HIF-1α protects nucleus pulposus cells from oxidative stress-induced mitochondrial impairment through PDK-1.

The pathogenesis of intervertebral disc degeneration (IVDD) involves complex signaling networks and various effector molecules, and our understanding of the pathogenesis of IVDD is limited. Hypoxia inducible factor-1α (HIF-1α) is closely related to IVDD, and there is excessive oxidative stress concurrent with IVDD. In this study, we found that HIF-1α could protect nucleus pulposus cells from excessive oxidative stress by reversing the imbalance between oxidants and antioxidants and thus mitigating the oxidative stress-induced mitochondrial impairment. With further exploration, we found that pyruvate dehydrogenase kinase 1 (PDK-1) was involved in the protective effect of HIF-1α on nucleus pulposus cells under oxidative stress. We suggested that HIF-1α could preserve the mitochondrial integrity and activate glycolysis in nucleus pulposus cells via PDK-1, and the addition of DCA, a PDK-1 inhibitor, could blunt the protective effect of HIF-1α. In addition, the HIF-1α/PDK-1 regulatory axis was also confirmed in vivo through HIF-1α knockout mice model. Therefore, we propose that HIF-1α protects nucleus pulposus cells from excessive oxidative stress by maintaining the mitochondrial integrity and glycolysis via PDK-1, thus enriching the insight into the protective mechanism of HIF-1α against IVDD, and providing a novel therapeutic target for the treatment of IVDD.

Automatic prediction of non-iodine-avid status in lung metastases for radioactive I131 treatment in differentiated thyroid cancer patients.

Objectives: The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI). Methods: Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter. Results: The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment. Conclusion: This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.

Photochemical Strategies toward Precision Targeting against Multidrug-Resistant Bacterial Infections.

Infectious diseases pose a serious threat and a substantial economic burden on global human and public health security, especially with the frequent emergence of multidrug-resistant (MDR) bacteria in clinical settings. In response to this urgent need, various photobased anti-infectious therapies have been reported lately. This Review explores and discusses several photochemical targeted antibacterial therapeutic strategies for addressing bacterial infections regardless of their antibiotic susceptibility. In contrast to conventional photobased therapies, these approaches facilitate precise targeting of pathogenic bacteria and/or infectious microenvironments, effectively minimizing toxicity to mammalian cells and surrounding healthy tissues. The highlighted therapies include photodynamic therapy, photocatalytic therapy, photothermal therapy, endogenous pigments-based photobleaching therapy, and polyphenols-based photo-oxidation therapy. This comprehensive exploration aims to offer updated information to facilitate the development of effective, convenient, safe, and alternative strategies to counter the growing threat of MDR bacteria in the future.

IDG-SW3 Cell Culture in a Three-Dimensional Extracellular Matrix.

Osteocytes are considered to be nonproliferative cells that are terminally differentiated from osteoblasts. Osteoblasts embedded in the bone extracellular matrix (osteoid) express the Pdpn gene to form cellular dendrites and transform into preosteocytes. Later, preosteocytes express the Dmp1 gene to promote matrix mineralization and thereby transform into mature osteocytes.This process is called osteocytogenesis. IDG-SW3 is a well-known cell line for in vitro studies of osteocytogenesis. Many previous methods have used collagen I as the main or the only component of the culturing matrix. However, in addition to collagen I, the osteoid also contains a ground substance, which is an important component in promoting cellular growth, adhesion, and migration. In addition, the matrix substance is transparent, which increases the transparency of the collagen I-formed gel and, thus, aids the exploration of dendrite formation through imaging techniques. Thus, this paper details a protocol to establish a 3D gel using an extracellular matrix along with collagen I for IDG-SW3 survival. In this work, dendrite formation and gene expression were analyzed during osteocytogenesis. After 7 days of osteogenic culture, an extensive dendrite network was clearly observed under a fluorescence confocal microscope. Real-time PCR showed that the mRNA levels of Pdpn and Dmp1 continually increased for 3 weeks. At week 4, the stereomicroscope revealed an opaque gel filled with mineral particles, consistent with the X-ray fluorescence (XRF) assay. These results indicate that this culture matrix successfully facilitates the transition from osteoblasts to mature osteocytes.

Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.

Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.

Urchin-like ceria nanoparticles for enhanced gene therapy of osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease in the world. Gene therapy based on delivering microRNAs (miRNAs) into cells has potential for the treatment of OA. However, the effects of miRNAs are limited by the poor cellular uptake and stability. Here, we first identify a type of microRNA-224-5p (miR-224-5p) from clinical samples of patients with OA that can protect articular cartilage from degeneration and further synthesize urchin-like ceria nanoparticles (NPs) that can load miR-224-5p for enhanced gene therapy of OA. Compared with traditional sphere ceria NPs, the thorns of urchin-like ceria NPs can efficiently promote the transfection of miR-224-5p. In addition, urchin-like ceria NPs have excellent performance of scavenging reactive oxygen species (ROS), which can regulate the microenvironment of OA to further improve the gene treatment of OA. The combination of urchin-like ceria NPs and miR-224-5p not only exhibits favorable curative effect for OA but also provides a promising paradigm for translational medicine.

MicroRNA-224-5p nanoparticles balance homeostasis via inhibiting cartilage degeneration and synovial inflammation for synergistic alleviation of osteoarthritis.

MicroRNAs play a crucial role in regulating cartilage extracellular matrix (ECM) metabolism and are being explored as potential therapeutic targets for osteoarthritis (OA). The present study indicated that microRNA-224-5p (miR-224-5p) could balance the homeostasis of OA via regulating cartilage degradation and synovium inflammatory simultaneously. Multifunctional polyamidoamine dendrimer with amino acids used as efficient vector to deliver miR-224-5p. The vector could condense miR-224-5p into transfected nanoparticles, which showed higher cellular uptake and transfection efficiency compared to lipofectamine 3000, and also protected miR-224-5p from RNase degradation. After treatment with the nanoparticles, the chondrocytes showed an increase in autophagy rate and ECM anabolic components, as evidenced by the upregulation of autophagy-related proteins and OA-related anabolic mediators. This led to a corresponding inhibition of cell apoptosis and ECM catabolic proteases, ultimately resulting in the alleviation of ECM degradation. In addition, miR-224-5p also inhibited human umbilical vein endothelial cells angiogenesis and fibroblast-like synoviocytes inflammatory hyperplasia. Integrating the above synergistic effects of miR-224-5p in regulating homeostasis, intra-articular injection of nanoparticles performed outstanding therapeutic effect by reducing articular space width narrowing, osteophyte formation, subchondral bone sclerosis and inhibiting synovial hypertrophy and proliferation in the established mouse OA model. The present study provides a new therapy target and an efficient intra-articular delivery method for improving OA therapy. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is the most prevalent joint disease worldwide. Gene therapy, which involves delivering microRNAs, has the potential to treat OA. In this study, we demonstrated that miR-224-5p can simultaneously regulate cartilage degradation and synovium inflammation, thereby restoring homeostasis in OA gene therapy. Moreover, compared to traditional transfection reagents such as lipofectamine 3000, G5-AHP showed better efficacy in both microRNA transfection and protection against degradation due to its specific surface structure. In summary, G5-AHP/miR-224-5p was developed to meet the clinical needs of OA patients and the high requirement of gene transfection efficiency, providing a promising paradigm for the future application and development of gene therapy.

Case Report: Long-term survival of a patient with advanced rectal cancer and multiple pelvic recurrences after seven surgeries.

Background: Rectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration. Case summary: A 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis. Conclusions: Patients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

Ultrasonic features of superficial angiomyxoma in the scrotum: A case image.

Superficial angiomyxoma in the scrotum is a well-circumscribed, ovoid-shaped, heterogeneously echogenic mass in the ultrasonography. On Doppler ultrasonography, vascular flow signals are visible in and around the mass(M).

Heterogeneity of Red Blood Cell Deformability Caused by Lipopolysaccharide based on a Microfluidic Chip.

