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1.
Sci Rep ; 14(1): 15343, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961222

ABSTRACT

This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis patients with chronic hepatitis B (CHB) which cannot be detected by conventional non-invasive examination methods but can only be diagnosed through invasive liver puncture for pathological examination. 72 patients with CHB were enrolled in this prospective study, and divided into S4 stage of liver cirrhosis and S0-S3 stage of non-liver cirrhosis according to pathological findings. Binary logistic regression analysis was performed to identify independent predictors, and a diagnostic nomogram was constructed for CHB-related early cirrhosis. It was validated and calibrated by bootstrap self-extraction. Binary logistic regression analysis showed that age (OR 1.14, 95% CI (1.04-1.27)), right hepatic vein diameter (OR 0.43, 95% CI 0.23-0.82), presence or absence of nodules (OR 31.98, 95% CI 3.84-266.08), and hepatic parenchymal echogenicity grading (OR 12.82, 95% CI 2.12-77.51) were identified as independent predictive indicators. The nomogram based on the 4 factors above showed good performance, with a sensitivity and specificity of 90.70% and 89.66%, respectively. The area under the curve (AUC) of the prediction model was 0.96, and the predictive model showed better predictive performance than APRI score (AUC 0.57), FIB-4 score (AUC 0.64), INPR score (AUC 0.63), and LSM score (AUC 0.67). The calibration curve of the prediction model fit well with the ideal curve, and the decision curve analysis showed that the net benefit of the model was significant. The nomogram in this study can detect liver cirrhosis in most CHB patients without liver biopsy, providing a direct, fast, and accurate practical diagnostic tool for clinical doctors.


Subject(s)
Hepatitis B, Chronic , Liver Cirrhosis , Nomograms , Ultrasonography , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Liver Cirrhosis/complications , Male , Female , Middle Aged , Prospective Studies , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Adult , Magnetic Resonance Imaging/methods , Liver/pathology , Liver/diagnostic imaging
2.
Mol Neurobiol ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38865079

ABSTRACT

Spinal cord injury (SCI) can lead to permanent paralysis and various motor, sensory and autonomic nervous system dysfunction. The complex pathophysiological processes limit the effectiveness of many clinical treatments. Mitochondria has been reported to play a key role in the pathogenesis of SCI; while mitophagy is a protective mechanism against mitochondrial dysfunction. However, there is recently little drugs that may targeted activate mitophagy to treat SCI. In this study, we evaluated the role of 20-Deoxyingenol (20-DOI) in SCI and explored its potential mechanisms. We used a SCI rat model and evaluated the functional outcomes after the injury. Western blotting and immunofluorescence techniques were used to analyze the levels of mitophagy, apoptosis, and TFEB-related signaling pathways. Our research results show that 20-DOI significantly improves the apoptosis of neural cells after TBHP stimulation and functional recovery after spinal cord injury. In addition, mitophagy, TFEB levels, and apoptosis are related to the mechanism of 20-DOI treatment for spinal cord injury. Specifically, our research results indicate that 20-DOI restored the autophagic flux after injury, thereby inducing mitophagy, eliminating the accumulation of Cyto C, and inhibiting apoptosis. Further mechanism research suggests that 20-DOI may regulate mitophagy by promoting TFEB nuclear translocation. These results indicate that 20-DOI can significantly promote recovery after spinal cord injury, which may be a promising treatment method for spinal cord injury.

