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1.
Mol Cell ; 83(10): 1588-1604.e5, 2023 05 18.
Article in English | MEDLINE | ID: mdl-37080207

ABSTRACT

Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or promoter-proximal termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here, we establish a rapid degradation system to dissect the functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces promoter-proximal termination, with its disruption leading to accumulation of elongation-incompetent polymerases and downregulation of highly expressed genes, while elongation-competent polymerases accumulate at lowly expressed genes and non-coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus, both INTAC catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control.


Subject(s)
Phosphoric Monoester Hydrolases , RNA Polymerase II , RNA Polymerase II/genetics , RNA Polymerase II/metabolism , Phosphoric Monoester Hydrolases/metabolism , Gene Expression Regulation , Transcriptional Activation , Up-Regulation , Transcription, Genetic
2.
Proc Natl Acad Sci U S A ; 121(3): e2308837121, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38198530

ABSTRACT

The development of individuality during learned behavior is a common trait observed across animal species; however, the underlying biological mechanisms remain understood. Similar to human speech, songbirds develop individually unique songs with species-specific traits through vocal learning. In this study, we investigate the developmental and molecular mechanisms underlying individuality in vocal learning by utilizing F1 hybrid songbirds (Taeniopygia guttata cross with Taeniopygia bichenovii), taking an integrating approach combining experimentally controlled systematic song tutoring, unbiased discriminant analysis of song features, and single-cell transcriptomics. When tutoring with songs from both parental species, F1 hybrid individuals exhibit evident diversity in their acquired songs. Approximately 30% of F1 hybrids selectively learn either song of the two parental species, while others develop merged songs that combine traits from both species. Vocal acoustic biases during vocal babbling initially appear as individual differences in songs among F1 juveniles and are maintained through the sensitive period of song vocal learning. These vocal acoustic biases emerge independently of the initial auditory experience of hearing the biological father's and passive tutored songs. We identify individual differences in transcriptional signatures in a subset of cell types, including the glutamatergic neurons projecting from the cortical vocal output nucleus to the hypoglossal nuclei, which are associated with variations of vocal acoustic features. These findings suggest that a genetically predisposed vocal motor bias serves as the initial origin of individual variation in vocal learning, influencing learning constraints and preferences.


Subject(s)
Individuality , Songbirds , Animals , Humans , Genetic Predisposition to Disease , Speech , Acoustics , Bias
3.
Nature ; 586(7829): 378-384, 2020 10.
Article in English | MEDLINE | ID: mdl-33057220

ABSTRACT

Neuromorphic computing draws inspiration from the brain to provide computing technology and architecture with the potential to drive the next wave of computer engineering1-13. Such brain-inspired computing also provides a promising platform for the development of artificial general intelligence14,15. However, unlike conventional computing systems, which have a well established computer hierarchy built around the concept of Turing completeness and the von Neumann architecture16-18, there is currently no generalized system hierarchy or understanding of completeness for brain-inspired computing. This affects the compatibility between software and hardware, impairing the programming flexibility and development productivity of brain-inspired computing. Here we propose 'neuromorphic completeness', which relaxes the requirement for hardware completeness, and a corresponding system hierarchy, which consists of a Turing-complete software-abstraction model and a versatile abstract neuromorphic architecture. Using this hierarchy, various programs can be described as uniform representations and transformed into the equivalent executable on any neuromorphic complete hardware-that is, it ensures programming-language portability, hardware completeness and compilation feasibility. We implement toolchain software to support the execution of different types of program on various typical hardware platforms, demonstrating the advantage of our system hierarchy, including a new system-design dimension introduced by the neuromorphic completeness. We expect that our study will enable efficient and compatible progress in all aspects of brain-inspired computing systems, facilitating the development of various applications, including artificial general intelligence.

