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Telocytes (TCs) are a distinctive cell entity of the stromal microenvironment of multiple tumors; to date, their existence in infantile hemangioma (IH) remains almost unexplored. This study was therefore undertaken to characterize the immunophenotype, location, morphology, and ultrastructure of telocytes in the IH by means of immunohistochemistry, immunofluorescence confocal microscopy, and transmission electron microscopy. Telocytes were initially identified by CD34, PDGFR-α, Vimentin, and AQP-1 immunostaining. Analyzing the spatial relationship among telocytes, stem cells, endothelial cells, pericytes in the IH with AQP-1/CD31, AQP-1/Glut-1, AQP-1/α-SMA, AQP-1/CD146 and AQP-1/CD133 double immunofluorescence. TCs were immunonegative for CD31, Glut-1, CD146, α-SMA, CD133, and C-kit in the IH. The ultrastructural examination confirmed the presence of TCs, namely stromal cells with characteristic cytoplasmic processes (i.e. telopodes) forming labyrinthine networks around microvessels and releasing extracellular vesicles. Our study provides evidence that telocytes are present and PDGFR-α and AQP-1 are specific antigenic markers in the IH.

Objective: To evaluate the feasibility and accuracy of three-dimensional (3D)-printed individualised guiding templates in total hip arthroplasty (THA) for the treatment of developmental dysplasia of the hip (DDH)., Methods: 12 hips in 12 patients with Crowe type IV DDH were treated with THA. A 3D digital model of the pelvis and lower limbs was reconstructed using the computed tomography data of the patients. Preoperative surgical simulations were performed to determine the most suitable surgical planning, including femoral osteotomy and prosthesis placement. Based on the ideal surgical planning, individualised guiding templates were designed by software, manufactured using a 3D printer, and used in acetabulum reconstruction and femoral osteotomy during surgery., Results: 12 patients were followed up for an average of 72.42 months (range 38-135 months). During surgery, the guiding template for each case was matched to the bony markers of the acetabulum and proximal femur. Preoperative and follow-up Harris Hip Scores were 34.2 ± 3.7 and 85.2 ± 4.2; leg-length discrepancy, 51.5 ± 6.5 mm and 10.2 ± 1.5 mm; and visual analogue scale scores, 6.2 ± 0.8 and 1.3 ± 0.3, respectively, with statistical difference. Shortened deformity and claudication of the affected limb were obviously improved after surgery. However, 1 patient had artificial hip dislocation 2 weeks after surgery, and another patient had sciatic nerve traction injury, both of whom recovered after physical treatment., Conclusions: Preoperative surgical simulation and 3D-printed individualised guiding templates can fulfil surgeon-specific requirements for the treatment of Crowe type IV DDH. Accurate THA can be achieved using 3D-printed individualised templates, which provide a new personalised surgical plan for the precise positioning and orientation of acetabular reconstruction and femoral osteotomy.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro . CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC., 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 © 2021 Wu, Liu, Hu, Li, Wu, Sun, Jiang, Wang, Qin, Ding and Zhao.)

Objective: This study aimed to explore the clinical application of three-dimensional (3D) printing technology in the surgical treatment of congenital scoliosis caused by hemivertebrae., Methods: Twenty-four patients (11 in the 3D-printing group and 13 in the conventional group) with scoliosis secondary to a single hemivertebra were retrospectively reviewed. All patients underwent hemivertebrectomy and short-segment fixation. Virtual preoperative planning, operation simulation, and intraoperative application of 3D-printed patient-specific templates were performed in the 3D-printing group. Hemorrhage volume, operation time, transfusion, and complications were noted. Radiographic parameters were evaluated preoperatively, postoperatively, and at final follow-up., Results: All patients had different degrees of successfully corrected scoliosis. There was a similar correction of the Cobb angle postoperatively between the 2 groups. The operation time, blood loss, transfusion, time for the insertion of each screw, accuracy of screw placement, and complication rate in the 3D-printing group were significantly superior to those in the control group. No patient experienced major complications. No significant correction loss or instrument dysfunction was observed during follow-up., Conclusions: As a viable and effective auxiliary technology, 3D printing makes it possible for surgery to meet both surgeon-specific and patient-specific requirements. 3D-printed individualized templates allow surgery for the correction of congenital scoliosis to enter a new stage of personalized precision surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP + -induced PD models in vivo and in vitro . It is necessary to evaluate the efficacy of the anti-PD effects under various models., Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex . Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD., Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining., Conclusion: KuA treatment might represent a neuroprotective treatment for PD., Competing Interests: Neither any of the authors have anything to disclose regarding this manuscript nor do they have any potential conflicts of interest to report concerning this article., (© 2020 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

EPHB6 is a metastasis inhibitory gene that is frequently decreased or deficiency in non-small cell lung cancer (NSCLC), which contributed to the subsequent development of distant metastasis. These suggested the possibility that reactivation of EPHB6 might prevent the metastasis of NSCLC. Nevertheless, EPHB6 expression might also promote cancer cell growth and inhibit cell apoptosis by activating Akt and ERK pathway, apart from inhibition of migration and invasion. In the present study, we developed a novel quinazolin-4(3H)-one analog (DFX24) as a potential PI3Kα inhibitor, which inhibited both cell proliferation and metastasis of NSCLC cell lines. Investigation to the molecular mechanisms revealed DFX24 inhibited the cell growth and metastasis via inhibition of PI3Kα and ERK activity, as well as the increase in EPHB6 expression. In addition, DFX24 also induced cell cycle arrest and tumor cell apoptosis by inhibiting PI3K/Akt pathway and activating mitochondria-dependent pathway, respectively. These findings suggested that DFX24 might be considered as a novel drug candidate and may provide a potential therapy for NSCLC., (Copyright © 2020. Published by Elsevier Ltd.)

Phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, such as proliferation, growth, autophagy and apoptosis. Class I PI3K is frequently mutated and overexpressed in a lot of human cancers and PI3K was considered as a target for therapeutic treatment of cancer. In this study, we designed and synthesized a series of 1,6-disubstituted-1H-benzo[d]imidazoles derivatives and evaluated their anticancer activity and the compound 8i was identified as a lead compound. Compound 8i with the most potent antiproliferative activity was selected for further biological mechanism. The PI3K kinase assay have shown potent efficiency against four subtypes of PI3K with an IC 50 of 0.5-1.9 nM. Molecular docking showed a possible formation of H-bonding with essential amino acid residues. Meanwhile, western blot assay indicated that 8i inhibited cell proliferation via suppression of PI3K kinase activity and subsequently blocked PI3K/Akt pathway activation in HCT116 cells. In addition, 8i could inhibit the migration and invasion ability of HCT116 cells and could induce apoptosis of HCT116 cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To report the outcomes of severe kyphoscoliosis secondary to ankylosing spondylitis (AS) corrected with 3D-printed individualized guiding templates., Methods: Computed tomography (CT) data of patients with severe kyphoscoliosis secondary to AS were used to reconstruct 3D models of the spine and to develop a surgical plan. An asymmetric wedge pedicle subtraction osteotomy (PSO) was simulated using medical computer design software. Before the actual surgery, continual surgical simulations were performed until the most suitable one was obtained, and personalized guiding templates were manufactured for the anticipated PSO. During operation, the osteotomy plane and trajectories for the pedicle screws were positioned by the designed patient-specific 3D-printed guiding templates., Results: In this study, we reviewed 9 patients who underwent correction of kyphoscoliosis using a 3D-printed individualized guiding template and were followed for a median of 21.4 months (range, 9-36 months). The average correction at the site of osteotomy was 65.9°. No patient experienced severe complications, such as misplaced pedicle screws or neurologic complications. At the last follow-up, no patient exhibited implant dysfunction on radiography., Conclusions: Preoperative surgical simulation using 3D-printed templates is a viable technique that enables surgery to meet both patient- and surgeon-specific requirements for correction of severe thoracolumbar kyphoscoliosis. These 3D-printed templates can guide the performance of planned PSO to provide functional restoration of severe kyphoscoliosis secondary to AS., (Copyright © 2019. Published by Elsevier Inc.)

A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for three PI3K isoforms with the IC 50 values of picomole. The western blot assay indicated that 7b could decrease the phospho-Akt (S473) in a dose-dependent manner. Further experiments showed that 7b could induce apoptosis in MCF-7 cells. Four key hydrogen bonding interactions were found in the docking of 7b with PI3K kinase. All these results suggested that 7b is a potent PI3K inhibitor and could be considered as a potential candidate for the development of anticancer agents., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To provide molecular evidence on the thermogenic mechanism of primary brown adipocytes, western blot analysis was used to detect brown adipose tissue (BAT)-specific gene expressions. BAT protects the mammals from hypothermia injury with a large amount of mitochondria and high expression of uncoupling Protein 1 (UCP1), which is the vital protein to determine the heat production in BAT. In our previous study, the compound ZW290 (the structure shown in Fig. 1) was obtained by molecular docking with a UCP1 inducer. In the present study, ZW290 not only significantly upregulated the expression of UCP1 protein (p < 0.01) and its related signaling pathway in the primary brown adipocytes, but also remarkably decreased the mitochondrial membrane potential and the concentration of adenosine triphosphate (ATP) (p < 0.01). Kunming (KM) mice were kept under acute cold exposure (-20°C) to evaluate the preventive and protective effects of ZW290 on cold injury, and revealed its regulating mechanism in vitro. The rectal and body temperatures of ZW290-treated mice were significantly higher than those of the control (or model) group both at room temperature and at -20°C (p < 0.001). Hematoxylin-eosin (HE) staining and immunohistochemistry indicated that ZW290 notably decreased the size of lipid droplets in BAT and increased the content of mitochondria and the expression of UCP1 in BAT and white adipose tissue (WAT). Furthermore, the survival rate showed that ZW290 could prolong the overall survival of mice. Therefore, we obtained the conclusion that ZW290 might transform energy into heat by inhibiting ATP synthesis and increasing the expression of UCP1. Additionally, ZW290 may enhance cold tolerance by increasing heat production through increasing the content of mitochondria and the expression of UCP1 in BAT and WAT., (© 2019 AOCS.)

Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect., Materials and Methods: Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI-8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial-mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI-8 in vivo., Results: We found that ZLDI-8 cell-specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI-8 synergistically improved the anti-tumour and anti-metastasis activity of 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI-8 promoted the anti-tumour effect of 5-fluorouracil through Notch and EMT reversal., Conclusions: A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways., (© 2018 John Wiley & Sons Ltd.)

The abnormal activation of PI3K signaling pathway leads to the occurrence of various cancers. The PI3Kα is frequently mutated and overexpressed in many human cancers. Therefore, the PI3Kα was considered as a promising target in therapeutic treatment of cancer. In this study, two series of compounds containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold were synthesized and evaluated antiproliferative activities against three cancer cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most potent antiproliferative activity was selected for further evaluation on normal cells and PI3K kinase. Studies indicated that compound 7f could decrease the phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding interactions were found in the docking of 7f with PI3K enzyme. All the results suggested that 7f was a potent PI3Kα inhibitor., (Copyright © 2018. Published by Elsevier Ltd.)

Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl 4 -induced acute liver injury mouse models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Melanoma is an extremely aggressive malignant skin tumor with a high mortality. Various long noncoding RNAs (lncRNAs) have been reported to be associated with the oncogenesis of melanoma. The purposes of this study were to investigate the potential role of lncRNA PVT1 in melanoma progression and to explore its possible mechanisms. A total of 35 patients who were diagnosed with malignant melanoma were enrolled in this study. Expression of PVT1 was significantly upregulated in melanoma tissue and was associated with a poor prognosis. Loss-of-function experiments showed that PVT1 knockdown markedly suppressed the proliferation activity, induced cell cycle arrest at the G0/G1 phase, and enhanced the apoptosis of melanoma cell lines. Bioinformatics analysis and dual-luciferase reporter assay revealed that PVT1 directly bound to miR-26b, which had been verified to be a tumor suppressor in melanoma. Moreover, further functional rescue experiments revealed that PVT1 knockdown could observably reverse the tumor-promoting role of the miR-26b inhibitor. Overall, our study demonstrates the oncogenic role of PVT1 as a miR-26b sponge, possibly providing a novel therapeutic target for melanoma.

Phosphatidylinositol 3-kinase (PI3K) signaling pathway has diverse functions, including the regulation of cellular survival, proliferation, cell cycle, migration, angiogenesis and apoptosis. Among class I PI3Ks (PI3Kα, β, γ, δ), the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in a large portion of human cancers. Therefore, the inhibition of PI3Kα has been considered as a promising target for the development of a therapeutic treatment of cancer. In this study, we designed and synthesized a series of 4-aminoquinazoline derivatives and evaluated their antiproliferative activities against six cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638, A549 and MCF-7. Compound 6b with the most potent antiproliferative activity and without obvious cytotoxicity to human normal cells was selected for further biological evaluation. PI3K kinase assay showed that 6b has selectivity for PI3Kα distinguished from other isoforms. The western blot assay and PI3K kinase assay indicated that 6b effectively inhibited cell proliferation via suppression of PI3Kα kinase activity with an IC 50 of 13.6 nM and subsequently blocked PI3K/Akt pathway activation in HCT116 cells. In addition, 6b caused G1 cell cycle arrest owing to the inhibition of PI3K signaling and induced apoptosis via mitochondrial dependent apoptotic pathway. Our findings suggested that 6b has a therapeutic value as an anticancer agent via PI3Kα inhibition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The overexpression of EGFR correlates with rapidly progressive disease, resistance to chemotherapy and poor prognosis. In certain human cancers, PI3K works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and PI3K has therapeutic advantage and was an attractive approach against tumors. In this work, based on the molecular docking and previous studies, a series of 4-aminoquinazolines derivatives containing 6-sulfonamide substituted pyridyl group were rationally designed and identified as potent EGFR and PI3K dual inhibitors. The cytotoxicity experiment results showed that this series of compounds could effectively inhibit cell growth. The kinase assay demonstrated that 6c and 6i had high inhibition for EGFR and selectivity for PI3Kα distinguished from other isoforms. Further experiments showed that 6c could induce cell cycle arrest in G1 phase and apoptosis in BT549 cells. The western blot assay indicated that 6c inhibited the proliferation of BT549 cell through EGFR and PI3Kα/Akt signaling pathway. Our study suggested that compound 6c was a potential dual inhibitors of EGFR and PI3Kα., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Phosphatidylinositol 3-kinase (PI3K) is a pivotal regulator of intracellular signaling pathways and considered as a promising target in the development of a therapeutic treatment of cancer. Among the different PI3K subtypes, the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in majority of human cancers. Therefore, the inhibition of PI3Kα has been considered to be an efficient approach for the treatment of cancer. In this study, two series compounds containing hydrophilic group in imidazo[1,2-a]pyridine and quinazolin-4(3H)-one were synthesized and their antiproliferative activities against five cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638 and A549, were evaluated. Compound 1i with most potent antiproliferative activity was selected for further biological evaluation. PI3K kinase assay showed that 1i has selectivity for PI3Kα distinguished from other isoforms. The western blot assay indicated that 1i is more effective than HS-173, an imidazopyridine-based PI3Ka inhibitor, in reducing the levels of phospho-Akt. All these results suggested that 1i is a potent PI3Kα inhibitor and could be considered as a potential candidate for the development of anticancer agents., (Copyright © 2017. Published by Elsevier Masson SAS.)

A flavonoid hesperetin is reported to have a variety of biological activities, including anticancer, antiviral, antioxidant, neuroprotective and anti-inflammatory properties. Thirty-one novel hesperetin derivatives were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells and CCl4-induced acute liver injury model. Among these compounds, 5b displayed the excellent anti-inflammatory activity on decreasing NO, IL-6 and TNF-α both in vitro and vivo. In addition, 5b could also reduce the release of NO, IL-6 and TNF-α production by LPS stimulated RAW 264.7 cell through MAPK and NF-κB signaling pathway in a concentration dependent manner. From in vivo study, it was also observed that 5b attenuated liver histopathologic changes in mouse models., (Copyright © 2017. Published by Elsevier B.V.)

In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H₂O₂-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer's disease.

Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl 4 -induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Adjacent vertebral fractures are common in patients with osteoporotic vertebral compression fractures (OVCFs) after kyphoplasty. This finite element study was to examine whether short segment pedicle screw fixation (PSF) with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae after kyphoplasty for OVCFs. By simulating cement augmentation with or without short segment pedicle screw fixation (PSF), two tridimensional, anatomically detailed finite element models of the T10-L2 functional spinal junction were developed. The insertion of pedicle screws into the intact vertebra apparently decreased the stress distribution of the treated vertebra in vertical compression and other load situations. The stress distribution in the bone structures of the intact vertebra adjacent to the intact-screwed vertebra was much less than that in the one adjacent to the treated vertebra. The insertion of pedicle screws into the intact vertebra greatly decreased the maximum displacement of the cortical bones and cancellous bones of the vertebrae. Our results indicated that short segment PSF with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae in the management of OVCFs.

