Comparison of Protective Effects of Polyphenol-Enriched Extracts from Thinned Immature Kiwifruits and Mature Kiwifruits against Alcoholic Liver Disease in Mice.

Alcoholic liver disease (ALD) is regarded as one of the main global health problems. Accumulated evidence indicates that fruit-derived polyphenols can lower the risk of ALD, this attributed to their strong antioxidant capacities. Thinned immature kiwifruits (TIK) are the major agro-byproducts in the production of kiwifruits, which have abundantly valuable polyphenols. However, knowledge about the protective effects of polyphenol-enriched extract from TIK against ALD is still lacking, which ultimately restricts their application as value-added functional products. To promote their potential applications, phenolic compounds from TIK and their corresponding mature fruits were compared, and their protective effects against ALD were studied in the present study. The findings revealed that TIK possessed extremely high levels of total phenolics (116.39 ± 1.51 mg GAE/g DW) and total flavonoids (33.88 ± 0.59 mg RE/g DW), which were about 7.4 times and 4.8 times greater than those of their corresponding mature fruits, respectively. Furthermore, the level of major phenolic components in TIK was measured to be 29,558.19 ± 1170.58 µg/g DW, which was about 5.4 times greater than that of mature fruits. In particular, neochlorogenic acid, epicatechin, procyanidin B1, and procyanidin B2 were found as the predominant polyphenols in TIK. In addition, TIK exerted stronger in vitro antioxidant and anti-inflammatory effects than those of mature fruits, which was probably because of their higher levels of polyphenols. Most importantly, compared with mature fruits, TIK exhibited superior hepatoprotective effects on alcohol-induced liver damage in mice. The administration of polyphenol-enriched extract from TIK (YK) could increase the body weight of mice, reduce the serum levels of ALP, AST, and ALT, lower the levels of hepatic TG and TC, and diminish lipid droplet accumulation and hepatic tissue damage. In addition, the treatment of YK could also significantly restore the levels of antioxidant enzymes (e.g., SOD and CAT) in the liver and lower the levels of hepatic proinflammatory cytokines (e.g., IL-6, IL-1ß, and TNF-α), indicating that YK could effectively ameliorate ALD in mice by reducing hepatic oxidative stress and hepatic inflammation. Collectively, our findings can provide sufficient evidence for the development of TIK and their extracts as high value-added functional products for the intervention of ALD.

Therapeutic potential of archaeal unfoldase PANet and the gateless T20S proteasome in P23H rhodopsin retinitis pigmentosa mice.

Neurodegenerative diseases are characterized by the presence of misfolded and aggregated proteins which are thought to contribute to the development of the disease. In one form of inherited blinding disease, retinitis pigmentosa, a P23H mutation in the light-sensing receptor, rhodopsin causes rhodopsin misfolding resulting in complete vision loss. We investigated whether a xenogeneic protein-unfolding ATPase (unfoldase) from thermophilic Archaea, termed PANet, could counteract the proteotoxicity of P23H rhodopsin. We found that PANet increased the number of surviving photoreceptors in P23H rhodopsin mice and recognized rhodopsin as a substate in vitro. This data supports the feasibility and efficacy of using a xenogeneic unfoldase as a therapeutic approach in mouse models of human neurodegenerative diseases. We also showed that an archaeal proteasome, called the T20S can degrade rhodopsin in vitro and demonstrated that it is feasible and safe to express gateless T20S proteasomes in vivo in mouse rod photoreceptors. Expression of archaeal proteasomes may be an effective therapeutic approach to stimulate protein degradation in retinopathies and neurodegenerative diseases with protein-misfolding etiology.

A highly potential Zn biofortification tool: MTP1 in Triticum aestivum.

TaMTPs belong to metal tolerance proteins (MTPs) family in common wheat and have significant potential to address the "hidden hunger" caused by inadequate dietary intake of a key micronutrient (Zn). In this study, a total of 33 MTP members in Triticum aestivum were identified, among which six TaMTP1-likes were closely related to Arabidopsis thaliana MTP1 and were designated as TaMTP1-A/B/D and TaMTP1.1-A/B/D. When heterologously expressed in yeast mutants, TaMTP1-likes complemented their hypersensitivity to Zn and Co, and three of the most metal-resistant members, TaMTP1-A, TaMTP1-D and TaMTP1.1-B, were selected for further subcellular localization and functional experiment in Arabidopsis and rice. The results showed that all three proteins were localized in the vacuole membrane, that TaMTP1-D was more resistant to Zn and less resistant to Co than other TaMTP1-like members, and that TaMTP1-D was expressed at a higher level in the endosperm than other members. All results reveal that the use of TaMTP1-D for biofortification can substantially increase the content of Zn in the edible part of wheat and avoid the overaccumulation of Co, suggesting that TaMTP1-D is a potential Zn biofortifier / bioreinforcement.

