Transcranial Low-Level Laser Therapy Improves Neurological Performance in Traumatic Brain Injury in Mice: Effect of Treatment Repetition Regimen

Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm[superscript 2], 18 J/cm[superscript 2], spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21–27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1- and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1- and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed.National Institutes of Health (U.S.) (Grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense. Congressionally Directed Medical Research Programs (W81XWH-09-1-0514)United States. Air Force Office of Scientific Research. Military Photomedicine Program (FA9550-11-1-0331

Duality and Dimensionality Reduction Discrete Line Generation Algorithm for a Triangular Grid

Vectors are a key type of geospatial data, and their discretization, which involves solving the problem of generating a discrete line, is particularly important. In this study, we propose a method for constructing a discrete line mathematical model for a triangular grid based on a “weak duality” hexagonal grid, to overcome the drawbacks of existing discrete line generation algorithms for a triangular grid. First, a weak duality relationship between triangular and hexagonal grids is explored. Second, an equivalent triangular grid model is established based on the hexagonal grid, using this weak duality relationship. Third, the two-dimensional discrete line model is solved by transforming it into a one-dimensional optimal wandering path model. Finally, we design and implement the dimensionality reduction generation algorithm for a discrete line in a triangular grid. The results of our comparative experiment indicate that the proposed algorithm has a computation speed that is approximately 10 times that of similar existing algorithms; in addition, it has better fitting effectiveness. Our proposed algorithm has broad applications, and it can be used for real-time grid transformation of vector data, discrete global grid system (DGGS), and other similar applications

Free fatty acid induces endoplasmic reticulum stress and apoptosis of β-cells by Ca2+/calpain-2 pathways.

Dysfunction of β-cells is a major characteristic in the pathogenesis of type 2 diabetes mellitus (T2DM). The combination of obesity and T2DM is associated with elevated plasma free fatty acids (FFAs). However, molecular mechanisms linking FFAs to β-cell dysfunction remain poorly understood. In the present study, we identified that the major endoplasmic reticulum stress (ERS) marker, Grp78 and ERS-induced apoptotic factor, CHOP, were time-dependently increased by exposure of β-TC3 cells to FFA. The expression of ATF6 and the phosphorylation levels of PERK and IRE1, which trigger ERS signaling, markedly increased after FFA treatments. FFA treatments increased cell apoptosis by inducing ERS in β-TC3 cells. We also found that FFA-induced ERS was mediated by the store-operated Ca(2+) entry through promoting the association of STIM1 and Orai1. Moreover, calpain-2 was required for FFA-induced expression of CHOP and activation of caspase-12 and caspase-3, thus promoting cell apoptosis in β-TC3 cells. Together, these results reveal pivotal roles for Ca(2+)/calpain-2 pathways in modulating FFA-induced β-TC3 cell ERS and apoptosis

Conversion of Glucose to 5-Hydroxymethylfurfural Catalyzed by Metal Halide in N,N-Dimethylacetamide

A simple strategy is reported for catalytic conversion of glucose to 5-hydroxymethylfurfural (HMF) over All(3) in N,N-dimethylacetamide (DMAC). When the reaction was conducted in DMAC at 120 degrees C for 15 min over All(3) catalyst, HMF was obtained with a yield of 52%. The reaction course was monitored by C-13 NMR spectroscopy and HPLC analysis. The results suggest that All(3) catalyzes the three consecutive reactions consisting of mutarotation of alpha-glucopyranose to beta-glucopyranose, isomerization of glucose to fructose, and dehydration of fructose to HMF

New radiocarbon and archaeobotanical evidence reveal the timing and route of southward dispersal of rice farming in south China

The origins and spreads of rice agriculture have been enduring topics, yet the timing and southward dispersal from the Yangtze River Basin have been difficult to trace, due to the scarcity of archaeobotanical data, especially systematic macro-plant remains examination, combined with the poor preservation in the humid climate and acidic soils of China’s southern provinces. Here, we report new radiocarbon dating and preserved rice phytolith evidence, derived from three Late Neolithic archaeological sites in south China, dated about 5,000–4,100 cal a BP. Our results demonstrate that rice farming had spread southward through the mountainous regions of Wuyi and Nanling, then entered the areas of Western Fujian and North Guangdong by 5,000 cal a BP, followed by continued expansion into coastal areas of East China Sea and South China Sea, also crossing the Taiwan Strait, around 4,500–4,000 cal a BP. The North River, East River, Min River, and possibly other river systems likely were influential as pathways or conduits.This work was supported by the National Natural Science Foundation of China (41371217, 41771231) and China Scholarship Council (201604910602). We thank for Dr. Deke Xu from the Institute of Geology and Geophysics, Chinese Academy of Sciences for the identification of phytoliths

Calpain-2 is required for FFA treatment-induced β-TC3 cell apoptosis.

