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1.
Nat Sci Sleep ; 16: 801-811, 2024.
Article in English | MEDLINE | ID: mdl-38911318

ABSTRACT

Background: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors. Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors. Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05-1.12), more depression (OR: 1.17; 95% CI = 1.06-1.29) and anxiety (OR: 1.16; 95% CI = 1.05-1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12-1.19), anxiety (OR: 1.10; 95% CI = 1.06-1.14), and depression (OR: 1.10; 95% CI = 1.06-1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP. Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.

2.
Int Immunopharmacol ; 138: 112557, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38936060

ABSTRACT

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations and organ damage. Despite its elusive etiology, dysregulated subsets and functions of B cells are pivotal in SLE pathogenesis. Peoniflorin-6'-O-benzene sulfonate (CP-25), an esterification modification of Paeoniflorin, exhibits potent anti-inflammatory and immunomodulatory properties in autoimmune diseases (AID). However, the involvement of CP-25 and its target, GRK2, in SLE development has not been explored. In this study, we demonstrate that both genetic deficiency and pharmacological inhibition of GRK2 attenuate autoantibodies production, reduce systemic inflammation, and mitigate histopathological alterations in the spleen and kidney in the pristane-induced mouse SLE model. Importantly, our findings highlight that both genetic deficiency and pharmacological inhibition of GRK2 suppress plasma cells generation and restore dysregulated B-cell subsets by modulating two crucial transcription factors, Blimp1 and IRF4. Collectively, targeting GRK2 with CP-25 emerges as a promising therapeutic approach for SLE.

3.
Front Immunol ; 15: 1421778, 2024.
Article in English | MEDLINE | ID: mdl-38919630

ABSTRACT

Background: CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation. Methods: A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Results: CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients. Conclusion: The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.


Subject(s)
Biomarkers, Tumor , Membrane Cofactor Protein , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/blood , Biomarkers, Tumor/blood , Middle Aged , Prognosis , Adult , Aged , Kaplan-Meier Estimate
4.
J Cardiothorac Surg ; 19(1): 373, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918860

ABSTRACT

BACKGROUND: Tracheobronchial injuries caused by blunt chest trauma are rare in children, and such injuries usually involve multiple organs. Most cases involve respiratory failure on the way to the hospital, and the mortality rate is high. Herein, we describe the case of a 5-year-old patient who fell from an electric vehicle, causing complete rupture of the bilateral main bronchus. CASE PRESENTATION: We treated a 5-year-old patient with complete bilateral main bronchus rupture. Chest computed tomography (CT) failed to detect bronchial rupture. Continuous closed thoracic drainage resulted in a large amount of bubble overflow. Tracheal rupture was suspected. Fibreoptic bronchoscopy revealed complete rupture of the right main bronchus and rupture of the left main bronchus. Emergency tracheoplasty was performed under cardiopulmonary bypass (CPB). During the operation, we found that the bilateral main bronchi were completely ruptured. Postoperative recovery was smooth. The traditional surgical method for treating these injuries is lateral thoracotomy. However, a median sternotomy provides a better opportunity for selective repair. Extracorporeal circulation-assisted surgery is required for patients with unstable breathing. CONCLUSION: Complete fractures of the bilateral main bronchi are rare. Bronchial rupture should be suspected in the presence of expansion defect-dropped lungs and massive air leakage despite tube thoracostomy in haemopneumothorax developing after thoracic trauma. Extracorporeal circulation-assisted tracheoplasty is a relatively safe option for children whose respiratory system is difficult to maintain, thus ensuring oxygenation ventilation and a clear surgical field.


Subject(s)
Bronchi , Bronchoscopy , Humans , Bronchi/injuries , Bronchi/surgery , Child, Preschool , Male , Bronchoscopy/methods , Wounds, Nonpenetrating/surgery , Wounds, Nonpenetrating/complications , Tomography, X-Ray Computed , Rupture/surgery , Thoracic Injuries/surgery , Thoracic Injuries/complications
5.
Reprod Biol Endocrinol ; 22(1): 69, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886751

ABSTRACT

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.


