Shape Control of Carbon Nanoparticles via a Simple Anion-Directed Strategy for Precise Endoplasmic Reticulum-Targeted Imaging.

Herein, small-sized fluorescent carbon nanoparticles (CNs) with tunable shapes ranging from spheres to various rods with aspect ratios (ARs) of 1.00, 1.51, 1.89, and 2.85 are prepared using a simple anion-directed strategy for the first time. Based on comprehensive morphological and structural characteristics of CNs, along with theoretical calculations of density functional theory and molecular dynamics simulations, their shape-control mechanism is attributed to interionic interactions-induced self-assembly, followed by carbonization. The endoplasmic reticulum-targeting accuracy of CNs is gradually enhanced as their shape changes from spherical to higher-AR rods, accompanied by a Pearson's correlation coefficient up to 0.90. This work presents a facile approach to control the shape of CNs and reveals the relationship between the shape and organelle-targeting abilities of CNs, thereby providing a novel idea to synthesize CNs that serve as precise organelle-targeted fluorescent probes.

The lymphocyte-to-monocyte ratio predicts intracranial atherosclerotic stenosis plaque instability.

Background and purpose: Gadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability. Methods: Consecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability. Results: Fifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity). Conclusion: The LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.

PTBP1 is a Novel Poor Prognostic Factor for Glioma.

Objective: Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein, which plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. However, little was known about the correlation between PTBP1 and glioma and its prognostic significance in glioma patients. Our aim was to investigate the expression, functional role, and prognostic value of PTBP1 in glioma. Methods: We explored the expression of PTBP1 protein using immunohistochemistry in 150 adult malignant glioma tissues and 20 normal brain tissues and evaluated its association with clinicopathological parameters by chi-square test. Kaplan-Meier method was used to evaluate the prognostic effect of PTBP1 in glioma. Univariate/multivariate Cox analyses were used to identify independent prognostic factors. Transcriptional regulation network was constructed based on differentially expressed genes (DEGs) of PTBP1 from TCGA/CGGA database. GO and KEGG enrichment analyses were used to explore the function and pathways of DEGs. Results: Out of the 150 malignant glioma tissues (60 LGG and 90 GBMs) and 20 normal brain tissues in our cohort, PTBP1 protein was high expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of PTBP1 was significantly higher in GBMs (P < 0.001). More than half of GBMs (62/90, 68.9%) were PTBP1 high expression. Chi-square test showed that the expression of PTBP1 was correlated with patient age, WHO grade, Ki-67 index, and IDH status. High expression of PTBP1 was significantly associated with poor prognosis in glioma, and it was an independent risk factor in glioma patients. Furthermore, we shed light on the underlying mechanism of PTBP1 by constructing a miR-218-TCF3-PTBP1 transcriptional network in glioma. Conclusion: PTBP1 was high expressed in glioma, and it significantly correlated with poor prognosis, suggesting a potential therapeutic target for glioma, particularly for GBM.

MALAT1/miR-127-5p Regulates Osteopontin (OPN)-Mediated Proliferation of Human Chondrocytes Through PI3K/Akt Pathway.

Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Chondrocytes present in various types of cartilage and are responsible for the growth and maintenance of the tissue. Over-proliferation of human chondrocytes may contributes to OA pathological process. Previously, we revealed that miR-127-5p could inhibit the proliferation of human chondrocytes through osteopontin (OPN). In the present study, we used online tools to figure out several candidates lncRNAs which were potentially correlated with miR-127-5p. Through assessing the expression levels of the candidates lncRNAs, metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was chosen as a further research subject. MALAT1 knockdown significantly repressed human OA chondrocyte proliferation, as well as the protein levels of OPN, p-PI3K, and p-Akt in OA chondrocytes. As verified by luciferase assays, MALAT1 directly bound to miR-127-5p to inhibit miR-127-5p expression. Then we achieved miR-127-5p inhibition through miR-127-5p inhibitor transfection; the miR-127-5p inhibition could promote chondrocyte proliferation, as well as the protein levels of OPN, p-PI3K, and p-Akt; in addition, the MALAT1 knockdown partially reversed the promotive effect of miR-127-5p inhibition on chondrocyte proliferation, OPN and PI3K/Akt signaling-related protein levels. Taken together, MALAT1 could directly bind to miR-127-5p to inhibit its expression, so as to rescue OPN expression and promote chondrocyte proliferation through PI3K/Akt pathway. Targeting MALAT1 so as to rescue miR-127-5p expression in OA might help to inhibit chondrocyte proliferation through miR-127-5p-mediated OPN regulation and downstream PI3K/Akt pathway. J. Cell. Biochem. 119: 431-439, 2018. © 2017 Wiley Periodicals, Inc.

JNK pathway in osteoarthritis: pathological and therapeutic aspects.

CONTEXT: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway. OBJECTIVE: In this study, we have reviewed the recent updates on the association of JNK pathway with OA. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OA Results: JNK has been shown by scientific studies to be activated (phosphorylated) in OA that can play a key role in the cartilage destruction. Activation of JNK causes the phosphorylation of c-Jun that causes decreased proteoglycan synthesis and enhanced production of matrix metalloproteinase 13 (MMP-13). Overproduction of MMP-13 by chondrocytes plays a central role in cartilage degeneration in OA. Thus, targeting JNK pathway might be a promising therapeutic application for the prevention and treatment of OA. A number of JNK-inhibitors have been used in vitro and in vivo studies; however, not yet been translated into human use. CONCLUSIONS: This review study indicates that JNK pathway plays an important role in development and progression of OA, and targeting the JNK pathway might be a potential approach for the treatment of OA in future.

Effect of active arm swing to local dynamic stability during walking.

Arm swing is an essential component in regulating dynamic stability of the whole body during walking, while the contribution of active arm swing to local dynamic stability of different motion segments remains unclear. This study investigated the effects of arm swing under natural arm swing condition and active arm swing condition on local dynamic stability and gait variability of the trunk segments (C7 and T10 joint) and lower extremity joints (hip, knee and ankle joint). The local divergence exponents (λs) and mean standard deviation over strides (MeanSD) of 24 young healthy adults were calculated while they were walking on treadmill with two arm swing conditions at their preferred walking speed (PWS). We found that in medial-lateral direction, both λs and MeanSD values of the trunk segments (C7 and T10 joint) in active arm swing condition were significantly lower than those in natural arm swing condition (p<0.05), while no significant difference of λs or MeanSD in lower extremity joints (hip, knee and ankle joint) was found between two arm swing conditions (p>0.05, respectively). In anterior-posterior and vertical direction, neither λs nor MeanSD values of all body segments showed significant difference between two arm swing conditions (p>0.05, respectively). These findings indicate that active arm swing may help to improve the local dynamic stability of the trunk segments in medial-lateral direction.

Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: involvement of Nrf2/HO-1 pathway.

AIMS: Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death. METHODS AND RESULTS: T3CA protected HT22 cells against high-concentration-glutamate-induced cell death in time- and concentration-dependent manners and potently attenuated glutamate-induced intracellular reactive oxygen species (ROS) production as well as mitochondrial membrane-potential (ΔΨ) disruption. Besides, T3CA significantly induced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased its transcriptional activity, which were demonstrated by Western blotting, immunofluorescence, and antioxidant response element (ARE)-luciferase reporter gene assay. Further studies showed that T3CA potently up-regulated heme oxygenase-1 (HO-1), an endogenous antioxidative enzyme and a downstream effector of Nrf2, at both mRNA and protein levels. The neuroprotective effects of T3CA were partially reversed by brusatol, which reduced protein level of Nrf2, or by inhibiting HO-1 with siRNA or ZnPP-IX, a specific inhibitor of HO-1. CONCLUSIONS: Taken together, these results clearly demonstrate that T3CA protects neurons against OS-induced cell death partially through Nrf2/ARE/HO-1 signaling pathway, which further supports that T3CA might be a promising novel therapeutic agent for OS-associated diseases.