<p>The cells were treated with calpain-2 siRNA, incubated for 24 h, and then stimulated with FFA or BSA for 16 h. (A) Cell death was quantified by annexin V/PI double staining. (B) Caspase-12 activity was detected after cells were treated with calpain-2 siRNA. (C) Caspase-3 activity was detected after cells were treated with calpain-2 siRNA. snc-RNA-treated cells were used as a negative control. Bars represent each sample performed in triplicate, and the error bars represent the standard deviations. *<i>P</i><0.05, by one-way ANOVA.</p

FFA treatments increase calpain-2 activity, thus inducing ERS in β-TC3 cells.

<p>(A) The activity of calpain-2 was tested in β-TC3 cells treated with 0.5 mM FFA or BSA for 16 h. (B) β-TC3 cells were treated with calpain-2 siRNA for 24 h. Western blot was performed to examine calpain-2 protein levels. (C) RT-PCR was used to analyze calpain-2 mRNA levels. (D) Calpain Activity Assay Kit was used to analyze calpain-2 activity. Silencer negative control siRNA (snc-RNA)-treated cells were used as a negative control. (E) β-TC3 cells were treated with calpain-2 siRNA for 24 h and then stimulated with FFA for 16 h, and western blot was used to examine the protein expression levels of Grp78 and CHOP. (F) RT-PCR was used to test Grp78 and CHOP mRNA levels. BSA-treated β-TC3 cells were used as a negative control. Bars represent each sample performed in triplicate, and the error bars represent the standard deviations. *<i>P</i><0.05, by the Student’s <i>t</i>-test.</p

FFA treatments increase Ca²⁺ influx to induce ERS in β-TC3 cells.

<p>(A) β-TC3 cells were incubated with FFA or BSA for 16 h, western blot was used to examine the protein expression levels of Grp78 and CHOP following the treatment with Ca²⁺ channel blocker NiCl₂. (B) β-TC3 cells were incubated with FFA or BSA for 16 h, and then stimulated with 4 µM thapsigargin for 20 min to activate store-operated Ca²⁺ entry. Fluorescence densities of Ca²⁺ change were monitored in Fluo-8/AM-loaded β-TC3 cells after FFA or BSA treatments. (C) The protein expression levels of STIM1 and Orai1 were tested by western blot following treatments with FFA or BSA for 16 h in β-TC3 cells. (D) β-TC3 cells were incubated with FFA or BSA for 16 h, and then stimulated with 4 µM thapsigargin for 20 min. Cell lysates were immunoprecipitated with anti-STIM1 antibody followed by western blot using anti-Orai1 antibody and with anti-Orai1 antibody followed by western blot using anti-STIM1 antibody. Immunoprecipitated with anti-IgG antibody was used as the negative control. Bars represent each sample performed in triplicate, and the error bars represent the standard deviations. *<i>P</i><0.05, by the Student’s <i>t</i>-test.</p

FFA treatments induce ERS in β-TC3 cells and increase cell apoptosis.

<p>(A) Cells were treated with 0.5 mM FFA or BSA for 0, 8, 16, or 24 h. Western blot was used to examine Grp78 and CHOP protein levels. (B) RT-PCR was used to test Grp78 and CHOP mRNA levels. (C) Cells were treated with 0.5 mM FFA or BSA for 16 h. Western blot was used to examine the expression levels of ATF6, p-PERK, PERK, p-IRE1 and IRE1. (D) Cells were treated with 0.5 mM FFA or BSA for 16 h. Cell death was quantified by annexin V/PI double staining. (E) Caspase-12 activity was detected after cells were treated with 0.5 mM FFA or BSA for 16 h. (F) Caspase-3 activity was detected after cells were treated with 0.5 mM FFA or BSA for 16 h. BSA-treated cells were used as a negative control. Bars represent each sample performed in triplicate, and the error bars represent the standard deviations. *<i>P</i><0.05, by the Student’s <i>t</i>-test.</p