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2.
Food Res Int ; 190: 114634, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945623

ABSTRACT

Drying is an important stage used to improve the quality of white tea (WT). However, the effect of the drying temperature on the key taste compounds in WT remains unclear. In this study, targeted metabolomics, molecular docking, and a simulated reaction were used to investigate the transformation mechanism of flavonoid glycosides (FGs) in WT during drying at 60, 80, and 100 °C and its impact on taste. There were 45 differential FGs in WT at three drying temperatures. Compared with the withering samples for 48 h, the total FGs contents at three drying temperatures showed a decreasing trend, with quercetin-3-O-galactoside and kaempferol-3-O-glucoside showing the most degradation. These results were confirmed via a simulated drying reaction of FGs standards. Drying at 80 and 100 °C contributed to the formation of flavonoid-C-glycosides, but only trace amounts of these compounds were observed. In addition, nine key taste FGs were selected using dose-over-threshold values. These FGs regulated the taste of WT, mainly by binding to taste receptors via hydrogen bond, hydrophobic and electrostatic interactions. Finally, the taste acceptability of WT dried at 60 °C was found to be the highest, as this method could properly reduce the contents of FGs, weaken the bitterness and astringency, and retain the sweet and umami taste. This study revealed for the first time the transformation mechanism of sensory-active FGs affected by drying temperature, which provides a novel perspective for the analysis of the formation mechanism of the unique flavor of WT and the optimization of this process.


Subject(s)
Flavonoids , Glycosides , Metabolomics , Molecular Docking Simulation , Tea , Flavonoids/chemistry , Flavonoids/analysis , Glycosides/chemistry , Tea/chemistry , Metabolomics/methods , Desiccation/methods , Taste , Temperature , Humans , Food Handling/methods , Camellia sinensis/chemistry
3.
Sci Total Environ ; 943: 173886, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38857791

ABSTRACT

Capturing long-term dynamics and the potential under climate change of woody aboveground biomass (AGB) is imperative for calculating and raising carbon sequestration of afforestation in dryland. It is always been a great challenge to accurately capture AGB dynamics of sparse woody vegetation mixed with grassland using only Landsat time-series, resulting in changing trajectory of woody AGB estimates cannot accurately reflect woody vegetation growth regularity in dryland. In this study, surface reflectance (SR) sensitive to woody AGB was firstly selected and interannual time-series of composited SR was smoothed using S-G filter for each pixel, and then optimal machine learning algorithm was selected to estimate woody AGB time-series. Pixels that have reached AGB potential were detected based on the AGB changing trajectory, and the potential was spatial-temporal extended using random forest model combining environmental variables under current climate condition and CMIP6 climate models. Results show that: 1) minimum value composite based on NIRv during Jul.-Sep. is more capable of explaining woody AGB variation in dryland (R = 0.87, p < 0.01), and Random Forest (RF) model has the best performance in estimating woody AGB (R2 = 0.75, RMSE = 4.74 t·ha-1) among sis commonly used machine learning models. 2) Annual woody AGB estimates can be perfectly fitted with a logistic growth curve (R2 = 0.97, p < 0.001) indicating explicit growth regularity of woody vegetation, which provides physiological foundation for determining woody AGB potential. 3) Woody AGB potential can be accurately simulated by RF combining environmental variables (R2 = 0.95, RMSE = 2.89 t·ha-1), and current woody AGB still has a potential of small increase, whereas the overall losses of woody AGB potential were observed in 2030, 2040 and 2050 under CMIP6 SSP-RCP scenarios.

4.
J Org Chem ; 89(12): 8363-8375, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38848119

ABSTRACT

Palladium-catalyzed decarboxylation of 5-methylene-1,3-oxazinan-2-ones and 5-methylene-1,3-dioxan-2-ones to generate aza-π-allylpalladium and oxa-π-allylpalladium 1,4-dipoles for [4 + 2] cycloaddition reaction with 1,3,5-triazinanes was developed, affording a wide range of hexahydropyrimidine and 1,3-oxazinane derivatives in good to excellent yields (up to 99%). The acyclic sulfonamido-substituted allylic carbonates as aza-π-allylpalladium 1,4-dipole precursors also apply to the developed synthesized strategy, achieving the synthesis of hexahydropyrimidines. Moreover, the in situ-generated aza-π-allylpalladium 1,4-dipoles undergoing dimeric [4 + 4] cycloaddition were also demonstrated by the construction of 1,5-diazocane derivatives.

