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1.
Chemosphere ; : 142525, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38838867

Pseudomonas sp. ZHL02, removing nitrogen via ammonia nitrogen (NH4+) → hydroxylamine (HN2OH) → nitrite (NO2-) → nitrate (NO3-) → NO2- → nitric oxide (NO) → nitrous oxide (N2O) pathway was employed for getting in-depth information on the heterotrophic nitrification-aerobic denitrification (HNAD) pathway from carbon oxidation, nitrogen conversion, electron transport process, enzyme activity, as well as gene expression while sodium succinate, sodium citrate, and sodium acetate were utilized as the carbon sources. The nitrogen balance analysis results demonstrated that ZHL02 mainly removed NH4+-N through assimilation. The carbon source metabolism resulted in the discrepancies in electron transport chain and nitrogen removal between different HNAD bacteria. Moreover, the prokaryotic strand-specific transcriptome method showed that, amo and hao were absent in ZHL02, and unknown genes may be involved in ZHL02 during the HNAD process. As a fascinating process for removing nitrogen, the HNAD process is still puzzling, and the relationship between carbon metabolism and nitrogen metabolism among different HNAD pathways should be studied further.

2.
Chem Sci ; 15(22): 8372-8379, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38846395

Here we report a diachronic evolvement from tetra-icosahedral Au30Ag12(C[triple bond, length as m-dash]CR)24 to quasi-hcp (hexagonal close-packed) Au47Ag19(C[triple bond, length as m-dash]CR)32 via a one-step reduction, in which the size/structure conversion of the two clusters is not a typical Oswald growth process, but involves interface shrinking followed by core rearrangement and surface polymerization. Au30Ag12(C[triple bond, length as m-dash]CR)24 has an aesthetic Au18Ag8 kernel that is composed of four interpenetrating Au10Ag3 icosahedra, while Au47Ag19(C[triple bond, length as m-dash]CR)32 has a twisted Au19 core capped by a Au12Ag19 shell that are stacked in a layer-by-layer manner with a quasi-hcp pattern. The discovery of the two clusters not only provides further evidence for icosahedral clusters with longer excited-state lifetime compared to hcp-like clusters, but also discloses a double increase in catalytic reactivity for electrocatalytic oxidation of ethanol over quasi-hcp clusters in comparison with icosahedral clusters. This work provides the rationale for reversing the bottom-up growth process to remake bimetal clusters.

3.
Heliyon ; 10(11): e31654, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38828289

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

4.
Ann Med ; 56(1): 2346546, 2024 Dec.
Article En | MEDLINE | ID: mdl-38847883

BACKGROUND: Although normal acute phase reactants (APRs) play an important role in assessing disease activity of rheumatoid arthritis (RA), some studies pointed out the discordance between disease activity and APR level. Neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs) and lymphocyte-to-monocyte ratios (LMRs) have been reported to be sensitive measures of inflammatory reaction. This study aims to explore the value of these haematological makers in assessment of APR-negative RA patients. METHODS: Out of a cohort of 418 consecutive patients with RA, we enrolled 135 patients with normal APR for this study. We performed ultrasound assessments to evaluate synovitis and bone erosion in the affected joints. Synovitis was evaluated by ultrasound grey scale (GS) and power Doppler (PD) with semi-quantitative scoring (0-3). Demographic, clinical and laboratory data were collected from the patients. Disease Activity Score-28 joints (DAS28), NLR, MLR and PLR were calculated. RESULTS: In RA patients with normal APR, PLR exhibited a positive correlation with ultrasound-detected synovitis and bone erosion, whereas NLR, MLR showed no significant correlation with ultrasonography parameters. The area under the ROC curve (AUC) for identifying synovitis with a GS grade ≥2 based on a PLR cutoff value of ≥159.6 was 0.7868 (sensitivity: 80.95%, specificity: 74.24%). For synovitis with a PD grade ≥2, the AUC was 0.7690, using a PLR cutoff value of ≥166.1 (sensitivity: 68.0%, specificity: 83.87%). CONCLUSIONS: Our findings suggested that PLR might be a reliable and cost-effective marker for identifying moderate-to-severe synovitis in RA patients with normal APR.


