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1.
Int J Biol Macromol ; : 134055, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038583

ABSTRACT

Gauze wound dressings have received considerable attention due to their cost-effectiveness, excellent mechanical properties, and widespread applications. However, their inability to actively combat microorganisms and effectively scavenge free radicals results in suboptimal wound management. In this study, a novel nonwoven-based gauze dressing coated with quaternized chitosan/tannic acid (QCS/TA), based on electrostatic interaction and hydrogen bonding, was successfully prepared using a spray-assisted layer-by-layer assembly method. The bio-based nonwoven dressing, assembled with multiple interlacing bilayers, demonstrated outstanding antimicrobial properties, eliminating 99.99 % of Staphylococcus aureus (S. aureus) and 85 % of Escherichia coli (E. coli). Compared to the pristine nonwoven dressing, the QCS/TA-coated nonwoven dressing scavenged >85 % of the surrounding radicals within 2 h. Additionally, the nonwoven dressing exhibits excellent coagulation properties. Notably, the facile spraying procedure preserved most of the softness and breathability of the nonwoven substrate. After the deposition of seven bilayers, the bending stiffness and drape coefficient increased by only 37.63 % and 3.85 %, respectively, while the air permeability and moisture permeability reached 1712 mm/s and 3683.58 g/m2/d, respectively. This bio-based nonwoven dressing, derived from safe and non-toxic ingredients, holds promise as the next generation of multifunctional gauze dressings.

2.
Anal Bioanal Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38953916

ABSTRACT

The majority of previously reported cathodic electrochemiluminescence (ECL) systems often required very negative potential to be carried out, which has greatly limited their applications in the sensing field. Screening high-performance cathodic ECL systems with low triggering potential is a promising way to broaden their applications. In this work, rhenium disulfide nanosheets (ReS2 NS) have been revealed as an efficient co-promoter to realize low-triggering-potential cathodic luminol ECL. One strong cathodic ECL signal appeared at a potential of -0.3 V and one anodic ECL peak was obtained at -0.15 V under the reverse potential scan, which were caused by electrogenerated reactive oxygen species (ROS) from hydrogen peroxide. The generation of strong luminol ECL at low potential was the result of the electrocatalytic effect of ReS2 NS on the reduction of H2O2. The scavenging effect of uric acid (UA) on the ROS could significantly inhibit the cathodic ECL. As a result, an ECL sensor was proposed, which showed outstanding performance for the detection of UA in the range of 10 nM to 0.1 mM with a low detection limit of 1.53 nM. Moreover, the ECL sensor was successfully applied in the sensitive detection of UA in real samples. This work provides a new avenue to establish a low-potential cathodic ECL system, which will sufficiently expand the potential application of cathodic ECL in the sensing field.

3.
Zhongguo Zhen Jiu ; 44(7): 797-802, 2024 Jul 12.
Article in Chinese | MEDLINE | ID: mdl-38986593

ABSTRACT

OBJECTIVE: To observe the effects of Zhoutian moxibustion on pain symptoms and serum inflammatory factors in patients with ankylosing spondylitis of cold-damp obstruction. METHODS: Eighty-four patients with ankylosing spondylitis of cold-damp obstruction were randomly divided into a Zhoutian moxibustion group (42 cases, 2 cases dropped out) and a governor vessel moxibustion group (42 cases, 2 cases dropped out, 1 case discontinued). Both groups were given oral administration of sulfasalazine enteric-coated tablets as basic treatment. The governor vessel moxibustion group was treated with moxibustion box from Dazhui (GV 14) to Yaoyangguan (GV 3), one hour per treatment; the Zhoutian moxibustion group was treated with moxibustion box from Tiantu (CV 22) to Zhongji (CV 3) in addition to the governor vessel moxibustion group, two hours per treatment. Both groups were treated once every 3 days, twice a week, for a total of 9 weeks. The pain symptom scores of the two groups were observed before treatment and at the 3rd, 6th, and 9th weeks into treatment. ELISA was used to detect the levels of serum interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α (TNF-α) before and after treatment, and the clinical efficacy of the two groups was evaluated after treatment. RESULTS: Except for the joint pain scores at the 3rd week into treatment, the total scores and the each sub-item score of pain symptom in the two groups were lower than those before treatment at the 3rd, 6th, and 9th weeks into treatment (P<0.05); at the 3rd, 6th, and 9th weeks into treatment, the total scores of pain symptom and the scores of lumbar sacral pain, back pain, joint cold pain, and limited mobility in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). After treatment, the levels of serum IL-1ß, IL-18 and TNF-α in both groups were lower than those before treatment (P<0.05), and the levels of serum IL-1ß, IL-18, and TNF-α in the Zhoutian moxibustion group were lower than those in the governor vessel moxibustion group (P<0.05). The total effective rate was 90.0% (36/40) in the Zhoutian moxibustion group, which was higher than 76.9% (30/39) in the governor vessel moxibustion group (P<0.05). CONCLUSION: Zhoutian moxibustion could effectively improve various pain symptoms in patients with ankylosing spondylitis of cold-damp obstruction, and reduce the expression of inflammatory factors.