5.
Plant J ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38838090

ABSTRACT

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

6.
3 Biotech ; 14(7): 174, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38855147

ABSTRACT

Due to the medicinal importance of the flowers of Xianglei type (XL) Lonicera macranthoides, it is important to understand the molecular mechanisms that underlie their development. In this study, we elucidated the transcriptomic and metabolomic mechanisms that underlie the flower development mechanism of two L. macranthoides varieties. In this study, 3435 common differentially expressed unigenes (DEGs) and 1138 metabolites were identified. These common DEGs were mainly enriched in plant hormone signal transduction pathways. Metabolomic analysis showed that amino acids were the main metabolites of differential accumulation in wild-type (WT) L. macranthoides, whereas in XL, they were flavonoids and phenylalanine metabolites. Genes and transcription factors (TFs), such as MYB340, histone deacetylase 1 (HDT1), small auxin-up RNA 32 (SAUR32), auxin response factor 6 (ARF6), PIN-LIKES 7 (PILS7), and WRKY6, likely drive metabolite accumulation. Plant hormone signals, especially auxin signals, and various TFs induce downstream flower organ recognition genes, resulting in a differentiation of the two L. macranthoides varieties in terms of their developmental trajectories. In addition, photoperiodic, autonomous, and plant hormone pathways jointly regulated the L. macranthoides corolla opening. SAUR32, Arabidopsis response regulator 9 (ARR9), Gibberellin receptor (GID1B), and Constans-like 10 (COL10) were closely related to the unfolding of the L. macranthoides corolla. These findings offer valuable understanding of the flower growth process of L. macranthoides and the excellent XL phenotypes at the molecular level. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04019-1.

7.
Tree Physiol ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857368

ABSTRACT

Flavonoids (especially anthocyanins and catechins) and amino acids represent the high abundance of health-promoting metabolites. Although we observed ABA accumulation in purple leaves and low levels in albino tea leaves, the specific mechanism behind its impact on flavor compounds remains unclear. In this study, we treated tea leaves with exogenous ABA and ABA biosynthesis inhibitors (Flu), measured physiological indicators, and conducted comprehensive transcriptomic and metabolomic analyses to elucidate the potential mechanisms underlying color change. Our results demonstrate that ABA treatment induces purple coloration, while Flu treatment causes discoloration in tea leaves. Metabolomic analysis revealed higher levels of four anthocyanins and six catechins in the group treated with ABA in comparison to the control group. Additionally, there was a notable increase in 15 amino acids in the Flu-treated group. Notably, the levels of flavonoids and amino acids showed an inverse relationship between the two treatments. Transcriptomic comparison between the treatments and the control group revealed upregulation of differentially expressed genes (DEGs) encoding DFR and UFGT in the ABA-treated group, leading to the accumulation of identified anthocyanins and catechins. In contrast, DEGs encoding NR and NRT exhibited elevated expression in the group treated with Flu, consequently facilitating the accumulation of amino acids, specifically L-theanine and L-glutamine. Furthermore, our co-expression network analysis suggests that MYB and bHLH transcription factors (TFs) may play crucial roles in regulating the expression of DEGs involved in the biosynthesis of flavonoids and amino acids. This study provides insights for targeted genetic engineering to enhance the nutritional and market value of tea, together with the potential application of purple and albino tea leaves as functional beverages. It also offers guidance for future breeding programs and production.