Hearing loss is one of the major public health problems in the world, which brings huge adverse effects to individuals and society. Sensorineural hearing loss (SNHL) is responsible for the majority of hearing loss. Mechanisms contributing to SNHL include excessive accumulation of reactive oxygen species; over-activation of inflammatory factors; impaired blood micro-circulation in the inner ear or Ca2+ homeostasis imbalance, etc. Natural products (NPs), which have a long history of use in traditional medicine and a favorable safety profile, can be developed into a library of drug candidates for the treatment or prevention of SNHL. In this paper, we summarized 24 NPs to exhibit their preventive or therapeutic effects on cellular and animal models of SNHL in terms of their anti-apoptotic, anti-inflammatory, microcirculation-improving, and calcium antagonist effects, as well as 5 NPs in current clinical application. Further, combination with advanced technologies such as drug delivery systems and network pharmacology are applied to improve the research of NPs in the prevention of SNHL. Overall, this review provides a strong reference for the mining and development of NPs in the prevention and treatment of SNHL. [ABSTRACT FROM AUTHOR]

In response to the current issue of low accuracy and robustness in the remaining useful life (RUL) model of lithium-ion batteries. In the framework of AdaBoost, a lithium-ion battery life prediction model based on an improved whale optimization algorithm to optimize the Kernel Extreme Learning Machine (IWOA-KELM) is proposed. The IWOA-KELM model is used as a weak predictor. A weighted voting mechanism is used to set a weight coefficient for each weak predictor and then combine the strong predictor of battery RUL. Constant current charge time, constant voltage charge time, internal resistance, and incremental capacity curves peak were extracted from the Cycle data set as health features to accurately describe battery degradation. Pearson correlation coefficient and Savitzky-Golay filter preprocessed health features. Tent chaotic mapping is used to initialize whale populations and maintain their diversity. The iterative updating strategy of the hunting speed control factor is introduced to reduce the probability of the local optimal case of the whale optimization algorithm. The kernel function parameters and regularization parameters of KELM are optimized by IWOA to improve the model prediction ability. After verification, the RUL error of the method proposed in this article can be as accurate as 4 cycles. [ABSTRACT FROM AUTHOR]

Thyroid cancer is one of the most common endocrine malignancies in clinical practice. Traditional surgery and radioactive iodine ablation have poor treatment results for poorly differentiated thyroid cancer, and there is a risk of metastasis and recurrence. In this study, caffeic acid, a natural herbal extract with certain biological activity, has been as precursor to prepare new caffeic acid carbon nanodots via a one-step hydrothermal method. The caffeic acid carbon nanodots retains part of the structure and biological activity of caffeic acid, and have good biocompatibility, water solubility and stability. The construction of the carbon nanodots could effectively improve their bio-absorption rate and the efficacy. In vitro cell experiments showed that low-dose caffeic acid carbon nanodots had a significant inhibitory effect on poorly differentiated papillary thyroid carcinoma BCPAP cells. At low concentrations of 16 µg/mL, the inhibition rate of human thyroid cancer cells BCPAP was ~ 79%. The anti-tumor mechanism was predicted and verified by transcriptome, real-time quantitative PCR and western blot experiments. The caffeic acid carbon nanodots showed to simultaneously downregulate the expression of KRAS, p-BRAF, p-MEK1 and p-ERK1/2, the four continuous key proteins in a MAPK classical signaling pathway. In vivo experiments further confirmed the caffeic acid carbon nanodots could significantly inhibit the tumorigenicity of xenografts in papillary thyroid carcinoma at quite low doses. This piece of work provides a new nanomedicine and therapeutic strategy for highly resistant poorly differentiated papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Background: To report the outcomes of computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee., Methods: Computed tomography (CT) and magnetic resonance imaging (MRI) data were input into computer software to produce three-dimensional (3D) models of the tumor extent. Imaging data was then used to create a template for surgical resection, and development of an individualized combined allogeneic bone/endoprosthesis. Surgical simulations were performed prior to the actual surgery., Results: This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years). There were 9 tumors in the distal femur and 3 in the proximal tibia. There were no surgical complications. In all cases pathologically confirmed clear surgical margins were obtained. Postoperative radiographs showed the range of tumor resection was in accordance with the preoperative design, and the morphological reconstruction of the bone defect was satisfactory with complete bilateral symmetry. The mean follow-up time was 26.5 months. Two patients died of their disease and the remaining are alive and well without evidence of recurrence. All patients are able to ambulate freely without restrictions. At the last follow-up, the average International Society of Limb Salvage score was 25.8 (range, 18 to 27), and was excellent in 8 cases and good in 4 cases., Conclusions: Computer-aided design and modeling for the surgical management of bone tumors and subsequent limb reconstruction provides accurate tumor removal with the salvage of a maximal amount of unaffected bone and precise endoprosthesis reconstruction.

Objective: To prepare a cisplatin-impregnated coral-derived hydroxyapatite (CCHA) drug delivery system (DDS), and evaluate its inhibitory effect on human osteosarcoma cells U-2 OS, human breast cancer and prostatic carcinoma cells PC-3 in vitro., Methods: The coral-derived hydroxyapatite (CHA) was manufactured by hydrothermal exchange and impregnated with cisplatin by vacuum freeze-drying techniques. The leaching solutions of this DDS was collected at different intervals in a course of 8 weeks and their inhibitory effect on the cells was tested in vitro by MTT assay., Results: Electron microscope showed that cisplatin was distributed homogeneously in the pores of CHA. The inhibition rates of the leaching solution on all the tumor cells exceeded 50% except for PC-3 cells, whose inhibition rate was 29.92% when treated with the solution collected at the eighth week., Conclusion: CCHA allows sustained drug release and maintains excellent inhibitory effect on human bone tumor cells within 8 weeks in vitro.

