Urinary proteomics for noninvasive monitoring of biomarkers of chronic mountain sickness in a young adult population using data-independent acquisition (DIA)-based mass spectrometry.

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SIGNIFICANCE: Our team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

The application of proteomics and phosphoproteomics to reveal the molecular mechanism of salidroside in ameliorating myocardial hypoxia.

Salidroside (SAL), belonging to a kind of the main active ingredient of Rhodiola rosea, is extensively utilized for anti-hypoxia and prevention of altitude sickness in the plateau region of China. However, the research on the systemic changes induced by SAL at intracellular protein level is still limited, especially at protein phosphorylation level. These limitations hinder a comprehensive understanding of the regulatory mechanisms of SAL. This study aimed to investigate the potential molecular mechanism of SAL in ameliorating the acute myocardial hypoxia induced by cobalt chloride using integrated proteomics and phosphoproteomics. We successfully identified 165 differentially expressed proteins and 266 differentially expressed phosphosites in H9c2 cells following SAL treatment under hypoxic conditions. Bioinformatics analysis and biological experiment validation revealed that SAL significantly antagonized CoCl2-mediated cell cycle arrest by downregulating CCND1 expression and upregulating AURKA, AURKAB, CCND3 and PLK1 expression. Additionally, SAL can stabilize the cytoskeleton through upregulating the Kinesin Family (KIF) members expression. Our study systematically revealed that SAL had the ability to protect myocardial cells against CoCl2-induced hypoxia through multiple biological pathways, including enhancing the spindle stability, maintaining the cell cycle, relieving DNA damage, and antagonizing cell apoptosis. This study supplies a comprehension perspective on the alterations at protein and protein phosphorylation levels induced by SAL treatment, thereby expanded our knowledge of the anti-hypoxic mechanisms of SAL. Moreover, this study provides a valuable resource for further investigating the effects of SAL.

The Effects of Cinobufagin on Hepatocellular Carcinoma Cells Enhanced by MRT68921, an Autophagy Inhibitor.

Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12-5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.

[Study on the sterilization effect of plasma jet and plasma activated water on Streptococcus mutans].

To explore the effects of plasma jet (PJ) and plasma activated water (PAW) on the sterilization of Streptococcus mutans ( S. mutans) and compare the advantages and disadvantages of the two methods, so as to provide a basis for plasma treatment of dental caries and to enrich the treatment means of dental caries, an atmospheric pressure plasma excitation system was built, and the effects of PJ and PAW on the sterilization rate of S. mutans and the changes of temperature and pH during treatment were studied under different excitation voltage ( U e ) and different excitation time ( t e ). The results showed that in the PJ treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.007, d=2.66) when U e = 7 kV and t e = 60 s, and complete sterilization was achieved at U e = 8 kV and t e = 120 s in the PJ treatment. In contrast, in the PAW treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.029, d = 1.71) when U e = 7 kV and t e = 30 s, and complete sterilization was achieved with PAW treatment when U e = 9 kV and t e = 60 s. Results of the monitoring of temperature and pH showed that the maximum temperature rise during PJ and PAW treatment did not exceed 4.3 °C, while the pH value after PAW treatment would drop to a minimum of 3.02. In summary, the optimal sterilization parameters for PJ were U e =8 kV and 90 s < t e ≤ 120 s, while the optimal sterilization parameters for PAW were U e = 9 kV and 30 s< t e ≤ 60 s. Both treatment methods achieved non-thermal sterilization of S. mutans, where PJ required only a smaller U e to achieve complete sterilization, while at pH < 4.7, PAW only required a shorter t e to achieve complete sterilization, but its acidic environment could cause some chemical damage to the teeth. This study can provide some reference value for plasma treatment of dental caries.

Dynamically Reversible Interconversion of Molecular Catalysts for Efficient Electrooxidation of Propylene into Propylene Glycol.

For the electrooxidation of propylene into 1,2-propylene glycol (PG), the process involves two key steps of the generation of *OH and the transfer of *OH to the C═C bond in propylene. The strong *OH binding energy (EB(*OH)) favors the dissociation of H2O into *OH, whereas the transfer of *OH to propylene will be impeded. The scaling relationship of the EB(*OH) plays a key role in affecting the catalytic performance toward propylene electrooxidation. Herein, we adopt an immobilized Ag pyrazole molecular catalyst (denoted as AgPz) as the electrocatalyst. The pyrrolic N-H in AgPz could undergo deprotonation to form pyrrolic N (denoted as AgPz-Hvac), which can be protonated reversibly. During propylene electrooxidation, the strong EB(*OH) on AgPz favors the dissociation of H2O into *OH. Subsequently, the AgPz transforms into AgPz-Hvac that possesses weak EB(*OH), benefiting to the further combination of *OH and propylene. The dynamically reversible interconversion between AgPz and AgPz-Hvac accompanied by changeable EB(*OH) breaks the scaling relationship, thus greatly lowering the reaction barrier. At 2.0 V versus Ag/AgCl electrode, AgPz achieves a remarkable yield rate of 288.9 mmolPG gcat-1 h-1, which is more than one order of magnitude higher than the highest value ever reported.

Highly Enhancing the Interfacial and Mechanical Properties of Basalt Fiber/Poly(phthalazinone ether nitrile ketone) Composite by Thermoplastic Sizing Agents with Different Structures.

The interfacial modification of basalt-fiber-reinforced polymer (BFRP) composites is an essential research field and many techniques have been developed to improve the adhesion between basalt fiber (BF) and the matrix. However, most studies were based on the matrixes of general plastics and epoxy resins. In this work, five different chain structures of thermoplastic sizing agents were used to improve the interfacial properties of unidirectional BF-reinforced soluble and high-temperature-resistant poly(phthalazinone ether nitrile ketone) (BF/PPENK) composites. DMA results showed that the poly(ether nitrile) (PEN)-sized BF/PPENK (BF-PEN/PPENK) composite exhibited the optimal interfacial performance, with a storage modulus (E') and glass transition temperature (Tg) up to 50 GPa and 288 °C, respectively. Moreover, the tensile strength, compressive strength, flexural strength, and interlaminar shear strength of the BF-PEN/PPENK composite reached 778 MPa, 600 MPa, 1115 MPa and 57 MPa, respectively, and increased by 42%, 49%, 20% and 30% compared with the desized BF/PPENK composite. This study provides some suggestions for the design of sizing agents to modify the interface of BF and high-performance thermoplastic resin.

Ambient-pressure hydrogenation of CO2 into long-chain olefins.

The conversion of CO2 by renewable power-generated hydrogen is a promising approach to a sustainable production of long-chain olefins (C4+=) which are currently produced from petroleum resources. The decentralized small-scale electrolysis for hydrogen generation requires the operation of CO2 hydrogenation in ambient-pressure units to match the manufacturing scales and flexible on-demand production. Herein, we report a Cu-Fe catalyst which is operated under ambient pressure with comparable C4+= selectivity (66.9%) to that of the state-of-the-art catalysts (66.8%) optimized under high pressure (35 bar). The catalyst is composed of copper, iron oxides, and iron carbides. Iron oxides enable reverse-water-gas-shift to produce CO. The synergy of carbide path over iron carbides and CO insertion path over interfacial sites between copper and iron carbides leads to efficient C-C coupling into C4+=. This work contributes to the development of small-scale low-pressure devices for CO2 hydrogenation compatible with sustainable hydrogen production.