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1.
Int J Food Microbiol ; 425: 110896, 2024 Dec 02.
Article in English | MEDLINE | ID: mdl-39226861

ABSTRACT

Apple pomace, an abundant agricultural by-product with low utilization rates, often leads to environmental pollution if not properly managed. This study aimed to enhance the nutritional value of apple pomace by comparing the effects of solid-state fermentation using complex probiotics and cellulase preparation. Additionally, the study investigated the dynamic changes in various components throughout the fermentation process with complex probiotics. The results of single-strain solid-state fermentation tests indicated that Lactiplantibacillus plantarum DPH, Saccharomyces cerevisiae SC9, and Bacillus subtilis C9 were the optimal strains for fermenting the most effective substrate combination, comprising 73 % apple pomace and 20 % millet bran. The strains (complex probiotics) and a cellulase preparation were used for the solid-state fermentation of the apple pomace mixture for nine days, respectively. The contents of acid detergent fiber, neutral detergent fiber, hemicellulose, and insoluble dietary fiber decreased by up to 9.99 %, 9.59 %, 23.21 %, and 14.34 %, respectively. In contrast, the content of soluble dietary fiber significantly increased by up to 29.74 %. Both methods reduced cellulose crystallinity and modified the substrate's surface structure, resulting in a looser arrangement. Fermentation with complex probiotics for three or six days increased the abundance of lactic acid bacteria, which comprised >87 % of the total microbial population. Concurrently, the abundance of detrimental bacteria, such as Salmonella, Acetobacter, Escherichia, and Pantoea, significantly decreased. Furthermore, fermentation with complex probiotics for six or nine days enhanced antioxidant properties, leading to a significant increase in beneficial metabolites, including amino acids, organic acids, gamma-aminobutyric acid, serotonin. In conclusion, complex probiotics can effectively substitute for cellulase preparation in the solid-state fermentation of apple pomace, with a six-day fermentation period yielding optimal results. This study provides valuable insights into enhancing the value of apple pomace in the feed industry and the effective application of agro-industrial by-products.


Subject(s)
Cellulase , Fermentation , Malus , Probiotics , Malus/microbiology , Probiotics/metabolism , Cellulase/metabolism , Dietary Fiber/metabolism , Saccharomyces cerevisiae/metabolism , Nutritive Value , Bacillus subtilis/metabolism , Lactobacillus plantarum/metabolism , Food Microbiology
2.
Nano Lett ; 24(37): 11512-11519, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39230027

ABSTRACT

Metal-oxo clusters show great promise in lithium ion battery applications as anode materials by virtue of their native nature of well-defined nanostructures and multielectron redox activities. However, their intrinsic unsatisfactory electrical conductivity and tendency to aggregation make them difficult to fully utilize. Herein, a well-dispersed Mn12O12(CH3COO)16(H2O)4 (denoted as Mn12) cluster is constructed by rationally adopting carbon dots (CDs) with nanosize and high conductivity as stabilizers. Thanks to the fully exposed redox sites of Mn12 clusters and additional interfacial energy storage mechanism, the optimized Mn12/CDs-1:20 anode delivers a high specific capacity of 1643 mAh g-1 at 0.2 A g-1 (0.25 C) and exhibits outstanding rate and cycling capabilities. This paper provides a green and efficient paradigm to synthesize well-dispersed manganese-oxo clusters for the first time and builds a new platform for cluster-based energy storage.

3.
Angew Chem Int Ed Engl ; 63(40): e202409255, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38984684

ABSTRACT

With the large-scale application of lithium-ion batteries (LIBs), a huge amount of spent LIBs will be generated each year and how to realize their recycling and reuse in a clean and effective way poses a challenge to the society. In this work, using the electrolyte of spent LIBs as solvent, we in situ fluorinate the conductive three-dimensional porous copper foam by a facile solvent-thermal method and then coating it with a cross-linked sodium alginate (SA) layer. Benefiting from the solid-electrolyte interphase (SEI) that accommodating the volume change of internal CuF2 core and SA layer that inhibiting the dissolution of CuF2, the synthesized CuF2@void@SEI@SA cathode with a pomegranate-like structure (yolk-shell) exhibits a large reversible capacity of ~535 mAh g-1 at 0.05 A g-1 and superb cycling stability. This work conforms to the development concept of green environmental protection and comprehensively realizes the unity of environmental, social and economic benefits.

