A thermo-responsive hydrogel for body temperature-induced spontaneous information decryption and self-encryption.

A thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel, exhibiting an interesting phenomenon of an opaque-transparent-opaque transition in the successive processes of heating and cooling, is reported. It is fabricated by means of both the porogenic effect of hydroxypropyl cellulose and the cononsolvency effect of PNIPAM in a mixed solvent of dimethyl sulfoxide and water. After being mildly triggered by body temperature, the hydrogel is used to spontaneously decrypt the quick response code within 4 min and then autonomously encrypts the code again within 10 min at room temperature. The mechanism for the transient transparency of hydrogels during the quenching process has been elucidated.

Down-film as a new non-frame porous material for sound absorption.

Down-polyethylene film material has been introduced for the first time as an excellent non-frame sound absorber, showing a distinctively outstanding performance. It contains down fiber adjacent to each other without firm connection in between, forming a structure of elastic fiber network. The unique structure has broadband response to sound wave, showing non-synchronous vibration in low and middle frequency and synchronous vibration in middle and high frequency. The broadband resonance in middle and high frequency allows the structure to achieve complete sound absorption in resonance frequency band. Moreover, down-polyethylene film material possesses forced vibration, corresponding sound absorption coefficient has been obtained based on vibration theory. The down-film sound absorption material has the characteristics of light weight, soft, environment-friendly, and has excellent broadband sound absorption performance.

Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of modified fasting therapy, and a retrospective study was conducted to analyze changes in clinical indicators of hospitalized fasting patients. METHODS: A total of 2054 hospitalized fasting patients were enrolled in this observational study. All participants underwent 7 days of modified fasting therapy. The clinical efficacy biomarkers, safety indicators, and body composition were measured before and after fasting. RESULTS: The modified fasting therapy reduced body weight, BMI, abdominal circumference, systolic blood pressure, and diastolic blood pressure significantly. Blood glucose and indicators of body composition were improved to various extents (all p < 0.05). There was a small increase in liver function, kidney function, uric acid, electrolytes, blood count, coagulation, and uric biomarkers. Subgroup analysis results showed that cardiovascular diseases benefited from modified fasting therapy. CONCLUSIONS: At present this study is the largest retrospective population-based study about modified fasting therapy. The results from 2054 patients showed that the modified fasting therapy lasting 7 days was efficient and safe. It led to improvements in physical health and body weight-associated indicators, as well as body composition and relevant cardiovascular risk factors.

Protective effects of calorie restriction on insulin resistance and islet function in STZ-induced type 2 diabetes rats.

BACKGROUND: Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms. METHODS: Sixty male Sprague-Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. RESULTS: We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. CONCLUSION: CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

Fasting Therapy Contributes to the Improvement of Endothelial Function and Decline in Vascular Injury-Related Markers in Overweight and Obese Individuals via Activating Autophagy of Endothelial Progenitor Cells.

BACKGROUND: High body mass index- (BMI-) related vascular injury contributes to the pathogenesis of the atherosclerotic cardiovascular disease (ASCVD). Rigorous calorie restriction is one of the major lifestyle interventions to reduce vascular risk in overweight or obese individuals. However, the effects of fasting therapy (FT) on vascular function and the mechanism are still unclear. This study was aimed to investigate the impacts of FT on endothelial function, arterial stiffness, and circulating arterial damage parameters in overweight and obese individuals and possible mechanism. METHODS: Overweight and obese individuals participated in FT intervention (7-day very low calorie diet). Arterial function including brachial arterial flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), vascular injury-related markers including trimethylamine N-oxide (TMAO), and leptin and endothelial microparticles (EMPs) were assessed. Endothelial progenitor cells (EPCs) of these participants were isolated and cultured to investigate EPCs function. mRFP-GFP-LC3 confocal microscopy scanning and western blot were carried out to determine autophagy. RESULTS: After FT, body weight and BMI significantly decreased (81.76 ± 12.04 vs. 77.51 ± 12.06 kg, P < 0.01; 29.93 ± 2.82 vs. 28.47 ± 2.83 kg/m2, P < 0.01). FT remarkably improved FMD (5.26 ± 1.34 vs. 6.25 ± 1.60%, P=0.01) while baPWV kept unchanged. TMAO and leptin levels decreased (3.96 ± 1.85 vs. 2.73 ± 1.33 µmol/L, P=0.044; 6814 ± 2639 vs. 3563 ± 2668 µmol/L, P < 0.01). EMPs showed a decreased tendency. EPCs function was significantly improved, autophagy fluorescence intensity was enhanced, and the level of Beclin1, Atg5, LC3 II/I also increased after starvation in vitro, and the effects were blocked by autophagy inhibitor. CONCLUSIONS: Our present study demonstrated for the first time that FT markedly improves endothelial function and reduces the levels of arterial injury markers through improving EPCs function via activating autophagy. These findings provide a novel insight into FT as a lifestyle intervention strategy to promote the maintenance of vascular homeostasis in overweight or obese individuals. The trial was registered with ChiCTR1900024290.

