Altered static and dynamic voxel-mirrored homotopic connectivity in subacute stroke patients: a resting-state fMRI study

Sixty-four subacute stroke patients and 55 age-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging scan using an echo-planar imaging sequence and high-resolution sagittal T1-weighted images using a three-dimensional magnetization-prepared rapid gradient echo sequence. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) was computed, respectively. The relationships between the clinical measures, including National Institutes of Health Stroke Scale (NIHSS), illness duration, Fugl-Meyer assessment for upper and lower extremities (FMA-total) and size of lesion volume, and the static/ dynamic VMHC variability alterations in stroke patients were calculated. The stroke patients showed significantly increased static VMHC in the corpus callosum, middle occipital gyrus and inferior parietal gyrus, and decreased static VMHC in the inferior temporal gyrus and precentral gyrus (PreCG) compared with those of HCs. For dynamic VMHC variability, increased dynamic VMHC variability in the inferior temporal gyrus and PreCG was detected in stroke patients relative to that in HCs. Correlation analysis exhibited that significant negative correlations were shown between the FMA scores and dynamic VMHC variability in PreCG. The present study suggests that combined static and dynamic VMHC could be helpful to evaluate the motor function of stroke patients and understand the intrinsic differences of inter-hemispheric coordination after stroke.

     

An Inherently Bifunctional Subset of Foxp3+ T Helper Cells Is Controlled by the Transcription Factor Eos

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Aldehyde dehydrogenase 1 expression correlated with malignant potential of oral lichen planus

Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral squamous cell carcinoma (OSCC). The objective of this study was to determine protein expression of cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) in a series of patients with OLP and evaluate the correlation between ALDH1 expression and the risk of progression to OSCC. In a retrospective study, ALDH1 expression was determined using immunohistochemistry in samples from 101 patients with OLP who received a mean follow-up of 5 years, including 89 patients with untransformed OLP that did not develop into OSCC and 12 patients with malignant transformed OLP that had developed into OSCC. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that ALDH1 expression was observed in 27 (30.3%) of 89 cases of untransformed OLP and in 8 (66.7%) of 12 cases of transformed OLP (P = .021). Aldehyde dehydrogenase 1 was not expressed in normal oral mucosa, but it overexpressed in the 6 cases (100%) of OSCC. Multivariate analysis revealed that ALDH1 expression was significantly associated with a 6.71-fold (95% confidence interval, 1.64-27.42; P = .008) increased risk of malignant transformation. Collectively, ALDH1 expression was significantly associated with malignant transformation in a large series of patients with OLP. Our findings suggested that ALDH1 expression may identify a subgroup of a higher risk of malignant transformation of OLP.     

Higher Dosage of HIFU Treatment May Lead to Higher and Longer Efficacy for Moderate to Severe Perennial Allergic Rhinitis

Objectives: This study was to compare the efficacies and side effects of high intensity focused ultrasound (HIFU) treatment for perennial allergic rhinitis (PAR) with regular and increased dosage.Study design: A prospectively assembled cohort was retrospectively analyzed through visual analogue scale (VAS).Methods: Regular dosage of HIFU treatment was applied to 56 PAR patients in group A. An increased dosage as twice as the regular one was applied to 48 patients in group B. Nasal obstruction, sneezing, rhinorrhea and rhinocnesmus, which were recognized as the four main symptoms of allergic rhinitis (AR), were evaluated before treatment, 3 months after treatment, and 1 year after treatment. The satisfaction of patients was also evaluated at 1 year postoperatively. Biopsy of the inferior turbinate and morphometric analysis were applied to 11 patients in group A and 10 in group B before HIFU treatment and 3 months after treatment.Results: Comparing the AR symptoms before treatment, There is no statistical difference observed between group A and B (p>0.05). The four main symptoms at 3 months and 1 year after treatment were all significantly improved (p<0.01) in both group A and B. The VAS scores of AR symptoms in Group B were lower than those in Group A at the same stage after treatment, especially at 1 year after treatment (p<0.05). Comparing the results at 3 months and 1 year after treatment, a tendency of recurrence of these symptoms was observed statistically in group A (p<0.05), but not in group B (p>0.05). More cases of nasal dryness and perirhinal swelling were found in group B than those in group A (p<0.05), while all side effects were mild and temporary. Patients in group B were more satisfied than those in group A (p=0.0866 >0.05), though not statistically significant. More reduction of the eosinophils, other inflammatory cells, and the submucosal glands was observed after HIFU treatment in group B than that in group A (p<0.05).Conclusions: A proper increment of HIFU dosage may be recommended to meet the needs of more improvement of AR symptoms and less recurrence.     

