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1.
Meat Sci ; 216: 109585, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38959640

ABSTRACT

In this study, the effect of sodium alginate and quaternized chitosan bis-polysaccharide-based shell transport curcumin nano-emulsions (Cur@QCS/SA) on the microbiological, physicochemical properties, quality characteristics of Harbin red sausage during storage is investigated. According to the microbiological results, the shelf life of Harbin red sausage is extended from 3 d to 6 d by adding 0.15% Cur@QCS/SA, and Bacillus is the most predominant bacterial before 6 d. Additionally, the physicochemical properties change significantly, the pH, weight loss (WL), water holding capacity (WHC), water activity (aw), L*, and a* of red sausage decrease gradually with the extension of storage time, as well as b*, lipid oxidation, proteolysis increase significantly (P < 0.05). Secondly, it is found that 0.15% treatment group can better maintain the quality characteristics of Harbin red sausage according to texture profile analysis (TPA), electronic nose (E-nose), and electronic tongue (E-tongue) (P < 0.05). This study provides a new way for nano-emulsions in food applications and a new option for the preservation of Harbin red sausage as well as other low-temperature meat products.

2.
Sci Adv ; 10(26): eado4390, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941471

ABSTRACT

Light-driven oxidative coupling of methane (OCM) for multi-carbon (C2+) product evolution is a promising approach toward the sustainable production of value-added chemicals, yet remains challenging due to its low intrinsic activity. Here, we demonstrate the integration of bismuth oxide (BiOx) and gold (Au) on titanium dioxide (TiO2) substrate to achieve a high conversion rate, product selectivity, and catalytic durability toward photocatalytic OCM through rational catalytic site engineering. Mechanistic investigations reveal that the lattice oxygen in BiOx is effectively activated as the localized oxidant to promote methane dissociation, while Au governs the methyl transfer to avoid undesirable overoxidation and promote carbon─carbon coupling. The optimal Au/BiOx-TiO2 hybrid delivers a conversion rate of 20.8 millimoles per gram per hour with C2+ product selectivity high to 97% in the flow reactor. More specifically, the veritable participation of lattice oxygen during OCM is chemically looped by introduced dioxygen via the Mars-van Krevelen mechanism, endowing superior catalyst stability.

3.
Am J Clin Nutr ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825185

ABSTRACT

BACKGROUND: Sarcopenia is known as a decline in skeletal muscle quality and function that is associated with age. Sarcopenia is linked to diverse health problems, including endocrine-related diseases. Environmental chemicals (ECs), a broad class of chemicals released from industry, may influence muscle quality decline. OBJECTIVES: In this work, we aimed to simultaneously elucidate the associations between muscle quality decline and diverse EC exposures based on the data from the 2011-2012 and 2013-2014 survey cycles in the National Health and Nutrition Examination Survey (NHANES) project using machine learning models. METHODS: Six machine learning models were trained based on the EC and non-EC exposures from NHANES to distinguish low from normal muscle quality index status. Different machine learning metrics were evaluated for these models. The Shapley additive explanations (SHAP) approach was used to provide explainability for machine learning models. RESULTS: Random forest (RF) performed best on the independent testing data set. Based on the testing data set, ECs can independently predict the binary muscle quality status with good performance by RF (area under the receiver operating characteristic curve = 0.793; area under the precision-recall curve = 0.808). The SHAP ranked the importance of ECs for the RF model. As a result, several metals and chemicals in urine, including 3-phenoxybenzoic acid and cobalt, were more associated with the muscle quality decline. CONCLUSIONS: Altogether, our analyses suggest that ECs can independently predict muscle quality decline with a good performance by RF, and the SHAP-identified ECs can be closely related to muscle quality decline and sarcopenia. Our analyses may provide valuable insights into ECs that may be the important basis of sarcopenia and endocrine-related diseases in United States populations.