3.
J Agric Food Chem ; 72(26): 14727-14746, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38907713

ABSTRACT

Background: Following spinal cord injury (SCI), autophagy plays a positive role in neuronal protection, whereas pyroptosis triggers an inflammatory response. Ginsenoside-Rh2 (GRh2), known for its neuroprotective effects, is considered a promising drug. However, the exact molecular mechanisms underlying these protective effects remain unclear. Aim of the Study: Explore the therapeutic value of GRh2 in SCI and its potential mechanisms of action. Materials and Methods: An SCI mouse model was established, followed by random grouping and drug treatments under different conditions. Subsequently, the functional recovery of SCI mice after GRh2 treatment was assessed using hematoxylin and eosin, Masson's trichrome, and Nissl staining, footprint analysis, Basso Mouse Scale scoring, and inclined plane tests. The expression levels of relevant indicators in the mice were detected using Western blotting, immunofluorescence, and a quantitative polymerase chain reaction. Network pharmacology analysis was used to identify the relevant signaling pathways through which GRh2 exerts its therapeutic effects. Results: GRh2 promoted functional recovery after SCI. GRh2 significantly inhibits pyroptosis by enhancing autophagy in SCI mice. Simultaneously, the neuroprotective effect of GRh2, achieved through the inhibition of pyroptosis, is partially reversed by 3-methyladenine, an autophagy inhibitor. Additionally, the increase in autophagy induced by GRh2 is mediated by the promotion of transcription factor EB (TFEB) nuclear translocation and dephosphorylation. Partial attenuation of the protective effects of GRh2 was observed after TFEB knockdown. Additionally, GRh2 can modulate the activity of TFEB in mice post-SCI through the EGFR-MAPK signaling pathway, and NSC228155 (an EGFR activator) can partially reverse the effect of GRh2 on the EGFR-MAPK signaling pathway. Conclusions: GRh2 improves functional recovery after SCI by upregulating TFEB-mediated autophagic flux and inhibiting pyroptosis, indicating its potential clinical applicability.


Subject(s)
Autophagy , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Ginsenosides , Recovery of Function , Spinal Cord Injuries , Animals , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/genetics , Ginsenosides/pharmacology , Ginsenosides/administration & dosage , Autophagy/drug effects , Mice , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Recovery of Function/drug effects , Humans , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , Neuroprotective Agents/administration & dosage , Male , Disease Models, Animal
4.
Molecules ; 29(10)2024 May 18.
Article in English | MEDLINE | ID: mdl-38792240

ABSTRACT

The photocatalyst (PC) zinc tetraphenylporphyrin (ZnTPP) is highly efficient for photoinduced electron/energy transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. However, ZnTPP suffers from poor absorbance of orange light by the so-called Q-band of the absorption spectrum (maximum absorption wavelength λmax = 600 nm, at which molar extinction coefficient εmax = 1.0×104 L/(mol·cm)), hindering photo-curing applications that entail long light penetration paths. Over the past decade, there has not been any competing candidate in terms of efficiency, despite a myriad of efforts in PC design. By theoretical evaluation, here we rationally introduce a peripheral benzo moiety on each of the pyrrole rings of ZnTPP, giving zinc tetraphenyl tetrabenzoporphyrin (ZnTPTBP). This modification not only enlarges the conjugation length of the system, but also alters the a1u occupied π molecular orbital energy level and breaks the accidental degeneracy between the a1u and a2u orbitals, which is responsible for the low absorption intensity of the Q-band. As a consequence, not only is there a pronounced hyperchromic and bathochromic effect (λmax = 655 nm and εmax = 5.2×104 L/(mol·cm)) of the Q-band, but the hyperchromic effect is achieved without increasing the intensity of the less useful, low wavelength absorption peaks of the PC. Remarkably, this strong 655 nm absorption takes advantage of deep-red (650-700 nm) light, a major component of solar light exhibiting good atmosphere penetration, exploited by the natural PC chlorophyll a as well. Compared with ZnTPP, ZnTPTBP displayed a 49% increase in PET-RAFT polymerization rate with good control, marking a significant leap in the area of photo-controlled polymerization.

5.
PLoS Comput Biol ; 20(3): e1011888, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38446830

ABSTRACT

Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.


