagnosis of breast cancer.

A novel lanthanide-organic framework (Eu-HODA), consisting of 2,2',3,3'-oxidiphthalic acids as efficient sensitizing units, is assembled and characterized. Eu-HODA features rare chiral helical channels despite the achiral nature of H 4 ODA. It is found that this MOF shows a unique luminescent response to methanol, in contrast to n-propanol and ethanol. Eu-HODA reveals a turn-off luminescence switching initiated by acetone molecules with an EC 50 of 0.03 vol %, which is below the occupational exposure limit of acetone stipulated by the American Conference of Governmental Industrial Hygienists. Furthermore, it also exhibits high sensitivity (Stern-Volmer constant K SV = 2.09 × 10 4 L/mol) and low detection limit (6.4 ppb) for Fe 3+ ions in pure water because of the existence of uncoordinated carboxyl groups within open frameworks. Eu-HODA-based test paper provides a simple and reliable detection method for Fe 3+ in practical applications.

Aim: To design pluronic F68 (PF68)-conjugated polyamidoamine (PAMAM) dendrimer conjugates for doxorubicin (DOX) delivery for overcoming multidrug resistance, and clarify the reversal mechanism., Materials & Methods: A series of PAMAM-PF68 conjugates were designed. The antitumor activity of the DOX-loaded conjugates was evaluated against MCF-7/ADR cells, tumor spheroids and tumors. Several bioinformatics were detected to characterize the reversal mechanism., Results: Increased antitumor activity of the DOX-loaded conjugates was achieved in vitro and in vivo. The complexes induced more DOX accumulation via caveolae-mediated endocytosis. After escaping from the endosome/lysosome, the nuclear trafficking of DOX was achieved. Apoptosis was significantly increased by regulating mitochondrial function and gene expression., Conclusion: With optimized PF68 modification, PAMAM-PF68 conjugates can significantly overcome multidrug resistance in vitro and in vivo.

The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P = 0.063; P = 0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P < 0.001; P < 0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P = 0.010; P = 0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8 % and a specificity of 90 %, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.

Background: Over-expression of tumor-associated antigens (TAAs) may trigger secretion of their auto-antibodies. The present work was designed to test whether circulating antibody to P16 protein-derived antigens was altered in cervical cancer., Methods: 141 cases of cervical cancer patients, 133 cases of cervical benign tumor patients, and 153 healthy volunteers matched in age were recruited. The level of circulating P16 auto-antibody was tested using an ELISA developed in-house with linear peptide antigens derived from the P16 protein., Results: The P16 auto-antibody in the malignant tumor group had a significantly higher level than the healthy control group and the benign tumor group (t = 4.016, p < 0.001; t = 3.879, p < 0.001). Patients with stage I cervical cancer have the highest level of P16 autoantibody and the sensitivity against > 90% specificity was 20.3%., Conclusions: The circulating auto-antibody to P16 may be one of a series of potential biomarkers with early prognostic values for cervical cancer.

Background: Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors., Methods: A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes., Results: Student's t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209-5.295)., Conclusion: The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer.

The aim of this study was to find a surgical approach to a vertical segment of the facial nerve (VFN) with a relatively wide visual field and small lesion by studying the location and structure of VFN with cross-sectional anatomy. High-resolution spiral computed tomographic multiplane reformation was used to reform images that were parallel to the Frankfort horizontal plane. To locate the VFN, we measured the distances as follows: from the VFN to the paries posterior bony external acoustic meatus on 5 typical multiplane reformation images, to the promontorium tympani and the root of the tympanic ring on 2 typical images. The mean distances from the VFN to the paries posterior bony external acoustic meatus are as follows: 4.47 mm on images showing the top of the external acoustic meatus, 4.20 mm on images with the best view of the window niche, 3.35 mm on images that show the widest external acoustic meatus, 4.22 mm on images with the inferior margin of the sulcus tympanicus, and 5.49 mm on images that show the bottom of the external acoustic meatus. The VFN is approximately 4.20 mm lateral to the promontorium tympani on images with the best view of the window niche and 4.12 mm lateral to the root of the tympanic ring on images with the inferior margin of the sulcus tympanicus. The other results indicate that the area and depth of the surgical wound from the improved approach would be much smaller than that from the typical approach. The surgical approach to the horizontal segment of the facial nerve through the external acoustic meatus and the tympanic cavity could be improved by grinding off the external acoustic meatus to show the VFN. The VFN can be found by taking the promontorium tympani and tympanic ring as references. This improvement is of high potential to expand the visual field to the facial nerve, remarkably without significant injury to the patients compared with the typical approach through the mastoid process.