Subject(s)
Anti-Mullerian Hormone , Birth Rate , Cryopreservation , Embryo Transfer , Live Birth , Humans , Female , Embryo Transfer/methods , Embryo Transfer/statistics & numerical data , Embryo Transfer/trends , Pregnancy , Adult , Retrospective Studies , Prognosis , Anti-Mullerian Hormone/blood , Live Birth/epidemiology , Pregnancy Rate , Ovarian Reserve/physiology , Age Factors , Fertilization in Vitro/methods , Pregnancy Outcome/epidemiology
7.
Ren Fail ; 46(1): 2349121, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38916144

ABSTRACT

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.


Subject(s)
Fatigue , Peritoneal Dialysis , Humans , Male , Female , Peritoneal Dialysis/adverse effects , Middle Aged , Adult , China/epidemiology , Fatigue/etiology , Anxiety/etiology , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , Pruritus/etiology , Aged , Symptom Assessment , Factor Analysis, Statistical , Cross-Sectional Studies , East Asian People
8.
Lab Chip ; 24(10): 2802-2810, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38693825

ABSTRACT

Liposomes have garnered significant attention owing to their favorable characteristics as promising carriers. Microfluidic based hydrodynamic flow focusing, or micro-mixing approaches enable precise control of liposome size during their synthesis due to the comparable size scale. However, current microfluidic approaches still have issues such as high flow rate dependency, complex chip structures, and ease of clogging. Herein, we present a novel microfluidic platform for size-tunable liposome synthesis based on an ultra-high-frequency acoustic resonator. By designing the shape and orientation of the acoustic resonator in the three-phase laminar flow, it combined the features of both hydrodynamic flow focusing and rapid micro-mixing. The distribution of lipid precursor solution in laminar flow and the mixing conditions could be regulated by the confined acoustic streaming vortex. We successfully synthesize liposomes with adjustable sizes and narrow size distributions. Notably, this platform regulates the product size by adjusting only the input power, which is less dependent on the flow rate. Furthermore, the vortex-like fluid flow generated along the device edge effectively prevents precipitation due to excessive lipid concentration or contact with the wall.

9.
BMC Genomics ; 25(1): 507, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778248

ABSTRACT

BACKGROUND: Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. METHODS: Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). RESULTS: From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. CONCLUSION: The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.


Subject(s)
Oncogene Proteins, Viral , Phylogeny , China , Humans , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/immunology , Female , Papillomavirus E7 Proteins/genetics , Papillomavirus E7 Proteins/immunology , Alphapapillomavirus/genetics , Alphapapillomavirus/immunology , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/genetics , Epitopes/immunology , Epitopes/genetics , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Papillomavirus Infections/virology , Amino Acid Sequence
11.
Angew Chem Int Ed Engl ; : e202404532, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38763910

ABSTRACT

The formation of phosphorus-rich alanes featuring butterfly-like geometries is achieved. The two-electron reduction products feature a unique P4 2- structure and can act as a source of P3-. The treatment of these phosphorus containing products with electrophiles under mild conditions results in the formation of different phosphines. This approach eliminates the need for high temperatures and/or high pressures, which are commonly required in industrial processes for the preparation of useful phosphines.The activation and further functionalization of white phosphorus (P4) by main group complexes has become an increasingly studied topic in recent times. Herein, we report the controlled formation of phosphorus-rich alanes featuring butterfly-like geometries from the selective reaction of P4 with dialumenes, ([L(IiPr)Al]2) (1: L=Tripp=2,4,6-iPr3C6H2; 2: L=tBu2MeSi; IiPr=[MeCN(iPr)]2C)). The two-electron-reduction product of P4 features a P4 2- structure and is shown to be able to act as a source of P3-. Treatments of different electrophiles (e.g., chlorotrimethylsilane (Me3SiCl), iodotrimethylsilane (Me3SiI), HCl, or acetyl chloride (CH3COCl)) with these alanes under mild conditions gave the corresponding phosphines (e.g., P(SiMe3)3, PH3, or P(COCH3)3).

