Chondroitin sulphate modified MoS2 nanoenzyme with multifunctional activities for treatment of Alzheimer's disease.

Nano-MoS2 exhibit oxidoreductase-like activities, and has been shown to effectively eliminate excessive intracellular ROS and inhibit Aß aggregation, thus demonstrating promising potential for anti-Alzheimer's disease (anti-AD) intervention. However, the low water dispersibility and high toxicity of nano-MoS2 limits its further application. In this study, we developed a chondroitin sulphate (CS)-modified MoS2 nanoenzyme (CS@MoS2) by harnessing the excellent biocompatibility of CS and the exceptional activities of nano-MoS2 to explore its potential in anti-AD research. Promisingly, CS@MoS2 significantly inhibited Aß1-40 aggregation and prevented toxic injury in SH-SY5Y cells caused by Aß1-40. In addition, CS@MoS2 protected these cells from oxidative stress damage by regulating ROS production, as well as promoting the activities of SOD and GSH-Px. CS@MoS2 also modulated the intracellular Ca2+ imbalance and downregulated Tau hyperphosphorylation by activating GSK-3ß. CS@MoS2 suppressed p-NF-κB (p65) translocation to the nucleus by inhibiting MAPK phosphorylation, and modulated the expression of downstream anti- and proinflammatory cytokines. Owing to its multifunctional activities, CS@MoS2 effectively improved spatial learning, memory, and anxiety in D-gal/AlCl3-induced AD mice. Taken together, these results indicate that CS@MoS2 has significant potential for improving the therapeutic efficacy of the prevention and treatment of AD, while also presenting a novel framework for the application of nanoenzymes.

Functionalised penetrating peptide-chondroitin sulphate­gold nanoparticles: Synthesis, characterization, and applications as an anti-Alzheimer's disease drug.

The purpose of this study was to construct a transmembrane peptide-chondroitin sulphate­gold nanoparticle (TAT-CS@Au) delivery system and investigate its activity as an anti-Alzheimer's disease (AD) drug. We successfully prepared TAT-CS@Au nanoparticles, investigated their anti-AD effects, and explored the possible mechanisms in in vitro models. TAT-CS@Au exhibited excellent cellular uptake and transport capacity, effectively inhibited the accumulation of Aß1-40, and significantly reduced Aß1-40-induced apoptosis in SH-SY5Y cells. Furthermore, TAT-CS@Au significantly reduced oxidative stress damage and cholinergic injury induced by Aß1-40 by regulating intracellular concentrations of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and acetylcholine (ACh). Western blotting results demonstrated that TAT-CS@Au inhibited aberrant tau phosphorylation (Ser199, Thr205, Ser404, and Ser396) through GSK3ß inactivation. TAT-CS@Au decreased the levels of inflammatory factors, specifically TNF-α, IL-6, and IL-1ß, by inhibiting NF-κB nuclear translocation by activating MAPK signalling pathways. Overall, these results indicate that TAT-CS@Au exhibits excellent transmembrane ability, inhibits Aß1-40 accumulation, antagonises oxidative stress, reduces aberrant tau phosphorylation, and suppresses the expression of inflammatory factors. TAT-CS@Au may be a multi-target anti-AD drug with good cell permeability, providing new insights into the design and research of anti-AD therapeutics.

Frailty and its association with health-related quality of life among older cancer patients: an evidence-based study from China.

BACKGROUND: There is limited information about the population characteristics and adverse health outcomes of older cancer patients in China. This study aimed to describe the prevalence of frailty and examine the association between frailty and health-related quality of life (HRQoL) among older cancer patients. METHODS: This was a cross-sectional study involving older patients diagnosed with cancer in two tertiary hospitals in Shandong Province, China. Frailty was assessed using Geriatric 8 (G-8). HRQoL was measured using the five-level EuroQol-5-dimension (EQ-5D-5L) questionnaire. The Tobit regression model and logistic regression model was used to identify the relationship between frailty and HRQoL. RESULTS: Of the 229 older patients, 175 (76.4%) were frail. Frail patients had lower EQ-5D-5L utility scores than those who were non-frail (0.830 vs. 0.889; P = 0.004). After adjustments for sociodemographic and cancer-related variables, frailty was statistically associated with worse health-related quality of life (OR = 6.024; P = 0.001). CONCLUSION: Frailty was associated with deteriorated HRQoL in older patients with cancer. Early frailty screening and preventive interventions are essential for improving quality of life through decision-making or pretreatment optimization in geriatric oncology.