Since complete redundancy between extant duplicates (paralogs) is evolutionarily unfavorable, some degree of functional congruency is eventually lost. However, in budding yeast, experimental evidence collected for duplicated metabolic enzymes and in global physical interaction surveys had suggested widespread functional overlap between paralogs. While maintained functional overlap is thought to confer robustness against genetic mutation and facilitate environmental adaptability, it has yet to be determined what properties define paralogs that can compensate for the phenotypic consequence of deleting a sister gene, how extensive this epistasis is, and how adaptable it is toward alternate environmental states. To this end, we have performed a comprehensive experimental analysis of epistasis as indicated by aggravating genetic interactions between paralogs resulting from an ancient whole-genome duplication (WGD) event occurring in the budding yeast Saccharomyces cerevisiae, and thus were able to compare properties of large numbers of epistatic and non-epistatic paralogs with identical evolutionary times since divergence. We found that more than one-third (140) of the 399 examinable WGD paralog pairs were epistatic under standard laboratory conditions and that additional cases of epistasis became obvious only under media conditions designed to induce cellular stress. Despite a significant increase in within-species sequence co-conservation, analysis of protein interactions revealed that paralogs epistatic under standard laboratory conditions were not more functionally overlapping than those non-epistatic. As experimental conditions had an impact on the functional categorization of paralogs deemed epistatic and only a fraction of potential stress conditions have been interrogated here, we hypothesize that many epistatic relationships remain unresolved.

Objective: To investigate the long term results of Majer-Piquet's operation in the treatment of glottic type of laryngeal carcinoma., Methods: A series of 32 cases operated on between October 1990 and February 1995 were analysed, of whom 21 were T1N0M0, 3 were T1N1M0, 5 were T2N0M0 and 1 each for T2N1M0, T3N0M0, T3N1M0., Results: In T1 cases, 2, 3 and 5 years survival rate were 95.8, 93.7 and 90.9% respectively, while in T2 cases, 2, 3 and 5 years survival rate were 100%, 83.3% and 60% respectively. Decannulation rate was 96.9%. All patients could finally take food by mouth without inspiration, and could speak as soon as decannulated. By modifing the operative technique, the cases operated on after 1994 got relatively better results in phonation., Conclusion: Majer-Piquet's operation not only is effective in the treatment of T1, T2 and some T3 glottic type of laryngeal carcinomas, but also can satisfactorily reserve laryngeal function and improve the quality of patient's life.

Microwave is used to treat temporal hearing loss caused by intravenous injection of the ethacrynic acid in guinea pigs. The recovery of hearing is much faster in the treated groups than in the control group. The article proposes possible mechanism of the effects against the ethacrynic acid induced deafness and assume that the result of this research can provide an experimental basis for treatment of some perceptive deafness due to ischemia of stria vascularis of the cochlea.

