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1.
Dev Cell ; 59(5): 645-660.e8, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38325371

ABSTRACT

Macropinocytosis, an evolutionarily conserved endocytic pathway, mediates nonselective bulk uptake of extracellular fluid. It is the primary route for axenic Dictyostelium cells to obtain nutrients and has also emerged as a nutrient-scavenging pathway for mammalian cells. How cells adjust macropinocytic activity in various physiological or developmental contexts remains to be elucidated. We discovered that, in Dictyostelium cells, the transcription factors Hbx5 and MybG form a functional complex in the nucleus to maintain macropinocytic activity during the growth stage. In contrast, during starvation-induced multicellular development, the transcription factor complex undergoes nucleocytoplasmic shuttling in response to oscillatory cyclic adenosine 3',5'-monophosphate (cAMP) signals, which leads to increased cytoplasmic retention of the complex and progressive downregulation of macropinocytosis. Therefore, by coupling macropinocytosis-related gene expression to the cAMP oscillation system, which facilitates long-range cell-cell communication, the dynamic translocation of the Hbx5-MybG complex orchestrates a population-level adjustment of macropinocytic activity to adapt to changing environmental conditions.


Subject(s)
Dictyostelium , Animals , Dictyostelium/metabolism , Pinocytosis/physiology , Cytoplasm , Cell Nucleus , Transcription Factors/metabolism , Mammals
2.
PLoS Pathog ; 20(2): e1012048, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38408104

ABSTRACT

The activation of stimulator of interferon genes (STING) signaling induces the production of type I interferons (IFNs), which play critical roles in protective innate immunity for the host to defend against viral infections. Therefore, achieving sustained or enhanced STING activation could become an antiviral immune strategy with potential broad-spectrum activities. Here, we discovered that various clinically used microtubule-destabilizing agents (MDAs) for the treatment of cancer showed a synergistic effect with the activation of STING signaling in innate immune response. The combination of a STING agonist cGAMP and a microtubule depolymerizer MMAE boosted the activation of STING innate immune response and showed broad-spectrum antiviral activity against multiple families of viruses. Mechanistically, MMAE not only disrupted the microtubule network, but also switched the cGAMP-mediated STING trafficking pattern and changed the distribution of Golgi apparatus and STING puncta. The combination of cGAMP and MMAE promoted the oligomerization of STING and downstream signaling cascades. Importantly, the cGAMP plus MMAE treatment increased STING-mediated production of IFNs and other antiviral cytokines to inhibit viral propagation in vitro and in vivo. This study revealed a novel role of the microtubule destabilizer in antiviral immune responses and provides a previously unexploited strategy based on STING-induced innate antiviral immunity.


Subject(s)
Interferon Type I , Membrane Proteins , Membrane Proteins/genetics , Immunity, Innate , Signal Transduction , Cytokines , Interferon Type I/pharmacology
3.
Comb Chem High Throughput Screen ; 27(1): 127-135, 2024.
Article in English | MEDLINE | ID: mdl-37264620

ABSTRACT

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA. BACKGROUND: Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy. METHODS: Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145. RESULTS: The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3' UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways. CONCLUSION: The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.


Subject(s)
MicroRNAs , Osteoarthritis , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Sequestosome-1 Protein/metabolism , Osteoarthritis/metabolism , Chondrocytes/metabolism , Autophagy/physiology , Apoptosis , Membrane Proteins/genetics , Adaptor Proteins, Signal Transducing
4.
Immunity ; 56(11): 2492-2507.e10, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37890481

ABSTRACT

Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity.


Subject(s)
Lipid Metabolism , Nucleotidyltransferases , Animals , Mice , Liver X Receptors/metabolism , Nucleotidyltransferases/metabolism , DNA , Nucleotides, Cyclic/metabolism , Immunity, Innate
5.
Clin Interv Aging ; 18: 1423-1436, 2023.
Article in English | MEDLINE | ID: mdl-37663122

ABSTRACT

Introduction: This study aimed to examine the impacts of DOACs compliance and prescribing preferences on clinical outcomes in elderly hip fracture patients with isolated calf deep vein thrombosis (ICDVT). Methods: We conducted a retrospective cohort study that evaluated 702 patients who underwent surgical treatment combined with ICDVT in an academic university hospital between January 2016 and October 2021. DOACs compliance was investigated through telephone and outpatient follow-up, and ICDVT clinical outcomes were collected 30 and 90 days post-discharge, respectively. Variables of interest were collected through the electronic medical record system, and data were analyzed after adjusting for predictors of non-completely dissolved (CD) of ICDVT. Results: The DOACs compliance survey revealed that 375 (53.42%) patients were fully adherent, 270 (38.46%) were fairly adherent, and 57 (8.12%) were poorly adherent. Approximately 62% of patients had ICDVT dissipation within 30 days after discharge, reaching 94% within 90 days. DOACs QD/BID regimen is often based on economic status, activity capacity, discharge destination and post-operative weight-bearing activities (p<0.05).The mechanism of injury, ASA classification, surgical technique and timing of ICDVT formation were significantly correlated with DOACs 14/28 days regimen (p<0.05).Multivariate analysis revealed that rural patients [OR 1.518 (95% CI, 1.117-2.236)], pre-operative ICDVT[OR 2.816 (95% CI, 1.862-4.259)] and thrombus length [OR 1.157 (95% CI, 1.263-1.821)] were ICDVT risk factors for non-CD. Furthermore, DOACs fair compliance [OR 0.087 (95% CI, 0.042-0.178)], DOACs full compliance [OR 0.283 (95% CI, 0.139-0.579)], and hospitalization duration [OR 0.793 (95% CI, 0.694-0.907)] were ICDVT protective factors for CD. Conclusion: Better compliance with DOACs benefits early ICDVT dissipation, but final clinical outcomes have to be validated with longer follow-up periods. When managing elderly patients with hip fractures, indications for anticoagulation should be considered and individualized protocols should be used.