The majority of cancer cases and cancer mortality occur in older adults. Aging is a heterogenic process, which results in great diversity in older cancer patients concerning physical, psychological, and social status. There is limited information about the population characteristics and adverse health outcomes of older cancer patients in China, and the magnitude of this problem is unclear, creating challenges in understanding health disparities in geriatric cancer care. In this study, we have described the prevalence of frailty and explored the relationship between frailty and health-related quality of life (HRQoL). This study demonstrated that frailty, not being currently married, advanced cancer stage, and cancer site were significant factors influencing the lower HRQoL. Furthermore, frail individuals had a higher probability belonging to the lowest HRQoL quartile group. This study is considered as the first step in highlighting the importance of staging the aging and assessing quality of life among older cancer patients in China.

Assessing the response of vegetation change to drought during 2009-2018 in Yunnan Province, China.

Yunnan Province in southwest China is characterized by a vast area, diverse climate types, rich ecosystem types, and unique biodiversity resources. With consideration of global climate change, there is an urgent need to evaluate the response of vegetation to drought in Yunnan. This study utilized the MOD13A3, MOD17A2, and Tropical Rainfall Measuring Mission (TRMM) 3B43 remote sensing products. The TRMM 3B43 downscaled monthly precipitation data were used to calculate the tropical rainfall condition index (TRCI) for Yunnan. The TRCI was used as a drought index, and the temporal and spatial changes in TRCI, gross primary productivity (GPP), and vegetation condition index (VCI) from 2009 to 2018 were explored. The response of vegetation to drought was evaluated under different time scales and varying land-use types. The results showed that during 2009-2018, (1) at an annual scale, the drought in Yunnan showed a weakening trend, and at a spatial scale, the drought showed a weakening trend from northwest to southeast. This weakening trend was more noticeable for cultivated land than for forest, grassland, and other land-use types. (2) GPP and VCI showed overall increasing trends at an annual scale, indicating gradual improvements in the GPP of vegetation and vegetation status, whereas the summer vegetation index showed a decreasing trend. (3) Although both the GPP and the growth state of vegetation were affected by drought, the responses of GPP and VCI to drought differed under different temporal scales and different land-use types. The responses of GPP and VCI to drought during spring were greater than those over other seasons, and the response of VCI to drought was more sensitive than that of GPP. Drought had a high impact on the GPP and vegetation growth of cultivated land and grassland with shallow root systems, whereas the impact of drought on forest was relatively stable.

Short-term clinical effect of conformal radiotherapy combined with tegafur gimeracil oteracil potassium in treating recurrent esophagus cancer.

OBJECTIVE: To observe clinical effects of three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy in the treatment of patients with recurrent esophagus cancer. METHODS: One hundred and twelve senile patients who suffered from esophagus cancer were selected and randomly divided into two groups, namely, observation group (56 cases) and control group (56 cases). The observation group adopted three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy and the control group adopted three-dimensional conformal radiotherapy only. RESULTS: All patients completed the treatment, with good compliance. Effective rate of the observation group was 82.1%, which was significantly higher than the control group (67.9%), and the difference was statistically significant (P<0.05). Main toxic and side effects of patients of two groups were radiation esophagitis, gastrointestinal reaction, hematologic toxicities and radiative skin reaction. Differences of incidence rates of all types of toxic and side effects were not statistically significant (P>0.05). The one-year and two-year survival rates of patients of the observation group were 80.4% and 53.6%, respectively, while the control group was 55.4% and 30.4%; differences between two groups were statistically significant (P<0.05). CONCLUSION: Three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy has definite curative effect in treating patients with recurrent esophagus cancer and can improve survival rate of patients, without increasing adverse reaction.

Polyunsaturated fatty acids trigger apoptosis of colon cancer cells through a mitochondrial pathway.

INTRODUCTION: Colorectal cancer is common in developed countries. Polyunsaturated fatty acids (PUFAs) have been reported to possess tumoricidal action, but the exact mechanism of their action is not clear. MATERIAL AND METHODS: In the present study, we studied the effect of various n-6 and n-3 fatty acids on the survival of the colon cancer cells LoVo and RKO and evaluated the possible involvement of a mitochondrial pathway in their ability to induce apoptosis. RESULTS: It was observed that n-3 α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (ALA, EPA and DHA respectively) and n-6 linoleic acid, gamma-linolenic acid and arachidonic acid (LA, GLA and AA respectively) induced apoptosis of the colon cancer cells LoVo and RKO at concentrations above 120 µM (p < 0.01 compared to control). The semi-differentiated colon cancer cell line RKO was more sensitive to the cytotoxic action of PUFAs compared to the undifferentiated colon cancer cell line LoVo. PUFA-treated cells showed an increased number of lipid droplets in their cytoplasm. PUFA-induced apoptosis of LoVo and RKO cells is mediated through a mitochondria-mediated pathway as evidenced by loss of mitochondrial membrane potential, generation of ROS, accumulation of intracellular Ca(2+), activation of caspase-9 and caspase-3, decreased ATP level and increase in the Bax/Bcl2 expression ratio. CONCLUSIONS: PUFAs induced apoptosis of colon cancer cells through a mitochondrial dependent pathway.