Subject(s)
Acupuncture Points , Moxibustion , Spondylitis, Ankylosing , Tumor Necrosis Factor-alpha , Humans , Male , Female , Adult , Spondylitis, Ankylosing/therapy , Spondylitis, Ankylosing/complications , Middle Aged , Young Adult , Tumor Necrosis Factor-alpha/blood , Interleukin-1beta/blood , Adolescent , Interleukin-18/blood , Pain Management
4.
J Gastrointest Oncol ; 15(3): 829-840, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38989431

ABSTRACT

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

5.
Comput Biol Chem ; 112: 108141, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38996756

ABSTRACT

Anticancer peptides(ACPs) have attracted significant interest as a novel method of treating cancer due to their ability to selectively kill cancer cells without damaging normal cells. Many artificial intelligence-based methods have demonstrated impressive performance in predicting ACPs. Nevertheless, the limitations of existing methods in feature engineering include handcrafted features driven by prior knowledge, insufficient feature extraction, and inefficient feature fusion. In this study, we propose a model based on a pretrained model, and dual-channel attentional feature fusion(DAFF), called ACP-PDAFF. Firstly, to reduce the heavy dependence on expert knowledge-based handcrafted features, binary profile features (BPF) and physicochemical properties features(PCPF) are used as inputs to the transformer model. Secondly, aimed at learning more diverse feature informations of ACPs, a pretrained model ProtBert is utilized. Thirdly, for better fusion of different feature channels, DAFF is employed. Finally, to evaluate the performance of the model, we compare it with other methods on five benchmark datasets, including ACP-Mixed-80 dataset, Main and Alternate datasets of AntiCP 2.0, LEE and Independet dataset, and ACPred-Fuse dataset. And the accuracies obtained by ACP-PDAFF are 0.86, 0.80, 0.94, 0.97 and 0.95 on five datasets, respectively, higher than existing methods by 1% to 12%. Therefore, by learning rich feature informations and effectively fusing different feature channels, ACD-PDAFF achieves outstanding performance. Our code and the datasets are available at https://github.com/wongsing/ACP-PDAFF.

6.
Front Endocrinol (Lausanne) ; 15: 1393904, 2024.
Article in English | MEDLINE | ID: mdl-38948527

ABSTRACT

Background: Medullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages. Methods: 3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied. Results: A linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45-50, 50-55, and 55-60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly "5%" increase in MTC-specific death risks and an approximately "3 times" increase in non-MTC-specific death risks. Conclusions: The survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.


Subject(s)
Carcinoma, Neuroendocrine , SEER Program , Thyroid Neoplasms , Humans , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology , Middle Aged , Male , Female , Carcinoma, Neuroendocrine/mortality , Carcinoma, Neuroendocrine/pathology , Retrospective Studies , Age Factors , Survival Rate , Aged , Prognosis , Adult , Cohort Studies , Follow-Up Studies
7.
ESC Heart Fail ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946662

