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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: 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.)

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.)

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.)

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.

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.

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]

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]

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]

Biosensors featuring single molecule detection present huge opportunities as well as challenges in food safety inspection, disease diagnosis, and environmental monitoring. Single‐molecule detection is largely lacking of high enough activity, precision molecule selectivity, and understanding in the exact operating mechanism. Single‐atom catalysts (SACs), especially those metals‐nitrogen‐carbon that mimic the natural metalloenzyme structure, and with well‐defined metal atom bond configurations, high level of molecular selectivity, and easy fabrication, endow single molecule detections with practical‐use feasibilities. The recent advances in single‐atom catalysts also present new pathways in the key mechanism understandings. In this short review, we will first visit the brief history and advantages of SACs that have been explored only recently for molecule‐scale biosensors, where they are analogous and also differentiated from those nanozymes and natural metalloenzymes. Their applications in electrochemical, photochemical, and photoelectrochemical sensors are then discussed comprehensively by focusing on the different molecule‐scale sensing modes in achieving local coordination‐modulated signal amplifications. Finally, we identify new opportunities and challenges faced by these SACs‐based single molecule detections in the further development of biosensors. [ABSTRACT FROM AUTHOR]

Rechargeable lithium-sulfur battery is considered to be one of the most promising candidates for the next-generation energy storage applications due to its high energy density, large theoretical specific capacity, low cost, and abundant sources. However, low conductivity of sulfur, shuttle effect, and volume expansion hindered its practical application. In this study, N,P co-doped hierarchical porous carbon has been fabricated from biomass fallen leaves through novel simple carbonization process with mild H3PO4 as an activator. By adjusting the mass ratio of H3PO4 and leaves, the porous carbon can be optimized to be tube-like morphology with a neatly arranged or monodispersed layout way. When serving as a sulfur host, the as-produced N,P dual-heteroatom doped porous carbon is favorable for advanced conductivity and binding polysulfides through physi-/chemisorption, so as to endow excellent electrochemical performance. An initial specific capacity of 1320 mAh·g−1 can be achieved and maintained above 1000 mAh·g−1 after 300 cycles at 0.1C. [ABSTRACT FROM AUTHOR]

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Background: For about 20 years we have been observing the development of three-dimensional (3D) printing. The aim of this study was to systematize the current knowledge on the use of 3D printing technology in neurosurgery and to attempt an outline the future paths of its development. Material and methods: The analysis was based on English-language literature from 2017-2021 indexed in the Mendeley and Scopus databases. Results: The application of 3D printing in neurosurgery concerns: 1) teaching students, 2) training of residents neurosurgeons, 3) individualized surgery planning, 4) dedicated cranial and spinal implants, 5) the future of 3D printing in neurosurgical implantology. There were 5 main neurosurgery subtopics in which 3D printing was used: "vascular neurosurgery" (31%), "skull, cranial neurosurgery" (22.4%), "neuro-oncology" (19.3%), "spine" (14.3%) and "others" (13%). The number of published articles has been steadily increasing by 11-33% annually. Conclusion: 3D printing has an enormous potential for clinical use and in the we will continue to observe its dynamic development. In neurosurgery 3D prints are currently most commonly used for didactic purposes as detailed anatomical models, for training residents and young surgeons and by specialists for the simulation of complex or innovative surgeries. The future of the use of additive 3D printing in neurosurgery lies in the biological 3D printing, the creation of artificial organs and the development of biological implants in tissue engineering. [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). What is the context? Platelets are produced from progenitor cells named megakaryocytes (MKs) differentiated from bone marrow-derived hematopoietic stem cells (HSCs). Thrombopoiesis refers to the process by which platelet-producing MKs release platelet granules into peripheral blood under the shear force of blood flow for further development and maturation. The process of megakaryocytopoiesis and thrombopoiesis is affected by multiple factors, wherein some ncRNAs also exert a significant regulatory role. miRNAs/lncRNAs play a promising role in t primary immune thrombocytopenia (ITP). What is new? This article reviewed the regulatory roles of ncRNAs, mainly microRNAs (miRNAs), circRNAs (circular RNAs), and long non-coding RNAs (lncRNAs), in thrombopoiesis. This article also reviewed the roles of ncRNAs in ITP. What is the impact? Changes in ncRNA expression are associated with changes in the production of MKs, thrombopoiesis, and platelet function, which allows a new understanding of the pathogenesis of many congenital or acquired platelet-related diseases. [ABSTRACT FROM AUTHOR]