Effect of n-3 and n-6 unsaturated fatty acids on prostate cancer (PC-3) and prostate epithelial (RWPE-1) cells in vitro.

Prostate cancer (PCa) is one of the leading causes of death in the elderly men. Polyunsaturated fatty acids (PUFAs) regulate proliferation of cancer cells. In the present study, we evaluated the effect of various PUFAs on the proliferation and survival of human prostate cancer (PC-3) and human prostate epithelial (RWPE-1) cells in vitro.LA, GLA, AA, ALA, EPA and DHA (linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid respectively) when tested at 50, 100, 150, and 200 µM inhibited proliferation of RWPE-1 and PC-3 cells, except that lower concentrations of LA (25 µM) and GLA (5, 10 µM) promoted proliferation. Though all fatty acids tested produced changes in the production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), lipoxin A4 and free radical generation by RWPE-1 and PC-3 cells, there were significant differences in their ability to do so. As expected, supplementation of various n-3 and n-6 fatty acids to RWPE-1 and PC-3 cells enhanced the content of the added fatty acids and their long-chain metabolites in these cells. In contrast to previous results, we did not find any direct correlation between inhibition of cell proliferation induced by various fatty acids and free radical generation. These results suggest that polyunsaturated fatty acids suppress proliferation of normal and tumor cells by a variety of mechanisms that may partly depend on the type(s) of cell(s) being tested and the way these fatty acids are handled by the cells. Hence, it is suggested that more deeper and comprehensive studies are needed to understand the actions of fatty acids on the growth of normal and tumor cells.

Tunable few-cycle and multicycle coherent terahertz radiation from relativistic electrons.

We report the generation of tunable, narrow-band, few-cycle and multicycle coherent terahertz (THz) pulses from a temporally modulated relativistic electron beam. We demonstrate that the frequency of the THz radiation and the number of the oscillation cycles of the THz electric field can be tuned by changing the modulation period of the electron beam through a temporally shaped photocathode drive laser. The central frequency of the THz spectrum is tunable from ∼0.26 to 2.6 THz with a bandwidth of ∼0.16 THz.

Optical fiber-based single-shot picosecond transient absorption spectroscopy.

A new type of single-shot transient absorption apparatus is described based on a bundle of optical fibers. The bundle contains 100 fibers of different lengths, each successively giving approximately 15 ps longer optical delay. Data are collected by imaging light from the exit of the bundle into a sample where it is overlapped with an electron pulse or laser excitation pulse, followed by imaging onto a charge coupled device (CCD) detector where the intensity of light from each fiber is measured simultaneously. Application to both ultrafast pump-probe spectroscopy and pulse radiolysis is demonstrated. For pulse radiolysis, the prototype bundle provides the ability to collect data with a time resolution limited only by the electron pulse width of 7-10 ps, over a total single-shot time window of approximately 1.5 ns. Tunable probe light is obtained from a titanium-sapphire laser and an optical parametric amplifier. Corrections are made to remove the fiber-to-fiber variations in signal magnitude due to the spatial overlap of the electron beam and probe image. High quality data can be collected over most of the sensitivity range of the CCD camera detectors. The single-shot instrument is valuable for measurement of samples that are only available in very limited quantities, are too viscous to flow, or are rigid. It is therefore excellent in applications, such as picosecond pulse radiolysis, where the thousands of pulses per kinetic trace typical in classical pump-probe experiments can damage the sample before useful results could be obtained.

Enhancement of two-photon emission in photonic crystals.

We report the influence of photonic stopgaps on two-photon excited emission from highly efficient nonlinear chromophores infiltrated into high-quality photonic crystals. We have observed a sharp decrease (filter effect) in emission within the frequency range and direction of the stopgap as well as sharp enhancement of the two-photon excited emission associated with the stopgap's edge. This effect may be important for the development of low-threshold upconversion lasers.