C9orf72 poly-PR helps p53 escape from the ubiquitin-proteasome system and promotes its stability.

C9orf72-derived dipeptide repeats (DPRs) proteins have been regarded as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). As the most toxic DPRs in C9-ALS/FTD, poly-proline-arginine (poly-PR) is associated with the stability and accumulation of p53, which consequently induces neurodegeneration. However, the exact molecular mechanism via which C9orf72 poly-PR stabilizes p53 remains unclear. In this study, we showed that C9orf72 poly-PR induces not only neuronal damage but also p53 accumulation and p53 downstream gene activation in primary neurons. C9orf72 (PR)50 also slows down p53 protein turnover without affecting the p53 transcription level and thus promotes its stability in N2a cells. Interestingly, the ubiquitin-proteasome system but not the autophagy function was impaired in (PR)50 transfected N2a cells, resulting in defective p53 degradation. Moreover, we found that (PR)50 induces mdm2 mistranslocation from the nucleus to the cytoplasm and competitively binds to p53, reducing mdm2-p53 interactions in the nucleus in two different (PR)50 transfected cells. Our data strongly indicate that (PR)50 reduces mdm2-p53 interactions and causes p53 to escape from the ubiquitin-proteasome system, promoting its stability and accumulation. Inhibiting or at least downregulating (PR)50 binding with p53 may be therapeutically exploited for the treatment of C9-ALS/FTD.

Experimental quasi-single-photon transmission from satellite to earth.

Free-space quantum communication with satellites opens a promising avenue for global secure quantum network and large-scale test of quantum foundations. Recently, numerous experimental efforts have been carried out towards this ambitious goal. However, one essential step--transmitting single photons from the satellite to the ground with high signal-to-noise ratio (SNR) at realistic environments--remains experimental challenging. Here, we report a direct experimental demonstration of the satellite-ground transmission of a quasi-single-photon source. In the experiment, single photons (~0.85 photon per pulse) are generated by reflecting weak laser pulses back to earth with a cube-corner retro-reflector on the satellite CHAMP, collected by a 600-mm diameter telescope at the ground station, and finally detected by single-photon counting modules after 400-km free-space link transmission. With the help of high accuracy time synchronization, narrow receiver field-of-view and high-repetition-rate pulses (76 MHz), a SNR of better than 16:1 is obtained, which is sufficient for a secure quantum key distribution. Our experimental results represent an important step towards satellite-ground quantum communication.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin and its potential gel mechanism.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin (TCHMP) were investigated in this study. The gelation capacity results revealed that the in situ gelation behavior of TCHMP only occurred when the pH value was higher than 6.25. The gel strength increased from 26.63 g to 42.77 g as the pH value increased from 7.4 to 8.9. Rheological measurements confirmed that the apparent viscosity and viscoelasticity of TCHMP were highly dependent on pH value and dialysis time. Compared with the control group, the apparent viscosity of TCHMP dialyzed in phosphate-buffered saline (PBS) of pH 8.9 for 180 min increased 695-fold. During the dialysis process of TCHMP at different pH values (7.4-8.9), the final thiol groups content decreased and the final disulfide bonds content increased with the increase in pH value. This illustrates that the mechanism of in situ gelation is mainly the oxidation of thiol-thiol groups to form disulfide bonds. These results can put forward new insights into the pH-responsive in situ gelling properties of TCHMP and provide a theoretical basis for the application of TCHMP in neutral and alkaline gel systems.

Compound treatment of thiolated citrus high-methoxyl pectin and sodium phosphate dibasic anhydrous improved gluten network structure.

The effects of pectin or thiolated pectin alone and combined with sodium phosphate dibasic anhydrous (Na2HPO4) on the performances of gluten were studied. Results showed that compared with pectin treated gluten, the thiols of thiolated pectin treated gluten increased by 8.7 times. Analysis of the extensibility and rheological properties revealed that pectin reduced gluten strength, whereas thiolated pectin improved the strength and viscoelasticity of gluten, especially with the assistance of Na2HPO4. Furthermore, thiolated pectin and Na2HPO4 compound increased enthalpy (ΔH, from 150.42 to 168.60 J/g) and decreased Imax (from 5255.33 to 2775.33) markedly, indicating gluten aggregation. The highest ß-sheet (76.47%) and the lowest α-helix/ß-sheet ratio (0.11) were found in gluten treated with thiolated pectin and Na2HPO4 and suggested gluten stability was enhanced. SEM observation confirmed that thiolated pectin and Na2HPO4 compound strengthened the gluten structure. These results are of great significance for the supplementation of pectin in wheat products.