Study on low-phase-noise optoelectronic oscillator and high-sensitivity phase noise measurement system.

An analytic model for an injection-locked dual-loop optoelectronic oscillator (OEO) is proposed and verified by experiments in this paper. Based on this theoretical model, the effect of injection power on the single-sideband phase noise of the OEO is analyzed, and results suggest that moderate injection is one key factor for a balance between phase noise and spur for OEO. In order to measure superlow phase noise of OEOs, a cross-correlation measurement system based on the fiber delay line is built, in which high linear photodetector and low-phase-noise amplifier are used to improve systematic sensitivity. The cross-correlation measurement system is validated by experiments, and its noise floor for the X band is about -130 dBc/Hz at 1 kHz and -168 dBc/Hz at 10 kHz after a cross correlation of 200 times.

[Phytoplankton' s community structure and its relationships with environmental factors in an aquaculture lake, Datong Lake of China].

From December 2008 to October 2009, a seasonal investigation was conducted on the phytoplankton' s community structure and its relationships with environmental factors in Datong Lake. With the comparison of the historical data in 1960, the potential effects of intensive aquaculture on the aquatic environment were analyzed, aimed to provide theoretical support for the sustainable fishery of freshwater lakes. A total of 98 phytoplankton species belonging to 7 phyla and 54 genera were collected, among which, Peridinium bipes, Chroomonas acuta, Chlorella vulgaris, Crytomonas ovate, Cyclotella meneghiniana, Crytomonas erosa, Anabaena circinalis, Microcystis aeruginosa, and Anabaena azotica were the dominant species, and had obvious seasonal variations. The mean annual cell density of the phytoplankton was 1.84 x 10(6) cells x L(-1), being the highest in summer (16.4 x 10(6) cells x L(-1)) and ranged from 1.71 x 10(6) to 1.98 x 10(6) cells x L(-1) in the other three seasons. The values of the abundance index, Shannon index, and Pielou index of the phytoplankton community were 2.01-4.55, 1.26-2.69, and 0.69-1.27, respectively. Canonical correlation analysis (CCA) showed that water depth, water temperature, transparency, and water total phosphorus content, oxidation-reduction potential, and electrical conductivity were the main environmental factors affecting the phytoplankton community structure in the Lake.

[Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial].

BACKGROUND: Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics. METHODS AND DESIGN: Clinical information of patients with chronic ulcer of the lower extremities will be first collected in a large, multicenter, epidemiological survey. Concurrently, a large multicenter, randomized, parallel-group, prospective study will be launched based on evidence-based medical principles to evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration. The evaluated indexes will include the wound healing percentage for primary outcome, wound healing time, wound healing rate, time and rate of removal of necrotic tissue, and TCM syndromes for secondary outcomes and routine blood test, routine urine test, liver and kidney function, blood mercury content and finally urine mercury content for adverse events. DISCUSSION: In this trial, the authors will evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration in cases of chronic ulcer of the lower extremities for standardizing external therapy of TCM for treatment of this condition, and establishing the clinical assessment system for TCM. TRIAL REGISTRATION NUMBER: The research program was registered in the Chinese Clinical Trial Registry in both English and Chinese in June 2011. REGISTRATION NUMBER: ChiCTR-TRC-11001365.

Therapy and prognosis of intracranial invasive olfactory neuroblastoma.