ABSTRACT

AIMS: We aim to integrate the parameters of two-dimensional (2D) echocardiography and identify the high-risk population for all-cause mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS: The study involved a retrospective cohort population with STEMI who were admitted to Yongchuan Hospital of Chongqing Medical University between January 2016 and January 2019. Baseline data were collected, including 2D echocardiography parameters and left ventricular ejection fraction (LVEF). The parameters of 2D echocardiography were subjected to cluster analysis. Logistic regression models were employed to assess univariate and multivariate adjusted odds ratios (ORs) of cluster information in relation to all-cause mortality. Four logistic regression models were generated, utilizing cluster information, clinical variables, clinical variables in conjunction with LVEF, and clinical variables in conjunction with LVEF and cluster information as predictive variables, respectively. The area under the curve (AUC) were utilized to evaluate the incremental risk stratification value of cluster information. RESULTS: The study included 633 participants with 28.8% female, a mean age of 65.68 ± 11.98 years. Over the course of a 3-year follow-up period, 108 (17.1%) patients experienced all-cause mortality. Utilizing cluster analysis of 2D echocardiography parameters, the patients were categorized into two distinct clusters, with statistically significant differences observed in most clinical variables, echocardiography, and survival outcomes between the clusters. Multivariate regression analysis revealed that cluster information was independently associated with the risk of all-cause mortality with adjusted OR 7.33 (95% confidence interval [CI] 3.99-14.06, P < 0.001). The inclusion of LVEF enhanced the predictive capacity of the model utilized with clinical variables with AUC 0.848 (95% CI 0.809-0.888) versus AUC 0.872 (95% CI 0.836-0.908) (P < 0.001), and the addition of cluster information further improved its predictive performance with AUC 0.906 (95% CI 0.878-0.934, P < 0.001). This cluster analysis was translated into a free available online calculator (https://app-for-mortality-prediction-cluster.streamlit.app/). CONCLUSIONS: The 2D echocardiographic diagnostic information based on cluster analysis had good prognostic value for STEMI population, which was helpful for risk stratification and individualized intervention.

8.
Brain Res Bull ; : 111034, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39053649

ABSTRACT

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16hours of fasting and 8hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia.

9.
Parasit Vectors ; 17(1): 317, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39044218

ABSTRACT

BACKGROUND: The primary pathogenic mechanism of schistosomiasis-associated liver fibrosis involves the deposition of schistosome eggs, leading to the formation of liver egg granulomas and subsequent liver fibrosis. Hepatic stellate cells are abnormally activated, resulting in excessive collagen deposition and fibrosis development. While specific long non-coding RNAs (lncRNAs) have been associated with fibrotic processes, their roles in schistosomiasis-associated liver fibrosis remain unclear. METHODS: Our previous research indicated that downregulating the ICOSL/ICOS could partially alleviate liver fibrosis. In this study, we established a schistosomiasis infection model in C57BL/6 and ICOSL knockout (KO) mice, and the liver pathology changes were observed at various weeks postinfection (wpi) using hematoxylin and eosin and Masson's trichrome staining. Within the first 4 wpi, no significant liver abnormalities were observed. However, mice exhibited evident egg granulomas and fibrosis in their livers at 7 wpi. Notably, ICOSL-KO mice had significantly smaller pathological variations compared with simultaneously infected C57BL/6 mice. To investigate the impact of lncRNAs on schistosomiasis-associated liver fibrosis, quantitative real-time polymerase chain reaction (RT-qPCR) was used to monitor the dynamic changes of lncRNAs in hepatic stellate cells of infected mice. RESULTS: The results demonstrated that lncRNA-H19, -MALAT1, -PVT1, -P21 and -GAS5 all participated in liver fibrosis formation after schistosome infection. In addition, ICOSL-KO mice exhibited significantly inhibited expression of lncRNA-H19, -MALAT1 and -PVT1 after 7 wpi. In contrast, they showed enhanced expression of lncRNA-P21 and -GAS5 compared with C57BL/6 mice, influencing liver fibrosis development. Furthermore, small interfering RNA transfection (siRNA) in JS-1 cells in vitro confirmed that lncRNA-H19, -MALAT1, and -PVT1 promoted liver fibrosis, whereas lncRNA-P21 and -GAS5 had the opposite effect on key fibrotic molecules, including α- smooth muscle actin and collagen I expression. CONCLUSIONS: This study uncovers that ICOSL/ICOS may play a role in activating hepatic stellate cells and promoting liver fibrosis in mice infected with Schistosoma japonicum by dynamically regulating the expression of specific lncRNAs. These findings offer potential therapeutic targets for schistosomiasis-associated liver fibrosis.