Tuning interlayer stacking of 2D covalent organic frameworks for high-resolution separation of C8 aromatic isomers.

Covalent organic frameworks (COFs) has shown great potential as stationary phase in gas chromatography separation. However, designing COF stationary phases with high separation performance remains challenging. Here, we report a novel strategy to enhance the separation ability of COF stationary phases through tuning the interlayer stacking of COF. A rare interlayer modulation of 2D COFs from eclipsed-AA to slipped-AA was achieved through a two-step synthesis method. Simply changing the solvent used in step 1 allowed an interlayer modulation from slipped-AA to eclipsed-AA. As the proof-of-concept, 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphyrin (Tph) and 2,5-dihydroxyterephthalaldehyde (DHTA) were condensed to prepare 2D COF Tph-DHTA. The interlayer stacking of the 2D COF Tph-DHTA was tuned from eclipsed-AA model to slipped-AA by changing the solvent from o-dichlorobenzene + n-butanol (3:1, v/v) to tetrahydrofuran + n-butanol (1:7, v/v) in step 1. The as-prepared Tph-DHTA with slipped-AA stacking (s-Tph-DHTA) showed higher resolution and faster separation of C8 aromatic isomers than that with eclipsed-AA stacking (e-Tph-DHTA). The formation of slipping stacking of s-Tph-DHTA facilitated the thermodynamics, but did not affect the mass transfer resistance for the separation of C8 aromatic isomers. This work not only provides a promising way to modulate the stacking structure of COFs, but also opens a new strategy to design COF stationary phases for the separation of intractable isomers.

Characterization, Antioxidant Capacity, and Anti-Inflammatory Activity of Polyphenol-Enriched Extracts Obtained from Unripe, Mature, and Overripe Fruits of Red-Fleshed Kiwifruit Cultivars.

Discarded unripe kiwifruits (DUKs) are regarded as the major agro-byproducts in the production of kiwifruits, which have abundantly valuable secondary metabolites. Nevertheless, owing to the limited knowledge about the differences in phytochemicals and bioactivity between DUKs and mature kiwifruits, the utilization of DUKs in the food industry remains scarce. Hence, to promote their food applications, the phenolic compounds and bioactivity of discarded unripe, mature, and overripe fruits from three red-fleshed kiwifruit cultivars were studied and compared. The results revealed that the levels of total phenolics, total flavonoids, and total procyanidins in kiwifruits varied significantly by maturity stage. In addition, our findings demonstrated that DUKs possessed much higher contents of valuable phenolic compounds (e.g., chlorogenic acid (CHA), neochlorogenic acid (NCHA), gallic acid (GA), protocatechuic acid (PA), procyanidin B1 (ProcB1), procyanidin B2 (ProcB2), procyanidin C1 (ProcC1), quercetin 3-O-glucoside (QueG), and quercetin 3-O-rhamnoside (QueR)) than mature and overripe kiwifruits. Furthermore, DUKs exerted much stronger in vitro antioxidant capacity, inhibitory effects on α-glucosidase, and anti-inflammatory activity than mature and overripe kiwifruits, which were mainly attributed to their higher contents of total polyphenols and individual phenolic components, such as GA, CHA, NCHA, PA, ProcB1, ProcB2, ProcC1, and QueR. Overall, these findings provide sufficient evidence for the development and utilization of DUKs in the food/functional food industry.

Combining network pharmacology, machine learning, molecular docking and molecular dynamic to explore the mechanism of Chufeng Qingpi decoction in treating schistosomiasis.