Lentivirus-based RNA Silencing of Nemo-like Kinase (NLK) Inhibits the CAL 27 Human Adenosquamos Carcinoma Cells Proliferation and Blocks G0/G1 Phase to S Phase

Background: The Nemo-like kinase (NLK) is a serine/threonine-protein kinase that involved in a number of signaling pathways regulating cell fate. Variation of NLK has been shown to be associated with the risk of cancer. However, the function of NLK in oral adenosquamous carcinoma cells line CAL-27 is unknown.Methods: In this study, we evaluated the function of NLK in CAL-27 cells by using lentivirus-mediated RNA silence. The targeted gene expression, cell proliferation and cell cycle are investigated by RT-PCR, western-blot, MTT method, colony forming assay and flow cytometry analysis respectively.Results: After NLK silencing, the number of colonies was significantly reduced (54±5 colonies/well compared with 262±18 colonies/well in non-infected or 226±4 colonies/well in negative control group (sequence not related to NLK sequence with mismatched bases). Using crystal violet staining, we also found that the cell number per colony was dramatically reduced. The RNA silencing of NLK blocks the G0/G1 phase to S phase progression during the cell cycle.Conclusions: These results suggest that NLK silencing by lentivirus-mediated RNA interference would be a potential therapeutic method to control oral squamous carcinoma growth.     

Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects

Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety. Herein, we designed and synthesized three weak-acid modified paclitaxel (PTX) derivatives with a one-step reaction for the remote loading of liposomal formulations. By comparison, PTX-succinic acid liposomes (PTX-SA LPs) exhibited the highest encapsulation efficiency (97.2 ± 1.8%) and drug loading (8.84 ± 0.16%); meanwhile, there was almost no change in their particle size or zeta potential within one month. Furthermore, compared with Taxol®, the PTX-SA LPs showed a 4.35-fold prolonged half-time, enhanced tumor accumulation, and an increased maximum tolerated dose (MTD) of more than 30 mg kg⁻¹. As a result, the PTX-SA LPs displayed significantly improved in vivo anti-cancer efficacy in comparison with Taxol®. Therefore, weak-acid modification is proved to be a simple and effective method to achieve remote loading and high encapsulation efficiency of poorly soluble drugs, showing great potential for clinical application.

A remote loading liposomal formulation of weak-acid paclitaxel derivative with high encapsulation efficiency and high drug loading, improved therapeutic efficiency and negligible toxicity.     

Regioselective O/C phosphorylation of α-chloroketones: a general method for the synthesis of enol phosphates and β-ketophosphonates via Perkow/Arbuzov reaction

A regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was performed for the first time, which employed solvent-free Perkow reaction and NaI-assisted Arbuzov reaction under mild conditions respectively. Versatile enol phosphates were prepared in good to excellent yields as well as β-ketophosphinates.

A highly regioselective O/C phosphorylation of α-chloroketones with trialkyl phosphites was developed in the preparation of enol phosphates and β-ketophosphonates.     

Distinguishing between halogenated alkanes containing the same halogen based on the reaction kinetic parameter using negative ion mobility spectrometry at atmospheric pressure

Electron adsorption ionization ion mobility spectrometry can be used to detect halogen-containing volatile organic compounds with high sensitivity. However, this traditional electron attachment detection method cannot distinguish between volatile organic compounds containing the same halogen. For different organic compounds containing the same halogen, the product ions formed by the dissociation electron attachment process are the same. In this article, we propose a novel negative corona discharge ion mobility spectrometry method to distinguish between and detect halogenated alkanes containing the same halogen according to the different electron attachment rates and reaction kinetic parameters of the different halogenated alkanes. Although these halogenated alkanes, which contain the same halogen, produce the same type of ions through the electron attachment process, their electron attachment rates are different from each other. In this work, the kinetic information is used as the fingerprint information for the tested samples to distinguish different halogenated alkanes. Five halogenated alkanes were successfully detected using this method. The results show that the method based on the electron attachment rate constant is feasible for the determination of halogenated alkanes containing the same halogen.

Electron attachment ionization ion mobility spectrometry can be used to detect halogen-containing volatile organic compounds with high sensitivity.