INTRODUCTION: Alterations in red blood cell deformability (RBC-df) provide important information for the diagnosis of various diseases. AIM: We evaluated individual differences of lipopolysaccharide (LPS)-induced oxidative damage of RBC-df and analyzed the correlation between RBC-df and biochemical parameters. METHODS: A microfluidic chip was developed to detect inter-individual variability of different concentrations of LPS-induced oxidative damage of RBC-df in 9 healthy volunteers. The relationships between various biochemical indicators (Na+-K+-ATPase activity, lipid peroxide (LPO) content, glutathione peroxidase (GSH-PX) activity, catalase (CAT) activity, superoxide dismutase (SOD) activity, adenosine triphosphate (ATP) content, and hemoglobin (HB) content) and RBCsdf were investigated. RESULTS: The obvious inter-individual variability of LPS-induced oxidative damage of RBC-df was revealed. The Na+-K+-ATPase activity, LPO content, GSH-PX activity, and CAT activity of RBCs showed significant correlations with RBC-df (P < 0.05). CONCLUSION: Oxidative damage and energy metabolism are the critical factors of RBC-df impairment induced by LPS, and the individual dependence on RBC-df is an important indicator for the treatment of infection-associated sepsis since antibiotics can kill pathogenic bacteria, which results in the release of LPS from the cell wall.

CircStrn3 targeting microRNA-9-5p is involved in the regulation of cartilage degeneration and subchondral bone remodelling in osteoarthritis.

AIMS: Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. METHODS: Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. RESULTS: Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. CONCLUSION: Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA.Cite this article: Bone Joint Res 2023;12(1):33-45.

Sensitive detection of microRNAs using polyadenine-mediated fluorescent spherical nucleic acids and a microfluidic electrokinetic signal amplification chip.

The identification of tumor-related microRNAs (miRNAs) exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications. Therefore, we developed a sensitive and efficient biosensor using polyadenine (polyA)-mediated fluorescent spherical nucleic acid (FSNA) for miRNA analysis based on strand displacement reactions on gold nanoparticle (AuNP) surfaces and electrokinetic signal amplification (ESA) on a microfluidic chip. In this FSNA, polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au. The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA, resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer. Reporter DNA was replaced in the presence of target miRNA, leading to the recovery of reporter-DNA fluorescence. Subsequently, reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA. Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM. This method could also be used to detect miRNA-21 in human serum and urine samples, with recoveries of 104.0%-113.3% and 104.9%-108.0%, respectively. Furthermore, we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs (miRNA-21, miRNA-141, and miRNA-375), which increased the detection efficiency. Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.

Label-free and highly sensitive detection of CRP based on the combination of nicking endonuclease-assisted signal amplification and capillary electrophoresis-UV assay.

Elevated C-reactive protein (CRP) levels are linked with bacterial infection, local inflammation in osteoarthritis and the increased risk of developing cardiovascular disease. Here, a sensitive and label-free CRP assay is developed by combining cyclic enzymatic signal amplification and capillary electrophoresis (CE) with UV detection. This assay is constructed of base pairing and target recognition. Thereinto, nicking endonuclease (NEase) can recognize the specific nucleotide sequences in double-stranded DNA (dsDNA), which is formed by a CRP aptamer and its complementary DNA (cDNA). Sequentially, NEase cleaves only cDNA to produce signal DNAs. Therefore, a large number of signal DNAs are generated through continuous enzyme cleavage. In the presence of CRP, the aptamer recognizes and binds to CRP with high affinity and selectivity, which results in a decrease in signal DNAs, and thus the UV absorption value of CE significantly decreases, too. A wide linear range was obtained between 0.0125 and 15 µg mL-1 (0.11-130.5 nM) in 1% human serum with a detection limit of 4 ng mL-1 (35 pM). Additionally, the proposed method is universal and can be applied to analyze other similar substances by altering the matched aptamer.

Evaluation of mining capacity of mines using the combination weighting approach: A case study in Shenmu Mining Area in Shaanxi Province, China.