Role of the C-terminal cysteines in virus-like particle formation and oligomerization of the hepatitis E virus ORF2 truncated proteins.

The hepatitis E virus (HEV) ORF2 truncated recombinant proteins can self-assemble into virus-like particles (VLPs) and were used as models to investigate the HEV capsid assembly. However, the structural function of the ORF2 C-terminal domain (C52aa from aa 608 to aa 660) remains unclear. Herein, by analyzing a set of ORF2 truncated proteins expressed in Escherichia coli, we found that the highly conserved C-terminal cysteines play a crucial role in the oligomerization of the truncated ORF2 proteins and in their assembly into VLPs, through the formation of dimer-dimer disulfide bonds; and the treatment of native HEV particles with dithiothreitol (DTT) induced the disassembly of the viral capsid, suggesting that the disulfide bonding is required for stabilizing the native HEV capsid. The present study sheds light on the structural role of the C-terminal region of the HEV capsid protein and contributes to the full understating of the viral capsid assembly process.

The Effects of the Surface Properties of a Gold Nanorod on Its In Vitro/Vivo Toxicity Against Cancer Cells.

Gold nano rods (GNRs) have showed cytotoxicity to cancer cells. At the same time, it shows little effects on non-tumor cells. Between GNRs and sub-cellular organelles, the understanding of interaction plays a very important role to determine the intracellular mechanisms. The purpose of what we done is to explain the effects of the surface properties of GNRs on specific cancer cell death. Three GNR samples with different aspect ratios were finely prepared by the seed-mediated growth method. Then the intracellular transport and the in vitro/vivo mechanisms of cancer cell death were studied by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser light scattering, and flow cytometry (FCM). It was found that GNRs700 exhibited the largest photothermal conversion efficiency. However, the GNR660 with or without light stimulation exhibited the highest cytotoxicity against cancer cells, which was contradict to the general knowledge. Detailed intracellular investigations showed that the lysosome was the key sub-organelle affecting the GNR function. Further experiments revealed that cytotoxicity was strongly affected by the GNR's surface potential. This potential was actually related to the density of surface cationic molecules, which further regulated lysosomal membrane penetration. The results obtained herein indicated that the physicochemical properties of the surface potential mediated the specific toxicity of GNRs against tumours.

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota.

BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear. AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota. METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing. RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota. CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.

L-carnitine ameliorated weight loss in fasting therapy: A propensity score-matched study.

l-carnitine infusion has been proven to reduce fasting-induced fatigue and hunger in patients with metabolic syndrome in our former study. However, the association between l-carnitine and clinical outcomes of fasting therapy is yet to be investigated. In this study, data from 192 patients who finished fasting therapy from September 2008 to July 2018 were reviewed, among which 142 patients received l-carnitine infusion in fasting regimen. Propensity matching was used to overcome retrospective bias. Patients' anthropometric measurements and metabolic markers were evaluated. After propensity matching, 40 patients were included in each group. Weight (-4.05 ± 1.65 kg vs -3.25 ± 1.68 kg, P = 0.031) and BMI (-1.51±0.61 kg/m2 vs -1.20 ± 0.62 kg/m2, P = 0.036) decreased in both groups, but significantly more in l-carnitine group, while diastolic blood pressure (-1.67±9.82 mmHg vs -6.21±8.83 mmHg, P = 0.043) and triglycerides (-0.18±0.63 mmol/L vs -1.05±1.70 mmol/L, P = 0.007) decreased significantly more in non-l-carnitine group compared between groups, blood glucose did not differ significantly between groups. l-carnitine can boost the positive effects of fasting therapy on weight loss and maintain the stability of blood pressure.