4.
Am J Surg Pathol ; 48(5): 511-520, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38567813

ABSTRACT

The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs. To further investigate the potential utility of ABCD1 as a diagnostic marker for SPN via immunohistochemistry staining, we conducted verification in a large-scale patient cohort with pancreatic tumors, including 127 SPN (111 primary, 16 metastatic samples), 108 NET (98 nonfunctional pancreatic neuroendocrine tumor, NF-NET, and 10 functional pancreatic neuroendocrine tumor, F-NET), 9 acinar cell carcinoma (ACC), 3 pancreatoblastoma (PB), 54 pancreatic ductal adenocarcinoma (PDAC), 20 pancreatic serous cystadenoma (SCA), 19 pancreatic mucinous cystadenoma (MCA), 12 pancreatic ductal intraepithelial neoplasia (PanIN) and 5 intraductal papillary mucinous neoplasm (IPMN) samples. Our results indicate that ABCD1 holds promise as an easily applicable diagnostic marker with exceptional efficacy (AUC=0.999, sensitivity=99.10%, specificity=100%) for differentiating SPN from NET and other pancreatic neoplasms through immunohistochemical staining.


Subject(s)
Carcinoma, Pancreatic Ductal , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreas/pathology , Carcinoma, Pancreatic Ductal/pathology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Pancreatic Ducts/chemistry , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , ATP Binding Cassette Transporter, Subfamily D, Member 1
5.
Int J Biol Macromol ; 266(Pt 2): 131322, 2024 May.
Article in English | MEDLINE | ID: mdl-38574924

ABSTRACT

In this study, the effect of oregano essential oil loaded in zein-pectin-chitosan (Zein-PC-CS-OEO) nanoparticles on the quality of Harbin red sausage during storage was examined. Zein-PC-CS-OEO nanoparticles exhibit the better encapsulation efficiency, antioxidant and antibacterial properties than these of other prepared nanoparticles, which were subsequently incorporated into Harbin red sausage with different concentrations. The physicochemical properties, bacterial community structure, and flavor characteristics of the Harbin red sausage were determined. Both thiobarbituric acid values and the growth of dominant spoilage bacteria in Harbin red sausage are inhibited by Zein-PC-CS-OEO nanoparticles, while the total aerobic bacteria count is reduced. These results indicate that the storage quality of Harbin red sausage is improved by Zein-PC-CS-OEO nanoparticles. It is worth noting that the shelf life of Harbin red sausage supplemented with 0.1 % Zein-PC-CS-OEO nanoparticles is extended to 9 d, and the flavor characteristics of which are better maintained. This study provides a new approach to extend the application of essential oil and improve the storage quality of Harbin red sausage.


Subject(s)
Chitosan , Food Storage , Meat Products , Nanoparticles , Oils, Volatile , Origanum , Pectins , Zein , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Zein/chemistry , Chitosan/chemistry , Origanum/chemistry , Nanoparticles/chemistry , Meat Products/microbiology , Meat Products/analysis , Pectins/chemistry , Food Storage/methods , Food Preservation/methods , Antioxidants/chemistry , Antioxidants/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
6.
Chemistry ; 30(36): e202400817, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38654445

ABSTRACT

Luminescent organometallic complexes of earth-abundant copper(I) have long been studied in organic light-emitting diodes (OLED). Particularly, Cu(I)-based carbene-metal-amide (CMA) complexes have recently emerged as promising organometallic emitters. However, blue-emitting Cu(I) CMA complexes have been rarely reported. Here we constructed two blue-emitting Cu(I) CMA emitters, MAC*-Cu-CF3Cz and MAC*-Cu-2CF3Cz, by introducing one or two CF3 substitutes into carbazole ligands. Both complexes exhibited high thermal stability and blue emission colors. Moreover, two complexes exhibited different emission origins rooting from different donor ligands: a distinct thermally activated delayed fluorescence (TADF) from ligand-to-ligand charge transfer excited states for MAC*-Cu-CF3Cz or a dominant phosphorescence nature from local triplet excited state of the carbazole ligand for MAC*-Cu-2CF3Cz. Inspiringly, MAC*-Cu-CF3Cz had high photoluminescence quantum yields of up to 94 % and short emission lifetimes of down to 1.2 µs in doped films, accompanied by relatively high radiative rates in the 105 s-1 order. The resultant vacuum-deposited OLEDs based on MAC*-Cu-CF3Cz delivered pure-blue electroluminescence at 462 nm together with a high external quantum efficiency of 13.0 %.