Aiming at the problem that the model parameters of YOLOv4 algorithm are large and difficult to deploy in edge computing devices, a lightweight target detection algorithm (Light-YOLOv4) is proposed based on YOLOv4 algorithm. The algorithm uses the GhostNet structure to replace the backbone feature extraction network in YOLOv4 algorithm, and introduces the depthwise separable convolution to replace the vanilla convolution, which greatly reduces the parameters of the original network model. Light-YOLOv4 also replaces the ReLU activation function in the deep structure of GhostNet with the improved lightweight activation function H-MetaACON, which improves the detection accuracy when the amount of model parameters and calculation are basically unchanged. Finally, the coordinate attention module is added to the effective feature layer and the PANet upsampling module, so that the model captures the cross-channel information while capturing the direction and position awareness information to further improve the detection accuracy. The experimental results show that the detection accuracy of the optimized model is improved by 0.89% and the size of the model is reduced to 17.48% compared to the original YOLOv4 model. The Light-YOLOv4 model can effectively reduce the inference calculation of the original model while maintaining high detection accuracy, and significantly improve the detection speed of the model on devices with insufficient computing power. [ABSTRACT FROM AUTHOR]

Random forest, a popular ensemble approach in machine learning, has received much attention of researchers in different fields due to its excellent performance. Especially, in the study of classification, it is often used as an effective classifier. Considering that the accuracy and diversity of each base classifier are two main factors that affect the performance of random forest, this paper proposes a new rotation forest ensemble method to increase the diversity of each tree in the forest, which is based on feature extension and transformation. Also, a weighting vote for base classifiers is applied to integrate the final ensemble results instead of to average the accuracy of ensemble learners. In order to illustrate the effectiveness of the proposed algorithm, the experiments conduct with thirty benchmark classification datasets available from the UCI repository and two face recognition databases. Experimental results demonstrate that the proposed algorithm can achieve higher classification accuracy in most cases compared to the other ensemble classifiers. [ABSTRACT FROM AUTHOR]

Water transportation is an important part of comprehensive transportation and plays a critical role in a country's economic development. The world's cargo transportation is dominated by waterway transportation, and maritime transportation Systems (MTS) are the main part of the waterway transportation system. The flow of goods plays a key role in the economic development of the ports along the route. The sustainable development of maritime transportation, the maritime transportation economy and the environment have great practical significance. In this paper, the principle of the BP (back propagation) neural network is used to predict the freight transportation volume of China's waterways, and the genetic algorithm (GA) is used to optimize the BP neural network, so as to construct the GA-BPNN (back propagation neural network) prediction model. By collecting and processing the data of China's water cargo transport volume, the experimental results show that prediction accuracy is significantly improved, which proves the reliability of the method. The experimental methods and results can provide certain reference information for the optimization, upgrade, and more scientific management of sustainable MTS in China and internationally, provide key information for port cargo handling plans, help optimize port layout, and improve transportation capacity and efficiency. [ABSTRACT FROM AUTHOR]