The synthesis of water-soluble phosphate pillar[5]arenes functionalized graphene as a fluorescent probe for sensitive detection of paraquat.

We describe a selective and sensitive fluorescence platform for the detection of paraquat (PQ) based on competitive host-guest recognition between phosphate pillar[5]arenes (PWP5) and probe (Safranine T, ST) with using PWP5 functionalized reduced graphene (PWP5-rGO) as the receptor. PQ is a positive charge molecule that is captured by PWP5 via electrostatic interactions. The host-guest interaction between PWP5 and PQ is studied by 1H NMR. Therefore, a selective and sensitive fluorescence sensing of detection PQ is developed. It has a linear response ranges of 0.01-2.0 and 2.0-50.0 µM and a low detection limit of 0.0035 µM (S/N = 3) for PQ. The sensing platform is also used to test PQ in two water samples with satisfying results. It suggests that this approach has potential applications for the determination of PQ.

Novel Competitive Fluorescence Sensing Platform for L-carnitine Based on Cationic Pillar[5]Arene Modified Gold Nanoparticles.

Supramolecular host-guest interaction and sensing between cationic pillar[5]arenes (CP5) and L-carnitine were developed by the competitive host-guest recognition for the first time. The fluorescence sensing platform was constructed by CP5 functionalized Au nanoparticles (CP5@Au-NPs) as receptor and probe (rhodamine 123, R123), which shown high sensitivity and selectivity for L-carnitine detection. Due to the negative charge and molecular size properties of L-carnitine, it can be highly captured by the CP5 via electrostatic interactions and hydrophobic interactions. The host-guest mechanism between PP5 and L-carnitine was studied by ¹H NMR and molecular docking, indicating that more affinity binding force of CP5 with L-carnitine. Therefore, a selective and sensitive fluorescent method was developed. It has a linear response of 0.1⁻2.0 and 2.0⁻25.0 µM and a detection limit of 0.067 µM (S/N = 3). The fluorescent sensing platform was also used to detect L-carnitine in human serum and milk samples, which provided potential applications for the detection of drugs abuse and had path for guarding a serious food safety issues.

Caloric restriction ameliorates acrolein-induced neurotoxicity in rats.

OBJECTIVE: Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and oxidative damage induced by acrolein is hypothesized to involve in the etiology of Alzheimer's disease (AD). Calorie restriction (CR) is the only non-genetic intervention that has consistently been verified to retard aging by ameliorating oxidative stress. Therefore, we investigated the effects of CR on acrolein-induced neurotoxicity in Sprague-Dawley (SD) rats. METHODS: A total of 45 weaned and specific-pathogen-free SD rats (male, weighing 180-220 g) were gavage-fed with acrolein (2.5 mg/kg/day) and fed ab libitum of 10 g/day or 7 g/day (representing 30% CR regimen), or gavage-fed with same volume of tap water and fed al libitum as vehicle control for 12 weeks. After behavioral test conducted by Morris Water Maze, SD rats were sacrificed and brain tissues were prepared for histochemical evaluation and Western blotting to detect alterations in oxidative stress, BDNF/TrkB pathway and key enzymes involved in amyloid precursor protein (APP) metabolism. RESULTS: Treatment with 30% CR in SD rats significantly attenuated acrolein-induced cognitive impairment. Oxidative damage including deletion of glutathione and superoxide dismutase and sharp rise in malondialdehyde were notably improved by 30% CR. Further study suggested that 30% CR showed protective effects against acrolein by modulating BDNF/TrkB signaling pathways. Moreover, 30% CR restored acrolein-induced changes of APP, ß-secretase, α-secretase and receptor for advanced glycation end products. CONCLUSION: These findings suggest that CR may provide a promising approach for the treatment of AD, targeting acrolein.

A Fluorescence Sensing Determination of 2, 4, 6-Trinitrophenol Based on Cationic Water-Soluble Pillar[6]arene Graphene Nanocomposite.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host⁻guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and a probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule, which is captured by PCP6 via electrostatic interactions and π⁻π interactions. Therefore, a selective and sensitive fluorescence probe for TNP detection is developed. It has a low detection limit of 0.0035 µM (S/N = 3) and a wider linear response of 0.01⁻5.0 and 5.0⁻125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

Ultrasensitive electrochemical detection of methyl parathion pesticide based on cationic water-soluble pillar[5]arene and reduced graphene nanocomposite.