7.
Angew Chem Int Ed Engl ; 63(18): e202401833, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38429247

ABSTRACT

Organic scintillators have recently attracted growing attention for X-ray detection in industrial and medical applications. However, these materials still face critical obstacles of low attenuation efficiency and/or inefficient triplet exciton utilization. Here we developed a new category of organogold(III) complexes, Tp-Au-1 and Tp-Au-2, through adopting a through-space interaction motif to realize high X-ray attenuation efficiency and efficient harvesting of triplet excitons for emission. Thanks to the efficient through-space charge transfer process, this panel of complexes achieved higher photoluminescence quantum yield and shorter radiative lifetimes compared with the through-bond reference complexes. Inspiringly, these organogold(III) complexes exhibited polarity-dependent emission origins: thermally activated delayed fluorescence and/or phosphorescence. Under X-ray irradiation, Tp-Au-2 manifested intense radioluminescence together with a record-high scintillation light yield of 77,600 photons MeV-1 for organic scintillators. The resulting scintillator screens demonstrated high-quality X-ray imaging with >16.0 line pairs mm-1 spatial resolution, outstripping most organic and inorganic scintillators. This finding provides a feasible strategy for the design of superior organic X-ray scintillators.

8.
Anal Chem ; 96(11): 4623-4631, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38456770

ABSTRACT

Developing new electrochemiluminescence (ECL) luminators with high stability, wide applicability, and strong designability is of great strategic significance to promote the ECL field to the frontier. Here, driven by the I···N bond, 1,3,5-trifluoro-2,4,6-triiodobenzene (TFTI) and 2,4,6-trimethyl-1,3,5-triazine (TMT) self-assembled into a novel halogen cocrystal (TFTI-TMT) through slow solution volatilization. Significant difference of charge density existed between the N atoms on TMT and the σ-hole of the I atoms on TFTI. Upon the induction of σ-hole effect, high-speed and spontaneous charge transferring from TMT to the σ-hole of TFTI occurred, stimulating exciting ECL signals. Besides, the σ-hole of the I atoms could capture iodine ions specifically, which blocked the original charge transfer from the N atoms to the σ-hole, causing the ECL signal of TFTI-TMT to undergo a quenching rate as high as 92.9%. Excitingly, the ECL sensing of TFTI-TMT toward I- possessed a wide linear range (10-5000 nM) and ultralow detection limit (3 nM) in a real water sample. The halogen cocrystal strategy makes σ-hole a remarkable new viewpoint of ECL luminator design and enables ECL analysis technology to contribute to addressing the environmental and health threats posed by iodide pollution.

9.
Nat Commun ; 15(1): 1273, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38341405

ABSTRACT

The meticulous design of active sites and light absorbers holds the key to the development of high-performance photothermal catalysts for CO2 hydrogenation. Here, we report a nonmetallic plasmonic catalyst of Mo2N/MoO2-x nanosheets by integrating a localized surface plasmon resonance effect with two distinct types of active sites for CO2 hydrogenation. Leveraging the synergism of dual active sites, H2 and CO2 molecules can be simultaneously adsorbed and activated on N atom and O vacancy, respectively. Meanwhile, the plasmonic effect of this noble-metal-free catalyst signifies its promising ability to convert photon energy into localized heat. Consequently, Mo2N/MoO2-x nanosheets exhibit remarkable photothermal catalytic performance in reverse water-gas shift reaction. Under continuous full-spectrum light irradiation (3 W·cm-2) for a duration of 168 h, the nanosheets achieve a CO yield rate of 355 mmol·gcat-1·h-1 in a flow reactor with a selectivity exceeding 99%. This work offers valuable insights into the precise design of noble-metal-free active sites and the development of plasmonic catalysts for reducing carbon footprints.