8.
Food Chem ; 455: 139931, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38850976

ABSTRACT

In this study, we characterized the aroma profiles of different Rougui Wuyi rock tea (RGWRT) aroma types and identified the key aroma-active compounds producing these differences. The roasting process was found to have a considerable effect on the aroma profiles. Eleven aroma compounds, including linalool, ß-ionone, geraniol, indole, and (E)-nerolidol, strongly affected the aroma profiles. An RGWRT aroma wheel was constructed. The rich RGWRT aroma was found to be dominated by floral, cinnamon-like, and roasty aromas. Human olfaction was correlated with volatile compounds to determine the aromatic characteristics of these compounds. Most key aroma-active compounds were found to have floral, sweet, and herbal aromas (as well as some other aroma descriptors). The differences in key compounds of different aroma types were found to result from the methylerythritol phosphate, mevalonic acid and shikimate metabolic pathways and the Maillard reaction. Linalool, geraniol, and (E,E)-2,4-heptadienal were found to spontaneously bind to olfactory receptors.

9.
Viruses ; 16(6)2024 May 27.
Article in English | MEDLINE | ID: mdl-38932147

ABSTRACT

Peanut stem rot is a soil-borne disease caused by Agroathelia rolfsii. It occurs widely and seriously affects the peanut yield in most peanut-producing areas. The mycoviruses that induce the hypovirulence of some plant pathogenic fungi are potential resources for the biological control of fungal diseases in plants. Thus far, few mycoviruses have been found in A. rolfsii. In this study, two mitoviruses, namely, Agroathelia rolfsii mitovirus 1 (ArMV1) and Agroathelia rolfsii mitovirus 2 (ArMV2), were identified from the weakly virulent A. rolfsii strain GP3-1, and they were also found in other A. rolfsii isolates. High amounts of ArMV1 and ArMV2in the mycelium could reduce the virulence of A. rolfsii strains. This is the first report on the existence of mitoviruses in A. rolfsii. The results of this study may provide insights into the classification and evolution of mitoviruses in A. rolfsii and enable the exploration of the use of mycoviruses as biocontrol agents for the control of peanut stem rot.


Subject(s)
Arachis , Fungal Viruses , Phylogeny , Plant Diseases , RNA Viruses , Arachis/virology , Arachis/microbiology , Plant Diseases/virology , Plant Diseases/microbiology , RNA Viruses/genetics , RNA Viruses/classification , RNA Viruses/isolation & purification , Fungal Viruses/classification , Fungal Viruses/isolation & purification , Fungal Viruses/genetics , Genome, Viral , Virulence , RNA, Viral/genetics
10.
Curr Med Sci ; 44(3): 561-567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38809380

ABSTRACT

OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Restenosis , Humans , Male , Female , Middle Aged , Coronary Restenosis/etiology , Coronary Restenosis/diagnostic imaging , Retrospective Studies , Aged , Angioplasty, Balloon, Coronary/methods , Angioplasty, Balloon, Coronary/adverse effects , Drug-Eluting Stents , Follow-Up Studies , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiopathology , Coronary Vessels/surgery
11.
Foods ; 13(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731686

ABSTRACT

Rougui Tea (RGT) is a typical Wuyi Rock Tea (WRT) that is favored by consumers for its rich taste and varied aroma. The aroma of RGT is greatly affected by the process of green-making, but its mechanism is not clear. Therefore, in this study, fresh leaves of RGT in spring were picked, and green-making (including shaking and spreading) and spreading (unshaken) were, respectively, applied after sun withering. Then, they were analyzed by GC-TOF-MS, which showed that the abundance of volatile compounds with flowery and fruity aromas, such as nerolidol, jasmine lactone, jasmone, indole, hexyl hexanoate, (E)-3-hexenyl butyrate and 1-hexyl acetate, in green-making leaves, was significantly higher than that in spreading leaves. Transcriptomic and proteomic studies showed that long-term mechanical injury and dehydration could activate the upregulated expression of genes related to the formation pathways of the aroma, but the regulation of protein expression was not completely consistent. Mechanical injury in the process of green-making was more conducive to the positive regulation of the allene oxide synthase (AOS) branch of the α-linolenic acid metabolism pathway, followed by the mevalonate (MVA) pathway of terpenoid backbone biosynthesis, thus promoting the synthesis of jasmonic acid derivatives and sesquiterpene products. Protein interaction analysis revealed that the key proteins of the synthesis pathway of jasmonic acid derivatives were acyl-CoA oxidase (ACX), enoyl-CoA hydratase (MFP2), OPC-8:0 CoA ligase 1 (OPCL1) and so on. This study provides a theoretical basis for the further explanation of the formation mechanism of the aroma substances in WRT during the manufacturing process.