Objective: To investigate the biomechanical effects of percutaneous vertebroplasty combined with cement pedicle plasty (PVCPP) on the unstable osteoporotic vertebral fractures (OVFs) through finite element (FE) analysis. The study compares the biomechanical stability of finite element models between percutaneous vertebroplasty (PVP) and percutaneous vertebroplasty combined with cement pedicle plasty. Methods: Two patients with unstable OVFs underwent computed tomography (CT) examination at the thoracolumbar vertebral body levels, respectively. The CT images were reconstructed into three-dimensional finite element models to simulate stress conditions across six dimensions and to evaluate the vertebral von Mises stress before and after bone cement reinforcement. Results: The study found that stress distribution differed between groups mainly at the pedicle base. In the surgical vertebral bodies, the maximum stress in the PVP group decreased during flexion and left bending, while it increased in other states. In the PVCPP group, all maximum stresses decreased. In the inferior vertebral bodies, the maximum stress in the PVP group generally increased, while it decreased in the PVCPP group. In the superior vertebral bodies, postoperatively, the maximum stress in the PVP group generally increased, while it almost remained unchanged in the PVCPP group. PVP group had higher cement stress and displacement. Conclusion: PVCPP is an effective treatment method for patients with unstable OVFs. It can quickly relieve pain and enhance the stability of the three columns, thereby reducing the risk of some complications. [ABSTRACT FROM AUTHOR]

Objective: Peroneus Longus Tendon (PLT), a viable anterior cruciate ligament (ACL) graft, shares similar biomechanics, making it suitable for reconstruction. Controversy exists over whether PLT transplants affects the donor ankle joint. The purpose of this study was to examine the recovery of knee joint function following arthroscopic ACL restoration using autologous PLT and its influence on the donor ankle joint. Methods: A retrospective analysis was conducted on 65 patients with ACL rupture who underwent PLT graft reconstruction in our hospital from January 2016 to December 2021. A three‐dimensional gait analysis of the bilateral knee and ankle joints was performed postoperatively using an Opti_Knee three‐dimensional motion measurement and analysis system—Yidong Medical Infrared Motion Gait Analyzer. Knee function scores and changes in the range of motion of the bilateral knee and ankle joints were collected. The analysis of preoperative and postoperative joint function scores, bilateral knee and ankle mobility was performed by t‐tests. Results: One year after surgery, the patients' International Knee Documentation Committee (IKDC) scores, Knee Injury and Osteoarthritis Outcome Scores (KOOSs), and Lysholm scores were significantly improved compared to preoperative scores, with statistically significant differences (p < 0.05). There was no statistical difference in the American Orthopedic Foot and Ankle Society (AOFAS) score of the donor ankle joint before and after surgery (p > 0.05). During different gait cycles, there was no statistical difference in knee joint mobility between the affected and healthy sides (p > 0.05), but there was a statistical difference in the inversion and eversion angle of the donor ankle joint during the support phase (p < 0.05). Conclusion: ACL reconstruction using the PLT can yield satisfactory knee joint function. However, it does affect inversion and eversion in the donor ankle joint, necessitating postoperative exercises. Similar subjective function ratings for both operated and non‐operated feet, despite increased inversion‐eversion motion in the operated foot, may be influenced by the subjective nature and margin of error in the AOFAS Ankle‐hindfoot score, along with the relatively small variation in ankle inversion‐eversion angles. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the influence of the location of the upper and lower cement on the sandwich vertebrae (SV) by computer finite element analysis. Materials and Methods: A finite element model of the spinal segment of T11‐L1 was constructed and 6 mL of cement was built into T11 and L1 simultaneously. According to the various distributions of bone cement at T11 and L1, the following four groups were formed: (i) Group B‐B: bilateral bone cement reinforcement in both T11 and L1 vertebral bodies; (ii) Group L‐B: left unilateral reinforcement in T11 and bilateral reinforcement in L1; (iii) Group L‐R: unilateral cement reinforcement in both T11 and L1 (cross); (iv) Group L‐L: unilateral cement reinforcement in both T11 and L1 (ipsilateral side). The maximum von Mises stress (VMS) and maximum displacement of the SV and intervertebral discs were compared and analyzed. Results: The maximum VMS of T12 was in the order of size: group B‐B < L‐B < L‐R < L‐L. Group B‐B showed the lowest maximum VMS values for T12: 19.13, 18.86, 25.17, 25.01, 19.24, and 20.08 MPa in six directions of load flexion, extension, left and right lateral bending, and left and right rotation, respectively, while group L‐L was the largest VMS in each group, with the maximum VMS in six directions of 21.55, 21.54, 30.17, 28.33, 19.88, and 25.27 MPa, respectively. Conclusion: Compared with the uneven distribution of bone cement in the upper and lower adjacent vertebrae (ULAV), the uniform distribution of bone cement in the ULAV reduced and uniformed the stress load on the SV and intervertebral disc. Theoretically, it can lead to the lowest incidence of sandwich vertebral fracture and the slowest rate of intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Cytochrome P 450 2C19 (CYP2C19) is involved in the metabolism of a number of clinically used drugs. Individuals can be characterized as extensive metabolizers (EMs) or poor metabolizers (PMs) , according to the drugs-metabolized ability of CYP2C19 in population studies. The incidence of poor metabolizer phenotype shows marked interracial differences. In this article we report the gene polymorphism of CYP2C19 in Zang population. There were 49 wild-type homozygotes (wt/wt) , 46 were heterozygotes (wt/m1) and 9 were homozygotes (m1/m1) among 104 unrelated Zang subjects. The frequency of CYP2C19(m1) allele was 0.308, which was in agreement with that in other published data.

