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1.
Photodiagnosis Photodyn Ther ; 49: 104348, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39366476

ABSTRACT

OBJECTIVE: Keloids are characterized by abnormal activation of fibroblasts and excessive collagen deposition. Keloids are notoriously difficult to treat effectively due to their high recurrence rate after therapy. Our study explored the use of the punch technique in conjunction with photodynamic therapy, a novel approach that may swiftly reduce keloid volume, promote collagen remodeling, mitigate inflammation and enhance the wound healing process. METHODS: In our study, we conducted a retrospective analysis of 47 keloid patients who were treated with cross-punch technique combined with photodynamic therapy (punch+PDT group), compared them with a control group of 42 patients who received cross-punch therapy alone (punch group). The visual Analog Scale (VAS) scoring system, the Dermatology Life Quality Index (DLQI) questionnaire and the subjective scoring of patients were implemented to assess the improvement rate at baseline (month 0) and 12-month follow-up (month 12). RESULTS: The results demonstrated significant enhancements in both VAS scores and DLQI scores on month 12 when compared with those on month 0. Notably, the subjective scoring indicated a marked difference, with 93.62 % of patients in the punch+PDT group and 59.52 % in the punch group reporting good or excellent improvement. CONCLUSION: Patients in the punch+PDT group had a significant improvement rate than those in the punch group.

2.
iScience ; 27(10): 110921, 2024 Oct 18.
Article in English | MEDLINE | ID: mdl-39386756

ABSTRACT

Bladder Ewing sarcoma/primitive neuroectodermal tumor (bladder ES/PNET) is a rare and highly malignant tumor associated with a poor prognosis, yet its underlying mechanisms remain poorly understood. Here, we employed a combination of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and functional analyses to delve into the pathogenesis of bladder ES/PNET. The investigation revealed the presence of specialized types of epithelial cells (referred to as bladder ES-Epi) and mast cells (referred to as bladder ES-Mast) within bladder ES/PNET in comparison to urothelial carcinoma. Notably, TNFRSF12A exhibited significant upregulation in bladder ES/PNET. Furthermore, mast cells possessed the ability to activate epithelial cells through the TNFSF12-TNFRSF12A ligand-receptor signaling pattern. In addition, Enavatuzumab can significantly inhibit the migratory ability of the Ewing sarcoma cell line RD-ES. This groundbreaking study provides unprecedented mechanistic insights into the progression of bladder ES/PNET and introduces a potential therapeutic avenue for treating this challenging malignancy.

3.
Angew Chem Int Ed Engl ; : e202414562, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39385346

ABSTRACT

The utilization of thin zinc (Zn) anodes with a high depth of discharge is an effective strategy to increase the energy density of aqueous Zn metal batteries (ZMBs), but challenged by the poor reversibility of Zn electrode due to the serious Zn-consuming side reactions at the Zn||electrolyte interface. Here, we introduce 2-bromomethyl-1,3-dioxolane (BDOL) and methanol (MeOH) as electrolyte additive into aqueous ZnSO4 electrolyte. In the as-formulated electrolyte, BDOL with a strong electron-withdrawing group (-CH2Br) tends to pair with the H2O-Zn-MeOH complex, leading to the formation of organobromine-partnered H2O-Zn-MeOH cluster ions. During the Zn electrodeposition process, the formed ZnO-dominated by-products induce the polymerization of BDOL monomers, which are previously adsorbed on the electrode. As a result, a uniform dual-layer SEI with ZnO-dominated outer layer and polyether-dominated inner layer is built on the surface of Zn electrode. With such an in-situ formed dual-layer SEI, the Zn||Mg0.9Mn3O7·2.7H2O pouch cell using a 10-um Zn anode (corresponding to a low negative to positive areal capacity ratio of 3.56) successfully operated for 300 cycles with a high capacity retention of 86%, promising a high practical energy density of > 120 Wh/kg (based on the total mass of Zn and Mg0.9Mn3O7·2.7H2O).

4.
Nucleic Acids Res ; 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39373517

ABSTRACT

Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of the Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that the RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics are controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.

5.
Haematologica ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363872

ABSTRACT

This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with lowdose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with haematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the GCSF/ ATG group were selected. In total, the PTCy group (n=122) was matched with G-CSF/ATG Group 1 (n=230), and the PTCy+ATGlow group (n=123) was matched with G-CSF/ATG Group 2 (n=226). Compared with those in the PTCy group, the incidences of 28-day neutrophil engraftment (P=0.005), 100- day platelet engraftment (P=0.002), median time to neutrophil engraftment (P.