Background: The treatment of infectious bone defects is a difficult problem to be solved in the clinic. In situ bone defect repair scaffolds with anti-infection and osteogenic abilities can effectively deal with infectious bone defects. In this study, an in situ polycaprolactone (PCL) scaffold containing ampicillin (Amp) and Mg microspheres was prepared by 3D printing technology. Results: Mg and Amp were evenly distributed in PCL scaffolds and could be released slowly to the surrounding defect sites with the degradation of scaffolds. In vitro experiments demonstrated that the PCL scaffold containing Mg and Amp (PCL@Mg/Amp) demonstrated good cell adhesion and proliferation. The osteogenic genes collagen I (COL-I) and Runx2 were upregulated in cells grown on the PCL@Mg/Amp scaffold. The PCL@Mg/Amp scaffold also demonstrated excellent antibacterial ability against E. coli and S. aureus. In vivo experiments showed that the PCL@Mg/Amp scaffold had the strongest ability to promote tibial defect repair in rats compared with the other groups of scaffolds. Conclusions: This kind of dual-function in situ bone repair scaffold with anti-infection and osteogenic abilities has good application prospects in the field of treating infectious bone defects. [ABSTRACT FROM AUTHOR]

The current study set out to elucidate the mechanism of miR-26b in OC cell proliferation and EMT via suppression of ERα. Initial findings illustrated that miR-26b was poorly expressed in OC tissues and cells. On the other hand, over-expression of miR-26b exerted a diminishing effect on SKOV3 cell proliferation, migration, invasion and EMT, whereas silencing of miR-26b conferred an enhancing effect on CAOV3 cell proliferation, migration, invasion and EMT. Subsequently, with help from the TargetScan database, a dual-luciferase reporter gene assay was carried out to verify the targeting relation between miR-26b and ERα, which revealed that miR-26b could negatively modulate ERα. Furthermore, the in vivo experimentation illustrated that over-expression of miR-26b led to down-regulation of ERα and suppression OC tumor growth and EMT. Meanwhile, silencing of ERα inhibited OC cell proliferation, migration, invasion and EMT. In conclusion, our findings indicated that miR-26b inhibited OC cell proliferation and EMT via negative-modulation of ERα. This investigation may offer potential strategy for OC treatment. [ABSTRACT FROM AUTHOR]

The PI3K/AKT pathway plays a central role in human cancers, aberrant activation of this pathway is associated with tumorigenesis, cancer progression and angiogenesis. Based on the importance of the PI3K/AKT pathway in malignancies, we developed a 4-aminoquinazoline derivative, ZDQ-0620, initially envisioned as a novel pan-PI3K inhibitor. This study aimed to evaluate the potential target of ZDQ-0620 and its anticancer effect in human colorectal carcinoma (CRC). PI3K-kinase activity test showed IC50 of ZDQ-0620 against PI3Ka was 0.5 nM; molecular docking, CETSA assay and western blotting was further performed to predict ZDQ-0620 was a PI3K/AKT pathway inhibitor by targeting PI3K. To identify the effect of ZDQ-0620 on CRC cells, Sulforhodamine B (SRB) assay, flow cytometry, and Cell morphology analysis were conducted. The results showed that ZDQ-0620 inhibited the proliferation, migration and invasion of CRC cells, induced apoptosis through G0/G1 cell cycle arrest and mitochondrial pathway. Additionally, ZDQ-0620 inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). In vivo , neovascularization of rat aortic ring and chick chorioallantoic membrane (CAM) induced by VEGF was diminished when treated with ZDQ-0620. These results indicate that ZDQ-0620 induce apoptosis and anti-angiogenesis via inhibits the PI3K/AKT pathway. We suggest that the great potential of ZDQ-0620 as an effective treatment candidate against CRC. [ABSTRACT FROM AUTHOR]

Determination of uric acid is very important for the clinical diagnosis of several diseases correlated with their variations in human serum. In this work, dual-emission arginine carbon dots (Arg-CDs) were synthesized for the determination of uric acid (UA). After optimization, the obtained Arg-CD was excited at 360 nm, which exhibited dual-emission fluorescence peaks at 445 nm and 514 nm, respectively. Because of the electrostatic interaction between the secondary amine group in UA and the carboxyl group on the Arg-CD, the formation of hydrogen bonds between the ketone/hydroxyl group in the UA molecule and the amino group on the surface of Arg-CD, the mixture could cause the fluorescent signal to be activated. Particularly, Arg-CD showed a good line relationship to UA between 330 and 630 µM (the concentration of uric acid in the serum for healthy people is 240–520 μM), and the lower detection limits are 7.14 µM. With the high selectivity and sensitivity to uric acid, Arg-CD could be applied in the UA determination of the human serum samples, whose accuracy rate was in the range of 98.5–101.5% and relative standard deviation (RSD) value was lower than 4%. And we also designed a miniaturized device for UA determination conveniently. [ABSTRACT FROM AUTHOR]