4.
iScience ; 27(7): 110226, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39021800

ABSTRACT

The pathogenesis of intestinal fibrosis in Crohn's disease (CD) remains unclear. Mer receptor tyrosine kinase (MerTK) is an immunosuppressive protein specifically expressed in macrophages. Osteopontin (OPN), also known as secreted phosphoprotein 1, contributes to inflammation and wound repair. This study investigates the potential profibrotic pathway in MerTK+ macrophages in order to provide a possible therapeutic target for intestinal fibrosis. MerTK expression in the inflamed and stenotic bowels was evaluated. The MerTK/ERK/TGF-ß1 pathway was overactivated in the fibrotic intestinal tissues of patients with CD. This pathway was induced by epithelial cell apoptosis, resulting in activated fibroblasts with increased TGF-ß1 secretion. OPN upregulated TGF production by altering ERK1/2 phosphorylation, as evidenced by OPN or MerTK knockdown and OPN overexpression in vitro. MerTK inhibitor UNC2025 alleviated intestinal fibrosis in mouse colitis models, suggesting a potential therapeutic target for intestinal fibrosis in patients with CD.

5.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167299, 2024 10.
Article in English | MEDLINE | ID: mdl-38878833

ABSTRACT

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.


Subject(s)
Fatty Acid Synthase, Type I , Lipoylation , Macrophages , Malonyl Coenzyme A , Membrane Proteins , Sepsis , Animals , Humans , Male , Mice , Fatty Acid Synthase, Type I/metabolism , Fatty Acid Synthase, Type I/genetics , Liver/metabolism , Liver/pathology , Macrophages/metabolism , Malonyl Coenzyme A/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice, Inbred C57BL , Mice, Knockout , Palmitic Acid/pharmacology , Sepsis/metabolism , Sepsis/complications , Sepsis/drug therapy , Signal Transduction/drug effects
6.
Article in English | MEDLINE | ID: mdl-38875097

ABSTRACT

Recently, perception task based on Bird's-Eye View (BEV) representation has drawn more and more attention, and BEV representation is promising as the foundation for next-generation Autonomous Vehicle (AV) perception. However, most existing BEV solutions either require considerable resources to execute on-vehicle inference or suffer from modest performance. This paper proposes a simple yet effective framework, termed Fast-BEV, which is capable of performing faster BEV perception on the on-vehicle chips. Towards this goal, we first empirically find that the BEV representation can be sufficiently powerful without expensive transformer based transformation nor depth representation. Our Fast-BEV consists of five parts, We innovatively propose (1) a lightweight deploymentfriendly view transformation which fast transfers 2D image feature to 3D voxel space, (2) an multi-scale image encoder which leverages multi-scale information for better performance, (3) an efficient BEV encoder which is particularly designed to speed up on-vehicle inference. We further introduce (4) a strong data augmentation strategy for both image and BEV space to avoid over-fitting, (5) a multiframe feature fusion mechanism to leverage the temporal information. Among them, (1) and (3) enable Fast-BEV to be fast inference and deployment friendly on the on-vehicle chips, (2), (4) and (5) ensure that Fast-BEV has competitive performance. All these make Fast-BEV a solution with high performance, fast inference speed, and deployment-friendly on the on-vehicle chips of autonomous driving. Through experiments, on 2080Ti platform, our R50 model can run 52.6 FPS with 47.3% NDS on the nuScenes validation set, exceeding the 41.3 FPS and 47.5% NDS of the BEVDepth-R50 model [1] and 30.2 FPS and 45.7% NDS of the BEVDet4D-R50 model [2]. Our largest model (R101@900x1600) establishes a competitive 53.5% NDS on the nuScenes validation set. We further develop a benchmark with considerable accuracy and efficiency on current popular on-vehicle chips. The code is released at: https://github.com/Sense-GVT/FastBEV.