Background: The surgical treatment of severe and complex adult spinal deformity (ASD) commonly required three-column osteotomy (3-CO), which was technically demanding with high risk of neurological deficit. Personalized three dimensional (3D)-printed guide template based on preoperative planning has been gradually applied in 3-CO procedure. The purpose of this study was to compare the efficacy, safety, and precision of 3D-printed osteotomy guide template and free-hand technique in the treatment of severe and complex ASD patients requiring 3-CO. Methods: This was a single-centre retrospective comparative cohort study of patients with severe and complex ASD (Cobb angle of scoliosis > 80° with flexibility < 25% or focal kyphosis > 90°) who underwent posterior spinal fusion and 3-CO between January 2020 to January 2023, with a minimum 12 months follow-up. Personalized computer-assisted three-dimensional osteotomy simulation was performed for all recruited patients, who were further divided into template and non-template groups based on the application of 3D-printed osteotomy guide template according to the surgical planning. Patients in the two groups were age- and gender- propensity-matched. The radiographic parameters, postoperative neurological deficit, and precision of osteotomy execution were compared between groups. Results: A total of 40 patients (age 36.53 ± 11.98 years) were retrospectively recruited, with 20 patients in each group. The preoperative focal kyphosis (FK) was 92.72° ± 36.77° in the template group and 93.47° ± 33.91° in the non-template group, with a main curve Cobb angle of 63.35° (15.00°, 92.25°) and 64.00° (20.25°, 99.20°), respectively. Following the correction surgery, there were no significant differences in postoperative FK, postoperative main curve Cobb angle, correction rate of FK (54.20% vs. 51.94%, P = 0.738), and correction rate of main curve Cobb angle (72.41% vs. 61.33%, P = 0.101) between the groups. However, the match ratio of execution to simulation osteotomy angle was significantly greater in the template group than the non-template group (coronal: 89.90% vs. 74.50%, P < 0.001; sagittal: 90.45% vs. 80.35%, P < 0.001). The operating time (ORT) was significantly shorter (359.25 ± 57.79 min vs. 398.90 ± 59.48 min, P = 0.039) and the incidence of postoperative neurological deficit (5.0% vs. 35.0%, P = 0.018) was significantly lower in the template group than the non-template group. Conclusion: Performing 3-CO with the assistance of personalized 3D-printed guide template could increase the precision of execution, decrease the risk of postoperative neurological deficit, and shorten the ORT in the correction surgery for severe and complex ASD. The personalized osteotomy guide had the advantages of 3D insight of the case-specific anatomy, identification of osteotomy location, and translation of the surgical planning or simulation to the real surgical site. [ABSTRACT FROM AUTHOR]

Background: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. Results: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. Conclusions: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes. [ABSTRACT FROM AUTHOR]

Mounting evidence progressively appreciates the vital interplay between immunity and metabolism in a wide array of immunometabolic chronic disorders, both autoimmune and non-autoimmune mediated. The immune system regulates the functioning of cellular metabolism within organs like the brain, pancreas and/or adipose tissue by sensing and adapting to fluctuations in the microenvironment's nutrients, thereby reshaping metabolic pathways that greatly impact a pro- or antiinflammatory immunophenotype. While it is agreed that the immune system relies on an adequate nutritional status to function properly, we are only just starting to understand how the supply of single or combined nutrients, all of them termed immunonutrients, can steer immune cells towards a less inflamed, tolerogenic immunophenotype. Polyphenols, a class of secondary metabolites abundant in Mediterranean foods, are pharmacologically active natural products with outstanding immunomodulatory actions. Upon binding to a range of receptors highly expressed in immune cells (e.g. AhR, RAR, RLR), they act in immunometabolic pathways through a mitochondria-centered multi-modal approach. First, polyphenols activate nutrient sensing via stress-response pathways, essential for immune responses. Second, they regulate mammalian target of rapamycin (mTOR)/AMP-activated protein kinase (AMPK) balance in immune cells and are well-tolerated caloric restriction mimetics. Third, polyphenols interfere with the assembly of NLR family pyrin domain containing 3 (NLRP3) in endoplasmic reticulum-mitochondria contact sites, inhibiting its activation while improving mitochondrial biogenesis and autophagosomelysosome fusion. Finally, polyphenols impact chromatin remodeling and coordinates both epigenetic and metabolic reprogramming. This work moves beyond the well-documented antioxidant properties of polyphenols, offering new insights into the multifaceted nature of these compounds. It proposes a mechanistical appraisal on the regulatory pathways through which polyphenols modulate the immune response, thereby alleviating chronic low-grade inflammation. Furthermore, it draws parallels between pharmacological interventions and polyphenol-based immunonutrition in their modes of immunomodulation across a wide spectrum of socioeconomically impactful immunometabolic diseases such as Multiple Sclerosis, Diabetes (type 1 and 2) or even Alzheimer's disease. Lastly, it discusses the existing challenges that thwart the translation of polyphenols-based immunonutritional interventions into long-term clinical studies. Overcoming these limitations will undoubtedly pave the way for improving precision nutrition protocols and provide personalized guidance on tailored polyphenol-based immunonutrition plans. [ABSTRACT FROM AUTHOR]