GLO:F2H7/01sep21:ctm2514-fig-0001.jpg PHOTO (COLOR): 1 DHW-221 is a PI3K/mTOR dual-target inhibitor and inhibits the PI3K/AKT/mTOR signaling pathway. Dual blocking of PI3K and mTOR signaling by DHW-221, a novel benzimidazole derivative, exerts antitumor activity in human non-small cell lung cancer (E, G) Western blot was also used to evaluate the effects of DHW-221 on PI3K/AKT/mTOR pathway-related proteins in non-small cell lung cancer (NSCLC) cells and tissues (n = 6). We previously designed and synthesized a novel benzimidazole compound, DHW-221.1 Here, we evaluated its anti-NSCLC activity as a PI3K/mTOR dual-target inhibitor and comprehensively described for the first time the mechanism underlying the PI3K/AKT/mTOR signaling pathway-mediated antitumor effects of DHW-221. [Extracted from the article]

The development of an effective scaffold for bone defect repair is an urgent clinical need. However, it is challenging to design a scaffold with efficient osteoinduction and antimicrobial activity for regeneration of bone defect. In this study, we successfully prepared a hydroxyapatite (HA) porous scaffold with a surface-specific binding of peptides during osteoinduction and antimicrobial activity using a three-dimensional (3D) printing technology. The HA binding domain (HABD) was introduced to the C-terminal of bone morphogenetic protein 2 mimetic peptide (BMP2-MP) and antimicrobial peptide of PSI10. The binding capability results showed that BMP2-MP and PSI10-containing HABD were firmly bound to the surface of HA scaffolds. After BMP2-MP and PSI10 were bound to the scaffold surface, no negative effect was observed on cell proliferation and adhesion. The gene expression and protein translation levels of type I collagen (COL-I), osteocalcin (OCN) and Runx2 have been significantly improved in the BMP2-MP/HABP group. The level of alkaline phosphatase significantly increased in the BMP2-MP/HABP group. The inhibition zone test against Staphylococcus aureus and Escherichia coli BL21 prove that the PSI10/HABP@HA scaffold has strong antibacterial ability than another group. These findings suggest that 3D-printed HA scaffolds with efficient osteoinduction and antimicrobial activity represent a promising biomaterial for bone defect reconstruction. [ABSTRACT FROM AUTHOR]