12.
bioRxiv ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38562900

ABSTRACT

Motile cilia have essential cellular functions in development, reproduction, and homeostasis. Genetic causes for motile ciliopathies have been identified, but the consequences on cellular functions beyond impaired motility remain unknown. Variants in CCDC39 and CCDC40 cause severe disease not explained by loss of motility. Using human cells with pathological variants in these genes, Chlamydomonas genetics, cryo-electron microscopy, single cell RNA transcriptomics, and proteomics, we identified perturbations in multiple cilia-independent pathways. Absence of the axonemal CCDC39/CCDC40 heterodimer results in loss of a connectome of over 90 proteins. The undocked connectome activates cell quality control pathways, switches multiciliated cell fate, impairs microtubule architecture, and creates a defective periciliary barrier. Both cilia-dependent and independent defects are likely responsible for the disease severity. Our findings provide a foundation for reconsidering the broad cellular impact of pathologic variants in ciliopathies and suggest new directions for therapies.

13.
J Glob Antimicrob Resist ; 37: 199-207, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38641225

ABSTRACT

OBJECTIVES: The blaNDM gene was prevalent among children and became the predominant cause of severe infection in infants and children. This study aimed to investigate the epidemiology and molecular characteristics of blaNDM in Enterobacteriaceae among children in China. METHODS: Carbapenem-resistant Enterobacteriaceae (CRE) were collected in the Children's Hospital of Fudan University from January 2016 to December 2022. Five carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) were screened by PCR method. Multilocus sequence typing (MLST) was conducted for phylogenetic analyses. blaNDM-carrying plasmids were typed by PCR-based Incompatibility (Inc) typing method. Moreover, plasmid comparison was performed with 213 publicly available IncX3 plasmids. RESULTS: A total of 330 CRE strains were enrolled, 96.4% of which carried carbapenemase genes. blaNDM gene accounted for 64.8% (214 strains) and included four variants, including blaNDM-1 (59.8%), blaNDM-5 (39.3%), blaNDM-7 (0.5%), and blaNDM-9 (0.5%). There were no predominant MLST lineages of blaNDM carrying strains. IncX3 was the major plasmid carrying blaNDM-1 (68.0%) and blaNDM-5 (72.6%) and was dominant in blaNDM-Klebsiella penumoniae (79.8%), blaNDM-Escherichia coli (58.2%), and blaNDM-Enterobacter cloacae (61.0%), respectively. Most (79.0%) clinical IncX3 plasmids in the world carried blaNDM, and the prevalence of blaNDM in IncX3 plasmids was more common in China (95.8%) than other countries (58.1%, P <0.01). CONCLUSION: blaNDM is highly prevalent in CRE among children in China. The spread of blaNDM was mainly mediated by IncX3 plasmids. Surveillance and infection control on the spread of blaNDM among children are important.


Subject(s)
Bacterial Proteins , Carbapenem-Resistant Enterobacteriaceae , Enterobacteriaceae Infections , Multilocus Sequence Typing , Plasmids , beta-Lactamases , Humans , China/epidemiology , Plasmids/genetics , beta-Lactamases/genetics , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/epidemiology , Child , Infant , Child, Preschool , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Bacterial Proteins/genetics , Microbial Sensitivity Tests , Female , Anti-Bacterial Agents/pharmacology , Phylogeny , Enterobacteriaceae/genetics , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Male
14.
Life Sci ; 344: 122578, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38537899