7.
Food Chem ; 457: 140125, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-38905826

ABSTRACT

Oyster is a low-carbon animal food enriched with protein, glycogen, and trace minerals. Nano-nutrients are increasingly perceived as an unignorable part of foods. Here, simulated gastrointestinal digestion released a considerable amount of nanoparticulate nutrients from raw and cooked oysters. They were identified as glycogen monomers with size of 20-40 nm and their aggregates, as well as 6 nm-sized bare cores of ferritin containing iron and zinc (4:1, w/w). FITC-labeling and flow cytometry unveiled the efficient uptake of oyster glycogen by polarized Caco-2 cells via macropinocytosis and receptor-mediated endocytosis. Calcein-fluorescence-quenching assay revealed divalent-metal-transporter-1- and macropinocytosis-mediated enterocyte iron absorption from oyster ferritin. Zinquin-fluorescence flow cytometry and ex-vivo mouse ileal loop experiments demonstrated the ready intestinal zinc absorption from oyster ferritin via macropinocytosis, as well as the good resistance of oyster ferritin to phytate's inhibition on zinc absorption. Overall, our results offer a new insight into the digestive and chemical properties of oysters.


Subject(s)
Crassostrea , Digestion , Ferritins , Glycogen , Zinc , Animals , Zinc/metabolism , Humans , Ferritins/metabolism , Ferritins/chemistry , Caco-2 Cells , Crassostrea/metabolism , Crassostrea/chemistry , Glycogen/metabolism , Mice , Nanoparticles/chemistry , Nanoparticles/metabolism , Gastrointestinal Tract/metabolism , Biological Availability , Shellfish/analysis
8.
Adv Sci (Weinh) ; 11(29): e2402616, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38828766

ABSTRACT

Although possessing well-defined nanostructures and excellent multi-electron redox properties, polyoxometalate clusters have poor intrinsic electrical conductivity and are prone to aggregation due to large surface energy, which makes them difficult to be fully utilized when applying as electrode materials for lithium-ion batteries. In this paper, monodisperse K7MnV13O38 (MnV13) clusters are achieved by rationally utilizing nano-sized high conductive carbon dots (CDs) as stabilizers. Benefiting from the fully exposed redox sites of MnV13 clusters (high utilization rate) and sufficient interfaces with carbon dots (extra interfacial energy storage), the optimized MnV13/10CDs anode delivers a high discharge capacity up to 1348 mAh g-1 at a current density of 0.1 A g-1 and exhibits superb rate/cycling capabilities. Density functional theory (DFT) calculations verify that ionic archway channels are formed between MnV13 and CDs, eliminating the bandgap and greatly improving the electron/ion conductivity of MnV13 and CDs. This paper paves a brand-new way for synthesis of monodisperse clusters and maximization of extra interfacial energy storage.

9.
Adv Mater ; 36(35): e2407705, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925587

ABSTRACT

Polyoxometalates (POMs) have been considered one of the most promising anode candidates for lithium-ion batteries (LIBs) in virtue of their high theoretical capacity and reversible multielectron redox properties. However, the poor intrinsic electronic conductivity, low specific surface area, and high solubility in organic electrolytes hinder their widespread applications in LIBs. Herein, a novel hybrid nanomaterial is synthesized by co-assembling POMs and porphyrins (PMo12/CoTPyP) through a facile solvothermal method. The POM clusters are stabilized by porphyrin units through electrostatic interactions, which simultaneously realize the uniform dispersion of POMs and porphyrin units. Benefiting from the generated sub-1 nm channels for fast ion transport and the synergistic effect between evenly distributed PMo12 clusters and high-conductive CoTPyP units, the LIB based on the optimized PMo12/CoTPyP anode exhibits significantly improved Li+ storage capability as well as superior rate and cycling performance. The results of density functional theory simulations further reveal that the co-assembly of PMo12 and CoTPyP can accelerate the mobility of Li+ and electrons, which in turn promotes the enhancement of LIBs performance. This work paves a strategy for synthesizing POMs-based anode materials with simultaneously high dispersibility, redox activity, and stability.

