Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokα inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways.

was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

ObjectivesSurgeons face a substantial risk of infection because of the occupational exposure to blood-borne pathogens (BBPs) from patients undergoing high-risk orthopaedic procedures. This study aimed to determine the seroprevalence of four BBPs among patients undergoing joint arthroplasty in Shanghai, China. In addition, we evaluated the significance of pre-operative screening by calculating a cost-to-benefit ratio.MethodsA retrospective observational study of pre-operative screening for BBPs, including hepatitis B and C viruses (HBV and HCV), human immunodeficiency virus (HIV) and Treponema pallidum (TP), was conducted for sequential patients in the orthopaedic department of a large urban teaching hospital between 01 January 2009 and 30 May 2016. Medical records were analysed to verify the seroprevalence of these BBPs among the patients stratified by age, gender, local origin, type of surgery, history of previous transfusion and marital status.ResultsOf the subjects who underwent arthroplasty surgery in our institution, pre-operative screening tests were available for 96.1% (11 609 patients). The seroprevalence of HBV, HCV, HIV and TP was 5.47%, 0.45%, 0.08% and 3.6%, respectively. A total of 761 seropositive cases (68.4%) were previously undiagnosed. Pre-operative screening for HIV resulted in a low cost to benefit ratio, followed by HCV and HBV.ConclusionRoutine HCV and HIV screening prior to joint arthroplasty is not a cost-effective strategy. Considering the high rate of undiagnosed patients and the shortage of protective options, targeted pre-operative screening for HBV and syphilis should be considered for the protection of healthcare workers in China who have not been vaccinated.Cite this article: Bone Joint Res 2017;6:566–571.

Over the last decade, a plethora of tools have been developed for neuroscientists to interface with the brain. Implementing these tools requires precise removal of sections of the skull to access the brain. These delicate cranial microsurgical procedures need to be performed on sub-millimeter thick bone without damaging the underlying tissue and therefore, require significant training. Automating some of these procedures would not only enable more precise microsurgical operations, but also democratize use of advanced neurotechnologies. Here, we describe the 'Craniobot', a cranial microsurgery platform that combines automated skull surface profiling with a computer numerical controlled (CNC) milling machine to perform a variety of cranial microsurgical procedures in mice. The Craniobot utilizes a low force contact sensor to profile the skull surface and uses this information to perform micrometer-scale precise milling operations within minutes. We have used the Craniobot to drill pilot holes to anchor cranial implants, perform skull thinning, and open small to large craniotomies. The Craniobot is built using off-the-shelf components for under $1000 and is controlled using open-source CNC programming software.

A series of investigations were carried out including epidemiology, etiology and pathology on hemorrhagic pneumonia in Moschus sifanicus, which had prevailed in Xinglong Mountain National Nature Reserve District in Gansu province of China. The results indicated that the prevalence of this disease could be correlated with local humidity in Xinglong Mountain in Gansu province of China. The disease is caused by single infection of Pasteurella multocida or mix of P. multocida, Escherichia coli and Pseudomonas aeruginosa, and is a contagious disease. The pathological changes were mainly manifested in the vessel wall of bronchia and bronchiole appeared congested, bleeding, edemic with infiltration of inflammatory cells, mucosa of bronchiole degenerates, with the presence of necrosis and exfoliation, pulmonary alveolus generated suppuration, disaggregation and necrosis. It was concluded that the diseases are mainly caused by local bacteria and affected M. sifanicus finally die of hemorrhagic or purulent, necrotic pneumonia.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia‐Pacific countries. Arecoline‐induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase‐1 (TPST‐1) to enhance the migration ability of FBs. Moreover, by RNA‐Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline‐induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST‐1 induction. Finally, in human OSF specimens, TPST‐1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline‐induced tyrosine sulphation of CXCR4, which is regulated by TPST‐1, might be a potential mechanism that contributes to FB migration in OSF.