Subject(s)
Genetic Phenomena , Neoplasms , Humans , Drug Evaluation, Preclinical , Neoplasms/drug therapy , Neoplasms/pathology
6.
J Colloid Interface Sci ; 662: 460-470, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38364471

ABSTRACT

The search for highly efficient and inexpensive electrocatalysts is crucial to the advancement of environmentally friendly and sustainable energy sources. Here, adopting a one-step hydrothermal method, we have effectively fabricated a self-supported multi-metal molybdenum-based oxide (FeCoNi-MoO4) on nickel foam (NF). In addition to changing the catalyst's microstructure, the introducing of Fe and Co, enhanced its active center count, improved its electronic structure, and in turn reduced the difficulty for high-valence Ni and Fe species to form, which accelerates the oxygen evolution reaction (OER) kinetics by promoting the development of the actual active materials, NiOOH and FeOOH. FeCoNi-MoO4 has outstanding OER performance, requiring just 204 mV overpotentials at 10 mA cm-2 and 271 mV at 100 mA cm-2. Its exceptional OER kinetics at both low and high currents are indicated by a Tafel slope of 50.6 mV dec-1, which is attributed to the combined effect of its multi-metal composition and a higher number of active sites. Moreover, the FeCoNi-MoO4 electrode was operated continuously for over 48 h. Furthermore, the density functional theory (DFT) results demonstrated that the introducing of Fe and Co, which quickens the rate of electron transfer during the electrocatalytic process, improves the ability of oxygen intermediate species to adsorb, and ultimately lowers the overpotential, is responsible for the increased electrocatalytic activity of FeCoNi-MoO4. This work offers hope for further developments in the sector by proposing an efficient approach for creating multi-active electrocatalysts that are stable, economical, and efficient.

7.
Polymers (Basel) ; 16(3)2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38337212

ABSTRACT

Thanks to their diversity, organic photocatalysts (PCs) have been widely used in manufacturing polymeric products with well-defined molecular weights, block sequences, and architectures. Still, however, more universal property-performance relationships are needed to enable the rational design of such PCs. That is, a set of unique descriptors ought to be identified to represent key properties of the PCs relevant for polymerisation. Previously, the redox potentials of excited PCs (PC*) were used as a good descriptor for characterising very structurally similar PCs. However, it fails to elucidate PCs with diverse chromophore cores and ligands, among which those used for polymerisation are a good representative. As showcased by model systems of organocatalysed atom transfer radical polymerisation (O-ATRP), new universal descriptors accounting for additional factors, such as the binding and density overlap between the PC* and initiator, are proposed and proved to be successful in elucidating the experimental performances of PCs in polymerisation. While O-ATRP is exemplified here, the approach adopted is general for studying other photocatalytic systems.

8.
Eur Spine J ; 33(3): 1069-1080, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38246903

ABSTRACT

PURPOSE: To compare the clinical outcomes and radiographic outcomes of cortical bone trajectory (CBT) and traditional trajectory (TT) pedicle screw fixation in patients treated with single-level transforaminal lumbar interbody fusion (TLIF). METHODS: This trial included a total of 224 patients with lumbar spine disease who required single-level TLIF surgery. Patients were randomly assigned to the CBT and TT groups at a 1:1 ratio. Demographics and clinical and radiographic data were collected to evaluate the efficacy and safety of CBT and TT screw fixation in TLIF. RESULTS: The baseline characteristic data were similar between the CBT and TT groups. Back and leg pain for both the CBT and TT groups improved significantly from baseline to 24 months postoperatively. The CBT group experienced less pain than the TT group at one week postoperatively. The postoperative radiographic results showed that the accuracy of screw placement was significantly increased in the CBT group compared with the TT group (P < 0.05). The CBT group had a significantly lower rate of FJV than the TT group (P < 0.05). In addition, the rate of fusion and the rate of screw loosening were similar between the CBT and TT groups according to screw loosening criteria. CONCLUSION: This prospective, randomized controlled analysis suggests that clinical outcomes and radiographic characteristics, including fusion rates and caudal screw loosening rates, were comparable between CBT and TT screw fixation. Compared with the TT group, the CBT group showed advantages in the accuracy of screw placement and the FJV rate. CLINICAL TRIALS REGISTRATION: This trial has been registered at the US National Institutes of Health Clinical Trials Registry: NCT03105167.