6.
Sci Prog ; 107(3): 368504241274998, 2024.
Article in English | MEDLINE | ID: mdl-39252493

ABSTRACT

OBJECTIVE: To evaluate the mid-term outcomes of different treatment strategies for the internal iliac artery (IIA) during EVAR. METHODS: This was a retrospective study. All patients undergoing EVAR, who required treatment of at least one side of IIA from January 2013 to July 2022 in a single center, were included. According to the different treatment strategies for IIA, the patients were divided into UP (unilateral preservation), BP (bilateral preservation) and BE (bilateral embolization) groups. The primary outcomes included buttock claudication, bowel ischemia and iliac-related reintervention. Then patients who underwent IIA reconstruction were divided into IPG (iliac parallel stent graft) and IBG (iliac branch stent graft) groups according to the reconstruction technique. The primary outcomes included endoleak, iliac branch occlusion and iliac-related reintervention. RESULTS: A total of 237 patients were included, including 167 in the UP group, 9 in the BP group and 61 in the BE group. The mean follow-up time was 39.0 ± 27.7, 50.0 ± 22.1 and 25.8 ± 18.9 months in UP, BP and BE groups, respectively. Thirty cases (12.7%) of buttock claudication occurred, and it was significantly higher in the BE group than the UP group (26.2% vs. 7.8%, p < 0.001). There were no significant differences in the other follow-up outcomes among three groups. The K-M analysis indicated that the patients in the BE group had a lower survival rate than those in the other two groups (p = 0.024). 24 patients underwent IIA reconstruction, including 8 in the IPG group and 16 in the IBG group. The endoleak in the IBG group was significantly lower than that in the IPG group (0% vs. 25.0%, p = 0.041). The iliac-related reintervention, iliac occlusion and mortality were similar between the two groups. CONCLUSION: Overall it is beneficial for patients to preserve at least one side of IIA during EVAR as much as possible. Compared with IPG, IBG might be more applicable for IIA reconstruction.


Subject(s)
Endovascular Procedures , Iliac Artery , Humans , Endovascular Procedures/methods , Endovascular Procedures/adverse effects , Male , Female , Aged , Iliac Artery/surgery , Retrospective Studies , Treatment Outcome , Stents , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Aged, 80 and over , Aortic Aneurysm, Abdominal/surgery , Iliac Aneurysm/surgery , Endoleak/surgery , Endoleak/etiology , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Embolization, Therapeutic/methods , Endovascular Aneurysm Repair
7.
Vision Res ; 224: 108475, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39217910

ABSTRACT

Glaucoma is a leading cause of blindness worldwide and glaucoma patients exhibit an early diffuse loss of retinal sensitivity followed by focal loss of RGCs. Combining some previous published results and some new data, this paper provides our current view on how high IOP (H-IOP) affects the light response sensitivity of a subset of RGCs, the alpha-ganglion cells (αGCs), as well as their presynaptic bipolar cells (DBCs and HBCs) and A2 amacrine cells (AIIACs) in dark-adapted mouse retinas. Our data demonstrate that H-IOP in experimental glaucoma mice significantly decreases light-evoked spike response sensitivity of sONαGCs and sOFFαGCs (i.e., raises thresholds by 1.5-2.5 log units), but not that of the tONαGCs and tOFFαGCs. The sensitivity loss in sONαGCs and sOFFαGCs is mediated by a H-IOP induced suppression of AIIAC response which is caused by a decrease of transmission efficacy of the DBCR→AIIAC synapse. We also provide evidence supporting the hypothesis that BK channels in the A17AC→DBCR feedback synapse are the H-IOP sensor that regulates the DBCR→AIIAC synaptic efficacy, as BK channel blocker IBTX mimics the action of H-IOP. Our results provide useful information for designing strategies for early detection and possible treatments of glaucoma as physiological changes occur before irreversible structural damage.