10.
Mol Ther Nucleic Acids ; 35(1): 102100, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38222302

ABSTRACT

Epigenetic regulation contributes to the dysregulation of gene expression involved in cancer biology. Nevertheless, the roles of epigenetic regulators (ERs) in tumor immunity and immune response remain basically unclear. Here, we developed the epigenetic regulator in immunology (EPRIM) approach to identify immune-related ERs and comprehensively dissected the ER regulation in tumor immune response across 33 cancers. The identified immune-related ERs were related to immune infiltration and could stratify cancer patients into two risk groups in multiple independent datasets. These patient groups were characterized by distinct immune functions, immune infiltrates, driver gene mutations, and prognoses. Furthermore, we constructed an immune ER-based signature and highlighted its potential utility in predicting clinical benefit from immunotherapy and selecting therapeutic agents. Taken together, our identification and evaluation of immune-related ERs highlight the usefulness of EPRIM for the understanding of ERs in immune regulation and the clinical relevance in evaluation of cancer patient prognosis and response to immune checkpoint blockade therapy.

11.
Food Res Int ; 174(Pt 1): 113634, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37986538

ABSTRACT

This study aims to enhance the stability and bioavailability of curcumin (Cur) using nanoemulsion coating technology. The nanoemulsion system was developed by encapsulating Cur with quaternized chitosan (QMNE), and the nanoemulsion containing Cur and medium-chain triglyceride (MCT) oil (MNE) was used as control sample. The microstructure of the nanoemulsion was examined using Dynamic light scattering (DLS), Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The storage, thermal, ionic strength, and pH stability of QMNE were also evaluated, respectively. The results indicate that QMNE demonstrates superior stability, in vitro gastric fluid stability, bioavailability compared to MNE. QMNE exhibits excellent emulsification activity and stability. In addition, QMNE shows significant protection against oxidation in both emulsion systems after different heat treatments. The antimicrobial activity results reveal that QMNE exhibits greater efficacy than that of MNE. Consequently, this study provides valuable insights into the formulation of a system to encapsulate Cur and the improvement of its stability and bioavailability.


Subject(s)
Chitosan , Curcumin , Curcumin/chemistry , Chitosan/chemistry , Biological Availability , Spectroscopy, Fourier Transform Infrared , Emulsions
12.
Int J Biol Macromol ; 253(Pt 5): 127130, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37776925

ABSTRACT

In this study, potassium-incorporated carbon dots (K-CDs) and nitrogen-incorporated carbon dots (N-CDs) were composted using the microwave-assisted method, in which the carbon source is citric acid. Subsequently, the prepared CDs were added into sodium alginate (NaAlg)/CaCO3 to form a hydrogel film. The Ca2+ in the system is tend to be released in the presence of acidic CDs to promote the cross-linking of NaAlg. This study presents a NaAlg hydrogel film preparation process that requires no additional acid and is natural and environmentally friendly. Moreover, it gives the NaAlg hydrogel film excellent antioxidant and antimicrobial properties and also improves its mechanical properties and gel strength. The release behaviors of the CDs in the hydrogel films were also explored. The prepared CD-incorporated NaAlg hydrogel films have potential applications in medical, biological engineering, food preservation, and other fields owing to their functional properties.