Subject(s)
Inducible T-Cell Co-Stimulator Ligand , Liver Cirrhosis , Mice, Inbred C57BL , Mice, Knockout , RNA, Long Noncoding , Schistosoma japonicum , Schistosomiasis japonica , Animals , RNA, Long Noncoding/genetics , Schistosomiasis japonica/parasitology , Schistosomiasis japonica/pathology , Liver Cirrhosis/parasitology , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Mice , Schistosoma japonicum/genetics , Inducible T-Cell Co-Stimulator Ligand/genetics , Hepatic Stellate Cells/parasitology , Disease Models, Animal , Liver/parasitology , Liver/pathology , Inducible T-Cell Co-Stimulator Protein/genetics , Female
10.
CNS Neurosci Ther ; 30(7): e14798, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39015099

ABSTRACT

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.


Subject(s)
ARNTL Transcription Factors , Cognitive Dysfunction , Maze Learning , Microglia , Propofol , Rats, Sprague-Dawley , Sleep Deprivation , Animals , Sleep Deprivation/complications , Microglia/drug effects , Microglia/metabolism , ARNTL Transcription Factors/metabolism , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/biosynthesis , Male , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Rats , Propofol/pharmacology , Maze Learning/drug effects , Up-Regulation/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/biosynthesis , Sleep/drug effects , Hippocampus/drug effects , Hippocampus/metabolism
11.
Dev Comp Immunol ; 159: 105224, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38969190

ABSTRACT

Stimulator of interferon genes (STING) mediates innate immune response upon binding to cyclic GMP-AMP (cGAMP). It recruits tank-binding kinase 1 (TBK1) and transcription factor interferon regulatory factor 3 (IRF3) through its C-terminal tail and facilitates TBK1-dependent phosphorylation of IRF3 via forming STING polymers in mammalian cells. However, the mechanism behind STING-mediated activation of NF-κB transcription factor, Relish, in insect cells is unknown. Our study revealed that insect STING formed oligomers and the cryptic RIP homotypic interaction motif (cRHIM) was required for its oligomerization and its anti-viral functions. Cells expressing cRHIM-deficient mutants exhibited lower levels of anti-viral molecules, higher viral load after viral infection and weak activation of Relish. Moreover, we observed that under cGAMP stimulation, insect STING interacted with IMD, and deletion of the cRHIM motif on either protein prevented this interaction. Finally, we demonstrated that cGAMP enhanced the amyloid-like property of insect STING aggregates by ThT staining. In summary, our research showed that insect STING employed a homotypic motif to form intermolecular interactions that are essential for its antiviral signaling.


Subject(s)
Immunity, Innate , Interferon Regulatory Factor-3 , Membrane Proteins , Signal Transduction , Animals , Membrane Proteins/metabolism , Membrane Proteins/genetics , Signal Transduction/immunology , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-3/genetics , Nucleotides, Cyclic/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Amino Acid Motifs/genetics , Humans , Cell Line , Protein Binding , Phosphorylation , Protein Multimerization , Drosophila melanogaster/immunology , Drosophila melanogaster/virology
12.
Behav Brain Res ; : 115156, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032867

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. Despite its prevalence, effective treatments remain elusive. Recent studies have highlighted the importance of the balance between GABAergic and glutamatergic neuronal synaptic functions in ASD development. Repetitive transcranial magnetic stimulation (RTMS) is a painless and effective treatment allowed for use in depression and obsessive-compulsive disorder. However, its efficacy in treating autism is still under investigation. Low-frequency RTMS (LF-RTMS), which shows promise in reducing autism-like behaviors, is considered to regulate synaptic function. OBJECTIVE: We observed and recorded the behaviors of mice to assess the impact of RTMS on their social interactions and repetitive activities. Subsequently, we examined GABAergic and glutamatergic neuronal markers along with synaptic marker proteins to understand the underlying changes associated with these behaviors. METHODS: To evaluate behaviors associated with autism spectrum disorder (ASD), several behavioral tests were conducted, focusing on sociability, repetitive behaviors, locomotion, anxiety, and depression. Additionally, Western blot and immunofluorescence staining were employed to investigate the activity of GABAergic and glutamatergic neurons in the hippocampus, aiming to understand the synaptic mechanisms underlying these behaviors. RESULTS: LF-RTMS treatment effectively relieved the social disability and normalized synaptic function in the hippocampus of ASD mice model induced by valproate (VPA). Importantly, this treatment did not lead to any adverse effects on repetitive behavior, locomotion, anxiety, or depression. CONCLUSION: LF-RTMS attenuated social disability without affecting repetitive behavior, locomotion, anxiety, or depression. Changes in the expression of GABAergic and glutamatergic neuronal synaptic proteins in the hippocampus were also observed.