Background: Although the Chufeng Qingpi Decoction (CQD) has demonstrated clinical effectiveness in the treatment of schistosomiasis, the precise active components and the underlying mechanisms of its therapeutic action remain elusive. To achieve a profound comprehension, we incorporate network pharmacology, bioinformatics analysis, molecular docking, and molecular dynamics simulations as investigative methodologies within our research framework. Method: Utilizing TCMSP and UniProt, we identified formula components and targets. Cytoscape 3.10.0 was used to construct an herb-target interaction network. Genecards, DisGeNET, and OMIM databases were examined for disease-related objectives. A Venn diagram identified the intersection of compound and disease targets. Using Draw Venn, overlapping targets populated STRING for PPI network. CytoNCA identified schistosomiasis treatment targets. GO & KEGG enrichment analysis followed High-scoring genes in PPI were analyzed by LASSO, RF, SVM-RFE. Molecular docking & simulations investigated target-compound interactions. Result: The component's target network encompassed 379 nodes, 1629 edges, highlighting compounds such as wogonin, kaempferol, luteolin, and quercetin. Amongst the proteins within the PPI network, PTGS2, TNF, TGFB1, BCL2, TP53, IL10, JUN, MMP2, IL1B, and MYC stood out as the most prevalent entities. GO and KEGG revealed that mainly involved the responses to UV, positive regulation of cell migration and motility. The signal pathways encompassed Pathways in cancer, Lipid and atherosclerosis, Fluid shear stress and atherosclerosis, as well as the AGE-RAGE. Bioinformatics analysis indicated TP53 was the core gene. Ultimately, the molecular docking revealed that wogonin, kaempferol, luteolin, and quercetin each exhibited significant affinity in their respective interactions with TP53. Notably, kaempferol exhibited the lowest binding energy, indicating a highly stable interaction with TP53. Lastly, we validated the stability of the binding interaction between the four small molecules and the TP53 through molecular dynamics simulations. The molecular dynamics simulation further validated the strongest binding between TP53 and kaempferol. In essence, our research groundbreaking in its nature elucidates for the first time the underlying molecular mechanism of CQD in the therapeutic management of schistosomiasis, thereby providing valuable insights and guidance for the treatment of this disease. Conclusion: This study uncovered the efficacious components and underlying molecular mechanisms of the Chufeng Qingpi Decoction in the management of schistosomiasis, thereby offering valuable insights for future fundamental research endeavors.

Utilizing diffusion tensor imaging as an image biomarker in exploring the therapeutic efficacy of forniceal deep brain stimulation in a mice model of Alzheimer's disease.

Objective.With prolonged life expectancy, the incidence of memory deficits, especially in Alzheimer's disease (AD), has increased. Although multiple treatments have been evaluated, no promising treatment has been found to date. Deep brain stimulation (DBS) of the fornix area was explored as a possible treatment because the fornix is intimately connected to memory-related areas that are vulnerable in AD; however, a proper imaging biomarker for assessing the therapeutic efficiency of forniceal DBS in AD has not been established.Approach.This study assessed the efficacy and safety of DBS by estimating the optimal intersection volume between the volume of tissue activated and the fornix. Utilizing a gold-electroplating process, the microelectrode's surface area on the neural probe was increased, enhancing charge transfer performance within potential water window limits. Bilateral fornix implantation was conducted in triple-transgenic AD mice (3 × Tg-AD) and wild-type mice (strain: B6129SF1/J), with forniceal DBS administered exclusively to 3 × Tg-AD mice in the DBS-on group. Behavioral tasks, diffusion tensor imaging (DTI), and immunohistochemistry (IHC) were performed in all mice to assess the therapeutic efficacy of forniceal DBS.Main results.The results illustrated that memory deficits and increased anxiety-like behavior in 3 × Tg-AD mice were rescued by forniceal DBS. Furthermore, forniceal DBS positively altered DTI indices, such as increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD), together with reducing microglial cell and astrocyte counts, suggesting a potential causal relationship between revised FA/MD and reduced cell counts in the anterior cingulate cortex, hippocampus, fornix, amygdala, and entorhinal cortex of 3 × Tg-AD mice following forniceal DBS.Significance.The efficacy of forniceal DBS in AD can be indicated by alterations in DTI-based biomarkers reflecting the decreased activation of glial cells, suggesting reduced neural inflammation as evidenced by improvements in memory and anxiety-like behavior.

Comparative Analysis of Gene Expression Profiles in Ovarian Clear Cell Carcinoma and High-Grade Serous Ovarian Cancer.