Subject(s)
Pedicle Screws , Spinal Fusion , Humans , Pedicle Screws/adverse effects , Spinal Fusion/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Prospective Studies , Treatment Outcome , Cortical Bone/diagnostic imaging , Cortical Bone/surgery , Pain/etiology
9.
Neural Netw ; 169: 685-697, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37972512

ABSTRACT

With the growing exploration of marine resources, underwater image enhancement has gained significant attention. Recent advances in convolutional neural networks (CNN) have greatly impacted underwater image enhancement techniques. However, conventional CNN-based methods typically employ a single network structure, which may compromise robustness in challenging conditions. Additionally, commonly used UNet networks generally force fusion from low to high resolution for each layer, leading to inaccurate contextual information encoding. To address these issues, we propose a novel network called Cascaded Network with Multi-level Sub-networks (CNMS), which encompasses the following key components: (a) a cascade mechanism based on local modules and global networks for extracting feature representations with richer semantics and enhanced spatial precision, (b) information exchange between different resolution streams, and (c) a triple attention module for extracting attention-based features. CNMS selectively cascades multiple sub-networks through triple attention modules to extract distinct features from underwater images, bolstering the network's robustness and improving generalization capabilities. Within the sub-network, we introduce a Multi-level Sub-network (MSN) that spans multiple resolution streams, combining contextual information from various scales while preserving the original underwater images' high-resolution spatial details. Comprehensive experiments on multiple underwater datasets demonstrate that CNMS outperforms state-of-the-art methods in image enhancement tasks.


Subject(s)
Generalization, Psychological , Image Enhancement , Neural Networks, Computer , Semantics , Image Processing, Computer-Assisted
10.
Small ; 20(13): e2308167, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37953455

ABSTRACT

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.


Subject(s)
Intervertebral Disc Degeneration , Nanoparticles , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/physiology , Reactive Oxygen Species/metabolism , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/metabolism , Gasdermins , Inflammasomes/metabolism , Mitochondria/metabolism , Polyphenols/pharmacology
11.
Phytomedicine ; 123: 155217, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37992492

ABSTRACT

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Flavonoids , Humans , Child , Mice , Male , Animals , Adolescent , NF-kappa B/metabolism , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , NF-E2-Related Factor 2/metabolism , AMP-Activated Protein Kinases , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy
12.
Eur J Pharmacol ; 964: 176298, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38145645

ABSTRACT

Low back pain, primarily caused by intervertebral disc degeneration (IVDD), lacks effective pharmacological treatments. Oxidative stress has been identified as a significant contributor to IVDD. This study aims to establish an in vitro model of IVDD induced by oxidative stress and identify potential therapeutic agents and their underlying mechanisms. By screening the natural product library, fisetin emerged as the most promising compound in suppressing cell death induced by oxidative stress in nucleus pulposus cells (NPCs). Furthermore, our investigation revealed that the cell death induced by oxidative stress was predominantly associated with ferroptosis, and fisetin demonstrated the ability to inhibit ferroptosis in NPCs. Mechanistic exploration suggested that the impact of fisetin on ferroptosis may be mediated through the Nrf2/HO-1 (Nuclear factor erythroid 2-related factor 2/heme oxygenase-1) axis. Notably, the in vivo study demonstrated that fisetin could alleviate IVDD in rats. These findings highlight fisetin as a potential therapeutic option for IVDD and implicate the involvement of the Nrf2/HO-1 pathway in its mechanism of action.