12.
Lancet Reg Health West Pac ; 46: 101078, 2024 May.
Article in English | MEDLINE | ID: mdl-38745974

ABSTRACT

Background: Parkinson's disease (PD) has become a public health concern with global ageing. However, comprehensive assessments of the temporal and geographical trend of PD disease burden in China remain insufficient. This study aimed to examine the burden of PD by age, gender, and geographical region in China during 1990-2021. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we analysed the incidence, prevalence, mortality, and DALY burden of PD in 33 Chinese provinces/regions. We compared the national figure with the global average and the corresponding estimates from the G20 countries. The estimated annual percentage change (EAPC) was used to quantify the temporal trends of PD burden during 1990-2021. We further assessed the PD burden by age and gender during 1990-2021. We used a decomposition analysis to investigate the changes in the number of new cases, patients, and deaths of PD during 1990-2021. Findings: In 2021, China recorded the highest age-standardised incidence and prevalence of PD among the G20 countries, at 24.3 per 100,000 and 245.7 per 100,000, respectively, figures that were much higher than the global average. During 1990-2021, the age-standardised incidence of PD in China increased by 89.7%, and the age-standardised prevalence by 167.8%, both marking the largest increases among the G20 countries. In contrast, the age-standardised mortality for PD has significantly decreased since 1990, whereas the age-standardised DALY rate for PD has remained relatively unchanged since 1990. The PD burden gradually increased with age, especially in the elderly population aged ≥65 years. During 1990-2021, the burden in males consistently surpassed that in females, with the gender difference widening over time. The increase in new cases and patients of PD was primarily driven by changes in age-specific rates, while the rise in PD-related deaths was largely attributable to population ageing. The disease burden of PD varied considerably across the Chinese provinces. In 2021, age-standardised incidence and prevalence of PD were generally higher in China's southeastern coastal regions than in the western regions, and age-standardised DALY rates were higher in the northern regions than in other regions. Interpretation: The disease burden of PD in China has consistently risen over the past three decades, particularly among elderly men. The increasing causative factors and population aging highlight the need for enhancing public health intervention and resource allocation, especially in etiological research, early diagnosis, preventive strategies, and region-specific management for PD. Funding: Ministry of Science and Technology of the People's Republic of China (2022YFC2304900, 2022YFC2505100); National Key R&D Program of China (2022YFC2505100, 2022YFC2505103, 2018YFC1315300); Outstanding Young Scholars Support Program (grant number: 3111500001); Epidemiology modeling and risk assessment (grant number: 20200344), and Xi'an Jiaotong University Young Scholar Support Grant (grant number: YX6J004).

14.
Front Plant Sci ; 15: 1393438, 2024.
Article in English | MEDLINE | ID: mdl-38766472

ABSTRACT

Peanuts (Arachis hypogaea) are an essential oilseed crop known for their unique developmental process, characterized by aerial flowering followed by subterranean fruit development. This crop is polyploid, consisting of A and B subgenomes, which complicates its genetic analysis. The advent and progression of omics technologies-encompassing genomics, transcriptomics, proteomics, epigenomics, and metabolomics-have significantly advanced our understanding of peanut biology, particularly in the context of seed development and the regulation of seed-associated traits. Following the completion of the peanut reference genome, research has utilized omics data to elucidate the quantitative trait loci (QTL) associated with seed weight, oil content, protein content, fatty acid composition, sucrose content, and seed coat color as well as the regulatory mechanisms governing seed development. This review aims to summarize the advancements in peanut seed development regulation and trait analysis based on reference genome-guided omics studies. It provides an overview of the significant progress made in understanding the molecular basis of peanut seed development, offering insights into the complex genetic and epigenetic mechanisms that influence key agronomic traits. These studies highlight the significance of omics data in profoundly elucidating the regulatory mechanisms of peanut seed development. Furthermore, they lay a foundational basis for future research on trait-related functional genes, highlighting the pivotal role of comprehensive genomic analysis in advancing our understanding of plant biology.