Subject(s)
Disease Models, Animal , Glaucoma , Intraocular Pressure , Mice, Inbred C57BL , Retinal Ganglion Cells , Animals , Mice , Intraocular Pressure/physiology , Retinal Ganglion Cells/physiology , Retinal Ganglion Cells/pathology , Glaucoma/physiopathology , Amacrine Cells/physiology , Dark Adaptation/physiology , Retinal Bipolar Cells/physiology
8.
PLoS Biol ; 22(9): e3002808, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39316635

ABSTRACT

Neural activity and behavior vary within an individual (states) and between individuals (traits). However, the mapping of state-trait neural variation to behavior is not well understood. To address this gap, we quantify moment-to-moment changes in brain-wide co-activation patterns derived from resting-state functional magnetic resonance imaging. In healthy young adults, we identify reproducible spatiotemporal features of co-activation patterns at the single-subject level. We demonstrate that a joint analysis of state-trait neural variations and feature reduction reveal general motifs of individual differences, encompassing state-specific and general neural features that exhibit day-to-day variability. The principal neural variations co-vary with the principal variations of behavioral phenotypes, highlighting cognitive function, emotion regulation, alcohol and substance use. Person-specific probability of occupying a particular co-activation pattern is reproducible and associated with neural and behavioral features. This combined analysis of state-trait variations holds promise for developing reproducible neuroimaging markers of individual life functional outcome.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/physiology , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Female , Young Adult , Adult , Brain Mapping/methods , Behavior/physiology , Cognition/physiology , Reproducibility of Results
9.
Stem Cell Res Ther ; 15(1): 309, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39289765

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related disease featured with abnormal fibrotic response and compromised lung function. Cellular senescence is now considered as an essential driving mechanism for IPF. Given the poor knowledge of the mechanisms underpinning IPF progression, understanding the cellular processes and molecular pathways is critical for developing effective therapies of IPF. METHODS: Lung fibrosis was induced using bleomycin in C57BL/6 mice. Cellular senescence was measured by immunofluorescence. The effects of FGF-4 on fibroblast activation markers and signaling molecules were assessed with western blot and qPCR. RESULTS: We demonstrated elevated abundance of senescent mesenchymal stem cells (MSCs) in IPF lung tissues, which was tightly correlated with the severity of pulmonary fibrosis in vivo. In addition, senescent MSCs could effectively induce the phenotype of pulmonary fibrosis both in vitro and in vivo. To further confirm how senescent MSCs regulate IPF progression, we demonstrate that FGF-4 is significantly elevated in senescent MSCs, which can induce the activation of pulmonary fibroblasts. In vitro, FGF-4 can activate Wnt signaling in a FOXM1-dependent manner. Inhibition of FOXM1 via thiostrepton effectively impairs FGF-4-induced activation of pulmonary fibroblast and dramatically suppresses the development of pulmonary fibrosis. CONCLUSION: These findings reveal that FGF-4 plays a crucial role in senescent MSCs-mediated pulmonary fibrogenesis, and suggests that strategies aimed at deletion of senescent MSCs or blocking the FGF-4/FOXM1 axis could be effective in the therapy of IPF.


Subject(s)
Cellular Senescence , Fibroblast Growth Factor 4 , Forkhead Box Protein M1 , Idiopathic Pulmonary Fibrosis , Lung , Mesenchymal Stem Cells , Mice, Inbred C57BL , Animals , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Mesenchymal Stem Cells/metabolism , Mice , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology , Lung/metabolism , Fibroblast Growth Factor 4/metabolism , Fibroblast Growth Factor 4/genetics , Humans , Bleomycin/pharmacology , Fibroblasts/metabolism , Wnt Signaling Pathway , Male
10.
Front Public Health ; 12: 1442728, 2024.
Article in English | MEDLINE | ID: mdl-39224554

ABSTRACT

Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , China/epidemiology , Retrospective Studies , Hospitalization/statistics & numerical data , Bayes Theorem , Health Policy , Pandemics
11.
Angew Chem Int Ed Engl ; : e202406548, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39218783

ABSTRACT

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

12.
Heliyon ; 10(16): e36232, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39253252

ABSTRACT

This paper presents an innovative fusion model called "CALSE-LSTM," which integrates Convolutional Neural Networks (CNNs), Long Short-Term Memory Networks (LSTMs), self-attention mechanisms, and squeeze-and-excitation attention mechanisms to optimize the estimation accuracy of the State of Charge (SoC). The model incorporates battery historical data as input and employs a dual-attention mechanism based on CNN-LSTM to extract diverse features from the input data, thereby enhancing the model's ability to learn hidden information. To further improve model performance, we fine-tune the model parameters using the Pelican algorithm. Experiments conducted under Urban Dynamometer Driving Schedule (UDDS) conditions show that the CALSE-LSTM model achieves a Root Mean Squared Error (RMSE) of only 1.73 % in lithium battery SoC estimation, significantly better than GRU, LSTM, and CNN-LSTM models, reducing errors by 31.9 %, 31.3 %, and 15 %, respectively. Ablation experiments further confirm the effectiveness of the dual-attention mechanism and its potential to improve SoC estimation performance. Additionally, we validate the learning efficiency of CALSE-LSTM by comparing model training time with the number of iterations. Finally, in the comparative experiment with the Kalman filtering method, the model in this paper significantly improved its performance by incorporating power consumption as an additional feature input. This further verifies the accuracy of CALSE-LSTM in estimating the State of Charge (SoC) of lithium batteries.