10.
Food Chem X ; 22: 101515, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38883914

ABSTRACT

To investigate the optimal processing of maize porridge, the volatile compounds and texture under different cooking methods and time have been studied. A total of 51 volatile compounds were identified in maize porridge. Notably, the major volatiles, aldehydes and esters exhibited a relatively high content in electric pressure cooker (EPC), and esters tend to significantly increase after cooking. Among aldehydes, nonanal and hexanal played a great role in flavor due to their relatively high content. Volatile compounds of maize porridge in different cooking methods could be clearly distinguished by multiple chemometrics. Furthermore, texture analysis revealed that almost all the indicators in the EPC can reach the lowest value at 60 min. To summarize, different cooking methods had a more significant influence on the volatile compounds and texture compared to time. This study helps to improve the sensory attributes of maize porridge, and thus contributes to healthier and more sustainable production.

11.
Angew Chem Int Ed Engl ; 63(33): e202405396, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-38818672

ABSTRACT

Reactive oxygen species (ROS) play a crucial role in determining photocatalytic reaction pathways, intermediate species, and product selectivity. However, research on ROS regulation in polymer photocatalysts is still in its early stages. Herein, we successfully achieved series of modulations to the skeleton of Pyrene-alkyne-based (Tetraethynylpyrene (TEPY)) conjugated porous polymers (CPPs) by altering the linkers (1,4-dibromobenzene (BE), 4,4'-dibromobiphenyl (IP), and 3,3'-dibromobiphenyl (BP)). Experiments combined with theoretical calculations indicate that BE-TEPY exhibits a planar structure with minimal exciton binding energy, which favors exciton dissociation followed by charge transfer with adsorbed O2 to produce ⋅O2 -. Thus BE-TEPY shows optimal photocatalytic activity for phenylboronic acid oxidation and [3+2] cycloaddition. Conversely, the skeleton of BP-TEPY is significantly distorted. Its planar conjugation decreases, intersystem crossing (ISC) efficiency increases, which makes it more prone for resonance energy transfer to generate 1O2. Therefore, BP-TEPY displays best photocatalytic activity in [4+2] cycloaddition and thioanisole oxidation. Both above reactant conversion and its product selectivity exceed 99 %. This work systematically reveals the intrinsic structure-activity relationship among the skeleton structure of CPPs, excitonic behavior, and selective generation of ROS, providing new insights for the rational design of highly efficient and selective CPPs photocatalysts.

12.
Anal Chem ; 96(6): 2610-2619, 2024 02 13.
Article in English | MEDLINE | ID: mdl-38306188

ABSTRACT

Laccase, a member of the copper oxidase family, has been used as a green catalyst in the environmental and biochemical industries. However, laccase nanoenzymes are limited to materials with copper as the active site, and noncopper laccase nanoenzymes have been scarcely reported. In this study, inspired by the multiple copper active sites of natural laccase and the redox Cu2+/Cu+ electron transfer pathway, a novel nitrogen/nickel single-atom nanoenzyme (N/Ni SAE) with high laccase-like activity was prepared by inducing Ni and dopamine precipitation through a controllable water/ethanol interface reaction. Compared with that of laccase, the laccase activity simulated by N/Ni SAE exhibited excellent stability and reusability. The N/Ni SAE exhibited a higher efficiency toward the degradation of 2,4-dichlorophenol, hydroquinone, bisphenol A, and p-aminobenzene. In addition, a sensitive electrochemical biosensor was constructed by leveraging the laccase-like activity of N/Ni SAE; this sensor offered unique advantages in terms of catalytic activity, selectivity, stability, and repeatability. Its detection ranges for quercetin were 0.01-0.1 and 1.0-100 µM, and the detection limit was 3.4 nM. It was also successfully used for the quantitative detection of quercetin in fruit juices. Therefore, the single-atom biomimetic nanoenzymes prepared in this study promote the development of a new electrochemical strategy for the detection of various bioactive molecules and show great potential for practical applications.