15.
IBRO Neurosci Rep ; 16: 560-566, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38764541

ABSTRACT

Background: Spinal cord injury (SCI) is a severe impairment of the central nervous system, leading to motor, sensory, and autonomic dysfunction. The present study investigates the efficacy of the polyethylene glycol (PEG)-mediated spinal cord fusion (SCF) techniques, demonstrating efficacious in various animal models with complete spinal cord transection at the T10 level. This research focuses on a comparative analysis of three SCF treatment models in beagles: spinal cord transection (SCT), vascular pedicle hemisected spinal cord transplantation (vSCT), and vascularized allograft spinal cord transplantation (vASCT) surgical model. Methods: Seven female beagles were included in the SCT surgical model, while four female dogs were enrolled in the vSCT surgical model. Additionally, twelve female dogs underwent vASCT in a paired donor-recipient setup. Three surgical model were evaluated and compared through electrophysiology, imaging and behavioral recovery. Results: The results showed a progressive recovery in the SCT, vSCT and vASCT surgical models, with no statistically significant differences observed in cBBB scores at both 2-month and 6-month post-operation (both P>0.05). Neuroimaging analysis across the SCT, vSCT and vASCT surgical models revealed spinal cord graft survival and fiber regrowth across transection sites at 6 months postoperatively. Also, positive MEP waveforms were recorded in all three surgical models at 6-month post-surgery. Conclusion: The study underscores the clinical relevance of PEG-mediated SCF techniques in promoting nerve fusion, repair, and motor functional recovery in SCI. SCT, vSCT, and vASCT, tailored to specific clinical characteristics, demonstrated similar effective therapeutic outcomes.

16.
Adv Mater ; 36(26): e2403489, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38556648

ABSTRACT

Rechargeable aqueous proton batteries with small organic molecule anodes are currently considered promising candidates for large-scale energy storage due to their low cost, stable safety, and environmental friendliness. However, the practical application is limited by the poor cycling stability caused by the shuttling of soluble organic molecules between electrodes. Herein, a cell separator is modified by a GO-casein-Cu2+ layer with a brick-and-mortar structure to inhibit the shuttling of small organic molecules. Experimental and calculation results indicate that, attributed to the synergistic effect of physical blocking of casein molecular chains and electrostatic and coordination interactions of Cu2+, bulk dissolution and shuttling of multiple small molecules can be inhibited simultaneously, while H+ transfer across the separators is not almost affected. With the protection of the GO-casein-Cu2+ separator, soluble small molecules, such as diquinoxalino[2,3-a:2',3'-c]phenazine,2,3,8,9,14,15-hexacyano (6CN-DQPZ) exhibit a high reversible capacity of 262.6 mA h g-1 and amazing stability (capacity retention of 92.9% after 1000 cycles at 1 A g-1). In addition, this strategy is also proved available to other active conjugated small molecules, such as indanthrone (IDT), providing a general green sustainable strategy for advancing the use of small organic molecule electrodes in proton cells.

17.
Autophagy ; : 1-18, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38566321

ABSTRACT

Lyssaviruses are well-known worldwide and often cause fatal encephalitis. Previous studies have shown that autophagy is beneficial for the replication of rabies virus (RABV), the representative lyssavirus, but the detailed mechanism remains obscure. In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular virus-like particles. We also found that M proteins of most lyssaviruses share the same mechanism to accumulate autophagosome by hijacking NEDD4. Collectively, this study revealed a novel strategy for lyssaviruses to achieve efficient viral replication by exploiting the host autophagy system.Abbreviations: ABLV: Australian bat lyssavirus; ATG5: autophagy related 5; Baf A1:bafilomycin A1;co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI:4',6-diamidino-2'-phenylindole; DMSO: dimethyl sulfoxide; EBLV:European bat lyssavirus; GFP: green fluorescent protein; GST:glutathione S-transferase; hpi: hours post-infection; hpt: hourspost-transfection; LIR: LC3-interactingregion;MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mCherry:red fluorescent protein; MOI: multiplicity of infection; NC: negativecontrol; MVB: multivesicular body; NEDD4: neural precursorcell-expressed developmentally down-regulated 4; RABV: rabies virus;SQSTM1/p62: sequestosome 1; VLP: virus-like particle; VPS4B: vacuolarprotein sorting 4B; TEM: transmission electron microscopy; WB:western blotting; WT: wild-type; µm: micrometer; µM: micromole.

