Wheel Running Improves Motor Function and Spinal Cord Plasticity in Mice With Genetic Absence of the Corticospinal Tract

Our previous studies showed that mutant mice with congenital absence of the corticospinal tract (CST) undergo spontaneous remodeling of motor networks to partially compensate for absent CST function. Here, we asked whether voluntary wheel running could further improve locomotor plasticity in CST-deficient mice. Adult mutant mice were randomly allocated to a “runners” group with free access to a wheel, or a “non-runners” group with no access to a wheel. In comparison with non-runners, there was a significant motor improvement including fine movement, grip strength, decreased footslip errors in runners after 8-week training, which was supported by the elevated amplitude of electromyography recording and increased neuromuscular junctions in the biceps. In runners, terminal ramifications of monoaminergic and rubrospinal descending axons were significantly increased in spinal segments after 12 weeks of exercise compared to non-runners. 5-ethynyl-2′-deoxyuridine (EDU) labeling showed that proliferating cells, 90% of which were Olig2-positive oligodendrocyte progenitors, were 4.8-fold more abundant in runners than in non-runners. In 8-week runners, RNAseq analysis of spinal samples identified 404 genes up-regulated and 398 genes down-regulated, and 69 differently expressed genes involved in signal transduction, among which the NF-κB, PI3K-Akt and cyclic AMP (cAMP) signaling were three top pathways. Twelve-week training induced a significant elevation of postsynaptic density protein 95 (PSD95), synaptophysin 38 and myelin basic protein (MBP), but not of brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and insulin like growth factor-1 (IGF-1). Thus, locomotor training activates multiple signaling pathways, contributes to neural plasticity and functional improvement, and might palliate locomotor deficits in patients

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of co-substrate on degradation of benzothiazole in MEC

Due to its persistence and bio-toxicity, benzothiazole (BTH) cannot be biodegraded efficiently. Recent work has shown that removal rates of biorefractory organics can be enhanced by the addition of co-substrates. In this work, ethanol, acetate, propionate and butyrate were added as co-substrates in order to promote the degradation of BTH in microbial electrolysis cell (MEC). By probing the changes in degradation rates of BTH in the presence of different co-substrates, it was observed that all the four co-substrates can enhance the BTH degradation in MEC, both the efficiency (E) and the rate (R). It was also found that acetate is more effective than others, which made the degradation efficiency of BTH up to 90% with acetate-C at 350 mg/L (measuring by the carbon content of co-substrate, the same below), within 6 h and the degradation rate of BTH arrived 0.001 2/(mg·h). The microbacteria in MEC have also been influenced by different co-substrates. This metabolism of the co-substrates enables the microbacteria on anode to generate ATP and thus grow to ensure the microbacteria activity. Therefore, this work showed that the addition of co-substrates such as acetate can be a novel and efficient approach for improving the elimination of BTH from wastewaters by MEC system

Antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection downregulates the levels of interferon-gamma/lambdas in porcine alveolar macrophages in vitro

Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2′, 5′-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-β1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies

Diffuse cavernous hemangioma of the skull misdiagnosed as skull metastasis in breast cancer patient: one case report and literature review

Abstract Background Primary intraosseous cavernous hemangiomas (PICHs) of the skull are extremely rare. To date, diffuse cranial hemangioma of skull has not been reported. In cancer patients, it is often misdiagnosed as metastasis. Case presentation Here, we presented a case of a 50-year-old female patient suffering from slightly headache who received breast cancer modified radical mastectomy in 2004, computed tomography and magnetic resonance imaging findings revealed abnormal lesions of diffuse skull which were misdiagnosed as skull metastasis, and the relevant literatures were also reviewed. Conclusions Diffuse cavernous hemangioma of the skull is exceedingly rare, and imaging data are not typical. The condition is often misdiagnosed, and pathological evaluation is necessary and important. In cases where the mass cannot be completely removed by surgery, radiotherapy could be beneficial

Expression and prognosis of GNG5 in lower-grade glioma using public database

Background: Glioma is the most common primary brain tumor, but its therapeutic effect is not very ideal up to now. The point of this study was to recognize the potential gene involved in lower-grade glioma (LGG) and to promote the treatment and prognosis for LGG patients. Method: During the investigation, we first studied the differential expression and the survival analysis of GNG5 in patients with glioma, LGG, and GBM, respectively. Then, independent prognostic analysis, the clinical relevance characteristics and the differential expressed genes (DEGs) were also evaluated. In addition, Metascape and GSEA analyses were carried out to achieve potential mechanism. Co-expression and immune infiltration analysis were finally conducted. Results: The results indicated that GNG5 as an independent prognostic indicator was negatively associated with the overall survival of LGG patients. Metascape and GSEA analyses showed that GNG5 may participate in complement and coagulation cascades pathway. The co-expression analysis was concluded that GNG5 was positively correlated with the following factors: C4B, PLAU, C1R, C1QC, C4A, SERPINA1, C1QB, CFI, C3. Conclusions: This study demonstrated that the highly expression of GNG5 in LGG may lead to poor prognosis. Besides, our research also revealed that GNG5 may be a promising immune-related biomarker for LGG patients

Amphiphilic Cationic Peptide-Coated PHA Nanosphere as an Efficient Vector for Multiple-Drug Delivery

Amphiphilic core–shell (ACS) nanoparticles are gaining increasing research interest for multi-drug delivery in cancer therapy. In this work, a new cationic peptide-coated PHA nanosphere was prepared by self-assembly of a hydrophobic core of biodegradable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a hydrophilic shell of fusion proteins of PHA granule-associated protein (PhaP) and cationic peptide RALA through a strong hydrophobic effect. The hydrophobic drug curcumin (Cur) was encapsulated in PHBHHx nanoparticles. The chemotherapy drug 5-fluorouracil (5-FU) was administered in the form of its metabolite oligomeric 5-fluorodeoxyuridine (FUdR). Fifteen consecutive FUdR (FUdR15S) were adsorbed on the surface of PHBHHx nanoparticles by electrostatic interaction with RALA to form Cur@PHBX-PR/FUdR15S. Such amphiphilic cationic nanospheres had 88.3% EE of Cur and the drug loading of Cur and FUdR were 7.8% and 12.1%. The dual-drug-loaded nanospheres showed a time-differential release of Cur and FUdR. In addition, Cur@PHBX-PR/FUdR15S exhibited excellent anticancer activity and played a vital role in promoting the synergistic effect of FUdR and Cur in gastric cancer cells. The exploration of antitumor mechanisms demonstrated that Cur improved the activity of apoptosis-related proteins and cancer cells sensitized to FUdR. This amphiphilic core–shell system can serve as a general platform for sequential delivery of multiple drugs to treat several cancer cells