Objective: To siscuss the clinical significance of the early diagnosis of knee varus and knee osteoarthritis with the combination of negative position and non‐negative position and radiography. Methods: One hundred and eighty patients whose femorotibial angles <182° (genu varus positive) measured by X‐ray at the weight‐bearing position and femorotibial angles ≥182° (genu varus negative) measured by X‐ray at the non‐weight‐bearing position were selected as the sample group from those patients who received knee joint Magnetic resonance imaging (MRI) examination from July 2015 to July 2017. One hundred and eighty patients whose femorotibial angles ≥182° (genu varus negative) measured at both the weight‐bearing position and the non‐weight‐bearing position were selected as the control group. Femorotibial angles of both groups were respectively measured, to respectively compare and analyze the effect of non‐weight‐bearing false‐negative genu varus on the occurrence and severity of injury of medial meniscus and femorotibial articular cartilage. The two groups of patients had no previous history of knee surgery, and no lower limb fracture, inflammation, tumor, metabolic bone disease, or congenital disease. Results: The weight‐bearing tibiofemoral angles of the non‐weight‐bearing false‐negative genu varus group and the negative genu varus group (180.998° ± 0.589°) were lower than the non‐weight‐bearing tibiofemoral angles (182.501° ± 0.290°), and they were positively correlated (t = −15.048, P < 0.01). The non‐weight‐bearing knee varus medial meniscus incidence of false‐ negative group. Medial meniscus injury that occurred in the sample group were 86.7% (156/180) in the anterior horn, 91.7% (165/180) in the body, 88.3% (159/180) in the posterior horn. Medial meniscus injury that occurred in the control group were 46.7% (84 /180) in the anterior horn, 40.6.3% (73/180) in the body, 43.3% (78/180) in the posterior horn. The incidence of degenerative groups, the differences were statistically significant. The incidence and severity of injury were as follows: medial meniscus anterior horn (χ2 = 41.966, P = 0.000), body (χ2 = 104.94, P = 0.000), posterior horn (χ2 = 81.025, P = 0.000). The incidence and severity of medial meniscus injury in the non‐weight‐bearing knee varus false negative group was higher than in the control group. The non‐weight‐bearing knee varus false‐negative group medial tibiofemoral articular cartilage degeneration rate was 95.0% (171/180); in the control group, medial tibiofemoral articular cartilage degeneration was 65.1% (117/180). Two medial tibiofemoral articular cartilage degeneration incidence were statistically significant. The incidence and severity of injury were as follows: medial tibiofemoral articular cartilage (χ2 = 50.625, P = 0.000). The incidence and severity of medial tibiofemoral articular cartilage injury in the non‐weight‐bearing knee varus false negative group was higher than in the control group. Conclusion: The combined weight‐bearing position and non‐weight‐bearing position imaging examination for diagnosing the non‐weight‐bearing false‐negative genu varus patients at an early date is of significant importance to the early diagnosis and treatment of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

The CoS2/NiS2-RGO composite with excellent electrochemical performance is first used as an anode material for sodium-ion capacitors (SICs) and sodium-ion batteries (SIBs). CoS2/NiS2-RGO is prepared by one-step hydrothermal process. In half-cell tests, CoS2/NiS2-RGO exhibits a remarkably high reversible capacity of 473.7 mA h g−1 after 50 cycles at the specific current of 100 mA g−1. SICs show an impressive energy density of 139.1 W h kg−1 at the power density of 14,000 W kg−1, which has great advantages compare to the commercial lithium ion batteries. SIBs also show a good capacity of 50 mA h g−1 at a rate of 5 °C. The excellent electrochemical performance of CoS2/NiS2-RGO is mainly attributed to the heterostructure formed by CoS2 and NiS2, which effectively improves the electrical conductivity. On the other hand, there is a good synergistic effect between RGO and CoS2/NiS2. The large specific surface area of RGO makes CoS2/NiS2 disperse uniformly on the surface of RGO, preventing agglomeration and reducing particle size of CoS2/NiS2. In turn, CoS2/NiS2 acting on the surface layer of RGO hinders the secondary overlap and increases the electrical conductivity of RGO. The mixed bimetallic sulfide/RGO system is expected to promote the rapid development of sodium storage devices. [ABSTRACT FROM AUTHOR]

Objectives: Liver is the most important and functional organ in the body to metabolize and detoxify endogenous compounds and xenobiotics. The major goal of the present narrative review is to assess the hepatoprotective properties of hesperidin against a variety of natural and chemical hepatotoxins via different mechanisms. Evidence acquisition: Scientific databases such as Scopus, Medline, Web of Science and Google scholar were thoroughly searched, based on different keywords. Results: A variety of natural hepatotoxins such as lipopolysaccharide, concanavalin A and microcystins, and chemical hepatotoxins such as ethanol, acrylamide and carbon tetrachloride have been shown to damage hepatocytes as well as other liver cells. In addition to hepatocytes, ethanol can also damage liver hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. In this regard, the flavanone hesperidin, occur in the rind of citrus fruits, had been demonstrated to possess widespread pharmacological properties. Hesperidin exerts its hepatoprotective properties via different mechanisms including elevation in the activities of nuclear factor-like 2/antioxidant response element and heme oxygenase 1 as well as the levels of enzymatic and non-enzymatic antioxidants. Furthermore, reduction in the levels of high-mobility group box 1 protein, inhibitor of kappa B protein-alpha, matrix metalloproteinase-9 and C-reactive protein are some other important hesperidin-derived hepatoprotective mechanisms. Conclusion: Based on several research papers, it could be concluded that hesperidin is able to protect against liver damage from inflammation and/or oxidative stress-mediated natural and chemical toxins. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator‐activated receptor gamma (PPARγ) is a vital subtype of the PPAR family. The biological functions are complex and diverse. PPARγ plays a significant role in protecting the liver from inflammation, oxidation, fibrosis, fatty liver and tumours. Natural products are a promising pool for drug discovery, and enormous research effort has been invested in exploring the PPARγ‐activating potential of natural products. In this manuscript, we will review the research progress of PPARγ agonists from natural products in recent years and probe into the application potential and prospects of PPARγ natural agonists in the therapy of various liver diseases, including inflammation, hepatic fibrosis, non‐alcoholic fatty liver and liver cancer. [ABSTRACT FROM AUTHOR]