Subject(s)
Carbon , Quantum Dots , Alginates , Microwaves , Hydrogels
13.
Med Image Anal ; 90: 102957, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37716199

ABSTRACT

Open international challenges are becoming the de facto standard for assessing computer vision and image analysis algorithms. In recent years, new methods have extended the reach of pulmonary airway segmentation that is closer to the limit of image resolution. Since EXACT'09 pulmonary airway segmentation, limited effort has been directed to the quantitative comparison of newly emerged algorithms driven by the maturity of deep learning based approaches and extensive clinical efforts for resolving finer details of distal airways for early intervention of pulmonary diseases. Thus far, public annotated datasets are extremely limited, hindering the development of data-driven methods and detailed performance evaluation of new algorithms. To provide a benchmark for the medical imaging community, we organized the Multi-site, Multi-domain Airway Tree Modeling (ATM'22), which was held as an official challenge event during the MICCAI 2022 conference. ATM'22 provides large-scale CT scans with detailed pulmonary airway annotation, including 500 CT scans (300 for training, 50 for validation, and 150 for testing). The dataset was collected from different sites and it further included a portion of noisy COVID-19 CTs with ground-glass opacity and consolidation. Twenty-three teams participated in the entire phase of the challenge and the algorithms for the top ten teams are reviewed in this paper. Both quantitative and qualitative results revealed that deep learning models embedded with the topological continuity enhancement achieved superior performance in general. ATM'22 challenge holds as an open-call design, the training data and the gold standard evaluation are available upon successful registration via its homepage (https://atm22.grand-challenge.org/).


Subject(s)
Lung Diseases , Trees , Humans , Tomography, X-Ray Computed/methods , Image Processing, Computer-Assisted/methods , Algorithms , Lung/diagnostic imaging
14.
Chemistry ; 29(59): e202301885, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37431981

ABSTRACT

Coinage metal (gold, silver, and copper) complexes are attractive candidates to substitute the widely studied noble metal complexes, such as, iridium(III) and platinum(II), as luminescent materials in organic light-emitting diodes (OLEDs). However, the development of coinage metal complexes exhibiting high emission quantum yields and short exciton lifetimes is still a formidable challenge. In the past few years, coinage metal complexes featuring a carbene-metal-amide (CMA) motif have emerged as a new class of luminescent materials in OLEDs. Thanks to the coinage metal-bridged linear geometry, coplanar conformation, and the formation of excited states with dominant ligand-to-ligand charge transfer character and reduced metal d-orbital participation, most CMA complexes have high radiative rates via thermally activated delayed fluorescence. Currently, the family of CMA complexes have rapidly evolved and remarkable progresses in CMA-based OLEDs have been made. Here, a Concept article on CMA complexes is presented, with a focus on molecular design principles, the correlation between molecular structure/conformation and optoelectronic properties, as well as OLED performance. The future prospects of CMA complexes are also discussed.

15.
Small ; 19(39): e2302254, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37236205

ABSTRACT

Covalent organic frameworks (COFs) show potentials in prominent photoelectric responses by judicious structural design. However, from the selections of monomers and condensation reactions to the synthesis procedures, the acquisition of photoelectric COFs has to meet overmuch high conditions, limiting the breakthrough and modulation in photoelectric responses. Herein, the study reports a creative "lock-key model" based on molecular insertion strategy. A COF with suitable cavity size, TP-TBDA, is used as the host to load guests. Merely through the volatilization of mixed solution, TP-TBDA and guests can be spontaneously assembled via non-covalent interactions (NCIs) to produce molecular-inserted COFs (MI-COFs). The NCIs between TP-TBDA and guests acted as a bridge to facilitate charge transfer in MI-COFs, unlocking the photoelectric responses of TP-TBDA. By exploiting the controllability of NCIs, the MI-COFs can realize the smart modulation of photoelectric responses by simply changing the guest molecule, thus avoiding the arduous selection of monomers and condensation reactions required by conventional COFs. The construction of molecular-inserted COFs circumvents complicated procedures for achieving performance improvement and modulation, providing a promising direction to construct late-model photoelectric responsive materials.