Aiming at the low mining rate in mines, Xingelao, Dabianyao, and Dongliang Coal Mines in Shenmu Mining Area, Shaanxi Province, China were taken as research objects. Based on this, this study constructed an evaluation index system for the mining capacity of the mines from the perspectives of geological factors, mechanical equipment, humans, and mining design. Moreover, the factors influencing the mining capacity of the mines were evaluated using a combination weighting approach based on an improved analytic hierarchy process and an entropy weight method. A standard cloud was generated based on the mapping standards of each index and a comprehensive cloud was obtained according to comprehensive weight and a backward cloud algorithm. Finally, by combining the comprehensive cloud with local and overall scores of the mines, the mining capacities of the mines were evaluated. The research results demonstrate that the key factor restricting the mining capacity of the mines is the geological environment and five major third-grade indexes affecting mining capacity are igneous rock intrusion, collapse column, scouring zone of the ancient river bed, mechanization level and coal pillar width. In addition, the corresponding suggestions and measures were put forward according to the main factors influencing the mining rate of the mines. In accordance with the weights and scores of each index, the overall scores of the mines were calculated. Dongliang, Dabianyao, and Xingelao Coal Mines were ranked in order based on scores. The research results provide a theoretical basis for improving the mining capacity of the mines under similar geological conditions.

Application of nomograms to predict overall and cancer-specific survival in patients with chordoma.

BACKGROUND: The survival prediction of patients with chordoma is difficult to make due to the rarity of this oncologic disease. Our objective was to apply a nomogram to predict survival outcomes in individuals with chordoma of the skull base, vertebral column, and pelvis. METHODS: A total of 558 patients with chordoma between 1973 and 2014 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors in patients with chordoma were identified via univariate and multivariate Cox analysis. Then these prognostic factors were incorporated into a nomogram to predict 3- and 5-year overall survival and cancer-specific survival rates. Internal and external data were used to validate the nomograms. Concordance indices (C-indices) were used to estimate the accuracy of this nomogram system. RESULTS: A total of 558 patients were randomly assigned into a training cohort (n = 372) and a validation cohort (n = 186). Age, surgical stage, tumor size, histology, primary site, and use of surgery were identified as independent prognostic factors via univariate and multivariate Cox analysis (all p < 0.05) and further included to establish the nomogram. The C-indices for overall survival and cancer-specific survival prediction of the training cohort were 0.775 (95% confidence interval, 0.770-0.779) and 0.756 (95% confidence interval, 0.749 -0.762). The calibration plots both showed an excellent consistency between actual survival and nomogram prediction. CONCLUSION: Nomograms were constructed to predict overall survival and cancer-specific survival for patients with chordoma of the skull base, vertebral column, and pelvis. The nomogram could help surgeons to identify high risk of mortality and evaluate prognosis in patients with chordoma.

Diffusion Tensor Magnetic Resonance Imaging in Chronic Spinal Cord Compression.

Chronic spinal cord compression is the most common cause of spinal cord impairment in patients with nontraumatic spinal cord damage. Conventional magnetic resonance imaging (MRI) plays an important role in both confirming the diagnosis and evaluating the degree of compression. However, the anatomical detail provided by conventional MRI is not sufficient to accurately estimate neuronal damage and/or assess the possibility of neuronal recovery in chronic spinal cord compression patients. In contrast, diffusion tensor imaging (DTI) can provide quantitative results according to the detection of water molecule diffusion in tissues. In the present study, we develop a methodological framework to illustrate the application of DTI in chronic spinal cord compression disease. DTI fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and eigenvector values are useful for visualizing microstructural pathological changes in the spinal cord. Decreased FA and increases in ADCs and eigenvector values were observed in chronic spinal cord compression patients compared to healthy controls. DTI could help surgeons understand spinal cord injury severity and provide important information regarding prognosis and neural functional recovery. In conclusion, this protocol provides a sensitive, detailed, and noninvasive tool to evaluate spinal cord compression.

Time course of diffusion tensor imaging metrics in the chronic spinal cord compression rat model.