This article describes the design of an IQ impedance modulator radio front-end which is used to generate long range (LoRa) symbols with backscattering techniques, allowing building low-power devices that may be compatible with the current LoRa networks. It is shown that a linear frequency modulated (LFM) chirp can be generated by properly varying the phase of a reflected wave instead of directly varying its instantaneous frequency. The proposed device consists of two radio frequency (RF) transistors that generate a set of impedances by changing their gate bias, allowing reflecting their incident wave with predefined phase values. By joining these two reflected waves in quadrature, a new set of impedances is obtained whose phases vary 360°, on a constant Voltage Standing Wave Ratio (VSWR) circle. In order to validate the proposed design, several LoRa symbols were generated and successfully transmitted and decoded. Measurements of the bit error rate (BER) versus signal-to-noise ratio (SNR) were conducted and shown to be in accordance with other related work. Moreover, the impact of intentional perturbations added to the control bias voltages was analyzed and tests over-the-air (OTA) were performed for different indoor propagation scenarios. [ABSTRACT FROM AUTHOR]

In recent decades, biomedical research has focused on understanding the functionality of the human translated genome, which represents a minor part of all genetic information transcribed from the human genome. However, researchers have become aware of the importance of non-coding RNA species that constitute the vast majority of the transcriptome. In addition to their crucial role in tissue development and homeostasis, mounting evidence shows non-coding RNA to be deregulated and functionally contributing to the development and progression of different types of human disease including cancer both in adults and children. Small non-coding RNAs (i.e., microRNA) are in the vanguard of clinical research which revealed that RNA could be used as disease biomarkers or new therapeutic targets. Furthermore, many more expectations have been raised for long non-coding RNAs, by far the largest fraction of non-coding transcripts, and still fewer findings have been translated into clinical applications. In this review, we center on PVT1, a large and complex long non-coding RNA that usually confers oncogenic properties on different tumor types. We focus on the compilation of early advances in the field of pediatric tumors which often lags behind clinical improvements in adult tumors, and provide a rationale to continue studying PVT1 as a possible functional contributor to pediatric malignancies and as a potential prognostic marker or therapeutic target. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death worldwide, and no obvious decline in incidence and mortality has occurred in recent years. It is imperative to further investigate the mechanisms underlying tumor progression. Long non-coding RNAs have received considerable attention in recent years because of their major regulatory roles in gene expression. Among them, PVT1 is well-studied, and substantial evidence indicates that PVT1 plays critical roles in the onset and development of cancers. Normally, PVT1 acts as an oncogenic factor by promoting cancer cell proliferation, invasion, metastasis, and drug resistance. Herein, we summarize current knowledge regarding the regulatory effects of PVT1 in cancer progression, as well as the related underlying mechanisms, such as interaction with Myc, modulation of miRNAs, and regulation of gene transcription and protein expression. In extracellular fluid, PVT1 mainly promotes cancer initiation, and it normally enhances cellular cancer characteristics in the cytoplasm and cell nucleus. Regarding clinical applications, its role in drug resistance and its potential use as a diagnostic and prognostic marker have received increasing attention. We hope that this review will contribute to a better understanding of the regulatory role of PVT1 in cancer progression, paving the way for the development of