Subject(s)
Laccase , Nickel , Laccase/metabolism , Nickel/chemistry , Quercetin , Biomimetics , Copper
13.
Dalton Trans ; 52(48): 18168-18176, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37971057

ABSTRACT

The potassium and proton mixed salt of mono-Nb substituted Keggin-type phosphomolybdate, KH3[PMo11NbO40], was isolated in a pure form by reacting Keggin-type phosphomolybdic acid (H3[PMo12O40]) and potassium hexaniobate (K8Nb6O19) in water, followed by freeze-drying. The all protonic form, H4[PMo11NbO40], was isolated via proton exchange with H-resin and subsequent freeze-drying. The most crucial factor to isolate KH3[PMo11NbO40] and H4[PMo11NbO40] in pure forms is the evaporation of water using the freeze-drying method. Using a similar procedure, the potassium salt of the di-Nb substituted compound K5[PMo10Nb2O40] was isolated. H4[PMo11NbO40] exhibited high catalytic activity for oxidizing isobutylaldehyde to methacrolein and moderate catalytic activity for the Wacker-type oxidation of allyl phenyl ether when combined with Pd(OAc)2.

14.
Nanoscale ; 15(46): 18883-18890, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37974481

ABSTRACT

Developing highly efficient, stable, and cost-effective two-dimensional (2D) conjugated polymers (CPs) for overall water splitting (OWS) is critical for producing clean and renewable hydrogen energy, yet it remains a great challenge. Here, we designed eight 2D CPs through the topological assembly of diacetylene and benzene-derived molecular linkers that can offer active sites for hydrogen and oxygen evolution reactions, and explored their structural, electronic, optical, and photocatalytic OWS properties by performing first-principles computations. It is shown that incorporating benzo-heterocyclic rings into CPs can significantly modulate the electronic structures of CPs and broaden the spectral absorption, suitable for visible-light-driven OWS. Remarkably, through a range of screening criteria, including stability, electronic band structures, band edge alignments, and photocatalytic activity, we found that CP-4 based on diacetylene and benzotrifuran can spontaneously trigger the OWS in a neutral environment under its own light-induced bias, eliminating the need for sacrificial agents or cocatalysts. Specifically, the HER active site is primarily located at diacetylene moieties, while the OER active site is mainly concentrated on the benzo-heterocyclic rings. Moreover, the ideal STH efficiency for OWS on CP-4 was estimated to be 13.87%, highlighting its potential as a prospective photocatalyst for large-scale industrial OWS. Our findings open a door to the rational design of novel polymer photocatalysts for OWS.

15.
Int J Biol Sci ; 19(15): 4931-4947, 2023.
Article in English | MEDLINE | ID: mdl-37781519

ABSTRACT

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.


Subject(s)
Gasdermins , Protein Processing, Post-Translational , Proteolysis , Endopeptidases , Immunity, Innate , Peptide Hydrolases
16.
Cell Mol Life Sci ; 80(11): 337, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37897551

ABSTRACT

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.


Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Humans , Klebsiella pneumoniae/genetics , Dysbiosis/drug therapy , Klebsiella Infections/drug therapy , Inflammation/drug therapy , Alkylation , Syk Kinase
17.
Angew Chem Int Ed Engl ; 62(45): e202312020, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37728941

ABSTRACT

Single-ion conductive electrolytes can largely eliminate electrode polarization, reduce the proportion of anion migration and inhibit side reactions in batteries. However, they usually suffer from insufficient ion conductivity due to the strong interaction between cations and cationic receptors. Here we report an ultrafast light-responsive covalent organic frameworks (COF) with sulfonic acid groups modification as the acrylamide polymerization initiator. Benefiting from the reduced electrostatic interaction between Zn2+ and sulfonic acid groups through solvation effects, the as-prepared COF-based hydrogel electrolyte (TCOF-S-Gel) receives an ion conductivity of up to 27.2 mS/cm and Zn2+ transference number of up to 0.89. In addition, sufficient hydrogen bonds endow the single-ion conductive TCOF-S-Gel electrolyte to have good water retention and superb mechanical properties. The assembled Zn||TCOF-S-Gel||MnO2 full zinc-ion battery exhibits high discharge capacity (248 mAh/g at 1C), excellent rate capability (90 mAh/g at 10C) and superior cycling performance. These enviable results enlist the instantaneously photocured TCOF-S-Gel electrolyte to be qualified to large-scaled flexible high-performance quasi-solid-state zinc-ion batteries.