16.
Invest Ophthalmol Vis Sci ; 64(3): 16, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36881408

ABSTRACT

Purpose: To determine whether SIRT1 regulates high glucose (HG)-induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses. Methods: HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. High mannitol groups were applied as the osmotic controls. Real-time PCR, Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1ß. Reactive oxygen species (ROS) generation, cell viability, and death were also assessed. Results: HG stress induced a decline in SIRT1 expression and caused TXNIP/NLRP3 inflammasome activation in a concentration-dependent manner in HLECs, which was not observed in the high mannitol-treated groups. Knocking down NLRP3 or TXNIP inhibited NLRP3 inflammasome-induced IL-1ß p17 secretion under HG stress. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. HG stress induced lens opacity and cataract formation in cultivated rat lenses, which was prevented by MCC950 or SRT1720 treatment, with concomitant reductions in ROS production and TXNIP/NLRP3/IL-1ß expression levels. Conclusions: The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1. This suggests viable strategies for treating diabetic cataract.


Subject(s)
Cataract , Inflammasomes , Sirtuin 1 , Animals , Humans , Rats , Carrier Proteins , Furans , Glucose/pharmacology , Inflammation , NLR Family, Pyrin Domain-Containing 3 Protein , Reactive Oxygen Species , Sirtuin 1/metabolism
17.
Redox Biol ; 62: 102675, 2023 06.
Article in English | MEDLINE | ID: mdl-36933392

ABSTRACT

The decreased antioxidant capacity in the retinal pigment epithelium (RPE) is the hallmark of retinal degenerative diseases including age-related macular degeneration (AMD). Nevertheless, the exact regulatory mechanisms underlying the pathogenesis of retinal degenerations remain largely unknown. Here we show in mice that deficiencies in Dapl1, a susceptibility gene for human AMD, impair the antioxidant capacity of the RPE and lead to age-related retinal degeneration in the 18-month-old mice homozygous for a partial deletion of Dapl1. Dapl1-deficiency is associated with a reduction of the RPE's antioxidant capacity, and experimental re-expression of Dapl1 reverses this reduction and protects the retina from oxidative damage. Mechanistically, DAPL1 directly binds the transcription factor E2F4 and inhibits the expression of MYC, leading to upregulation of the transcription factor MITF and its targets NRF2 and PGC1α, both of which regulate the RPE's antioxidant function. When MITF is experimentally overexpressed in the RPE of DAPL1 deficient mice, antioxidation is restored and retinas are protected from degeneration. These findings suggest that the DAPL1-MITF axis functions as a novel regulator of the antioxidant defense system of the RPE and may play a critical role in the pathogenesis of age-related retinal degenerative diseases.


Subject(s)
Macular Degeneration , Retinal Degeneration , Animals , Mice , Antioxidants/metabolism , Cell Line , Macular Degeneration/genetics , Macular Degeneration/pathology , Membrane Proteins/metabolism , Oxidative Stress , Retinal Degeneration/metabolism , Retinal Pigment Epithelium/metabolism , Transcription Factors/metabolism
18.
Hortic Res ; 10(3): uhad007, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36960430