We report a rapid, sensitive and selective electrochemical sensor based on pillar[5]arene (CP5) reduced graphene (rGO) nanohybrid-modified glassy carbon electrode CP5-rGO/GCE for the trace detection of methyl parathion (MP) by differential pulse voltammetry (DPV) for the first time. Compared to beta-cyclodextrin (ß-CD)-functionalized reduced graphene (rGO)-modified GCE ß-CD-rGO/GCE, the proposed CP5-rGO/GCE sensor exhibits excellent electrochemical catalytic activity, rapid response, high sensitivity, good reproducibility and anti-interference ability towards MP. The recognition mechanism of ß-CD/MP and CP5/MP was studied by 1H NMR. The results indicate a higher supramolecular recognition capability between CP5 and MP compared to that between ß-CD and MP. The ß-CD-rGO and CP5-rGO nano-composites were prepared via a wet chemistry approach. The resulting nano-composites have been characterized by thermogravimetric analysis (TGA), fourier transform infrared spectrometry (FTIR), charge transfer resistance (R ct) and zeta potential. The CP5-rGO/GCE combines the merits of CP5 and rGO, and is used for quantitative detection of MP. It has a low detection limit of 0.0003 µM (S/N = 3) and a linear response range of 0.001-150 µM for MP. This method has been used to detect MP in soil and waste water samples with satisfactory results. This study provides a promising electrochemical sensing platform and is a promising tool for the rapid, facile and sensitive analysis of MP.

[Preparation and application of a novel HCV diagnostic antigen fused to streptavidin].

OBJECTIVE: To prepare streptavidin-tagged hepatitis C virus (HCV) fusion protein and explore its application for the detection of antibody against HCV infection. METHODS: A recombinant plasmid pET-11d-C44P-SA was constructed, which coding a novel HCV diagnostic antigens (C44P) and streptavidin (SA) fusion protein, and the fusion protein was generated with BL21 (DE3) E Coli and identified by Western Blot analysis. Then the fusion protein was purified through the Ni-NTA affinity chromatography and over 90% purity has been achieved. Anti-HCV ELISAs were developed when the fusion protein was used in the biotin-pre-coated microplate or ordinary microplate, and then the sensitivity and specificity of the ELISA were evaluated with confirmed human sera panels. RESULTS: The fusion protein was expressed in high yields and purified successfully, the ELISA detection of anti-HCV with human sera panel indicated that its sensitivity and specificity is higher when SA-tagged HCV antigen (C44P-SA) coated in biotin-pre-coated microplate, compared to C44P or C44P-SA coated in ordinary microplate. CONCLUSION: The sensitivity and specificity of anti-HCV ELISA can be improved when a novel HCV diagnostic antigen fused to SA combined with the biotin- pre-coated microplate. This study laid a foundation for improving the performance of HCV diagnostics.

[Expression and purification of different segments from HCoV-NL63 nucleocapsid protein and their application in detection of antibodies].

Prokaryotic expression plasmids carrying N-terminal(1-163aa) and C-terminal(141-306aa) gene of HCoV-NL63 nucleocapsid protein were constructed with pET-30a(+) vector. Consequently, we prepared two purified proteins, Np and Cp, respectively, and established a Western blotting-based line assay (WBLA) for detection of antibodies against HCoV-NL63 using three purified proteins: Np , Cp and Nf, a full-length HCoV-NL63 nucleocapsid protein as previously reported. We detected anti-HCoV-NL63 antibodies among 50 sera samples collected from adult for health-examination by WBLA. The results showed that: 25 (50%), 27 (54%), 36 (72%) of 50 sera were indentified as anti-HCoV-NL63 antibody positive when the antigen was from Nf, Np and Cp, respectively. Among these sera with positive anti-HCoV-NL63 antibody,Cp showed highest antibody positive rate in WBLA,and consistent rates of detection were 64% between Nf and Np, 54% between Nf and Cp, 54% between Np and Cp. Our study provides the foundation for development of HCoV-NL63 serological detection reagents and an experimental tool for immunological research of HCoV-NL63 infection.