13.
Autophagy ; : 1-18, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38964379

ABSTRACT

Macroautophagic/autophagic and endocytic pathways play essential roles in maintaining homeostasis at different levels. It remains poorly understood how both pathways are coordinated and fine-tuned for proper lysosomal degradation of diverse cargoes. We and others recently identified a Golgi-resident RAB GTPase, RAB2A, as a positive regulator that controls both autophagic and endocytic pathways. In the current study, we report that TBC1D4 (TBC1 domain family member 4), a TBC domain-containing protein that plays essential roles in glucose homeostasis, suppresses RAB2A-mediated autophagic and endocytic pathways. TBC1D4 bound to RAB2A through its N-terminal PTB2 domain, which impaired RAB2A-mediated autophagy at the early stage by preventing ULK1 complex activation. During the late stage of autophagy, TBC1D4 impeded the association of RUBCNL/PACER and RAB2A with STX17 on autophagosomes by direct interaction with RUBCNL via its N-terminal PTB1 domain. Disruption of the autophagosomal trimeric complex containing RAB2A, RUBCNL and STX17 resulted in defective HOPS recruitment and eventually abortive autophagosome-lysosome fusion. Furthermore, TBC1D4 inhibited RAB2A-mediated endocytic degradation independent of RUBCNL. Therefore, TBC1D4 and RAB2A form a dual molecular switch to modulate autophagic and endocytic pathways. Importantly, hepatocyte- or adipocyte-specific tbc1d4 knockout in mice led to elevated autophagic flux and endocytic degradation and tissue damage. Together, this work establishes TBC1D4 as a critical molecular brake in autophagic and endocytic pathways, providing further mechanistic insights into how these pathways are intertwined both in vitro and in vivo.Abbreviations: ACTB: actin beta; ATG9: autophagy related 9; ATG14: autophagy related 14; ATG16L1: autophagy related 16 like 1; CLEM: correlative light electron microscopy; Ctrl: control; DMSO: dimethyl sulfoxide; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; FL: full length; GAP: GTPase-activating protein; GFP: green fluorescent protein; HOPS: homotypic fusion and protein sorting; IP: immunoprecipitation; KD: knockdown; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; OE: overexpression; PG: phagophore; PtdIns3K: class III phosphatidylinositol 3-kinase; SLC2A4/GLUT4: solute carrier family 2 member 4; SQSTM1/p62: sequestosome 1; RUBCNL/PACER: rubicon like autophagy enhancer; STX17: syntaxin 17; TAP: tandem affinity purification; TBA: total bile acid; TBC1D4: TBC1 domain family member 4; TUBA1B: tubulin alpha 1b; ULK1: unc-51 like autophagy activating kinase 1; VPS39: VPS39 subunit of HOPS complex; WB: western blot; WT: wild type.

14.
RSC Adv ; 14(30): 21250-21259, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38974229

ABSTRACT

Simultaneous extraction of anthocyanins and removal of sugars from Kushui rose was performed using an ethanol-ammonium sulphate aqueous two-phase system (ATPS). The effects of different parameters, such as type of salt, concentrations of salt and ethanol, temperature and pH on the partition coefficient and recovery of anthocyanins in the top system and sugars in the bottom system were studied. Furthermore, an experimental design of a three-level three-factor Box-Behnken design response surface methodology (RSM) was used to obtain optimal extraction conditions. The maximum partition coefficient (5.64) and recovery (78%) of anthocyanins in the top system within the investigated range were obtained at 22% (w/w) concentration of ammonium sulphate, 25% (w/w) concentration of ethanol, pH 5 and 33.5 °C. During the discussion of the main factors, the maximum recovery of sugars reached 70.09%. The HPLC profile of anthocyanins obtained from the ATPS top phase was similar to that of anthocyanins extracted by ethanol, which indicated that the ethanol-ammonium sulphate ATPS was suitable for the extraction of anthocyanins. On the basis of the anthocyanin stability experiment, anthocyanins extracted from Kushui rose should be stored at low pH and temperature.

