Search

Objective To explore the characteristics of macroautophagy and molecular chaperone-mediated autophagy (CMA) in the oxidative stress injury of human umbilical vein endothelial cells (HUVECs). Methods After HUVECs were treated with oxidized low density lipoprotein (OX-LDL) at different concentrations(0、20、50、100、200 μg/mL), the production of reactive oxygen species (ROS) was measured to screen the optimal concentration to induce HUVECs oxidative stress. The cells were divided into 4 groups: control group (without any treatment), macroautophagy inhibition group (treated with 10 mmol/L 3-MA, specific inhibitor of macroautophagy), oxidative stress group (treated with 50 μg/mL OX-LDL), and macroautophagy inhibition-oxidative stress group (treated with 10 mmol/L 3-MA+50 μg/mL OX-LDL). The expression levels of proliferation marker protein PCNA, apoptosis marker Caspase-3, macroautophagy marker Beclin-1, and CMA markers Hsc70 and Lamp-2 were detected in each group with Western blotting. The proliferation, apoptosis, 2 kinds of autophagy under different treatments were evaluated respectively. After the cells of the oxidative stress group and macroautophagy inhibition-oxidative stress group were treated for different duration (1, 3, 6, 12 and 48 h), the proliferation and apoptosis of HUVECs were tested by CCK-8 assay and Annexin-V/PI double staining, respectively. Western blotting was adopted to determine the protein levels of Beclin-1, Hsc70 and Lamp-2. Finally, the time regulation characteristics of the 2 autophagy pathways before and after macroautophagy inhibition were analyzed. Results Under OX-LDL induced oxidative stress, the ROS level was elevated with the increase of OX-LDL concentration, and 50 μg/mL was finally selected as the appropriate concentration for subsequent experiments. As compared with the control group, the levels of Caspase-3, Beclin-1, Hsc70 and Lamp-2 were up-regulated, while that of PCNA was down-regulated in the oxidative stress group (P < 0.05). With the prolongation of treatment time, proliferation inhibition rate, overall apoptotic rate and Lamp-2 level were increased within 48 h, Hsc70 level was elevated after 6 h, and that of Beclin-1 was improved within 12 h in the oxidative stress group (P < 0.05). In the macroautophagy inhibition-oxidative stress group, the expression levels of Caspase-3, Hsc70 and Lamp-2 were also up-regulated, that of PCNA down-regulated (P < 0.05), those of Hsc70 and Lamp-2 were increased at the same time and that of Hsc70 was in an elevation after 3 h of treatment (P < 0.05). Conclusion Macroautophagy and CMA are activated successively during the process of oxidative stress, and CMA can be enhanced after macroautophagy inhibition. The early activation contributes to attenuate oxidative stress-induced damage to endothelial cells.

Introduction: This study aimed to investigate the effects of Isalo scorpion cytotoxic peptide (IsCT) on the growth performance, immune function, and gut microbiota of yellow-feathered broilers. Methods: The experiment involved supplementing a corn-soybean meal-based diet with various dietary levels of IsCT. The experiment adopted a completely randomized design. A total of 240 one-day-old yellow-feathered broilers were randomly divided into six groups: a control group (CON), a chlortetracycline group (CTC), and four groups receiving a basal diet with 50, 100, 150, or 200 mg/ kg IsCT (IsCT50, IsCT100, IsCT150, and IsCT200). The trial period lasted 60 days. Results: The results showed that the average final body weight and average daily weight gain of the IsCT150 and IsCT200 groups were significantly higher than those of the CON group (p < 0.05). Compared to the CTC group, the average daily feed intake in group III was significantly lower (p < 0.05). The feed conversion ratios of the IsCT150 and IsCT200 groups were significantly lower than those of the IsCT50 and CON groups (p < 0.05). Albumin levels in the CTC and IsCT150 groups were significantly higher than those in the CON, IsCT100, and IsCT50 groups. Alanine transaminase levels in the IsCT150 group were significantly lower than those in the IsCT50, IsCT200, CON, and CTC groups (p < 0.05), but there was no significant difference compared with the IsCT100 group (p < 0.05). IgA levels in the IsCT150, IsCT200, and CTC groups were significantly higher than those in the IsCT50 group (p < 0.05). IgG levels in the CTC, IsCT100, IsCT150, and IsCT200 groups were significantly higher than those in the IsCT50 and CON groups (p < 0.05). 16S rRNA sequencing indicated significant differences in the caecal microbiota between the IsCT and CON groups (p < 0.05). The abundance of Bacteroidetes increased, whereas that of Firmicutes decreased in the IsCT groups; however, the difference was not significant (p < 0.05). The relative abundances of Actinobacteriota and Patescibacteria were significantly different in the IsCT100 group (p < 0.05). Discussion: In conclusion, supplementing the basal diet with IsCT improved growth performance, immune function, and gut microbiota of yellow-feathered broilers at an optimal supplementation level of 150 mg/kg. [ABSTRACT FROM AUTHOR]