Arthritis, Rheumatoid , Biomarkers , Lymphocytes , Synovitis , Humans , Synovitis/diagnostic imaging , Synovitis/blood , Synovitis/diagnosis , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/complications , Female , Male , Middle Aged , Biomarkers/blood , Adult , Blood Platelets , Acute-Phase Proteins/analysis , Aged , Severity of Illness Index , Platelet Count , ROC Curve , Lymphocyte Count , Neutrophils
5.
Chem Sci ; 15(18): 6906-6915, 2024 May 08.
Article En | MEDLINE | ID: mdl-38725488

Vibrational coherence has attracted considerable research interests because of its potential functions in light harvesting systems. Although positive signs of vibrational coherence in metal nanoclusters have been observed, the underlying mechanism remains to be verified. Here, we demonstrate that robust vibrational coherence with a lifetime of 1 ps can be clearly identified in Ag44(SR)30 core-shell nanoclusters, in which an icosahedral Ag12 core is well protected by a dodecahedral Ag20 cage. Ultrafast spectroscopy reveals that two vibrational modes at around 2.4 THz and 1.6 THz, corresponding to the breathing mode and quadrupolar-like mode of the icosahedral Ag12 core, respectively, are responsible for the generation of vibrational coherence. In addition, the vibrational coherence of Ag44 has an additional high frequency mode (2.4 THz) when compared with that of Ag29, in which there is only one low frequency vibration mode (1.6 THz), and the relatively faster dephasing in two-layer Ag29 relative to that in Ag44 further supports the fact that the robust vibrational coherence in Ag44 is ascribed to its unique matryoshka-like core-shell structure. Our findings not only present unambiguous experimental evidence for a multi-layer core-shell structure protected vibrational coherence under ambient conditions but also offers a practical strategy for the design of highly efficient quantum optoelectronic devices.

6.
Angew Chem Int Ed Engl ; : e202404978, 2024 May 02.
Article En | MEDLINE | ID: mdl-38697945

Integrating aggregation-induced emission (AIE) into thermally activated delayed fluorescence (TADF) emitters holds great promise for the advancement of highly efficient organic light emitting diodes (OLEDs). Despite recent advancements, a thorough comprehension of the underlying mechanisms remains imperative for the practical application of such materials. In this work, we introduce a novel approach aimed at modulating the TADF process by manipulating dynamic processes in excited states through aggregation effect. Our findings reveal that aggregation not only enhances both prompt and delayed fluorescence simultaneously but also imposes constraints on molecular reorientation. This constraint reinforces spin-orbit coupling and reduces the energy gap between singlets and triplets. These insights deepen our understanding of the fundamental mechanisms governing the aggregation effect on TADF materials and provide valuable guidance for the design of high-efficiency photoluminescent materials.

7.
Drug Des Devel Ther ; 18: 1439-1457, 2024.
Article En | MEDLINE | ID: mdl-38707616

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.


Diabetes Mellitus, Experimental , Diabetic Nephropathies , Glucosides , Molecular Docking Simulation , Network Pharmacology , Phenols , Polyphenols , Streptozocin , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Animals , Rats , Glucosides/pharmacology , Glucosides/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Phenols/pharmacology , Phenols/chemistry , Rats, Sprague-Dawley
8.
Exp Eye Res ; 244: 109929, 2024 May 30.
Article En | MEDLINE | ID: mdl-38750783

Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina. The integrated analysis of co-expression and protein-protein interactions identified an active interconnected module comprising 5 co-expressed proteins (Fga, Serpina1a, Hpd, Slc38a4, and Ahsg) associated with the complement and coagulation cascades. Finally, 5 mRNAs (Fga, Serpinala, Hpd, Slc38a4, and Ahsg), 2 miRNAs (miR-671-5p and miR-3057-5p), and 6 lncRNAs (MSTRG. 1830.1, Gm10814, A530013C23Rik, Gm40634, MSTRG.9514.1, A330023F24Rik) were identified by qPCR in the injured retina, and some of them were validated as critical components of a ceRNA network active in 661W and HEK293T cells through dual-luciferase reporter assays. In conclusion, our study provides comprehensive insight into the complex and dynamic biological mechanisms involved in retinal injury responses and highlights promising potential targets to enhance neuroprotection and restore vision.