Subject(s)
Hip Fractures , Mesenteric Ischemia , Aged , Humans , Patient Discharge , Aftercare , Retrospective Studies , Hip Fractures/drug therapy , Hip Fractures/surgery
6.
Eur J Trauma Emerg Surg ; 49(6): 2467-2477, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37436467

ABSTRACT

BACKGROUND: There is a general clinical consensus that early surgical stabilization of rib fractures (SSRF, ≤ 48-72 h after admission) can benefit patients, and this is only regarding the surgeon's opinions. This study assessed the true outcomes of young and middle-aged patients at different surgical timings. METHODS: This retrospective cohort study was conducted among patients aged 30-55 years who were hospitalized with a diagnosis of isolated rib fractures and underwent SSRF between July 2017 and September 2021. The patients were divided into early (≤ 3 days), mid- (4-7 days) and late (8-14 days) groups, according to the interval (days) between surgery and injury date. The impact of different surgical timings on clinical outcomes, patients, and families was assessed by comparing SSRF-related data during hospitalization and follow-up studies of clinicians, patients themselves, and family caregivers 1-2 months after surgery. RESULTS: In this study, 155 complete patient data were finally included, including 52, 64, and 39 patients in the early, mid, and late groups, respectively. Length of operation, preoperative closed chest drainage rate, length of hospital stay, intensive care unit length of stay, duration of invasive mechanical ventilation in the early group were lower than those in the intermediate and late groups. Additionally, hemothorax and excess pleural fluid incidence after SSRF was lower in the early group than in the intermediate and late groups. Postoperative follow-up results showed that patients in the early group had higher SF-12 physical component summary scores and shorter duration of absence from work. Family caregivers had lower Zarit Burden Interview scores than those in the mid- and late groups. CONCLUSION: From the experience of our institution's SSRF, early surgery is safe and offers additional potential benefits for young and middle-aged patients and families with isolated rib fractures.


Subject(s)
Physicians , Rib Fractures , Middle Aged , Humans , Rib Fractures/surgery , Retrospective Studies , Feedback , Caregivers , Length of Stay
7.
Cell Rep ; 42(3): 112185, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36857187

ABSTRACT

It is widely known that stimulator of interferon genes (STING) can trigger nuclear factor κB (NF-κB) signaling. However, whether and how the NF-κB pathway affects STING signaling remains largely unclear. Here, we report that Toll-like receptor (TLR)-, interleukin-1 receptor (IL-1R)-, tumor necrosis factor receptor (TNFR)-, growth factor receptor (GF-R)-, and protein kinase C (PKC)-mediated NF-κB signaling activation dramatically enhances STING-mediated immune responses. Mechanistically, we find that STING interacts with microtubules, which plays a crucial role in STING intracellular trafficking. We further uncover that activation of the canonical NF-κB pathway induces microtubule depolymerization, which inhibits STING trafficking to lysosomes for degradation. This leads to increased levels of activated STING that persist for a longer period of time. The synergy between NF-κB and STING triggers a cascade-amplified interferon response and robust host antiviral defense. In addition, we observe that several gain-of-function mutations of STING abolish the microtubule-STING interaction and cause abnormal STING trafficking and ligand-independent STING autoactivation. Collectively, our data demonstrate that NF-κB activation enhances STING signaling by regulating microtubule-mediated STING trafficking.


Subject(s)
NF-kappa B , Signal Transduction , Interferons , NF-kappa B/metabolism , Signal Transduction/genetics , Toll-Like Receptors , Membrane Proteins
8.
Article in English | MEDLINE | ID: mdl-36231385

ABSTRACT

This study, based on the theory of restorative environmental, uses virtual reality (VR) technology to construct interactive restorative environments and discusses the influence of the experience of virtual restorative environment on individual creativity. A total of 72 college students were selected as participants in the study. Through psychological scales, three creativity tests, and EEG feedback data, the following conclusions were drawn: (1) The VR restorative environment experience improves individual creativity, especially the creative quality of cohesion; (2) the experience of the VR restorative environment enables participants to experience a desirable sense of presence. Compared with the restorative scene experience without interactive activities, the addition of interactive activities improves the individual sensory fidelity to a greater extent. (3) We cannot simply assume that the experience of the VR restorative environment with interactive activities will make individual creative performance better than non-interactive experience. Interaction with certain difficulty will increase cognitive load, thus disrupting individual creative performance. Garden scenes that can be explored freely and have no interaction can better promote individual creativity. (4) In the environmental experience, participants paid greater attention to natural elements, and the restorative environment they described was very similar to the environment they believed could foster creativity. This study's results provide evidence for the positive effects of the VR restorative environment experience on individuals and contributes to the cognitive exploration of the interaction between restorative environments and individuals in the future.