4.
Mol Biol Evol ; 41(10)2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39302728

ABSTRACT

Transcriptional enhancers orchestrate cell type- and time point-specific gene expression programs. Genetic variation within enhancer sequences is an important contributor to phenotypic variation including evolutionary adaptations and human disease. Certain genes and pathways may be more prone to regulatory evolution than others, with different patterns across diverse organisms, but whether such patterns exist has not been investigated at a sufficient scale. To address this question, we identified signatures of accelerated sequence evolution in conserved enhancer elements throughout the mammalian phylogeny at an unprecedented scale. While different genes and pathways were enriched for regulatory evolution in different parts of the tree, we found a striking overall pattern of pleiotropic genes involved in gene regulatory and developmental processes being enriched for accelerated enhancer evolution. These genes were connected to more enhancers than other genes, which was the basis for having an increased amount of sequence acceleration over all their enhancers combined. We provide evidence that sequence acceleration is associated with turnover of regulatory function. Detailed study of one acceleration event in an enhancer of HES1 revealed that sequence evolution led to a new activity domain in the developing limb that emerged concurrently with the evolution of digit reduction in hoofed mammals. Our results provide evidence that enhancer evolution has been a frequent contributor to regulatory innovation at conserved developmental signaling genes in mammals.


Subject(s)
Conserved Sequence , Enhancer Elements, Genetic , Evolution, Molecular , Mammals , Phylogeny , Animals , Mammals/genetics , Humans , Genes, Developmental , Gene Expression Regulation, Developmental
5.
Development ; 149(14)2022 07 15.
Article in English | MEDLINE | ID: mdl-35781558

ABSTRACT

Formation of highly unique and complex facial structures is controlled by genetic programs that are responsible for the precise coordination of three-dimensional tissue morphogenesis. However, the underlying mechanisms governing these processes remain poorly understood. We combined mouse genetic and genomic approaches to define the mechanisms underlying normal and defective midfacial morphogenesis. Conditional inactivation of the Wnt secretion protein Wls in Pax3-expressing lineage cells disrupted frontonasal primordial patterning, cell survival and directional outgrowth, resulting in altered facial structures, including midfacial hypoplasia and midline facial clefts. Single-cell RNA sequencing revealed unique transcriptomic atlases of mesenchymal subpopulations in the midfacial primordia, which are disrupted in the conditional Wls mutants. Differentially expressed genes and cis-regulatory sequence analyses uncovered that Wls modulates and integrates a core gene regulatory network, consisting of key midfacial regulatory transcription factors (including Msx1, Pax3 and Pax7) and their downstream targets (including Wnt, Shh, Tgfß and retinoic acid signaling components), in a mesenchymal subpopulation of the medial nasal prominences that is responsible for midline facial formation and fusion. These results reveal fundamental mechanisms underlying mammalian midfacial morphogenesis and related defects at single-cell resolution.


Subject(s)
Gene Regulatory Networks , Transcriptome , Animals , Face , Mammals/genetics , Mice , Morphogenesis/genetics , Transcriptome/genetics , Wnt Proteins/metabolism
6.
J Am Chem Soc ; 146(1): 660-667, 2024 01 10.
Article in English | MEDLINE | ID: mdl-38131111

ABSTRACT

Conjugated oligoelectrolytes (COEs) comprise a class of fluorescent reporters with tunable optical properties and lipid bilayer affinity. These molecules have proven effective in a range of bioimaging applications; however, their use in characterizing specific subcellular structures remains restricted. Such capabilities would broaden COE applications to understand cellular dysfunction, cell communication, and the targets of different pharmaceutical agents. Here, we disclose a novel COE derivative, COE-CN, which enables the visualization of mitochondria, including morphological changes and lysosomal fusion upon treatment with depolarizing agents. COE-CN is characterized by the presence of imidazolium solubilizing groups and an optically active cyanovinyl-linked distyrylbenzene core with intramolecular charge-transfer characteristics. Our current understanding is that the relatively shorter molecular length of COE-CN leads to weaker binding within lipid bilayer membranes, which allows sampling of internal cellular structures and ultimately to different localization relative to elongated COEs. As a means of practical demonstration, COE-CN can be used to diagnose cells with damaged mitochondria via flow cytometry. Coupled with an elongated COE that does not translocate upon depolarization, changes in ratiometric fluorescence intensity can be used to monitor mitochondrial membrane potential disruption, demonstrating the potential for use in diagnostic assays.