Gypenoside IX restores Akt/GSK-3ß pathway and alleviates Alzheimer's disease-like neuropathology and cognitive deficits.

The main pathological changes of Alzheimer's disease (AD), a progressive neurodegenerative disorder, include senile plaque (deposited by amyloid beta), neurofibrillary tangle (formed by paired helical filaments composed of hyperphosphorylated tau), and massive loss of neurons. Currently there is a lack of ideal drugs to halt AD progression. Gypenosides (GPs), a kind of natural product, possesses potential therapeutic effects for neurodegenerative diseases, including AD. However, the specific role and mechanism of GPs for AD remain unclear. In the current study, we used staurosporine (STP), an inducer of apoptosis and causing tau hyperphosphorylation, to mimic AD models, and explored the role and mechanism of Gypenoside IX (one of the extracts of Gynostemma, GP for short name in our experiments) in STP treated primary hippocampal neurons and rats. We found STP not only increased apoptosis and tau hyperphosphorylation, but also significantly increased Aß production, resulting in synaptic dysfunction and cognitive decline in mimic AD models by STP. GP was found to rescue apoptosis and cognitive impairments caused by STP treatment. Moreover, GP recovered the decreased synaptic proteins PSD95, Synaptophysin and GluR2, and blocked dendritic spine loss. Interestingly, GP decreased the STP induced tau hyperphosphorylation at different sites including S-199, S-202, T-205, T-231, S-262, S-396, and S-404, and at the same time decreased Aß production through down-regulation of BACE1 and PS1. These effects in STP treated primary hippocampal neurons and rats were accompanied with a restoration of AKT/GSK-3ß signaling axis with GP treatment, supporting that dysregulation of AKT/GSK-3ß pathway might be involved in STP related AD pathogenesis. The results from our research proved that GP might be a potential candidate compound to reduce neuronal damage and prevent the cognitive decline in AD.

Ultrasonic Assisted Extraction of Quinoa (Chenopodium quinoa Willd.) Protein and Effect of Heat Treatment on Its In Vitro Digestion Characteristics.

To extract and utilise the protein in quinoa efficiently, we investigated the effect of rate of quinoa protein isolate (QPI) extraction by ultrasound-assisted alkaline extraction and traditional alkaline extraction methods using single-factor experiments and Box-Behnken design. The effect of different heat treatment temperature and time on QPI functional properties and in vitro digestion characteristics were also investigated. The results showed that the optimal conditions of ultrasound- assisted alkaline extraction process were: ultrasonic time 99 min, solid-liquid ratio 1:20 w:v, ultrasonic temperature 47 °C, and pH 10, and its extraction rate and purity were 74.67 ± 1.08% and 87.17 ± 0.58%, respectively. It was 10.18% and 5.49% higher than that of the alkali-soluble acid precipitation method, respectively. The isoelectric point (pI) of QPI obtained by this method was 4.5. The flexibility and turbidity of QPI had maximum values at 90 °C, 30 min, and 121 °C, 30 min, which were 0.42 and 0.94, respectively. In addition, heat treatment changed the 1.77-2.79 ppm protein characteristic region in QPI's nuclear magnetic resonance hydrogen spectroscopy (1H NMR). After heating at 90 °C and 121 °C for 30 min, the hydrolysis degree and total amino acid content at the end of digestion (121 °C, 30 min) were significantly lower than those of untreated QPI by 20.64% and 27.85%. Our study provides basic data for the efficient extraction and utilisation of QPI.

Effect of change in pH, heat and ultrasound pre-treatments on binding interactions between quercetin and whey protein concentrate.