OBJECTIVE: There is currently no consensus on a standardized treatment strategy for olfactory neuroblastoma (ONB), especially for intracranial invasion. This purpose of this study is to explore the appropriate treatment modality and prognostic factors of intracranial invasive ONB. STUDY DESIGN: Case series with chart review. SETTING: The study was conducted at the Sun Yat-sen Memorial Hospital and the Cancer Center of Sun Yat-sen University, China. SUBJECTS AND METHODS: Twenty-five cases of intracranial invasive ONB were collected and investigated using a retrospective review analysis from patients diagnosed between 1980 and 2005. RESULTS: The 1-, 3-, and 5-year overall survival rates for the group were 55%, 46%, and 31%, respectively. The subgroups who did not receive surgical treatment had worse survival rates than those who did receive treatment. In particular, patients who did not receive any therapy did not live past 1 year. In contrast, the group of patients treated by intranasal resection in combination with radiotherapy and/or chemotherapy showed a slightly better survival rate. It is important to note that the group of patients treated by craniofacial surgery combined with radiotherapy and/or chemotherapy had a markedly favorable prognosis, with 1-, 3-, and 5-year overall survival rates of up to 100%, 88%, and 66%, respectively. CONCLUSIONS: Craniofacial surgery in combination with radiotherapy and/or chemotherapy was an effective treatment for intracranial invasive ONB. In addition, it was found that age may not be an important prognostic factor for intracranial invasive ONB; however, the rate of intracalvarial invasion was found to be a potent marker for predicting the prognosis of patients.

The orally combined neuroprotective effects of sodium ferulate and borneol against transient global ischaemia in C57 BL/6J mice.

OBJECTIVES: This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice. METHODS: The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining). The blood-brain barrier permeability (Evans blue tracing), brain oedema and oxidative stress were assayed and histological sections were also immunostained for gliofibrillar acid protein (GFAP) expression. KEY FINDINGS: The ischaemia reperfused mice were associated with long-lasting spatial learning deficits in the absence of other behavioural impairments and with neurodegeneration in the hippocampal CA1 region. However, the histological injuries were significantly attenuated by oral co-administration of sodium ferulate and borneol. Furthermore, combined treatment with sodium ferulate and borneol resulted in a significant reduction in brain oedema, GFAP-positive cells, malonaldialdehyde levels and blood-brain barrier permeability, but an increase in superoxide dismutase activity. CONCLUSIONS: Borneol may have benefits for the neuroprotective effect of sodium ferulate against injury induced in the brain by ischaemia/reperfusion.

Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) carries a high mortality rate, with survivors commonly left with permanent neurological deficits. Mesenchymal stem cell (MSC) transplantation promotes functional recovery in experimental ICH, and treatment with hepatocyte growth factor (HGF) is beneficial in ischemic stroke. OBJECTIVE: We hypothesize that transplantation of MSCs with previous transduction of HGF has an additive effect in promoting neurological recovery through myelin and axonal regeneration. METHODS: HGF transduction to human umbilical cord-derived MSCs using lentiviral plasmid pWPI-HGF-GFP was prepared. One week after a collagenase-induced ICH, 80 male Sprague-Dawley rats were divided into 3 groups for stereotactic injection of phosphate-buffered saline (group I), MSC transplant (group II), and HGF-transduced MSC transplant (group III), respectively, into the left ventricle. The animals were assessed weekly for 5 weeks using the Rotarod motor function test, at which time they were killed for Luxol fast blue myelin staining and appropriate immunohistochemistry and Western blotting. RESULTS: Animals receiving transplanted HGF-transduced MSCs (group III) exhibited significantly better motor function recovery than animals treated with MSCs alone (group II), which in turn performed better than the phosphate-buffered saline controls at 2 weeks after transplantation. Luxol fast blue staining of myelin displayed significantly less demyelination and significantly higher reactivity in myelin basic protein and growth-associated protein-43 in immunohistochemistry and Western blotting and significantly reduced myelin-associated glycoprotein activity in group III animals. CONCLUSION: Animals transplanted with HGF-transduced MSCs 1 week after experimental ICH were shown to achieve a better neurological recovery. This improved neurological recovery from ICH is attributed to nerve fiber remyelination and axonal regeneration.