Subject(s)
Electrolytes , Lipid Bilayers , Lipid Bilayers/chemistry , Electrolytes/chemistry , Coloring Agents , Flow Cytometry
7.
BMC Biotechnol ; 24(1): 30, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720310

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. RESULTS: The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. CONCLUSION: Our chemiluminescence assay performs comparably to Sysmex's method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.


Subject(s)
Luminescent Measurements , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Male , Middle Aged , Luminescent Measurements/methods , Female , Aged , Antithrombin III/metabolism , Antithrombin III/analysis , Thrombomodulin/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , alpha-2-Antiplasmin/metabolism , alpha-2-Antiplasmin/analysis , Adult , Fibrinolysin/metabolism , Fibrinolysin/analysis , Venous Thromboembolism/diagnosis , Venous Thromboembolism/blood , Peptide Hydrolases
8.
Small ; 20(25): e2308724, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38229571

ABSTRACT

In future information storage and processing, magnonics is one of the most promising candidates to replace traditional microelectronics. Yttrium iron garnet (YIG) films with perpendicular magnetic anisotropy (PMA) have aroused widespread interest in magnonics. Obtaining strong PMA in a thick YIG film with a small lattice mismatch (η) has been fascinating but challenging. Here, a novel strategy is proposed to reduce the required minimum strain value for producing PMA and increase the maximum thickness for maintaining PMA in YIG films by slight oxygen deficiency. Strong PMA is achieved in the YIG film with an η of only 0.4% and a film thickness up to 60 nm, representing the strongest PMA for such a small η reported so far. Combining transmission electron microscopy analyses, magnetic measurements, and a theoretical model, it is demonstrated that the enhancement of PMA physically originates from the reduction of saturation magnetization and the increase of magnetostriction coefficient induced by oxygen deficiency. The Gilbert damping values of the 60-nm-thick YIG films with PMA are on the order of 10-4. This strategy improves the flexibility for the practical applications of YIG-based magnonic devices and provides promising insights for the theoretical understanding and the experimental enhancement of PMA in garnet films.

9.
Mol Carcinog ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136583

ABSTRACT

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.

10.
Opt Lett ; 49(10): 2813-2816, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748168

ABSTRACT

This work proposes and investigates a bent multimode-no-core-multimode optical fiber structure for vector magnetic field sensing applications. The bent no-core fiber (NCF) serves as the sensing area, and the gold film is deposited on its surface to excite the surface plasmon resonance effect. Due to the strong evanescent field of the unclad and bent NCF, the as-fabricated sensor exhibits a high sensitivity of 5630 nm/RIU in the refractive index range of 1.36-1.39. Magnetic fluid is employed as the magneto-sensitive material for magnetic field sensing, exhibiting a high magnetic field intensity sensitivity of 5.74 nm/mT and a high magnetic field direction sensitivity of 0.22 nm/°. The proposed sensor features a simple structure, low cost, point sensing, and excellent mechanical performance.

11.
J Vasc Interv Radiol ; 2024 Oct 18.
Article in English | MEDLINE | ID: mdl-39428064

ABSTRACT

PURPOSE: To determine how low inorganic phosphate stress (LIPS) induced by sevelamer transartieral embolization (S-TAE) affects immune regulation and angiogenesis in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Transcatheter arterial embolization (TAE) using conventional lipiodol plus Poly (vinyl alcohol) (PVA) microsphere and S-TAE were conducted on a McA-RH7777 orthotopic liver tumor model in rats, followed by the assessment of alterations in immunity- and angiogenesis-related factors. The cells were cultured under hypoxic conditions and stimulated with LIPS to analyze the modulation of programmed cell death 1 ligand 1 (PD-L1), vascular endothelial growth factor (VEGFα), and transforming growth factor-ß1 (TGF-ß1) expression through Western blotting, qRT‒PCR, and immunofluorescence assays. Cell migratory capacity and angiogenesis were also evaluated. RESULTS: TAE increased the expression of neoplastic PD-L1 and VEGFα, and S-TAE, which depletes intratumoral Pi, downregulated the expression of PD-L1, VEGFα and TGF-ß1, and augmented the infiltration of CD8+ T-cells, thereby inhibited angiogenesis and activated anticancer immunity. In vitro, the study demonstrated that LIPS inhibits hypoxia-induced upregulation of PD-L1 expression and the HIF-1α/VEGFα axis. Moreover, LIPS inhibited the tube formation ability of Human Umbilical Vein Endothelial Cells (HUVECs) and the migration ability and epithelial-mesenchymal transition (EMT) process of cancer cells under hypoxic conditions. CONCLUSIONS: S-TAE inhibited the expression of PD-L1 and VEGFα, thereby activated anti-tumor immunity and suppressing tumor angiogenesis. All the findings reveal the biology of tumors under low Pi stress and suggest the potential therapeutic value of S-TAE.