15.
J Genet Genomics ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39009303

ABSTRACT

Shandong province, located in the Lower Yellow River, is one of the birthplaces of ancient Chinese civilization. However, the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes. Here, we present 21 ancient genomes from Shandong dating from the Warring States period to the Jin-Yuan Dynasties. Unlike the early Neolithic samples from Shandong, the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin, suggesting a population turnover in Shandong from the Neolithic Age to the Historical era. In addition, we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese, showing long-term genetic stability in Han Chinese at least since the Warring States period.

16.
J Chem Phys ; 161(3)2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39007385

ABSTRACT

Temperature is an important parameter to be monitored in new wearable electronic devices. Layered black phosphorus (BP) has inherent good thermal stability and semiconductor properties and has a promising application as a temperature sensing layer. Here, we investigate the temperature sensing properties of BP, using in situ Raman spectroscopy and x-ray diffraction techniques. Flexible sensors are constructed, and temperature response is investigated in the range of 6-38 °C. The prospect application for monitoring the temperature of human body parts is demonstrated. The results show that the BP-based temperature sensors demonstrate good negative temperature coefficient characteristics and display high sensitivity and reproducible sensing performance. The temperature-dependent performance suggests the feasibility of BP as a sensitive layer in a wide temperature range. This work paves the way for exploring new applications of amazing layered materials, such as BP, in wearable electronic devices.

17.
Clin Cosmet Investig Dermatol ; 17: 1613-1619, 2024.
Article in English | MEDLINE | ID: mdl-39006130

ABSTRACT

Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.

18.
Bone ; 187: 117199, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992453

ABSTRACT

Cementum is a vital component of periodontium, yet its regeneration remains a challenge. Pentraxin 3 (PTX3) is a multifunctional glycoprotein involved in extracellular matrix remodeling and bone metabolism regulation. However, the role of PTX3 in cementum formation and cementoblast differentiation has not been elucidated. In this study, we initially observed an increase in PTX3 expression during cementum formation and cementoblast differentiation. Then, overexpression of PTX3 significantly enhanced the differentiation ability of cementoblasts. While conversely, PTX3 knockdown exerted an inhibitory effect. Moreover, in Ptx3-deficient mice, we found that cementum formation was hampered. Furthermore, we confirmed the presence of PTX3 within the hyaluronan (HA) matrix, thereby activating the ITGB1/FAK/YAP1 signaling pathway. Notably, inhibiting any component of this signaling pathway partially reduced the ability of PTX3 to promote cementoblast differentiation. In conclusion, our study indicated that PTX3 promotes cementum formation and cementoblast differentiation, which is partially dependent on the HA/ITGB1/FAK/YAP1 signaling pathway. This research will contribute to our understanding of cementum regeneration after destruction.

19.
Int J Oncol ; 65(2)2024 Aug.
Article in English | MEDLINE | ID: mdl-38994758

ABSTRACT

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronavirus pandemic, the development of mRNA vaccines has seen substantial progress and widespread adoption. In the present review, the development of mRNA vaccines, their mechanisms of action, factors influencing their function and the current clinical applications of the vaccine are discussed. A focus is placed on the application of mRNA vaccines in cancer, with the aim of highlighting unique advances and the remaining challenges of this novel and promising therapeutic approach.


Subject(s)
Cancer Vaccines , Neoplasms , Vaccine Development , mRNA Vaccines , Humans , Neoplasms/immunology , Neoplasms/therapy , Cancer Vaccines/therapeutic use , Cancer Vaccines/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , COVID-19/prevention & control , COVID-19/immunology , RNA, Messenger/genetics , RNA, Messenger/immunology , Precision Medicine/methods , Immunotherapy/methods
20.
J Colloid Interface Sci ; 673: 411-425, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38878375

ABSTRACT

Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines.


Subject(s)
Bone Regeneration , Dopamine , Glass , Tissue Scaffolds , Animals , Dopamine/chemistry , Dopamine/pharmacology , Rats , Rabbits , Tissue Scaffolds/chemistry , Glass/chemistry , Bone Regeneration/drug effects , Skin/drug effects , Skin/injuries , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Rats, Sprague-Dawley , Gels/chemistry , Tissue Engineering , Bone and Bones/drug effects , Porosity , Surface Properties , Regeneration/drug effects , Particle Size , Male
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