The effects of change in pH, heat and ultrasound pre-treatments on the binding mechanism of quercetin (Q) with whey protein concentrate (WPC) were investigated, as well as the antioxidant capacity and stability of Q in the complexes. The main interaction between WPC and Q was hydrophobic and was not affected by pre-treatments. The binding affinity for Q with WPC at pH 7.4 after heating at 80 °C for 30 min, was the strongest, resulting in a WPC-Q complex with a more compact structure, the smallest particle size (184.43 ± 10.47 nm) and the largest ζ-potential (-20.58 ± 0.60 mV). This complex also provided the greatest stabilization of Q, when exposed to 37 °C and light. Complexation of WPC with Q reduced the ABTS radical scavenging capacity of Q, but enhanced its DPPH radical scavenging capacity and reducing power. These findings provide valuable information for optimizing the formation conditions of WPC-Q.

Heat treatment of quinoa (Chenopodium quinoa Willd.) albumin: Effect on structural, functional, and in vitro digestion properties.

Quinoa seeds are rich in protein, polyphenols, phytosterols, and flavonoid substances, and excellent amino acid balance that has been revisited recently as a new food material showing potential applied in fitness and disease prevention. Heat treatment is one of the most effective strategies for improving the physiochemical characteristics of a protein. However, research examining the effects of temperature on quinoa albumin (QA) properties is limited. In this study, QA was subjected to thermal treatment (50, 60, 70, 80, 90, 100, and 121°C). SDS-PAGE revealed that QA is composed of several polypeptides in the 10-40 kDa range. Amino acid (AA) analysis showed that the branched-chain amino acids (BCAAs), negatively charged amino acid residues (NCAAs), and positively charged amino acids (PCAAs) contents of QA were more than double that of the FAO/WHO reference standard. Additionally, heating induced structural changes, including sulfhydryl-disulfide interchange and the exposure of hydrophobic groups. Scanning electron microscopy demonstrated that the albumin underwent denaturation, dissociation, and aggregation during heating. Moreover, moderate heat treatment (60, 70, and 80°C) remarkably improved the functional properties of QA, enhancing its solubility, water (oil) holding capacity, and emulsification and foaming characteristics. However, heating also reduced the in vitro digestibility of QA. Together, these results indicate that heat treatment can improve the structural and functional properties of QA. This information has important implications for optimizing quinoa protein production, and various products related to quinoa protein could be developed. which provides the gist of commercial applications of quinoa seeds for spreading out in the marketplace.

Effect of Hydrothermal Treatment on the Structure and Functional Properties of Quinoa Protein Isolate.

The aim of this study was to investigate the effects of hydrothermal treatment at different temperatures and times on the structure and functional properties of quinoa protein isolate (QPI). The structure of QPI was investigated by analyzing changes in the intrinsic fluorescence spectrum, ultra-violet (UV) spectrum, and Fourier transform infrared spectrum. The solubility, water/oil-holding capacity, emulsifying activity, and emulsion stability of QPI were studied, as were the particle size and the thermogravimetric properties of QPI. The results showed that the average particle size of QPI gradually increased with the increase in hydrothermal treatment time and temperature, and reached a maximum value of 121 °C for 30 min. The surface morphology also became rough and its thermal stability also increased. The endogenous fluorescence and UV spectral intensity at 280 nm decreased gradually with increasing hydrothermal treatment time and temperature, and reduced to the minimum values at 121 °C for 30 min, respectively. After hydrothermal treatment, the secondary structure of QPI tended to be disordered. The functional properties of QPI after treatment were all superior to those of the control. The results of this study might provide a basis for the processing and utilization of QPI.

Evidence construction of baicalin for treating myocardial ischemia diseases: A preclinical meta-analysis.