18.
Blood ; 142(22): 1879-1894, 2023 11 30.
Article in English | MEDLINE | ID: mdl-37738652

ABSTRACT

The use of Bruton tyrosine kinase inhibitors, such as ibrutinib, to block B-cell receptor signaling has achieved a remarkable clinical response in several B-cell malignancies, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Acquired drug resistance, however, is significant and affects the long-term survival of these patients. Here, we demonstrate that the transcription factor early growth response gene 1 (EGR1) is involved in ibrutinib resistance. We found that EGR1 expression is elevated in ibrutinib-resistant activated B-cell-like subtype DLBCL and MCL cells and can be further upregulated upon ibrutinib treatment. Genetic and pharmacological analyses revealed that overexpressed EGR1 mediates ibrutinib resistance. Mechanistically, TCF4 and EGR1 self-regulation induce EGR1 overexpression that mediates metabolic reprogramming to oxidative phosphorylation (OXPHOS) through the transcriptional activation of PDP1, a phosphatase that dephosphorylates and activates the E1 component of the large pyruvate dehydrogenase complex. Therefore, EGR1-mediated PDP1 activation increases intracellular adenosine triphosphate production, leading to sufficient energy to enhance the proliferation and survival of ibrutinib-resistant lymphoma cells. Finally, we demonstrate that targeting OXPHOS with metformin or IM156, a newly developed OXPHOS inhibitor, inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting EGR1-mediated metabolic reprogramming to OXPHOS with metformin or IM156 provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory DLBCL or MCL.


Subject(s)
Antineoplastic Agents , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Mantle-Cell , Metformin , Humans , Adult , Animals , Mice , Agammaglobulinaemia Tyrosine Kinase/metabolism , Oxidative Phosphorylation , Drug Resistance, Neoplasm , Cell Line, Tumor , Antineoplastic Agents/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Metformin/pharmacology , Early Growth Response Protein 1/metabolism
19.
Bioresour Technol ; 385: 129457, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37422095

ABSTRACT

Low-value agricultural by-products can be converted into high-value biological products by fermentation with probiotic strains or by enzymatic hydrolysis. However, the high costs of enzyme preparations significantly limit their applications in fermentation. In this study, the solid-state fermentation of millet bran was performed using a cellulase preparation and compound probiotics producing cellulase (CPPC), respectively. The results showed that both factors effectively destroyed the fiber structure, reduced the crude fiber content by 23.78% and 28.32%, respectively, and significantly increased the contents of beneficial metabolites and microorganisms. Moreover, CPPC could more effectively reduce the anti-nutrient factors and increase the content of anti-inflammatory metabolites. The correlation analysis revealed that Lactiplantibacillus and Issatchenkia had synergistic growth during fermentation. Overall, these results suggested that CPPC could replace cellulase preparation and improve antioxidant properties while reducing anti-nutrient factors of millet bran, thus providing a theoretical reference for the efficient utilization of agricultural by-products.


Subject(s)
Cellulase , Probiotics , Cellulase/metabolism , Fermentation , Millets/metabolism , Carbohydrates , Hydrolysis
20.
Angew Chem Int Ed Engl ; 62(30): e202305843, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37232089

ABSTRACT

The development of a new electrolytic water hydrogen production coupling system is the key to realize efficient and low-cost hydrogen production and promote its practical application. Herein, a green and efficient electrocatalytic biomass to formic acid (FA) coupled hydrogen production system has been developed. In such a system, carbohydrates such as glucose are oxidized to FA using polyoxometalates (POMs) as the redox anolyte, while H2 is evolved continuously at the cathode. Among them, the yield of glucose to FA is as high as 62.5 %, and FA is the only liquid product. Furthermore, the system requires only 1.22 V to drive a current density of 50 mA cm-2 , and the Faraday efficiency of hydrogen production is close to 100 %. Its electrical consumption is only 2.9 kWh Nm-3 (H2 ), which is only 69 % of that of traditional electrolytic water. This work opens up a promising direction for low-cost hydrogen production coupled with efficient biomass conversion.

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