12.
J Cardiovasc Pharmacol ; 83(3): 207-219, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37989137

ABSTRACT

ABSTRACT: Worldwide, type 2 diabetes is predominant form of diabetes, and it is mainly affected by the environment. Furthermore, the offspring of patients with type 2 diabetes and metabolic disorder syndrome may have a higher risk of diabetes and cardiovascular disease, which indicates that the environmental impact on diabetes prevalence can be transmitted across generations. In the process of diabetes onset and intergenerational transmission, the genetic structure of the individual is not directly changed but is regulated by epigenetics. In this process, genes or histones are modified, resulting in selective expression of proteins. This modification will affect not only the onset of diabetes but also the related onset of atherosclerosis. Acetylation and deacetylation may be important regulatory factors for the above lesions. Therefore, in this review, based on the whole process of atherosclerosis evolution, we explored the possible existence of acetylation/deacetylation caused by diabetes. However, because of the lack of atherosclerosis-related acetylation studies directly based on diabetic models, we also used a small number of experiments involving nondiabetic models of related molecular mechanisms.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/metabolism , Histone Code , Histones/metabolism , Epigenesis, Genetic , Protein Processing, Post-Translational , Acetylation
13.
Analyst ; 149(4): 1318-1326, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38251970

ABSTRACT

Conventional single-signal or emerging sandwich-type double-signal electrochemiluminescence (ECL) immunosensors/aptasensors have offered accurate detection of small molecules, yet suffer from complicated setup, long processing time, and non-reusability. Here, we demonstrate a simplified molecularly imprinted ECL sensor based on Mn2SnO4 nanocubes. As an n-type semiconductor, Mn2SnO4 has numerous active sites that can capture electrons to accelerate chemical reactions, resulting in enhanced ECL activity and stability. For the first time, we verify a robust cathodic ECL emission of Mn2SnO4 luminophores in the presence of K2S2O8 coreactants. The proposed ECL sensor applies to the sensitive detection of ribavirin (RBV), endowing a wide linear range (1-2000 ng mL-1), low detection limit (0.85 ng mL-1, S/N = 3), high stability, specificity, and reproducibility, and the detection capability in real milk and chicken samples. This work highlights single semiconductor luminophore-driven molecularly imprinted ECL sensors, meeting the original aspiration of uncomplicated but high-performance sensing in food safety inspection.


Subject(s)
Biosensing Techniques , Molecular Imprinting , Luminescent Measurements/methods , Ribavirin , Molecular Imprinting/methods , Limit of Detection , Biosensing Techniques/methods , Reproducibility of Results , Immunoassay/methods , Electrochemical Techniques/methods
14.
Fish Shellfish Immunol ; 144: 109231, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37984613

ABSTRACT

This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg-1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining-with a maximum value in group X4-which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg-1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.