13.
Clin Transl Med ; 14(8): e1763, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39107958

ABSTRACT

BACKGROUND: Breast cancer (BC) is one of the most prevalent malignant tumours that threatens women health worldwide. It has been reported that circular RNAs (circRNAs) play an important role in regulating tumour progression and tumour microenvironment (TME) remodelling. METHODS: Differentially expression characteristics and immune correlations of circRNAs in BC were verified using high-throughput sequencing and bioinformatic analysis. Exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. The biological function of circ-0100519 in BC development was demonstrated both in vitro and in vivo. Western blotting, RNA pull-down, RNA immunoprecipitation, flow cytometry, and luciferase reporter were conducted to investigate the underlying mechanism. RESULTS: Circ-0100519 was significant abundant in BC tumour tissues and related to poor prognosis. It can be encapsulated into secreted exosomes, thereby promoting BC cell invasion and metastasis via inducing M2-like macrophages polarisation.Mechanistically, circ-0100519 acted as a scaffold to enhance the interaction between the deubiquitinating enzyme ubiquitin-specific protease 7 (USP7) and nuclear factor-like 2 (NRF2) in macrophages, inducing the USP7-mediated deubiquitination of NRF2. Additionally, HIF-1α could function as an upstream effector to enhance circ-0100519 transcription. CONCLUSIONS: Our study revealed that exosomal circ-0100519 is a potential biomarker for BC diagnosis and prognosis, and the HIF-1α inhibitor PX-478 may provide a therapeutic target for BC.


Subject(s)
Breast Neoplasms , Exosomes , NF-E2-Related Factor 2 , RNA, Circular , Ubiquitin-Specific Peptidase 7 , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Female , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Ubiquitin-Specific Peptidase 7/genetics , Ubiquitin-Specific Peptidase 7/metabolism , Exosomes/metabolism , Exosomes/genetics , Macrophages/metabolism , Mice , Disease Progression , Animals , Cell Line, Tumor
14.
J Neuroinflammation ; 21(1): 208, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39169375

ABSTRACT

BACKGROUND: Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. METHODS: C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. RESULTS: IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. CONCLUSION: Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH.


Subject(s)
Cognitive Dysfunction , Hippocampus , Mice, Inbred C57BL , Proto-Oncogene Proteins , Sleep Apnea, Obstructive , Wnt Signaling Pathway , Animals , Hippocampus/metabolism , Hippocampus/pathology , Mice , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Wnt Signaling Pathway/physiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Cognitive Dysfunction/etiology , Sleep Apnea, Obstructive/metabolism , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/pathology , Male , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , 5-Methylcytosine/analogs & derivatives , 5-Methylcytosine/metabolism , DNA Methylation , DNA-Binding Proteins
15.
Proc Natl Acad Sci U S A ; 121(35): e2403424121, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39159367

ABSTRACT

Many virus genomes encode proteases that facilitate infection. The molecular mechanism of plant recognition of viral proteases is largely unexplored. Using the system of Vigna unguiculata and cowpea mosaic virus (CPMV), we identified a cowpea lipid transfer protein (LTP1) which interacts with CPMV-encoded 24KPro, a cysteine protease, but not with the enzymatically inactive mutant 24KPro(C166A). Biochemical assays showed that LTP1 inhibited 24KPro proteolytic cleavage of the coat protein precursor large coat protein-small coat protein. Transient overexpression of LTP1 in cowpea reduced CPMV infection, whereas RNA interference-mediated LTP1 silencing increased CPMV accumulation in cowpea. LTP1 is mainly localized in the apoplast of uninfected plant cells, and after CPMV infection, most of the LTP1 is relocated to intracellular compartments, including chloroplast. Moreover, in stable LTP1-transgenic Nicotiana benthamiana plants, LTP1 repressed soybean mosaic virus (SMV) nuclear inclusion a protease activity, and accumulation of SMV was significantly reduced. We propose that cowpea LTP1 suppresses CPMV and SMV accumulation by directly inhibiting viral cysteine protease activity.