Study Design: Systematic Review Objective: 3DP technology use has become increasingly more common in the field of medicine and is notable for its growing utility in spine surgery applications. Many studies have evaluated the use of pedicle screw placement guides and spine models in adult spine patients, but there is little evidence assessing its efficacy in pediatric spine patient populations. This systematic review identifies and evaluates the current applications and surgical outcomes of 3-Dimensional Printing (3DP) technology in pediatric spinal surgery. Methods: A search of publications was conducted using literature databases and relevant keywords in concordance with PRISMA guidelines. Inclusion criteria consisted of original studies, and studies focusing on the use of 3DP technology in pediatric spinal surgery. Studies with a focus on adult populations, non-deformity surgery, animal subjects, systematic or literature reviews, editorials, or non-English studies were excluded from further analysis. Results: After application of inclusion/exclusion criteria, we identified 25 studies with 3DP applications in pediatric spinal surgery. Overall, the studies found significantly improved screw placement accuracy using 3DP pedicle screw placement guides but did not identify significant differences in operative time or blood loss. All studies that utilized 3D spine models in preoperative planning found it helpful and noted an increased screw placement accuracy rate of 89.9%. Conclusions: 3DP applications and techniques are currently used in pre-operative planning using pedicle screw drill guides and spine models to improve patient outcomes in pediatric spinal deformity patients. [ABSTRACT FROM AUTHOR]

For probing the influence of kukoamine A on interleukin-1 beta-evoked damage of chondrocytes and its possible mechanism. Interleukin-1 beta was used to induce human knee joint chondrocytes to establish a cell injury model, and different concentrations of kukoamine A were used to treat chondrocytes. Following anti-microRNA-302b-3p introduction into chondrocytes, interleukin-1 beta (10 ng/ml) was employed for treating cells for 24 h. microRNA-NC and microRNA-302b-3p mimics were respectively transfected into chondrocytes and treated with kukoamine A (40 µmol/l) and interleukin-1 beta (10 ng/ml) for 24 h. Enzymelinked immunosorbent assay method was used for detecting the levels of interleukin-6, tumour necrosis factor alpha, and interferon gamma. Flow cytometry was used for detecting the rate of cell apoptosis. The quantitative reverse transcription polymerase chain reaction was utilized for detecting microRNA-302b-3p level. Western blot was employed for detecting Bcl-2 associated X, apoptosis and B-cell lymphoma 2 protein levels. Kukoamine A could reduce interleukin-6, tumour necrosis factor alpha, and interferon gamma levels in chondrocytes induced by interleukin-1 beta, and could reduce the rate of apoptosis and the protein level of Bcl-2 associated X, apoptosis, and could also reduce the level of micoRNA-302b-3p, whereas it promoted B-cell lymphoma 2 level dose-dependently. After anti-microRNA-302b-3p introduction, interleukin-6, tumour necrosis factor alpha, and interferon gamma were downregulated, the rate of apoptosis and the protein level of Bcl-2 associated X, apoptosis were declined, whereas B-cell lymphoma 2 level was elevated. Transfection of microRNA-302b-3p mimics reversed kukoamine A impact on inflammation and apoptosis in interleukin-1 betaevoked chondrocytes. Kukoamine A could inhibit cell inflammatory reaction and apoptosis by downregulating microRNA-302b-3p level, thereby reducing interleukin-1 beta induced chondrocyte damage. [ABSTRACT FROM AUTHOR]

The Danxia geoheritage has emerged as a compelling subject of study, while the Tethys-Himalayan tectonic domain continues to captivate scholarly attention. However, a noteworthy gap exists in the literature concerning the intricate relationship between Danxia formation and the evolution of regional tectonics. In this study, we conducted a comprehensive analysis involving structure interpretation and terrain assessment, utilizing Landsat8 imagery and ASTER Global Digital Elevation Model. Additionally, field investigations were carried out on 35 Danxia landforms in the southern Sichuan Basin. Our findings revealed four distinct types of Danxia heritages—cliff (32 sites), peak (7 sites), cave (5 sites), and valley (6 sites)—with a predominant presence on slopes exceeding 40°. Moreover, valley-type sites exhibited a propensity for development at altitudes surpassing 400 m. The observed formations were intricately linked to Late Jurassic to Cretaceous red beds, influenced by the synergistic effects of the southward thrusting of the Qinling Orogen and the northwestward expansion of the Jiangnan Orogen. The control exerted by Cenozoic faults, folds, and joints—resulting from the eastward expansion of the Tibetan Plateau and the southeastward extrusion of the Chuandian terrane—further shaped these Danxia landscapes. Notably, the eastward expansion of the Tibetan Plateau induced the Cenozoic uplift of the southern Sichuan Basin, initiating a rapid denudation process of red beds crucial to the formation of Danxia landforms. Consequently, the Tethys-Himalayan tectonic evolution not only provided the material and structural foundations for these formations but also exerted a profound influence on their development in the southern Sichuan Basin. This study significantly contributes to our enhanced understanding of the spatial distribution of Danxia landforms in China. [ABSTRACT FROM AUTHOR]

Purpose: Spine surgery entails a wide spectrum of complicated pathologies. Over the years, numerous assistive tools have been introduced to the modern neurosurgeon's armamentarium including neuronavigation and visualization technologies. In this review, we aimed to summarize the available data on 3D printing applications in spine surgery as well as an assessment of the future implications of 3D printing., Methods: We performed a comprehensive review of the literature on 3D printing applications in spine surgery., Results: Over the past decade, 3D printing and additive manufacturing applications, which allow for increased precision and customizability, have gained significant traction, particularly spine surgery. 3D printing applications in spine surgery were initially limited to preoperative visualization, as 3D printing had been primarily used to produce preoperative models of patient-specific deformities or spinal tumors. More recently, 3D printing has been used intraoperatively in the form of 3D customizable implants and personalized screw guides., Conclusions: Despite promising preliminary results, the applications of 3D printing are so recent that the available data regarding these new technologies in spine surgery remains scarce, especially data related to long-term outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Based on establishing a mathematical model of the system provided system parameters, using the discrete-time Markov chain and a function set by a nonnegative integer random variable as probabilistic methods, the discrete time variable, two-queue different-gated polling system is fully analyzed, the low- and higher-order properties and cycle period of the system are deduced, and the average queue pair length and average waiting delay for message packets are calculated accurately. The simulation experiments agree well with the theoretical calculations. The analysis further deepens the understanding of the asymmetric threshold polling system, lays the foundation for research on the asymmetric threshold polling system, and has positive significance for a better and more flexible control periodic query polling work system. [ABSTRACT FROM AUTHOR]