PVT1-based therapeutic approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been reported to be associated with oncogenesis. However, the functional role of PVT1 in Burkitt lymphoma has not yet been addressed. The purpose of the present study was to investigate the effect of PVT1 knockdown by small interfering RNA (siRNA) on the proliferation of Burkitt lymphoma Raji cells and to explore its possible mechanism of action. An effective siRNA targeting PVT1 was screened and the corresponding short hairpin RNA (shRNA) was reconstructed into a lentiviral vector. Cell proliferation and cell cycle distribution were assessed by Cell Counting kit-8 assay and flow cytometry, respectively. Protein expression levels of c-Myc, cyclin-dependent kinase inhibitor1A (CDKN1A, P21) and cyclin E1 (CCNE1) were detected by western blotting. A polymerase chain reaction (PCR) array was used to analyse the expression of genes associated with the cell cycle. PVT1 knockdown markedly suppressed proliferation, and induced cell cycle arrest at the G0/G1 phase in Raji cells. Protein expression levels of c-Myc and CCNE1 were reduced, whereas P21 protein expression was markedly increased following downregulation of PVT1 in Raji cells. The cell cycle PCR array revealed that 54 genes were upregulated and 26 genes were downregulated in Raji cells following PVT1 knockdown. Reverse transcription-quantitative PCR demonstrated that cyclin G2 (CCNG2), CDKN1A, Retinoblastoma-like 2 (RBL2, p130), HUS1 checkpoint homolog, cyclin dependent kinase inhibitor 3 (CDKN3) and cyclin dependent kinase inhibitor 1B (CDKN1B) expression were upregulated, whereas the expression levels of CCNE1, cyclin D1 (CCND1) and cell division cycle 20 (CDC20) were downregulated in Raji cells with PVT1 knockdown. In conclusion, PVT1 knockdown may inhibit the proliferation of Raji cells by arresting cells in G0/G1 phase. Furthermore, inhibition of cell proliferation may be associated with a reduction inc-Myc expression and alterations in the expression levels of cell cycle-associated genes. [ABSTRACT FROM AUTHOR]

In this paper, directional modulation (DM) transmitters, designed for orthogonal frequency-division multiplexing (OFDM) wireless data transfer are proposed using time-modulated arrays. It is shown that by properly designing the switch controlling time sequences the proposed time-modulated OFDM DM systems exhibit promising features, such as 1) requires only one radio frequency chain, 2) the conventional efficient OFDM signal construction approach, i.e., by using inverse fast Fourier transform modules, can be adopted, 3) it is “DM synthesis-free,” meaning that there is no need to resynthesize the array excitation vectors for different secure communication directions, different modulation schemes, and different DM power efficiencies, and 4) the tradeoff between secrecy performance and power efficiency can be flexibly adjusted. [ABSTRACT FROM AUTHOR]

Long non‐coding RNAs (lncRNAs) are non‐protein coding transcripts containing more than 200 nucleotides. In the past, lncRNAs were considered as 'transcript noise' or 'pseudogenes' and were thus ignored. However, in recent years, lncRNAs have been proven to regulate gene expression at the epigenetic, transcriptional and translational level, and thereby influence cell proliferation, apoptosis, viability, immune response and oxidative stress. Furthermore, increasing evidence points to their involvement in different diseases, including cancer and heart diseases. Recently, lncRNAs were shown to be differentially expressed in ocular tissues and play a significant role in the pathogenesis of ophthalmological disorders such as glaucoma, corneal diseases, cataract, diabetic retinopathy, proliferative vitreoretinopathy and ocular tumors. In this review, we summarize the classification and mechanisms of known lncRNAs, while detailing their biological functions and roles in ocular diseases. Moreover, we provide a concise review of the clinical relevance of lncRNAs as novel, potential therapeutic targets in the treatment of eye diseases. [ABSTRACT FROM AUTHOR]