Background: Detection of gastric cancer (GC) at early stages is an effective strategy for decreasing mortality. This study aimed to construct a prediction nomogram based on a questionnaire to assess the risk of developing GC. Methods: Our study comprised a total of 4379 participants (2326 participants from outpatient at Fengqing People's Hospital were considered for model development and internal validation, and 2053 participants from outpatients at the endoscopy center at the Seventh Affiliated Hospital of Sun Yat-Sen University were considered for independent external validation) and gastric mucosa status was determined by endoscopy and biopsies. The eligible participants in development cohort from Fengqing people's Hospital were randomly separated into a training cohort (n=1629, 70.0%) and an internal validation cohort (n=697, 30.0%). The relevant features were selected by a least absolute shrinkage and selection operator (LASSO), and the ensuing features were evaluated through multivariable logistic regression analysis. Subsequently, the variables were selected to construct a prediction nomogram. The discriminative ability and predictive accuracy of the nomogram were evaluated by the C-index and calibration plot, respectively. Decision curve analysis (DCA) curves were used for the assessment of clinical benefit of the model. This model was developed to estimate the risk of developing neoplastic lesions according to the "transparent reporting of a multivariable prediction model for individual prognosis or diagnosis" (TRIPOD) statement. Results: Six variables, including age, sex, alcohol consumption, cigarette smoking, education level, and Hp infection status, were independent risk factors for the development of neoplastic lesions. Thus, these variables were incorporated into the final nomogram. The AUC of the nomogram were 0.701, 0.657 and 0.699 in the training, internal validation, and external validation cohorts, respectively. The calibration curve showed that the nomogram was in good agreement with the observed outcomes. Compared to treatment of all patients or none, our nomogram showed a notably higher clinical benefit. Conclusion: This nomogram proved to be a convenient, cost-effective tool to effectively predict an individual's risk of developing neoplastic lesions, and it can act as a prescreening tool before gastroscopy. [ABSTRACT FROM AUTHOR]

The industrial application of pea protein is limited due to its poor gelation properties. This study aimed to evaluate the effects of psyllium husk powder (PHP) on improving the rheological, textural, and structural properties of heat-induced pea protein isolate (PPI) gel. Scanning electron microscopy (SEM), intermolecular forces analysis, the quantification of the surface hydrophobicity and free amino groups, and Fourier transform infrared spectroscopy (FTIR) were conducted to reveal the inner structures of PPI-PHP composite gels, conformational changes, and molecular interactions during gelation, thereby clarifying the underlying mechanism. The results showed that moderate levels of PHP (0.5–2.0%) improved the textural properties, water holding capacity (WHC), whiteness, and viscoelasticity of PPI gel in a dose-dependent manner, with the WHC (92.60 ± 1.01%) and hardness (1.19 ± 0.02 N) peaking at 2.0%. PHP significantly increased surface hydrophobicity and enhanced hydrophobic interactions, hydrogen bonding, and electrostatic interactions in PPI-PHP composite gels. Moreover, the electrostatic repulsion between anionic PHP and negatively charged PPI in a neutral environment prevented the rapid and random aggregation of proteins, thereby promoting the formation of a well-organized gel network with more β-sheet structures. However, the self-aggregation of excessive PHP (3.0%) weakened molecular interactions and disrupted the continuity of protein networks, slightly reducing the gel strength. Overall, PHP emerged as an effective natural gel enhancer for the production of pea protein gel products. This study provides technical support for the development of innovative plant protein-based foods with strong gel properties and enriched dietary fiber content. [ABSTRACT FROM AUTHOR]