9.
Int J Biol Macromol ; 269(Pt 2): 131878, 2024 Jun.
Article En | MEDLINE | ID: mdl-38692530

Excessive accumulation of exudate from wounds often causes infection and hinders skin regeneration. To handle wound exudate quickly and prevent infection, we developed an antibacterial Janus nanofibrous dressing with a unidirectional water-transport function. The dressing consists of a hydrophilic chitosan aerogel (CS-A) as the outer layer and a hydrophobic laurylated chitosan (La-CS) nanofibrous membrane as the inner layer. These dressings achieved excellent liquid absorption performance (2987.8 ±â€¯123.5 %), air and moisture permeability (997.8 ±â€¯23.1 g/m2/day) and mechanical strength (5.1 ±â€¯2.6 MPa). This performance was obtained by adjusting the density of CS-A and the thickness of the La-CS membrane. Moreover, the dressing did not induce significant toxicity to cells and can prevent bacterial aggregation and infection at the wound site. Animal experiments showed that the dressing can shorten the inflammatory phase, enhance blood vessel generation, and accelerate collagen deposition, thus promoting wound healing. Overall, these results suggest that this Janus dressing is a promising material for clinical wound care.


Anti-Bacterial Agents , Bandages , Chitosan , Nanofibers , Water , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Wound Healing/drug effects , Nanofibers/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Water/chemistry , Mice , Hydrophobic and Hydrophilic Interactions , Permeability , Rats , Staphylococcus aureus/drug effects , Male
10.
Medicine (Baltimore) ; 103(21): e38203, 2024 May 24.
Article En | MEDLINE | ID: mdl-38788018

To analyze the correlation between Balthazar CT grading and contrast-enhanced CT necrosis volume and attenuation value and prognosis of patients with acute necrotizing pancreatitis. Ninety-two patients with acute necrotizing pancreatitis who were treated in the hospital were selected between June 2019 and June 2021, and they were divided into the poor prognosis group and the good prognosis group according to the clinical prognosis at 6 months of follow-up. Balthazar CT, contrast-enhanced CT necrosis volume, and attenuation value were compared between the 2 groups. Multivariate logistic regression analysis was used to analyze the influencing factors. Receiver operating characteristic curve was adopted to analyze the predictive value. Among the 92 participants, there were 28 cases with good prognosis (30.43%) and 64 cases with poor prognosis (69.57%). The Acute Physiology and Chronic Health Evaluation II score, C-reactive protein, urea nitrogen, Balthazar CT, necrotic volume, and average attenuation value of the poor prognosis group were significantly higher than those of the good prognosis group (all P values <.05). The results of the multivariate logistic analysis showed that Balthazar CT grade, necrotic volume, and average attenuation value were independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis (all P values <.05). The area under the curve of Balthazar CT grade, necrotic volume, average attenuation value, and the joint detection in predicting the prognosis of patients with acute necrotizing pancreatitis were 0.765, 0.624, 0.764, and 0.861, respectively. The Balthazar CT grading, necrosis volume, and average attenuation value are significantly higher among patients with acute necrotizing pancreatitis complicated with poor prognosis, and they are also independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis, and can help clinically predict the prognosis of patients with acute necrotizing pancreatitis, and the combined detection has better application effects.


Pancreatitis, Acute Necrotizing , Tomography, X-Ray Computed , Humans , Pancreatitis, Acute Necrotizing/diagnostic imaging , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/pathology , Male , Female , Middle Aged , Tomography, X-Ray Computed/methods , Prognosis , Adult , Necrosis/diagnostic imaging , ROC Curve , Aged , Severity of Illness Index , Retrospective Studies , Risk Factors , Contrast Media , Predictive Value of Tests
11.
Biomed Pharmacother ; 175: 116694, 2024 Jun.
Article En | MEDLINE | ID: mdl-38713943

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.


Atherosclerosis , Diabetes Mellitus , Kaempferols , Non-alcoholic Fatty Liver Disease , Obesity , Humans , Kaempferols/pharmacology , Kaempferols/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Obesity/drug therapy , Obesity/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Signal Transduction/drug effects
12.
Animals (Basel) ; 14(9)2024 Apr 29.
Article En | MEDLINE | ID: mdl-38731349

Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination rates of both sexes using approximately 52 K SNP genotypes in a total of 3279 pigs from four different Chinese and Western breeds. We then constructed a high-resolution historical recombination map using approximately 16 million SNPs from a sample of unrelated individuals. Comparative analysis of porcine recombination events from different breeds and at different resolutions revealed the following observations: Firstly, the 1Mb-scale pig recombination maps of the same sex are moderately conserved among different breeds, with the similarity of recombination events between Western pigs and Chinese indigenous pigs being lower than within their respective groups. Secondly, we identified 3861 recombination hotspots in the genome and observed medium- to high-level correlation between historical recombination rates (0.542~0.683) and estimates of meiotic recombination rates. Third, we observed that recombination hotspots are significantly far from the transcription start sites of pig genes, and the silico-predicted PRDM9 zinc finger domain DNA recognition motif is significantly enriched in the regions of recombination hotspots compared to recombination coldspots, highlighting the potential role of PRDM9 in regulating recombination hotspots in pigs. Our study analyzed the variation patterns of the pig recombination map at broad and fine scales, providing a valuable reference for genomic selection breeding and laying a crucial foundation for further understanding the molecular mechanisms of pig genome recombination.

13.
Front Mol Biosci ; 11: 1379124, 2024.
Article En | MEDLINE | ID: mdl-38712344

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

14.
Article En | MEDLINE | ID: mdl-38639703

INTRODUCTION: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis. METHODS: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models. RESULTS: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models. CONCLUSIONS: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge.

15.
J Phys Chem Lett ; 15(15): 4197-4205, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38598694

Multiresonance thermally activated delayed fluorescence (MR-TADF) emitters are excellent candidates for high-performance organic light-emitting diodes (OLEDs) due to their narrowband emission properties. However, the inherent mechanism of regulating the rate of intersystem crossing (ISC) is ambiguous in certain MR-TADF skeletons. Herein, we propose a mechanism of accelerating ISC in B/S-based MR-TADF emitters by peripheral modifications of electron-donating groups (EDGs) without affecting the narrowband emission property. The long-range charge transfer (LRCT) stems from the introduced EDG leading to high-lying singlet and triplet excited states. The ISC process is accelerated by the enhanced spin-orbital coupling (SOC) between the singlet short-range charge transfer (SRCT) and triplet LRCT manifolds. Meanwhile, the narrowband emission derived from the MR-type SRCT state is well retained as expected in the peripherally modified MR-TADF emitters. This work reveals the regulation mechanism of photophysical properties by high-lying LRCT excited states and provides a significant theoretical basis for modulating the rate of ISC in the further design of MR-TADF materials.

16.
Hepatology ; 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38683582

BACKGROUND AIMS: Hepatocellular carcinoma (HCC), particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. APPROACH RESULTS: Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking (MAMH) for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. MAMH has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. CONCLUSIONS: The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.

17.
Antioxidants (Basel) ; 13(4)2024 Apr 04.
Article En | MEDLINE | ID: mdl-38671885

The application of cottonseed protein concentrate (CPC) is an effective strategy to moderate the shortage of fish meal (FM) for the aquafeed industry. However, little attention has been paid to the effects of replacing fishmeal with CPC on cyprinid fish. This study used common carp (Cyprinus carpio) as the biological model and assessed the potential of applying CPC as a substitute for fishmeal in the diet of common carp. The proportion of fish meal substituted with CPC in the six diets was 0% (CPC0), 25% (CPC25), 50% (CPC50), 75% (CPC75), and 100% (CPC100). Each diet was fed to three replicate groups of common carp (4.17 ± 0.02 g) for 56 days. Results revealed that the CPC50 group significantly increased the growth indexes via up-regulating the genes of the GH/IGF axis and the TOR pathway. The intestinal digestive ability was also elevated in the CPC50 group via markedly increasing intestinal villus height, protease and lipase activities in the whole intestine, and the amylase activity of the foregut and midgut. The CPC50 group captured significantly higher activities and gene expressions of antioxidant enzymes and lower malonaldehyde contents via evoking the Nrf2/Keap1 signal pathway. The CPC50 group enhance the intestinal mechanical barrier via up-regulating the gene expressions of tight junction proteins and heighten the intestinal biological barrier by increasing the probiotics (Lactococcus) and decreasing the harmful bacteria (Enterococcus). But excessive substitution levels (75% and 100%) would compromise growth performance, intestinal antioxidant capacity, and immune function. The optimum substitution level was estimated to be 46.47%, 47.72%, and 46.43% using broken-line regression analyses based on mass gain rate, protein efficiency ratio, and feed conversion rate. Overall, the fishmeal in common carp feed could be substituted up to 50% by CPC without negative influence on growth, feed utilization, and or intestinal health.