Subject(s)
Antioxidants , Gastrointestinal Microbiome , Animals , Antioxidants/metabolism , Methionine/metabolism , Astacoidea/metabolism , Zinc/pharmacology , Dietary Supplements/analysis , Diet/veterinary , Racemethionine/pharmacology , Immunity, Innate , Superoxide Dismutase/pharmacology , Animal Feed/analysis
15.
J Chem Phys ; 160(6)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38349637

ABSTRACT

We present an approximate analytical approach to the adsorption problem of ABA triblock copolymers confined between two parallel plates in a θ solvent and give the expression of the propagator q(x, t) as a piece-wise function by solving the modified diffusion equation. In this way, the role of separation between the two plates, adsorption energy and block lengths on segment concentration profile, chain conformations, and interaction potential is then investigated, which agrees well with the numerical results. It is demonstrated that there are parallels between lengthening adsorbing A blocks and increasing surface affinity: strong adsorption and long adsorbing blocks favor the formation of loops and bridges, whereas more tails and free chains exist in the case of weak adsorption and short A blocks at large separations. For moderate and strong adsorptions, the bridging fraction begins to plummet at a separation larger than the end-to-end distance of non-adsorbing B block RB and becomes negligible at above 2RB owing to the entropy effect. The depth of the potential well in the interaction potential profile depends on the adsorption energy and A block length, while the location of the potential minimum corresponds to the onset of the sharp decrease in bridges.

16.
J Nanobiotechnology ; 22(1): 521, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39210346

ABSTRACT

Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.


Subject(s)
Cell Proliferation , Extracellular Vesicles , Hepatectomy , Hepatocytes , Liver Regeneration , Liver , Liver Regeneration/physiology , Extracellular Vesicles/metabolism , Hepatocytes/metabolism , Animals , Liver/metabolism , Mice , Humans , Male , Mice, Inbred C57BL , Regenerative Medicine/methods , CDC2 Protein Kinase/metabolism , Proteomics
17.
BMC Ophthalmol ; 24(1): 460, 2024 Oct 21.
Article in English | MEDLINE | ID: mdl-39434062

ABSTRACT

BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) has become the dominant keratoplasty procedure. However, the impact of high intraocular pressure (IOP) on the DMEK prognosis in patients without preexisting glaucoma remains unknown. METHODS: Non-glaucoma patients who underwent DMEK in Peking University Third Hospital between July 2017 and March 2023 with a follow-up duration longer than six months were included in this cohort study. Eyes were divided into three groups: Group A) normal IOP; Group B) early IOP elevation (IOP ≥ 30 mmHg or increase of more than 10 mmHg from baseline within 3 days); Group C) intermediate-term IOP elevation (IOP > 21 mmHg or increase of more than 10 mmHg from baseline after 14 days postoperatively). The postoperative IOP, endothelial cell density (ECD), central corneal thickness (CCT), best-corrected visual acuity (BCVA) and rate of graft failure were analysed. RESULTS: Forty-seven eyes from forty-seven patients were included. Thirty-seven eyes were bullous keratopathy, and ten were Fuchs endothelial corneal dystrophy. Twenty-five eyes were classified as Group A, six as Group B and sixteen as Group C. The mean peak IOP was 49.00 ± 4.99 mmHg in Group B eyes and 31.89 ± 11.75 mmHg in Group C eyes. The postoperative BCVA significantly differed from that before surgery (P < 0.001). The ECD at 3 months after surgery in eyes with intermediate-term IOP elevation was lower (P = 0.032). Four eyes with intermediate-term IOP elevation developed graft failure (P = 0.001). CONCLUSIONS: Intermediate-term IOP elevation after DMEK may reduce the graft ECD and lead to graft failure within six months after surgery. However, early IOP elevation had no effect on the prognosis. Careful IOP monitoring and intermediate-term IOP management should be conducted for graft protection.


Subject(s)
Descemet Stripping Endothelial Keratoplasty , Endothelium, Corneal , Glaucoma , Intraocular Pressure , Visual Acuity , Humans , Descemet Stripping Endothelial Keratoplasty/methods , Female , Male , Intraocular Pressure/physiology , Aged , Middle Aged , Visual Acuity/physiology , Endothelium, Corneal/pathology , Glaucoma/surgery , Glaucoma/physiopathology , Retrospective Studies , Postoperative Complications , Aged, 80 and over , Follow-Up Studies , Graft Survival/physiology , Cell Count , Ocular Hypertension/physiopathology , Postoperative Period , Adult , Corneal Diseases/surgery , Corneal Diseases/physiopathology , Corneal Endothelial Cell Loss/diagnosis , Corneal Endothelial Cell Loss/physiopathology
18.
BMC Ophthalmol ; 24(1): 315, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075405

ABSTRACT

AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.