An integrated transcriptome and metabolome profiling was used to investigate how exogenous H2O2 affects amino acid metabolism and its underlying regulatory mechanism involved in post-harvest broccoli's yellowing and senescence processes. This approach found 86 differentially expressed genes (DEGs) and 28 differentially accumulated metabolites (DAMs) associated with amino acid metabolism during broccoli storage in the Control, H2O2, and DPI (diphenylene iodonium, an H2O2 inhibitor) treatments on 2 or 4 d. Furthermore, H2O2 treatment promoted the biosynthesis and accumulation of amino acids (e.g., tryptophan, valine, isoleucine, arginine, lysine, histidine, and glutamate) while inhibiting the degradation of seven amino acids (e.g., tyrosine, valine, leucine, isoleucine, β-alanine, glutamate, and proline) into tricarboxylic acid (TCA) cycle precursor (pyruvate) and intermediates (fumarate, acetyl-CoA, and 2-oxoglutarate). This inhibition alleviated metabolic disorders and ammonium-induced toxicity of post-harvest broccoli. Additionally, H2O2 treatment promoted the NH3 conversion into glutamine and the urea cycle, further mitigating ammonium-induced toxicity. H2O2 treatment also down-regulated the expressions of S-adenosylmethionine synthases (SAM), 1-aminocyclopropane-1-carboxylate synthases (ACS), and 1-aminocyclopropane-1-carboxylate oxidases (ACO), which reduced the S-adenosyl-L-methionine content, thereby inhibiting ethylene biosynthesis from methionine. Therefore, this study provides insights into the role and potential underlying regulatory mechanism of H2O2 on amino acid metabolism during broccoli senescence, thus offering a theoretical basis for delaying senescence in post-harvest horticultural products by regulating their amino acid metabolism. [ABSTRACT FROM AUTHOR]

To understand the effects and related potential mechanism of H2O2 on pigment metabolism in postharvest broccoli, an integrated analysis of transcriptome and metabolome was performed. Results suggested that 65 differentially expressed genes and 26 differentially accumulated metabolites involved in chlorophyll, carotenoid, and flavonoid metabolism were identified. H2O2 treatment delayed the decrease of chlorophyll content by upregulating the expressions of chlorophyll synthetic genes, thylakoid synthetic genes, and 15 light‐harvesting complex genes compared with the control and diphenylene iodonium treatments. H2O2 treatment decreased the accumulation of 11 flavonoids and 5 flavonols by downregulating the flavonoid synthetic genes. In addition, H2O2 treatment promoted carotenoid biosynthesis to eliminate reactive oxygen species in thylakoids, thereby protecting chlorophyll molecules from degradation. The inhibition of flavonoids and flavonols accumulation and chlorophyll decrease was the crucial reason for the delayed yellowing in H2O2 treatment. This study provides a new method and theoretical support for delaying the yellowing process in postharvest broccoli. [ABSTRACT FROM AUTHOR]

The electromagnetic environment faced by modern radar is becoming increasingly complex. One effective means to improve the performance of radar systems is testing in an anti-jamming ability test chamber, where the increased complexity has also led to higher performance requirements for radar jamming simulators. Based on the requirements for modern radar system testing, this paper presents a study of a large-bandwidth real-time radar jamming simulator and describes its overall design architecture; the simulator covers the L-Ku and Ka frequency bands and the instantaneous bandwidth is ≥2 GHz, which means that the system is able to simulate 11 interference patterns. Synchronous control of the system is realized in 1 ms through use of the reflection memory interrupt mechanism, the synchronous pulse signal mechanism, synchronous timing design, and a real-time control software architecture. An overall design scheme for real-time simulation of a radar target jamming echo is given and baseband signal processing resources are saved through information preprocessing, a large-capacity high-speed storage board is designed to improve the data reading speed, a multiphase filtering structure is used to achieve high sampling rates and save hardware resources, and a high-speed parallel computing method is used to improve computing efficiency; the actual measured baseband signal processing time is less than 500 ns. Finally, a measurement platform is built, and the main interference patterns are verified through experimental measurements. [ABSTRACT FROM AUTHOR]