OBJECTIVE: To evaluate disparities in gene expression profiles between Ovarian Clear Cell Carcinoma (OCCC) and High-Grade Serous Ovarian Carcinoma (HGSOC). STUDY DESIGN: A descriptive study. Place and Duration of the Study: The Second People's Hospital of Jingdezhen, Jiangxi, China, between 31st December 2017 and December 2023. METHODOLOGY: Basic and clinical diagnostic information, along with genetic test reports, were compiled from all patients within the included groups. Differential gene expression between the two cohorts was scrutinised to elucidate its clinical significance. RESULTS: Comparative analysis revealed nine differentially expressed genes in OCCC relative to HGSOC, with six exhibiting significant disparities (p <0.05). These genes are implicated in pivotal cellular processes including the cell cycle, apoptosis, DNA damage repair, and the PI3K pathway. Notably, aberrant expression patterns, such as overexpression of MET and downregulation of PTEN and SMARCA4, correlated with adverse prognosis and survival outcomes in selected patients. CONCLUSION: Distinctive gene expression profiles between OCCC and HGSOC underscore disparate tumorigenic mechanisms, thereby laying a foundation for the tailored therapeutic interventions. Further elucidation of the identified differentially expressed genes is warranted to delineate their role in OCCC pathogenesis and prognostic significance. KEY WORDS: Ovarian clear cell carcinoma, High-grade serous ovarian cancer, Gene expression profiles, Homologous recombination repair.

Multiphysical field and multiobjective mathematical modeling of grain-oilseed storage: Current status and future trends.

Storage is an important process involved in the postharvest treatment of grain-oilseed and is necessary for maintaining high quality and ensuring the long-term supply of these commodities in the food industry. Proper storage practices help prevent spoilage, maintain nutritional value, and preserve marketable quality. It is of great interest for storage to investigate flow, heat and mass transfer processes, and quality change for optimizing the operation parameters and ensuring the quality of grain-oilseed. This review discusses the mathematical models developed and applied to describe the physical field, biological field, and quality change during the storage of grain-oilseed. The advantages, drawbacks, and industrial relevance of the existing mathematical models were also critically evaluated, and an organic system was constructed by correlating them. Finally, the future research trends of the mathematical models toward the development of multifield coupling models based on biological fields to control quality were presented to provide a reference for further directions on the application of numerical simulations in this area. Meanwhile, artificial intelligence (AI) can greatly enhance our understanding of the coupling relationships within grain-oilseed storage. AI's strengths in both qualitative and quantitative analysis, as well as its effectiveness, make it an invaluable tool for this purpose.

Identification and analysis correlation between hub genes and immune cell infiltration related to LPS-induced cognitive impairment.

Background: The occurrence of immunity and inflammation outside the central nervous system frequently results in acute cognitive impairment among elderly patients. However, there is currently a lack of standardized methods for diagnosing acute cognitive impairment. The objective of our study was to identify potential mRNA biomarkers and investigate the pathogenesis of acute cognitive impairment in mice brains. Methods: To analyze changes in hub genes associated with acute cognitive impairment, bioinformatics analysis was performed on the mouse brain injury data of sterile saline control group and lipopolysaccharide (LPS) induced experimental group in Gene Expression Omnibus (GEO). Functional analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), which facilitated to identify some potential mRNA biomarkers for hub gene expression in mice brains. Additionally, the "CIBERSORT X″ R kit was employed to examine immune cell infiltrations of mice brains in LPS group and saline group. Results: In the LPS and saline group, 102 significantly upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were identified. The pathway enrichment analysis using GO and KEGG revealed that these DEGs were mainly related to the regulation of cytokine, cytokine-cytokine receptor interaction, as well as protein interaction with cytokine and cytokine receptor. Immune cell infiltration analysis indicated potential involvement of M1 macrophages, NK cells resting, T cells CD4 memory, and T cells CD8 naive in the process of cognitive impairment. By constructing a protein-protein interaction (PPI) network, five hub genes (Cxcl10, Cxcl12, Cxcr3, Gbp2, and Ifih1) showed significant associations with immune cell types by using a threshold Spearman's rank correlation coefficient of R > 0.50 and p < 0.05. Conclusion: The mRNA expression profile of the mice brain tissues in the LPS group differed from that in the normal saline group. These significantly expressed mRNAs may act an importance in the pathogenesis of acute cognitive impairment through mechanisms involving immunity and neuroinflammation.