Subject(s)
Brain , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Adult , Magnetic Resonance Imaging/methods , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Young Adult , Brain Mapping/methods , Myopia, Degenerative/physiopathology , Rest/physiology
19.
Nucleic Acids Res ; 50(20): 11529-11549, 2022 11 11.
Article in English | MEDLINE | ID: mdl-36330957

ABSTRACT

Increasing studies have revealed that a subset of circular RNAs (circRNAs) harbor an open reading frame and can act as protein-coding templates to generate functional proteins that are closely associated with multiple physiological and disease-relevant processes, and thus proper regulation of synthesis of these circRNA-derived proteins is a fundamental cellular process required for homeostasis maintenance. However, how circRNA translation initiation is coordinated by different trans-acting factors remains poorly understood. In particular, the impact of different eukaryotic translation initiation factors (eIFs) on circRNA translation and the physiological relevance of this distinct regulation have not yet been characterized. In this study, we screened all 43 Drosophila eIFs and revealed the conflicting functions of eIF3 subunits in the translational control of the translatable circRNA circSfl: eIF3 is indispensable for circSfl translation, while the eIF3-associated factor eIF3j is the most potent inhibitor. Mechanistically, the binding of eIF3j to circSfl promotes the disassociation of eIF3. The C-terminus of eIF3j and an RNA regulon within the circSfl untranslated region (UTR) are essential for the inhibitory effect of eIF3j. Moreover, we revealed the physiological relevance of eIF3j-mediated circSfl translation repression in response to heat shock. Finally, additional translatable circRNAs were identified to be similarly regulated in an eIF3j-dependent manner. Altogether, our study provides a significant insight into the field of cap-independent translational regulation and undiscovered functions of eIF3.


Subject(s)
Eukaryotic Initiation Factor-3 , RNA, Circular , Cytoplasm/metabolism , Eukaryotic Initiation Factor-3/metabolism , Protein Biosynthesis , RNA, Circular/genetics , Drosophila , Animals , Drosophila Proteins/metabolism
20.
BMC Public Health ; 24(1): 228, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38243241

ABSTRACT

BACKGROUND: The altered respiratory patterns have a significant impact on our health. However, the links between respiration patterns during spontaneous breathing and physical fitness remain unknown. Therefore, we sought to examine how the respiratory pattern during spontaneous breathing interacts with physical fitness. METHODS: A total of 610 participants (aged 20-59 years) were enrolled; 163 men (age = 41 ± 11) and 401 women (age = 42 ± 9) were included for analysis. The parameters of the respiration pattern were respiration rate (RR) and inhalation/exhalation (I/E) ratio. The physical fitness components were body size, visuomotor reaction time, balance, flexibility, hand grip strength, back extension strength, vertical jump height, number of push-ups, number of sit-ups, and the maximum rate of oxygen consumption. The data were analyzed separately for two gender groups. Participants within each gender group were further divided into two age categories (young: 20-39 years, middle-aged: 40-59 years) for the analysis, and both correlational and comparative tests were used to solidify the results. RESULTS: Neither RRs nor the I/E ratios were substantially correlated with physical fitness in women. In addition, the I/E ratios showed no significant correlation with physical fitness in young men, while the results from correlational and comparative tests were inconsistent in middle-aged men. Consistently, men with lower RRs exhibited significantly shorter visuomotor reaction times in two age groups, and demonstrated significantly higher vertical jump heights in the middle-aged group. CONCLUSIONS: In women, respiratory patterns were not correlated with physical fitness. The relationship between middle-aged men's I/E ratios and their physical fitness warrants further investigation. Men with lower RRs may have better visual-motor coordination and/or sustained attention, while middle-aged men with lower RRs may also have greater leg explosive power and neuromuscular coordination, which should be considered for physical assessment and health improvement.


Subject(s)
Hand Strength , Physical Fitness , Adult , Male , Middle Aged , Humans , Female , Cross-Sectional Studies , Exercise , Exercise Test
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