ABSTRACT

AIMS: Diabetic nephropathy (DN) is one of the most common complications of diabetes and represents a prototypical form of chronic kidney disease (CKD). Interstitial fibrosis is a key pathological feature of DN. During DN-associated renal fibrosis, resident fibroblasts trans-differentiate into myofibroblasts to remodel the extracellular matrix, the underlying epigenetic mechanism of which is not entirely clear. METHODS: Diabetic nephropathy was induced in C57B6/j mice by a single injection with streptozotocin (STZ). Gene expression was examined by quantitative PCR and Western blotting. Renal fibrosis was evaluated by PicroSirius Red staining. RESULTS: We report that expression of Brg1, a chromatin remodeling protein, in renal fibroblasts was up-regulated during DN pathogenesis as assessed by single-cell RNA-seq. Treatment with high glucose similarly augmented Brg1 expression in primary renal fibroblasts in vitro. Importantly, Brg1 ablation in quiescent renal fibroblasts or in mature myofibroblasts equivalently attenuated renal fibrosis in the context of diabetic nephropathy in mice. Additionally, administration with a small-molecule Brg1 inhibitor PFI-3 ameliorated renal fibrosis and improved renal function in mice induced to develop DN. SIGNIFICANCE: In conclusion, our data provide novel genetic evidence that links Brg1 to fibroblast-myofibroblast transition and renewed rationale for targeting Brg1 in the intervention of DN-associated renal fibrosis.


Subject(s)
DNA Helicases , Diabetic Nephropathies , Fibroblasts , Nuclear Proteins , Transcription Factors , Animals , Mice , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Fibroblasts/metabolism , Fibrosis , Kidney/metabolism , Myofibroblasts/metabolism , DNA Helicases/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism
15.
J Cell Mol Med ; 28(7): e18242, 2024 04.
Article in English | MEDLINE | ID: mdl-38509736

ABSTRACT

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (µCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.


Subject(s)
Cartilage Diseases , Cartilage, Articular , Iridoid Glucosides , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Mice , Cartilage, Articular/pathology , X-Ray Microtomography , Cell Differentiation , Cartilage Diseases/metabolism , Mesenchymal Stem Cell Transplantation/methods , Chondrogenesis
16.
Life Sci ; 341: 122498, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38340980

ABSTRACT

AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic. Excessive fibrogenesis, characterized by activation of hepatic stellate cells (HSCs), is a hallmark event in late stages of NAFLD. HSC activation is metabolically programmed by anaerobic glycolysis. In the present study we investigated the involvement of suppressor of variegation 3-9 homolog 1 (Suv39h1), a lysine methyltransferase, in NAFLD-associated liver fibrosis. METHODS AND MATERIALS: Liver fibrosis was induced by feeding the mice with a methionine-and-choline deficient (MCD) diet for 8 weeks. RESULTS: We report that germline deletion of Suv39h1 attenuated liver fibrosis in mice fed an MCD diet. In addition, HSC conditional deletion of Suv39h1 similarly ameliorated liver fibrosis in the NAFLD mice. Interestingly, co-culturing with hepatocytes exposed to palmitate promoted glycolysis in wild type HSCs but not in Suv39h1 deficient HSCs. Mechanistically, Suv39h1 facilitated the recruitment of hypoxia induced factor (HIF-1α) to stimulate the transcription of hexokinase 2 (HK2) in HSCs thereby enhancing glycolysis. Importantly, a positive correlation between Suv39h1, HK2, and myofibroblast markers was identified in liver specimens from NAFLD patients. SIGNIFICANCE: In conclusion, our data identify a novel pathway that contributes to the liver fibrosis and points to the possibility of targeting Suv39h1 for the intervention of liver fibrosis in NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Humans , Mice , Anaerobiosis , Choline/metabolism , Hepatic Stellate Cells/metabolism , Liver/metabolism , Liver Cirrhosis/pathology , Methionine , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism
17.
Elife ; 122024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376133

ABSTRACT

Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased ß-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting ß-catenin signaling in glucocorticoid-induced GONFH rats. Col2+ lineage largely contributes to BMSCs and was found an osteogenic commitment in the femoral head through 9 mo of lineage trace. Specific deletion of ß-catenin gene (Ctnnb1) in Col2+ cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that ß-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH and identify an ideal genetic-modified mouse model of GONFH.