Subject(s)
Carrier Proteins , Comovirus , Nicotiana , Plant Diseases , Plant Proteins , Vigna , Comovirus/metabolism , Comovirus/physiology , Comovirus/genetics , Vigna/virology , Vigna/metabolism , Nicotiana/virology , Nicotiana/metabolism , Nicotiana/genetics , Carrier Proteins/metabolism , Carrier Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Plant Diseases/virology , Cysteine Proteases/metabolism , Cysteine Proteases/genetics , Plants, Genetically Modified , Viral Proteins/metabolism , Viral Proteins/genetics , Capsid Proteins/metabolism , Capsid Proteins/genetics , Potyvirus/physiology , Potyvirus/metabolism , Endopeptidases
16.
Biology (Basel) ; 13(8)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39194497

ABSTRACT

Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography-mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.

17.
Biomed Eng Comput Biol ; 15: 11795972241271569, 2024.
Article in English | MEDLINE | ID: mdl-39156985

ABSTRACT

Cancer is the leading cause of mortality in the world. And among all cancers lung and colon cancers are 2 of the most common causes of death and morbidity. The aim of this study was to develop an automated lung and colon cancer classification system using histopathological images. An automated lung and colon classification system was developed using histopathological images from the LC25000 dataset. The algorithm development included data splitting, deep neural network model selection, on the fly image augmentation, training and validation. The core of the algorithm was a Swin Transform V2 model, and 5-fold cross validation was used to evaluate model performance. The model performance was evaluated using Accuracy, Kappa, confusion matrix, precision, recall, and F1. Extensive experiments were conducted to compare the performances of different neural networks including both mainstream convolutional neural networks and vision transformers. The Swin Transform V2 model achieved a 1 (100%) on all metrics, which is the first single model to obtain perfect results on this dataset. The Swin Transformer V2 model has the potential to be used to assist pathologists in classifying lung and colon cancers using histopathology images.

18.
Int Ophthalmol ; 44(1): 323, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980416

ABSTRACT

BACKGROUND: Cataract is the leading cause of blindness worldwide and surgery can restore vision in most patients. Some patients have little access to surgical services due to lack of cataract surgeons and the unaffordable costs. In 2005 we built a service model that trained rural non-ophthalmologist physicians to perform cataract surgeries in rural China. This study evaluates the long-term impacts of this model. METHODS: We conducted a retrospective cohort study to analyze patients' hand-written medical records and electronic outpatient record between January 2005 and December 2019 at two rural health clinics in Southern China. RESULTS: In total, 34,601 patients (49,942 eyes) underwent cataract surgery by non-ophthalmologist physicians from 2005 to 2019.Visual acuity was clearly documented in 38,251 eyes. Before surgery, the unaided distance visual acuity (UDVA) of 60.7% (23,205/38,251) eyes was less than 0.05 decimal. On the first day after surgery, the percentage of UDVA < 0.05 eyes was reduced to 6.0%, and 96.7% (36,980/38,251) of the eyes achieved a better UDVA compared to pre-operation. Surgical-related complications occurred in 218 eyes. The most common complication was posterior capsule rupture (114, 0.23%). 44.3% (15,341/34,601) of the patients chose to have a second eye cataract surgery (SECS) in the same clinic. At one of the outpatient clinics, 21,595 patients received basic eye care apart from cataract surgery between 2018 and 2020. CONCLUSIONS: Non-ophthalmologist physicians trained for cataract surgeries in rural clinics can improve cataract related visual acuity and basic eye care to the local population.


Subject(s)
Cataract Extraction , Cataract , Visual Acuity , Humans , Retrospective Studies , Cataract Extraction/statistics & numerical data , Cataract Extraction/methods , Male , Female , Aged , Cataract/epidemiology , Cataract/complications , Middle Aged , China/epidemiology , Rural Population/statistics & numerical data , Rural Health Services/statistics & numerical data , Aged, 80 and over , Ophthalmologists/statistics & numerical data , Adult
19.
Am J Cancer Res ; 14(6): 2921-2933, 2024.
Article in English | MEDLINE | ID: mdl-39005667

ABSTRACT

Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.

20.
Front Immunol ; 15: 1403376, 2024.
Article in English | MEDLINE | ID: mdl-39072323

ABSTRACT

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Capillary Leak Syndrome , Lymphohistiocytosis, Hemophagocytic , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Capillary Leak Syndrome/etiology , Capillary Leak Syndrome/diagnosis , Capillary Leak Syndrome/therapy , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Vincristine/therapeutic use , Male , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Rituximab/therapeutic use , Middle Aged
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