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Dysfunctional mitochondria have been shown to enhance cancer cell proliferation, reduce apoptosis, and increase chemoresistance. Chemoresistance develops in nearly all patients with colorectal cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. However, the effect of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission on chemoresistance in colorectal cancer is unclear. Here, we found that the release of high-mobility group box 1 protein (HMGB1) in conditioned medium from dying cells by chemotherapeutic drugs and resistant cells, which triggered Drp1 phosphorylation via its receptor for advanced glycation end product (RAGE). RAGE signals ERK1/2 activation to phosphorylate Drp1 at residue S616 triggerring autophagy for chemoresistance and regrowth in the surviving cancer cells. Abolishment of Drp1 phosphorylation by HMGB1 inhibitor and RAGE blocker significantly enhance sensitivity to the chemotherapeutic treatment by suppressing autophagy. Furthermore, patients with high phospho-Drp1Ser616 are associated with high risk on developing tumor relapse, poor 5-year disease-free survival (DFS) and 5-year overall survival (OS) after neoadjuvant chemoradiotherapy (neoCRT) treatment in locally advanced rectal cancer (LARC). Moreover, patients with RAGE-G82S polymorphism (rs2070600) are associated with high phospho-Drp1Ser616 within tumor microenvironment. These findings suggest that the release of HMGB1 from dying cancer cells enhances chemoresistance and regrowth via RAGE-mediated ERK/Drp1 phosphorylation.

The surface formation oxide assists of visible to ultraviolet photoelectric conversion in α-In2Se3 hexagonal microplates has been explored. Hexagonal α-In2Se3 microplates with the sizes of 10s to 100s of micrometers were synthesized and prepared by the chemical vapor transport method using ICl3 as a transport agent. Many vacancies and surface imperfection states have been found in the bulk and on the surface of the microplate because of the intrinsic defect nature of α-In2Se3. To discover physical and chemical properties and finding technological uses of α-In2Se3, several experiments including transmission electron miscopy (TEM), X-ray photoelectron spectroscopy (XPS), surface photovoltage (SPV), photoluminescence (PL), surface photoresponse (SPR), photoconductivity (PC), and thermoreflectance (TR) measurements have been carried out. Experimental results of TEM, XPS, SPV, PL, and SPR measurements show that a surface oxidation layer α-In2Se3-3xO3x (0 ≤ x ≤ 1) has formed on the crystal face of α-In2Se3 in environmental air with the inner layer content close to In2Se3 but the outermost layer content approaching In2O3. The near band edge transitions of α-In2Se3 microplates have been probed experimentally by TR and PC measurements. The direct band gap of α-In2Se3 has been determined to be 1.453 eV. The SPV result shows a maximum quantum efficiency of the surface oxide α-In2Se3-3xO3x (0 ≤ x ≤ 1) that presents a peak photoresponse near 2.18 eV. The analyses of SPV, SPR, PL, TR, and PC measurements revealed that the surface oxide layer facilitates the conversion of the ultraviolet to the visible range while the native defects (Se and In vacancies) sustain photoconductivity in the near-infrared region. On the basis of the experimental results a wide-energy-range photodetector that combines PC- and SPR-mode operations for α-In2Se3 microplate has been made. The testing results show a well-behaved function of photoelectric conversion in the near-infrared to ultraviolet region via the auxiliary forming of surface oxide on the crystalline face of the α-In2Se3 microplates.

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Tetrahydrofuran (THF) has commonly been used to deliver carotenoids to cells but the use of THF is associated with cytotoxicity and low uptake efficiency of carotenoids. Here, we used fetal bovine serum (FBS) as the delivery vehicle for lycopene in comparison with THF, THF containing 0·0025 % butylated hydroxytoluene (THF/BHT), methyl-b-cyclodextrin (M-b-CD) and micelles in two human prostate cancer cell lines, DU145 and PC-3. Lycopene (10 mM) solubilized in THF/BHT and then diluted in FBS at ratios of 5 and 10 gave the highest lycopene uptake in DU145 cells. Using a dilution factor of 10, we found that lycopene (10 mM) carried in FBS in a cell-free system led to significantly less loss of lycopene than in THF, THF/BHT and M-b-CD within 24 h of incubation. Lycopene solubilized in micelles was more stable than that in FBS within 24 h, but the micelle itself led to marked cytotoxicity to DU145 cells. Lycopene at 10 mM in FBS led to significantly higher uptake of lycopene in both cell lines than that in THF, THF/BHT or M-b-CD within 24 h of incubation. When FBS was replaced with lipoprotein-deficient serum, the uptake of lycopene by DU145 cells was markedly decreased and was not significantly different from that of THF or THF/BHT. These results demonstrate that FBS is superior to THF, THF/BHT, M-b-CD and micelles as a delivery vehicle for lycopene in prostate cell lines and that the lipoprotein of FBS is likely responsible for the improved stability and cellular uptake of lycopene.

Sub-sensory electrical or mechanical stimulation can enhance the sensitivity of the human somatosensory system to improve the balance control capabilities of elderly. In addition, clinical studies suggest that visual-auditory biofeedback can improve sensory compensation for the elderly. This study hypothesizes that the static balance and gait performance of single leg quiet standing and treadmill walking could be improved for providing proprioceptive neuromuscular facilitation using sub-sensory stimulation and visual-auditory biofeedback in amputee subjects. To test this, a computerized foot pressure biofeedback sensory compensation system using sub-threshold low-level electrical stimulation combined with visualauditory biofeedback was developed. Seven unilateral trans-tibial amputees who wore prostheses over 2 years were recruited. The subjects performed multiple single leg quiet standing trials with sub-sensory electrical stimulation applied at the quadriceps muscle during half of the trials. Static balance performance was characterized by using a Zebris motion analysis system to measure the sway distance and duration of the centre of mass on the second sacral (S2) of the subjects. In addition, multiple treadmill ambulatory trials with or without visual-auditory biofeedback was performed. Dynamic gait performance was characterized with a Zebris instrumented insole to measure the temporal responses of foot pressure sensors. Experimental results showed an improvement in three balance performance indices (Holding Time Index, HTI, Maximum Sway Distance Index, MSDI, and Average Sway Distance Index, ASDI) during single leg quiet standing by applying sub-sensory stimulation. The improvement ratio of these balance performance indices across subjects for single leg quiet standing tests resulted in 132.34% in HTI, 44.61% in MSDI, and 61.45% in ASDI. With visual-auditory biofeedback as a cue for heel contact and toe push-off condition during treadmill ambulation, the improvement of four dynamic gait performance measures (Double Support Period, DSP, Constant Time Cadence, CTC, Single Support Period, SSP, and Stance/Swing Ratio, SSR) in amputees was verified. This resulted in 7.89% in DSP (affected side), 5.09% in CTC, 16.67% in SSP (sound side), 45.30% in SSR (sound side), and 40.30% in SSR (affected side) respectively. These findings suggest that sub-threshold electrical stimulation and visual-auditory biofeedback rehabilitation strategies may be effective in compensating sensory loss and improving static balance and dynamic ambulation performance for amputees.