ABSTRACT

Fruit shape and size are important appearance and yield traits in cucumber, but the underlying genes and their regulatory mechanisms remain poorly understood. Here we identified a mutant with spherical fruits from an Ethyl Methane Sulfonate (EMS)-mutagenized library, named the qiu mutant. Compared with the cylindrical fruit shape in 32X (wild type), the fruit shape in qiu was round due to reduced fruit length and increased fruit diameter. MutMap analysis narrowed the candidate gene in the 6.47 MB range on Chr2, harboring the FS2.1 locus reported previously. A single-nucleotide polymorphism (SNP) (11359603) causing a truncated protein of CsaV3_2G013800, the homolog of tomato fruit shape gene SlTRM5, may underlie the fruit shape variation in the qiu mutant. Knockout of CsTRM5 by the CRISPR-Cas9 system confirmed that CsaV3_2G013800/CsTRM5 was the causal gene responsible for qiu. Sectioning analysis showed that the spherical fruit in qiu resulted mainly from increased and reduced cell division along the transverse and longitudinal directions, respectively. Meanwhile, the repressed cell expansion contributed to the decreased fruit length in qiu. Transcriptome profiling showed that the expression levels of cell-wall-related genes and abscisic acid (ABA) pathway genes were significantly upregulated in qiu. Hormone measurements indicated that ABA content was greatly increased in the qiu mutant. Exogenous ABA application reduced fruit elongation by inhibiting cell expansion in cucumber. Taken together, these data suggest that CsTRM5 regulates fruit shape by affecting cell division direction and cell expansion, and that ABA participates in the CsTRM5-mediated cell expansion during fruit elongation in cucumber.

19.
J Mater Chem B ; 11(16): 3484-3510, 2023 04 26.
Article in English | MEDLINE | ID: mdl-36988384

ABSTRACT

Messenger RNA (mRNA) has become a key focus in the development of therapeutic agents, showing significant potential in preventing and treating a wide range of diseases. The COVID-19 pandemic in 2020 has accelerated the development of mRNA nucleic therapeutics and attracted significant investment from global biopharmaceutical companies. These therapeutics deliver genetic information into cells without altering the host genome, making them a promising treatment option. However, their clinical applications have been limited by issues such as instability, inefficient in vivo delivery, and low translational efficiency. Recent advances in molecular design and nanotechnology have helped overcome these challenges, and several mRNA formulations have demonstrated promising results in both animal and human testing against infectious diseases and cancer. This review provides an overview of the latest research progress in structural optimization strategies and delivery systems, and discusses key considerations for their future clinical use.


Subject(s)
COVID-19 , Pandemics , Animals , Humans , RNA, Messenger/genetics , RNA, Messenger/therapeutic use , Nanotechnology/methods , Drug Delivery Systems/methods
20.
Cell Death Dis ; 14(2): 158, 2023 02 25.
Article in English | MEDLINE | ID: mdl-36841807

ABSTRACT

Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a hallmark of the pathogenesis of proliferative vitreoretinopathy (PVR) that can lead to severe vision loss. Nevertheless, the precise regulatory mechanisms underlying the pathogenesis of PVR remain largely unknown. Here, we show that the expression of death-associated protein-like 1 (DAPL1) is downregulated in PVR membranes and that DAPL1 deficiency promotes EMT in RPE cells in mice. In fact, adeno-associated virus (AAV)-mediated DAPL1 overexpression in RPE cells of Dapl1-deficient mice inhibited EMT in physiological and retinal-detachment states. In a rabbit model of PVR, ARPE-19 cells overexpressing DAPL1 showed reduced ability to induce experimental PVR, and AAV-mediated DAPL1 delivery attenuated the severity of experimental PVR. Furthermore, a mechanistic study revealed that DAPL1 promotes P21 phosphorylation and its stabilization partially through NFκB (RelA) in RPE cells, whereas the knockdown of P21 led to neutralizing effects on DAPL1-dependent EMT inhibition and enhanced the severity of experimental PVR. These results suggest that DAPL1 acts as a novel suppressor of RPE-EMT and has an important role in antagonizing the pathogenesis of experimental PVR. Hence, this finding has implications for understanding the mechanism of and potential therapeutic applications for PVR.


Subject(s)
Membrane Proteins , Retinal Pigment Epithelium , Vitreoretinopathy, Proliferative , Animals , Mice , Rabbits , Epithelial-Mesenchymal Transition , Retinal Pigment Epithelium/metabolism , Vitreoretinopathy, Proliferative/drug therapy , Vitreoretinopathy, Proliferative/metabolism , Vitreoretinopathy, Proliferative/pathology , Membrane Proteins/metabolism
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