A reliable animal model of acute type of endolymphatic hydrops was made with injection of artificial endolymph into the cochlear duct. In 12 animals without Reissner's membrane rupture, the endolymphatic potentials (EP) were kept normal after injection of artificial endolymph, but their electrocochleography (ECoG) showed as: a rise of summating potentials (SP) amplitude, a decrease of action potentials (AP) amplitude, an increase of SP/AP ratio, as well as a delay of N1 latency. In 7 animals with membrane rupture, the EP significantly decreased. ECoG showed as: a decrease of hearing function in all test frequencies, a distortion of SP-AP wave and even a loss of AP. Based on the results of our experiment it can be assumed that the dominant -SP may be seen in the acute stage of endolymphatic hydrops without a rupture of Reissner's membrane. Therefore, the dominant -SP may only be of value in the clinical diagnosis during episodic vertigo and fluctuating hearing loss of Meniere's disease.

The development of middle-ear structures in the mouse was examined in nine groups of pups between 1 and 45 days of age. The area of the tympanic membrane (pars tensa and pars flaccida), the length of the lever arms of the malleus and incus, the surface area of the oval window, and the volume of the bulla all showed systematic changes during neonatal life. The area of the oval window reached maturity first and the lever arms achieved 90% of their adult size on day 11. The tympanic membrane achieved the same criterion on day 18. These data help us further to understand the processes that contribute to the functional ontogeny of the middle ear.

The dynamics of perilymph flow in the cochlea was studied in guinea pigs. After placement of sodium chloride crystals on the round window membrane, the potassium ion concentration in the scala vestibuli in the basal turn does not change. The potassium ion concentrations in the scala tympani in the basal turn increases rapidly, while the potassium ion concentration in the scala tympani in the third turn increases slowly and to a lesser extent. The cochlear microphonic potential decreases in the basal turn and to a lesser extent in the third turn. After placement of sodium chloride on the fenestra in the scala tympani of the third turn, the chochlear microphonic potential in the basal turn does not change. These data lend support to the theory of longitudinal flow of perilymph in the scala tympani.

The scala vestibuli or the scala tympani of guinea pigs was perfused with artificial perilymph containing 1, 5, 10, 20, 30, 40 and 50 mM of potassium chloride in a total concentration of 150 mM with the background composed of sodium chloride. With the perfusion of the scala vestibuli, each concentration failed to alter the magnitude of the negative endocochlear DC potential produced by anoxia or the intravenous injection of 100 mg/kg of body weight of furosemide. With the perfusion of the scala tympani, the negative endocochlear DC potential disappeared precipitously and the maximum output of the cochlear microphonic was severely depressed with concentrations of potassium chloride of 30 mM or greater. The magnitude of the negative endocochlear DC potential appears to be closely related to the maximum output of the cochlear microphonic. These results suggest that the site of production of the negative EP is in the hair cells of the organ of Corti.

Three case studies are presented to illustrate the clinical usefulness of serial electrophysiologic and behavioral audiologic assessments in describing CNS function in severe head injury. There was an association among acute auditory brain stem and middle-latency evoked response findings, computed tomography of brain abnormality and neurologic status, and rate of recovery. Auditory evoked response findings 4 days after injury were also correlated with long-term outcome of diagnostic speech audiometry.

Changes in endocochlear DC potential (EP) and potassium ion concentrations in endolymph were measured simultaneously during anoxia or during perfusion of the perilymphatic space with furosemide, 10(-2)M, in normal and kanamycin-deafened guinea pigs. The potassium ion conductance (Gk) through the cochlear partitions was calculated. Thirty minutes after the onset of anoxia, the Gk is 22.1 microM/min/mV in normal guinea pigs and 4.8 microM/min/mV in kanamycin-deafened guinea pigs. At that time the EP is -29.5 mV in normal guinea pigs and 1.4 mV in kanamycin-deafened guinea pigs. In the early stage of anoxia the rate of potassium ion concentration decrease in the endolymph per unit time is greater in normal guinea pigs than in kanamycin-deafened guinea pigs. These results suggest a rapid increase in the permeability of potassium ions in the organ of Corti in the early stage of anoxia might produce a large negative potassium ion diffusion potential or negative EP in normal guinea pigs and the failure to develop the negative EP in kanamycin-deafened guinea pigs might be due to the lack of such a rapid increase in the permeability because of the loss of the hair cells.