BACKGROUND: Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis Georgi, has shown potential pharmacological effects on myocardial ischemia diseases. Nevertheless, systematic preclinical studies on baicalin in the treatment of ischemic diseases are scarce. PURPOSE: To assess the efficacy and potential mechanisms of baicalin in myocardial ischemia (RI), myocardial ischemia-reperfusion (IR) injury and myocardial infarction (MI) animal models for future clinical research. METHODS: Preclinical studies published prior to August 27th, 2022 were retrieved from PubMed, Embase, Web of Science and Cochrane Library. CAMARADES list was used to evaluate the quality of included researches. Meta-analyses of cardiac pathology and function parameters, myocardial injury markers and other indicators were performed by STATA 15.0 software. Potential mechanisms are categorized and summarized. Dose-response interval analyses were used to analyze the dose-response relationship between baicalin and myocardial ischemia disease. RESULTS: Fourteen studies and 222 animals were included in the analysis. The results showed that compared with the control group, baicalin could reduce myocardial infarction size associated with cardiac pathological condition and the corresponding cardiac pathological index containing CK-MB, CK and cTnT. Additionally, heart function indicators including LVSP, LVFS, LVEF, -dp/dt max, dp/dt max were increased by baicalin. As for subgroup analyses, baicalin also demonstrated certain effect on CK-MB and LVSP by administration method or stage. Furthermore, it displayed obvious effect on myocardial ischemia diseases when the dose is maintained at 100-150 mg/kg based on dosage analyses. CONCLUSION: Based on the relevant literature retrieved, this is the first meta-analysis on baicalin in treating myocardial ischemia diseases. Notably, we linked the dynamic development of the disease and discussed it pertinently, from RI, IR injury to MI. Baicalin exhibits positive effects on myocardial ischemia diseases (especially when the dose is 100-150 mg/kg), which is achieved by regulating key pathological indicators and various signaling pathways.

Isolation of antioxidant peptides from yak casein hydrolysate.

Enzymatic hydrolysis of protein is a principal method to obtain antioxidant peptides. A yak casein hydrolysate (YCH) was prepared by alcalase and trypsin digestion. An ultrafiltration membrane system was used to divide the hydrolysate into four molecular weight fractions; YCH-4 (<3 kDa) had the highest antioxidant activity. Fraction YCH-4 was separated into six subfractions by gel filtration chromatography; reverse-phase high performance liquid chromatography (RP-HPLC) was then used to partition sixteen antioxidant peptide subfractions. Liquid chromatography/electrospray tandem mass spectrometry (LC-ESI-MS/MS) was used to determine the amino acid sequence of a purified antioxidant peptide to be Arg-Glu-Leu-Glu-Glu-Leu (787.41 Da). Finally, a synthetic Arg-Glu-Leu-Glu-Glu-Leu peptide was evaluated for its superoxide anion and hydroxyl radical scavenging activity (IC50 = 0.52 and 0.69 mg mL-1), which confirmed the activity of the native purified peptide. Our results suggested that isolation and purification of antioxidant peptides from yak casein could be an important means to obtain natural antioxidant peptides.

Differences in metabolic potential between particle-associated and free-living bacteria along Pearl River Estuary.

Particulate organic matter (POM) in aquatic ecosystem is critical for biogeochemical cycling and host distinct communities of microbes, compared to its surrounding water. In this study, the structures and functional potentials of microbial communities associated with particles or free-living in water samples from the Pearl River Estuary were investigated using 16S rRNA gene sequencing and GeoChip 5.0 analysis. Significant differences in the community structure and genetic functional potentials between particle-associated bacteria and free-living bacteria were observed across all eight sampling sites. In particle-associated bacteria communities, Rhodobacteraceae and Flavobacteriaceae were more abundant, while SAR11 clade and SAR86 clade were the most abundant in free-living bacteria communities. The richness and abundance of functional genes involved in nutrient cycling and stress response, including carbon degradation, nitrogen fixation, DMSP degradation, and polyphosphate degradation, were much higher in particle-associated bacteria compared with free-living bacteria. Thus, the particle-associated bacteria seem to play a much more important role in the biogeochemical cycles than free-living bacteria. In conclusion, the results from this study highlight the central role played by particle-associated bacteria in structuring microbial assemblages, and their importance for mediating biogeochemical cycling in the estuarine ecosystem.

Codonopsis pilosula polysaccharide attenuates Aß toxicity and cognitive defects in APP/PS1 mice.

Codonopsis pilosula Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aß toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aß42 and Aß40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPß and Aß42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aß pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.