18.
Angew Chem Int Ed Engl ; : e202405333, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38623864

Electrically conducting two-dimensional (2D) metal-organic frameworks (MOFs) have garnered significant interest due to their remarkable structural tunability and outstanding electrical properties. However, the design and synthesis of high-performance materials face challenges due to the limited availability of specific ligands and pore structures. In this study, we have employed a novel highly branched D3h symmetrical planar conjugated ligand, dodechydroxylhexabenzotrinaphthylene (DHHBTN) to fabricate a series of 2D conductive MOFs, named M-DHHBTN (M=Co, Ni, and Cu). This new family of MOFs offers two distinct types of pores, elevating the structural complexity of 2D conductive MOFs to a more advanced level. The intricate tessellation patterns of the M-DHHBTN are elucidated through comprehensive analyses involving powder X-ray diffraction, theoretical simulations, and high-resolution transmission electron microscope. Optical-pump terahertz-probe spectroscopic measurements unveiled carrier mobility in DHHBTN-based 2D MOFs spanning from 0.69 to 3.10 cm2 V-1 s-1. Among M-DHHBTN famility, Cu-DHHBTN displayed high electrical conductivity reaching 0.21 S cm-1 at 298 K with thermal activation behavior. This work leverages the "branched conjugation" of the ligand to encode heteroporosity into highly conductive 2D MOFs, underscoring the significant potential of heterogeneous double-pore structures for future applications.

19.
Biochem Pharmacol ; 224: 116240, 2024 Jun.
Article En | MEDLINE | ID: mdl-38679210

Hepatic steatosis is a critical factor in the development of nonalcoholic steatohepatitis (NASH). Sesamin (Ses), a functional lignan isolated from Sesamum indicum, possesses hypolipidemic, liver-protective, anti-hypertensive, and anti-tumor properties. Ses has been found to improve hepatic steatosis, but the exact mechanisms through which Ses achieves this are not well understood. In this study, we observed the anti-hepatic steatosis effects of Ses in palmitate/oleate (PA/OA)-incubated primary mouse hepatocytes, AML12 hepatocytes, and HepG2 cells, as well as in high-fat, high-cholesterol diet-induced NASH mice. RNA sequencing analysis revealed that cluster of differentiation 36 (CD36), a free fatty acid (FA) transport protein, was involved in the Ses-mediated inhibition of hepatic fat accumulation. Moreover, the overexpression of CD36 significantly increased hepatic steatosis in both Ses-treated PA/OA-incubated HepG2 cells and NASH mice. Furthermore, Ses treatment suppressed insulin-induced de novo lipogenesis in HepG2 cells, which was reversed by CD36 overexpression. Mechanistically, we found that Ses ameliorated NASH by inhibiting CD36-mediated FA uptake and upregulation of lipogenic genes, including FA synthase, stearoyl-CoA desaturase 1, and sterol regulatory element-binding protein 1. The findings of our study provide novel insights into the potential therapeutic applications of Ses in the treatment of NASH.


CD36 Antigens , Dioxoles , Hepatocytes , Lignans , Lipid Metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Animals , Lignans/pharmacology , Lignans/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Mice , Humans , CD36 Antigens/metabolism , CD36 Antigens/genetics , Hepatocytes/drug effects , Hepatocytes/metabolism , Hep G2 Cells , Male , Lipid Metabolism/drug effects , Dioxoles/pharmacology , Dioxoles/therapeutic use , Diet, High-Fat/adverse effects
20.
Angew Chem Int Ed Engl ; : e202404129, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38651974

Designing luminophores bright in both isolate species and aggregate states is of great importance in many emerging cutting-edge applications. However, the conventional luminophores either emit in isolate species but quench in aggregate state or emit in aggregate state but darken in isolate species. Here we demonstrate that the precise regulation of noncovalent interactions can realize luminophores bright in both isolate species and aggregate states. It is firstly discovered that the intra-cluster interaction enhances the emission of atomically precise Au25(pMBA)18 (pMBA=4-mercaptobenzoic acid), a nanoscale luminophore, while the inter-cluster interaction quenches the emission. The emission enhancing strategies are then well-designed by both introducing exogenous substances to block inter-cluster interaction and surface manipulation of Au25(pMBA)18 at the molecular level to enhance intra-cluster interaction, opening new possibilities to controllably enhance the luminophore's photoluminescence in both isolate species and aggregate states in different phases including aqueous solution, solid state and organic solvents.

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