Lappaconitine (LA), a diterpenoid alkaloid extracted from the root of Aconitum sinomontanum Nakai, exhibits broad pharmacological effects, including anti-tumor activity. The inhibitory effect of lappaconitine hydrochloride (LH) on HepG2 and HCT-116 cells and the toxicity of lappaconitine sulfate (LS) on HT-29, A549, and HepG2 cells have been described. But the mechanisms of LA against human cervical cancer HeLa cells still need to be clarified. This study was designed to investigate the effects and molecular mechanisms of lappaconitine sulfate (LS) on the growth inhibition and apoptosis in HeLa cells. The cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2´-deoxyuridine (EdU) assay, respectively. The cell cycle distribution and apoptosis were detected by flow cytometry analysis and 4', 6-diamidino-2-phenylindole (DAPI) staining. The mitochondrial membrane potential (MMP) was determined through the 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimi-dazolyl carbocyanine iodide (JC-1) staining. The cell cycle arrest-, apoptosis-, and the phosphatidylinositol-3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/AKT/GSK3β) pathway-related proteins were estimated by western blot analysis. LS markedly reduced the viability and suppressed the proliferation of HeLa cells. LS induced G0/G1 cell cycle arrest through the inhibition of Cyclin D1, p-Rb, and induction of p21 and p53. Furthermore, LS triggered apoptosis through the activation of mitochondrial-mediated pathway based on decrease of Bcl-2/Bax ratio and MMP and activation of caspase-9/7/3. Additionally, LS led to constitutive downregulation of the PI3K/AKT/GSK3β signaling pathway. Collectively, LS inhibited cell proliferation and induced apoptosis through mitochondrial-mediated pathway by suppression of the PI3K/AKT/GSK3β signaling pathway in HeLa cells. [ABSTRACT FROM AUTHOR]

Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot encode proteins, and a better understanding of the complex interaction networks coordinated by ncRNAs will provide a theoretical basis for the development of therapeutics targeting the regulatory effects of ncRNAs. Platelets are produced upon the differentiation of hematopoietic stem cells into megakaryocytes, 1011 per day, and are renewed every 8-9 days. The process of thrombopoiesis is affected by multiple factors, in which ncRNAs also exert a significant regulatory role. This article reviewed the regulatory roles of ncRNAs, mainly microRNAs (miRNAs), circRNAs (circular RNAs), and long non-coding RNAs (lncRNAs), in thrombopoiesis in recent years as well as their roles in primary immune thrombocytopenia (ITP). [ABSTRACT FROM AUTHOR]

This study aimed to explore the biomechanical effects on adjacent vertebra of thoracolumbar Osteoporotic Vertebra Compression Fracture (OVCF) after Percutaneous Kyphoplasty (PKP) with intraoperative intradiscal cement leakage (ICL) by applying a Finite-Element Analysis. We collected pre- and post-operative computer tomography (CT) images of a 71-year-old female patient with single T12 OVCF, who underwent an intraoperative cement leakage into the T12–L1 disc. Three-dimensional finite element models of thoracolumbar spine (T10–L2) were built with the support of Materialise Interactive Medical Image Control System (MIMICS) and ABAQUS software. The stress on adjacent vertebrae and endplates under the uniform compressive pressure (0.3 MPa) and during different loading moments were analyzed. The three-dimensional finite element models reveal an asymmetrical distribution of von Mises stresses on the adjacent endplate unaffected by the surgical intervention. The maximum von Mises stress on adjacent vertebral bodies increased during different loading conditions, especially for lateral bending and rotation loading conditions, whereas the maximum von Mises stress on distal non-treated vertebrae decreased on anteflexion and backward extension loading conditions. Post-operative adjacent vertebra compression fractures after PKP with intraoperative intradiscal cement leakage (ICL) may be closely related to the biomechanical changes of adjacent vertebrae of thoracolumbar OVCF, and it may increase the risk of postoperative fracture. [ABSTRACT FROM AUTHOR]

Purpose: Due to its poor performance, clayey soil needs to be replaced to meet the requirements of engineering projects, which causes environmental damage and resource waste. To avoid the aforementioned problems, this study aims to develop an in situ microwave treatment for clayey soil, investigate the effect of microwaves in different soil regions, and evaluate the feasibility of microwave heating in situ treatment of wasted clayey soil. Method: A soil model was exposed to microwaves with a frequency of 2.45 GHz and a power of 1.25 kW for 72 h. The temperatures of various locations were monitored in several sections of the model. And the moisture content, macroscopic and microscopic properties, Vickers hardness, free swelling rate, and water stability were measured by a series of tests after irradiation. Results: The effects of soil heating, drying, and performance improvement under in situ microwave irradiation are regional. It can be summarized as follows. (1) The soil can be divided into three areas: the microwave heating area, the heat transfer area, and the unaffected area under microwave radiation. (2) Water intensely evaporates in the microwave heating area and migrates in the heat transfer area and unaffected area under microwave irradiation. (3) The soil mechanical properties and water stability are evidently improved in the microwave heating area, and the improvement effect is better than that of traditional heating. Conclusion: These findings make it possible to achieve environmental protection and resource conservation by the in situ microwave treatment of clayey soils. [ABSTRACT FROM AUTHOR]

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)