18.
medRxiv ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38559070

ABSTRACT

Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimen to prevent antagonistic effects. Thus, this work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

19.
NanoImpact ; 34: 100505, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38579989

ABSTRACT

The increasing application of quantum dots (QDs) increases interactions with organisms. The inflammatory imbalance is a significant manifestation of immunotoxicity. Macrophages maintain inflammatory homeostasis. Using macrophages differentiated by phorbol 12-myristate 13-acetate-induced THP-1 cells as models, the study found that low-dose (5 µM) cadmium telluride QDs (CdTe-QDs) hindered monocyte-macrophage differentiation. CD11b is a surface marker of macrophage, and the addition of CdTe-QDs during induction resulted in a decrease in CD11b expression. Moreover, exposure of differentiated THP-1 macrophage (dTHP-1) to 5 µM CdTe-QDs led to the initiation of M1 polarization. This was indicated by the increased surface marker CD86 expression, along with elevated level of NF-κB and IL-1ß proteins. The potential mechanisms are being explored. The transcription factor EB (TFEB) plays a significant role in immune regulation and serves as a crucial regulator of the autophagic lysosomal pathway. After exposed to CdTe-QDs, TFEB activation-mediated autophagy and M1 polarization were observed to occur simultaneously in dTHP-1. The mTOR signaling pathway contributed to TFEB activation induced by CdTe-QDs. However, mTOR-independent activation of TFEB failed to promote M1 polarization. These results suggest that mTOR-TFEB is an advantageous target to enhance the biocompatibility of CdTe-QDs.


Subject(s)
Cadmium Compounds , Macrophages , Quantum Dots , TOR Serine-Threonine Kinases , Tellurium , Tellurium/pharmacology , Cadmium Compounds/pharmacology , Humans , Macrophages/drug effects , Macrophages/metabolism , TOR Serine-Threonine Kinases/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , THP-1 Cells , Autophagy/drug effects , Cell Differentiation/drug effects , Signal Transduction/drug effects
20.
Plants (Basel) ; 13(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38674465

ABSTRACT

Trehalose-6-phosphate phosphatase (TPP) is a pivotal enzyme in trehalose biosynthesis which plays an essential role in plant development and in the abiotic stress response. However, little is currently known about TPPs in groundnut. In the present study, a total of 16 AhTPP genes were identified, and can be divided into three phylogenetic subgroups. AhTPP members within the same subgroups generally displayed similar exon-intron structures and conserved motifs. Gene collinearity analysis revealed that segmental duplication was the primary factor driving the expansion of the AhTPP family. An analysis of the upstream promoter region of AhTPPs revealed eight hormone- and four stress-related responsive cis-elements. Transcriptomic analysis indicated high expression levels of AhTPP genes in roots or flowers, while RT-qPCR analysis showed upregulation of the six tested genes under different abiotic stresses, suggesting that AhTPPs play roles in growth, development, and response to various abiotic stresses. Subcellular localization analysis showed that AhTPP1A and AhTPP5A were likely located in both the cytoplasm and the nucleus. To further confirm their functions, the genes AhTPP1A and AhTPP5A were individually integrated into yeast expression vectors. Subsequent experiments demonstrated that yeast cells overexpressing these genes displayed increased tolerance to osmotic and salt stress compared to the control group. This study will not only lay the foundation for further study of AhTPP gene functions, but will also provide valuable gene resources for improving abiotic stress tolerance in groundnut and other crops.

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