PM2.5-mediated cardiovascular disease in aging: Cardiometabolic risks, molecular mechanisms and potential interventions.

Air pollution, particularly fine particulate matter (PM2.5) with <2.5 µm in diameter, is a major public health concern. Studies have consistently linked PM2.5 exposure to a heightened risk of cardiovascular diseases (CVDs) such as ischemic heart disease (IHD), heart failure (HF), and cardiac arrhythmias. Notably, individuals with pre-existing age-related cardiometabolic conditions appear more susceptible. However, the specific impact of PM2.5 on CVDs susceptibility in older adults remains unclear. Therefore, this review addresses this gap by discussing the factors that make the elderly more vulnerable to PM2.5-induced CVDs. Accordingly, we focused on physiological aging, increased susceptibility, cardiometabolic risk factors, CVDs, and biological mechanisms. This review concludes by examining potential interventions to reduce exposure and the adverse health effects of PM2.5 in the elderly population. The latter includes dietary modifications, medications, and exploration of the potential benefits of supplements. By comprehensively analyzing these factors, this review aims to provide a deeper understanding of the detrimental effects of PM2.5 on cardiovascular health in older adults. This knowledge can inform future research and guide strategies to protect vulnerable populations from the adverse effects of air pollution.

Comparative analysis of phenolic compounds in different thinned unripe kiwifruits and their biological functions.

Thinned unripe kiwifruits (TUK) are considered the major agro by-products in kiwifruit production. To promote their potential applications, polyphenols and biological effects of unripe fruits from nine commercial kiwifruit cultivars were compared. Our findings showed that TUK were rich in bioactive polyphenols, which varied greatly by different cultivars. Indeed, catechin, epicatechin, procyanidin PB1, procyanidin B2, protocatechuic acid, neochlorogenic acid, and gallic acid were measured as the major phenolic components in most TUK, with the highest levels observed in 'Hongao' and 'Cuiyu' cultivars. Furthermore, TUK exerted strong in vitro antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory activities. Particularly, their stronger antioxidant effects and inhibitory effects on digestive enzymes were probably attributed to their higher contents of phenolic compounds, especially procyanidin B2. Collectively, our findings reveal that TUK are potential resources of valuable polyphenols, which can be exploited as natural antioxidants and natural inhibitors of α-glucosidase and α-amylase.

Treatment outcome of bridge mechanical thrombectomy with different IV-tPA dosages in the standard and extended time window in real-world practice.

BACKGROUND: Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows. MATERIALS AND METHODS: Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9 mg/kg) or reduced (<0.9 mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6 h of acute ischemic stroke onset, while those beyond 6 h as the extended window (EW) cohort. 90 days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. RESULTS: A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90 days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199). CONCLUSION: In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.

Diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules.

OBJECTIVES: To investigate the diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. METHODS: The clinical data, ultrasonic images, C-TIRADS categories and CEUS images of 192 patients with indeterminate FNA cytological thyroid nodules confirmed by the surgical pathology were analyzed retrospectively. The diagnostic efficacy of CEUS, C-TIRADS and CEUS-TIRADS were calculated. RESULTS: The AUCs of CEUS, C-TIRADS and CEUS-TIRADS were 0.905 (95% CI: 0.862∼0.949), 0.881 (95% CI: 0.825∼0.938) and 0.954 (95% CI: 0.922∼0.986), respectively. The sensitivity, specificity, PPV, NPV, accuracy, LR- and LR+ were 84.7% (116/137), 85.5% (47/55), 93.5% (116/124), 69.1% (47/68), 84.9% (163/192), 0.179, 5.82 and 84.7% (116/137), 83.6% (46/55), 92.8% (116/125), 68.7% (46/67), 84.4% (162/192), 0.183, 5.17, 92.7% (127/137), 89.1% (49/55), 95.5% (127/133), 83.1% (49/59), 91.7% (176/192), 0.082, and 8.50, respectively. Compared with CEUS and C-TIRADS, CEUS-TIRADS had improved the AUC, sensitivity and accuracy (all P < 0.05). CONCLUSIONS: CEUS and C-TIRADS had high diagnostic values in indeterminate FNA cytological thyroid nodules. CEUS-TIRADS improved AUC, diagnostic sensitivity and accuracy, and helped to distinguish indeterminate FNA cytological nodules.