Subject(s)
Glucocorticoids , Mesenchymal Stem Cells , Osteonecrosis , beta Catenin , Animals , Humans , Mice , Rats , Adipogenesis/genetics , beta Catenin/genetics , Cell Differentiation , Femur Head/pathology , Glucocorticoids/adverse effects , Homeostasis , Osteogenesis/genetics , Osteonecrosis/pathology
18.
Front Public Health ; 12: 1323273, 2024.
Article in English | MEDLINE | ID: mdl-38389940

ABSTRACT

Purpose: The regularity of epidemic prevention and control measures in China has meant that nursing students have been exposed to more electronic devices, while problematic smartphone use has increased. The purpose of this study is to determine the prospective associations among time management tendency, negative emotions, and problematic smartphone use in nursing students during the COVID-19 pandemic. Methods: A longitudinal study was conducted between November 2021 and May 2022. A total of 989 nursing students participated. The convenience sampling method was adopted and the following tools were used: the Adolescence Time Management Disposition Scale, the Depression Anxiety Stress Scales - 21, and the Mobile Phone Addiction Index. Multiple parallel mediation models were used by Mplus. Results: Time management tendency had a significantly negative effect on problematic smartphone use (p < 0.05). Further tests using mediation models showed that stress as a negative emotion mediated the relationship between time management tendency and problematic smartphone use (p < 0.05) over time. Conclusion: Nursing educators need to strengthen the stress resistance and time management ability of nursing students.


Subject(s)
COVID-19 , Students, Nursing , Adolescent , Humans , Time Management , Longitudinal Studies , COVID-19/epidemiology , Pandemics , Smartphone , China/epidemiology , Emotions
19.
Gut ; 73(5): 810-824, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38176898

ABSTRACT

OBJECTIVE: Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. DESIGN: HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat-Cre mice or the Postn-CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. RESULTS: We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice. More importantly, Suv39h1 inhibition by a small-molecule compound chaetocin dampened HSC-myofibroblast transition in cell culture and mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed HMOX1 transcription. HMOX1 depletion blunted the effects of Suv39h1 inhibition on HSC-myofibroblast transition in vitro and liver fibrosis in vivo. Transcriptomic analysis revealed that HMOX1 might contribute to HSC-myofibroblast transition by modulating retinol homeostasis. Finally, myofibroblast-specific HMOX1 overexpression attenuated liver fibrosis in both a preventive scheme and a therapeutic scheme. CONCLUSIONS: Our data demonstrate a previously unrecognised role for Suv39h1 in liver fibrosis and offer proof-of-concept of its targetability in the intervention of cirrhosis.


Subject(s)
Hepatic Stellate Cells , Liver Cirrhosis , Humans , Mice , Animals , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/pathology , Liver/metabolism , Myofibroblasts
20.
Nano Lett ; 24(4): 1367-1375, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38227970

ABSTRACT

Fluorescence imaging is a vital way to delineate the tumor boundaries. Here, we achieve a NIR-II aggregation-induced emission luminogen (AIEgen) with a fluorescence quantum yield (QY) of 12.6% in water through straightforward alkyl side chain modification. After loading of NIR-II AIEgen into polystyrene (PS) nanospheres, the thermal deactivation pathway is extremely limited, thereby concentrating absorption excitation on fluorescence emission. The fluorescence intensity is further enhanced by 5.4 times, the QY increases to 21.1%, and the NIR-II imaging signal is accordingly enhanced by 8.7 times, surpassing conventional DSPE-PEG carriers. The NIR-II@PS nanoprobe showcases superior resolution and tissue penetration depth compared to indocyanine green (ICG) and short-range near-infrared AIEgens. In vivo investigations underscore its tumor-to-normal tissue ratio (3.9) at 24 h post intravenous injection, enabling complete resection of ≤1 mm metastases under NIR-II bioimaging guidance. Additionally, the PS carrier-nanoparticles exhibit low toxicity in vivo, laying a promising foundation for the future design of medical nanomaterials.


Subject(s)
Nanospheres , Nanostructures , Neoplasms , Humans , Neoplasms/diagnostic imaging , Neoplasms/surgery , Optical Imaging/methods , Nanostructures/chemistry , Fluorescent Dyes/chemistry
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