Subject(s)
Ferroptosis , Flavonols , Intervertebral Disc Degeneration , Animals , Rats , Ferroptosis/drug effects , Flavonols/pharmacology , Flavonols/therapeutic use , Intervertebral Disc Degeneration/drug therapy , NF-E2-Related Factor 2/metabolism
13.
J Agric Food Chem ; 72(1): 245-258, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38148374

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) has become a major global health problem with no approved pharmacological treatment for this disease. Thus, it is urgent to develop effective therapeutic targets for clinical intervention. Here, we show for the first time that ZFP30, a member of the KRAB-ZFP family, is significantly increased in NAFLD models. ZFP30 silencing ameliorates free fatty acid (FFA)-induced lipid accumulation; in contrast, the ZFP30 overexpression exacerbates the triglyceride accumulation and steatosis in hepatocytes. Further investigation revealed that the effects of ZFP30 on hepatic lipid accumulation were mainly attributed to the PPARα downregulation in the NAFLD model. Mechanistically, ZFP30 directly binded to the promoter of PPARα and recruited KAP1 to suppress its transcription. Moreover, chlorogenic acid (CGA) reversed the upregulation of ZFP30 in NAFLD, promoting the PPARα expression, resulting in enhanced fatty acid oxidation and alleviated hepatic steatosis. Collectively, our study indicates ZFP30 as a potential target for NAFLD treatment.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Animals , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Chlorogenic Acid/pharmacology , Chlorogenic Acid/metabolism , PPAR alpha/genetics , PPAR alpha/metabolism , Liver/metabolism , Lipid Metabolism , Fatty Acids, Nonesterified/metabolism , Mice, Inbred C57BL , Diet, High-Fat
14.
Mater Today Bio ; 23: 100840, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38075254

ABSTRACT

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/ß-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.

15.
Front Chem ; 11: 1259016, 2023.
Article in English | MEDLINE | ID: mdl-38025061

ABSTRACT

Open-shell molecules rarely fluoresce, due to their typically faster non-radiative relaxation rates compared to closed-shell ones. Even rarer is the fluorescence from states that have two more unpaired electrons than the open-shell ground state, since they involve excitations from closed-shell orbitals to vacant-shell orbitals, which are typically higher in energy compared to excitations from or out of open-shell orbitals. States that are dominated by the former type of excitations are known as tripdoublet states when they can be described as a triplet excitation antiferromagnetically coupled to a doublet state, and their description by unrestricted single-reference methods (e.g., U-TDDFT) is notoriously inaccurate due to large spin contamination. In this work, we applied our spin-adapted TDDFT method, X-TDDFT, and the efficient and accurate static-dynamic-static second order perturbation theory (SDSPT2), to the study of the excited states as well as their relaxation pathways of copper(II) porphyrin; previous experimental works suggested that the photoluminescence of some substituted copper(II) porphyrins originate from a tripdoublet state, formed by a triplet ligand π → π* excitation antiferromagnetically coupled with the unpaired d electron. Our results demonstrated favorable agreement between the X-TDDFT, SDSPT2 and experimental excitation energies, and revealed noticeable improvements of X-TDDFT compared to U-TDDFT, not only for vertical excitation energies but also for adiabatic energy differences. These suggest that X-TDDFT is a reliable tool for the study of tripdoublet state fluorescence. Intriguingly, we showed that the aforementioned tripdoublet state is only slightly above the lowest doublet excited state and lies only slightly higher than the lowest quartet state, which suggests that the tripdoublet of copper(II) porphyrin is long-lived enough to fluoresce due to a lack of efficient non-radiative relaxation pathways; an explanation for this unusual state ordering is given. Indeed, thermal vibration correlation function (TVCF)-based calculations of internal conversion, intersystem crossing, and radiative transition rates confirm that copper(II) porphyrin emits thermally activated delayed fluorescence (TADF) and a small amount of phosphorescence at low temperature (83 K), in accordance with experiment. The present contribution is concluded by a few possible approaches of designing new molecules that fluoresce from tripdoublet states.