(1) Background: Mianning ham is a dry-cured ham from Southwest China, known for its distinct regional characteristics and delicious taste. It is particularly favored by consumers due to its safety, as no artificial nitrites are added during processing. The microbial changes during its different processing stages significantly influence the final product's flavor. This study aims to investigate the changes in microbial communities and flavor compounds across the nine stages of Mianning ham production, from raw material preparation to salting, drying, fermentation, and maturation, using 16S and ITS sequencing, as well as solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS). The goal is to explore the correlation between these changes and provide a basis for process improvement from the initial raw material preparation. (2) Results: The microbiota of Mianning ham across different processing stages mainly consisted of Proteobacteria, Firmicutes, and Ascomycota. A total of 324 volatile compounds were identified, of which 27 were key contributors to the ham's flavor. Aldehydes contributed the most to flavor, with octanal, trans-2-nonenal, and trans, trans-2,4-decadienal being the most significant contributors at various stages. Mature Mianning ham, fermented for 1–3 years, exhibited fresh grass and earthy aromas, buttery and fatty flavors, and a distinctive roasted potato note. Correlation analysis revealed that Cobetia was the primary bacterial contributor to the main flavor compounds, especially prominent in the second year of fermentation. Among fungi, Yamadazyma and Aspergillus positively influenced several key aldehyde flavor compounds throughout the processing stages, significantly contributing to the flavor profile of Mianning ham. (3) Conclusions: Correlation analysis showed that the Mianning ham that matured for two years had the richest and most characteristic flavor. The positive and consistent impact of fungi on the ham's flavor suggests that they may warrant further research and application in Mianning ham production. This provides a theoretical basis for improving the flavor quality and enhancing the market competitiveness of Mianning ham. One of the key features of Mianning ham is its substantial accumulation of hydrocarbons, which surpasses that of hams from other regions in China. A notable characteristic of Mianning ham processing is the absence of artificially added nitrites as antioxidants and color fixatives. Whether this absence is a contributing factor to the significant accumulation of hydrocarbons warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the specific areas of knowledge gaps regarding lactose intolerance among neonatologists in Chinese outpatient settings as well as to assess the availability of lactose intolerance testing in hospitals. Methods: A total of 278 neonatologists in outpatient settings from 144 hospitals were surveyed. To explore the awareness level, diagnosis, and treatment of neonatal lactose intolerance among neonatologists in outpatient settings, a multicenter cross-sectional survey was designed. Descriptive analysis based on frequency and percent distribution was performed for all variables. Results: Most respondents were senior doctors (256, 92.09%) from general hospitals and maternity/maternal and child health hospitals, had over 10 years of experience, and were dominantly associate chief physicians and chief physicians (211, 75.90%). A significant proportion of the participants (236, 84.89%) believed that neonatal lactose intolerance tends to be overlooked during clinical practice. When the most common symptoms of neonatal lactose intolerance were surveyed, diarrhea was selected by 142 (51.08%) respondents, followed by bloating and milk regurgitation or emesis (71, 25.54%). Other symptoms included unexplained crying (36, 12.85%), stool with milk flap or foam (15, 5.40%), and increased venting (14, 5.04%). Furthermore, the survey results indicated that the most common method for diagnosing neonatal lactose intolerance in the respondents' hospitals was qualitative test for urinary galactose (78, 28.06%). Of the respondents, 137 (49.28%) stated that their hospital could not test for lactose intolerance. For treating lactose intolerance, the neonatologists primarily opted for exogenous lactase rather than lactose-free formula milk. Conclusions: This study sheds light on Chinese neonatologists' awareness of neonatal lactose intolerance, revealing some knowledge gaps. The expeditious popularization and conduct of lactose intolerance-related examinations in hospitals will have a positive stimulative effect on the management of lactose intolerance in newborns. [ABSTRACT FROM AUTHOR]