BACKGROUND: Diffusion tensor imaging (DTI) provides information about water molecule diffusion in spinal cord. PURPOSE: This study was aimed to investigate DTI changes in the different stages of compressive spinal cord induced by water-absorbing material implantation. MATERIAL AND METHODS: The spinal cord compression was administered over the fourth cervical vertebral level in rat. Rat models were divided into five subgroups according to compression stages: sham group, group A: three-day compression rat models; group B: 12-day compression rat models; group C: 20-day compression rat models; group D: 60-day compression rat models. DTI including fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the compressive spinal cord were collected. The relationship between the Basso, Beattie, and Bresnahan (BBB) scores and DTI metrics was further explored. RESULTS: Compared with the sham group, BBB scoring of rat model showed a decreased tendency from group A ( P < 0.05) to group B ( P < 0.05). Then the motor function of rat model hindlimbs was recovered in some degree from group C ( P < 0.05) to group D ( P < 0.05) but had significant motor defects when compared with the normal level ( P < 0.05). The DTI metrics results revealed that chronic spinal cord compression resulted in lower FA value and higher ADC value at the compressive spinal cord level assessed at all four time-points ( P < 0.05). DTI metrics also showed a close correlation with motor function ( P < 0.05). CONCLUSION: DTI is an optimal pre-clinical imaging tool to reflect locomotor performance and pathological status of compressive spinal cord epicenter in chronic spinal cord compression rat model.

Nomogram application to predict overall and cancer-specific survival in osteosarcoma.

PURPOSE: A prognostic nomogram was applied to predict survival in osteosarcoma patients. PATIENTS AND METHODS: Data collected from 2,195 osteosarcoma patients in the Surveillance, Epidemiology, and End Results (SEER) database between 1983 and 2014 were analyzed. Independent prognostic factors were identified via univariate and multivariate Cox analyses. These were incorporated into a nomogram to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Internal and external data were used for validation. Concordance indices (C-indices) were used to estimate nomogram accuracy. RESULTS: Patients were randomly assigned into a training cohort (n=1,098) or validation cohort (n=1,097). Age at diagnosis, tumor site, histology, tumor size, tumor stage, use of surgery, and tumor grade were identified as independent prognostic factors via univariate and multivariate Cox analyses (all P<0.05) and then included in the prognostic nomogram. C-indices for OS and CSS prediction in the training cohort were 0.763 (95% CI 0.761-0.764) and 0.764 (95% CI 0.762-0.765), respectively. C-indices for OS and CSS prediction in the external validation cohort were 0.739 (95% CI 0.737-0.740) and 0.740 (95% CI, 0.738-0.741), respectively. Calibration plots revealed excellent consistency between actual survival and nomogram prediction. CONCLUSION: Nomograms were constructed to predict OS and CSS for osteosarcoma patients in the SEER database. They provide accurate and individualized survival prediction.

Nickel-Catalyzed Cyanation of Unactivated Alkyl Chlorides or Bromides with Zn(CN)2.

A nickel-catalyzed cyanation of unactivated secondary alkyl chlorides or bromides using less toxic Zn(CN)2 as the cyanide source has been developed. The reaction features the use of air-stable and inexpensive NiCl2·6H2O or Ni(acac)2 as the precatalysts and offers an efficient synthesis of a broad range of alkyl nitriles. Cyanation of primary alkyl chlorides or bromides was also achieved by reaction with Zn(CN)2 in the presence of n-Bu4NCl without the need of nickel catalyst.

Identification of key target genes and biological pathways in multiple sclerosis brains using microarray data obtained from the Gene Expression Omnibus database.

OBJECTIVE: The purpose of this study was to investigate critical genes in multiple sclerosis (MS) using microarray data from brain tissue in MS. MATERIALS: The expression profile data set of MS (GSE38010) downloaded from the Gene Expression Omnibus database contained gene information from five plaque tissues from MS brains and two white matter tissues from healthy controls. An R package was applied to process these raw chip data. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network analysis were performed to investigate interactions between differentially expressed genes (DEGs) in MS brain tissues. RESULTS: This study identified a total of 1065 DEGs, including 530 up-regulated genes and 535 down-regulated genes, in MS brain tissue samples compared to those in normal white matter tissue samples. GO and KEGG pathway enrichment analyses showed that the up-regulated DEGs were mainly related to neuron development, neuron projection morphogenesis and neuron differentiation. Furthermore, the down-regulated DEGs were largely related to axon ensheathment, ensheathment of neurons and nervous system development. Seven key genes were found as hub genes in the maintenance of the PPI network. CONCLUSION: Several key target genes and their GO and KEGG pathway enrichment identified in the present study may serve as feasible targets for MS therapies.