16.
Biochem Pharmacol ; 218: 115865, 2023 12.
Article in English | MEDLINE | ID: mdl-37863322

ABSTRACT

Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease with significant adverse implications for patients' quality of life and socioeconomic status. Although the precise etiology of IVDD remains elusive, the senescence of nucleus pulposus cells is recognized as the primary pathogenic factor of IVDD; however, drugs that may targetedly inhibit senescence are still lacking. In the current study, we evaluated the small-molecule active drug 20-Deoxyingenol(20-DOI) for its effects on combating senescence and delaying the progression of IVDD. In vitro experiments revealed that the administration of 20-DOI displayed inhibitory effects on senescence and the senescence-related cGAS-STING pathway of nucleus pulposus cells. Additionally, it exhibited the ability to enhance lysosome activity and promote autophagy flux within nucleus pulposus cells. Subsequent investigations elucidated that the inhibitory impact of 20-DOI on nucleus pulposus cell senescence was mediated through the autophagy-lysosome pathway. This effect was diminished in the presence of transcription factor EB (TFEB) small hairpin RNA (shRNA), thereby confirming the regulatory role of 20-DOI on the autophagy-lysosome pathway and senescence through TFEB. In vivo experiments demonstrated that 20-DOI effectively impeded the progression ofIVDD in rats. These findings collectively illustrate that 20-DOI may facilitate the autophagy-lysosomal pathway by activating TFEB, thereby suppressing the senescence in nucleus pulposus cells, thus suggesting 20-DOI as a promising therapeutic approach for IVDD.


Subject(s)
Intervertebral Disc Degeneration , Nucleus Pulposus , Humans , Rats , Animals , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Quality of Life , Autophagy , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
17.
Proc Natl Acad Sci U S A ; 120(42): e2313034120, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37812726

ABSTRACT

Meiosis is essential for generating genetic diversity and sexual spores, but the regulation of meiosis and ascosporogenesis is not clear in filamentous fungi, in which dikaryotic and diploid cells formed inside fruiting bodies are not free living and independent of pheromones or pheromone receptors. In this study, Gia1, a non-pheromone GPCR (G protein-coupled receptor) with sexual-specific expression in Fusarium graminearum, is found to be essential for ascosporogenesis. The gia1 mutant was normal in perithecium development, crozier formation, and karyogamy but failed to undergo meiosis, which could be partially rescued by a dominant active mutation in GPA1 and activation of the Gpmk1 pathway. GIA1 orthologs have conserved functions in regulating meiosis and ascosporogenesis in Sordariomycetes. GIA1 has a paralog, GIP1, in F. graminearum and other Hypocreales species which is essential for perithecium formation. GIP1 differed from GIA1 in expression profiles and downstream signaling during sexual reproduction. Whereas the C-terminal tail and IR3 were important for intracellular signaling, the N-terminal region and EL3 of Gia1 were responsible for recognizing its ligand, which is likely a protein enriched in developing perithecia, particularly in the gia1 mutant. Taken together, these results showed that GIA1 encodes a non-pheromone GPCR that regulates the entry into meiosis and ascosporogenesis via the downstream Gpmk1 MAP kinase pathway in F. graminearum and other filamentous ascomycetes.


Subject(s)
Ascomycota , Fusarium , Triticum/microbiology , Pheromones/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fusarium/genetics , Ascomycota/genetics , Ascomycota/metabolism , Meiosis/genetics , Spores, Fungal
18.
Nat Plants ; 9(10): 1627-1642, 2023 10.
Article in English | MEDLINE | ID: mdl-37735254

ABSTRACT

Parasitic plants have evolved to be subtly or severely dependent on host plants to complete their life cycle. To provide new insights into the biology of parasitic plants in general, we assembled genomes for members of the sandalwood order Santalales, including a stem hemiparasite (Scurrula) and two highly modified root holoparasites (Balanophora) that possess chimaeric host-parasite tubers. Comprehensive genome comparisons reveal that hemiparasitic Scurrula has experienced a relatively minor degree of gene loss compared with autotrophic plants, consistent with its moderate degree of parasitism. Nonetheless, patterns of gene loss appear to be substantially divergent across distantly related lineages of hemiparasites. In contrast, Balanophora has experienced substantial gene loss for the same sets of genes as an independently evolved holoparasite lineage, the endoparasitic Sapria (Malpighiales), and the two holoparasite lineages experienced convergent contraction of large gene families through loss of paralogues. This unprecedented convergence supports the idea that despite their extreme and strikingly divergent life histories and morphology, the evolution of these and other holoparasitic lineages can be shaped by highly predictable modes of genome reduction. We observe substantial evidence of relaxed selection in retained genes for both hemi- and holoparasitic species. Transcriptome data also document unusual and novel interactions between Balanophora and host plants at the host-parasite tuber interface tissues, with evidence of mRNA exchange, substantial and active hormone exchange and immune responses in parasite and host.


Subject(s)
Host-Parasite Interactions , Plants , Host-Parasite Interactions/genetics , Plants/genetics
19.
Sci Rep ; 13(1): 15813, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37740022

ABSTRACT

Series compensation grids connected with type-3 wind turbine generator (WTG)-based wind farms have suffered numerous subsynchronous oscillation (SSO) events worldwide. For early alerting of SSO and effective development of protection and control strategies, it is critical to monitor and identify SSO accurately and quickly. Ambient data is continuously available, which is useful for online monitoring. This paper proposes an ambient data-driven SSO online monitoring method based on the Kalman filter (KF) combined with the multi-model partitioning filter (MMPF). The KF is utilized to fit the measured ambient data with an auto regressive (AR) model. Then, the damping factor (or damping ratio) and frequency in the SSO mode can be acquired by solving the roots of the characteristic polynomial corresponding to the AR model. Moreover, the MMPF is an effective model order selection method applied to the KF for better identification. The performance of the MMPF-KF method is demonstrated by simulations and real-time experiments. The results of case studies validate the effectiveness of the proposed method under various conditions.

20.
Environ Sci Pollut Res Int ; 30(50): 109266-109282, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37759064

ABSTRACT

In recent years, the solid wastes from the coal industry have been widely used as soil amendments. Nevertheless, the impact of utilizing coal slime for copper tailing restoration in terms of plant growth, physicochemical characteristics of the tailing soil, and microbial succession remains uncertain.Herein, the coal slime was employed as a modifier into copper tailings. Their effect on the growth and physiological response of Ryegrass, and the soil physicochemical properties as well as the bacterial community structure were investigated. The results indicated that after a 30-day of restoration, the addition of coal slime at a ratio of 40% enhanced plant growth, with a 21.69% rise in chlorophyll content, and a 62.44% increase in peroxidase activity. The addition of 40% coal slime also increased the content of nutrient elements in copper tailings. Following a 20-day period of restoration, the concentrations of available copper and available zinc in the modified tailings decreased by 39.6% and 48.51%, respectively, with 40% of coal slime added. In the meantime, there was an observed augmentation in the species diversity of the bacterial community in the modified tailings. The alterations in both community structure and function were primarily influenced by variations in pH value, available nitrogen, phosphorus, potassium, and available copper. The addition of 40% coal slime makes the physicochemical properties and microbial community evolution of copper tailings reach a balance point. The utilization of coal slime has the potential to enhance the physicochemical characteristics of tailings and promote the proliferation of microbial communities, hence facilitating the soil evolution of two distinct solid waste materials. Consequently, the application of coal slime in the restoration of heavy metal tailings is a viable approach, offering both cost-effectiveness and efficacy as an enhancer.


Subject(s)
Metals, Heavy , Soil Pollutants , Copper , Soil/chemistry , Coal , Soil Microbiology , Metals, Heavy/analysis , Soil Pollutants/analysis
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