Subject(s)
Virtual Reality , Creativity , Humans
9.
Am J Transl Res ; 14(8): 5326-5342, 2022.
Article in English | MEDLINE | ID: mdl-36105058

ABSTRACT

BACKGROUND: Mesenchymal stem cells derived from human tissues have been widely used for tissue regeneration because of their strong self-renewal capacity and multi-potential properties. Autophagy plays a vital role in maintaining bone homeostasis. However, the mechanism underlying this role for autophagy in the osteogenic differentiation of mesenchymal stem cells remains to be elucidated. METHODS: Two microarray datasets were downloaded from the GEO database. Fourteen bone marrow mesenchymal stem cell samples comprising control and induction groups were selected to identify differentially expressed autophagy-related genes via multiple bioinformatics approaches, followed by functional analysis. Interactions among differentially expressed autophagy genes, miRNAs, and transcription factors were analyzed and visualized using Cytoscape software. The association between hub differentially expressed genes and autophagy was validated by qRT-PCR. RESULTS: Ten autophagy-related genes (including VPS8, NDRG4, and CYBB) were identified as osteogenic hub genes. Correlation analysis revealed that CYBB was highly correlated with the sensitivity to multiple drugs, such as imexon, megestrol acetate, and isotretinoin. The regulatory network displayed a complex connection among miRNAs, transcription factors, and differentially expressed autophagy genes. Friends' analysis showed that NDRG4 was highly closely related to other hub genes (P < 0.05). Furthermore, NDRG4 expression was downregulated in the induction group (P < 0.01). NDRG4 was significantly correlated with infiltrating immune cells, including monocytes, eosinophils, type 17 T helper cells, neutrophils, activated CD8 T cells, and immature B cells. Levels of the 10 autophagy-related genes (including VPS8, NDRG4, and CYBB) were successfully validated based on in vitro experiments. CONCLUSION: We identified candidate molecules to further investigate their functions in osteogenesis, providing novel insights into the role of autophagy in mesenchymal stem cell differentiation.

10.
Front Public Health ; 10: 906969, 2022.
Article in English | MEDLINE | ID: mdl-35968447

ABSTRACT

The outbreak of the COVID-19 epidemic intensified the volatility of commodity markets (the energy and precious metals markets), which created a significant negative impact on the volatility spillovers among these markets. It may also have triggered a new volatility risk contagion. In this paper, we introduce the DCC-GARCH-CONNECTEDNESS approach to explore the volatility spillover level and multi-level spillover structure characteristics among the commodity markets before and during the COVID-19 epidemic in order to clarify the new volatility risk contagion patterns across the markets. The results implied several conclusions. (i) The COVID-19 epidemic has significantly improved the total volatility spillover level of the energy and precious metals markets and has enhanced the risk connectivity among the markets. (ii) The COVID-19 epidemic has amplified the volatility of the crude oil market, making it the main volatility spillover market, namely the source of volatility risk contagion. (iii) The COVID-19 epidemic outbreak enhanced the external risk absorption capacity of the natural gas and silver markets, and the absorption level of the external volatility spillover improved significantly. Furthermore, the risk absorption capacity of the gold market weakened, while the gold market has remained the endpoint of external volatility risk during the epidemic and has acted as a risk stabilizer. (iv) The volatility spillover among markets has clear time-varying characteristics and a positive connectedness with the severity of the COVID-19 epidemic. As the severity of the COVID-19 epidemic increases, the volatility risk connectivity among the markets rapidly increases.


Subject(s)
COVID-19 , COVID-19/epidemiology , DCC Receptor , Gold , Humans
11.
Article in English | MEDLINE | ID: mdl-35805535

ABSTRACT

Anxiety and depression have been growing global mental health problems. The following studies explored the effect of interactive VR scenarios to find a low-cost and high-efficiency solution. Study 1 designed a 2 (anxiety and depression state) × 4 (interactive VR scenarios) experiment, the results of 20 participants showed that the designed scenarios had good restoration and presence, assisting to improve depression mood for people with mild to moderate anxiety and depression. Study 2 further investigated the intervention effects of two environment types (urban and park) and four interactive activities (automatic viewing, free-roaming, fishing, and watering plants in the park environment), based on data from a 10-minute experiment conducted by 195 participants with mild to moderate anxiety and depression. The subjective scales, EEG and EMG, and scenario experience were analyzed and the results showed that: (1) the restorative and present VR scenarios were beneficial in alleviating state anxiety and depression; (2) the restorative environment and presence were significantly and positively related to the reduction of anxiety and depression respectively, moreover, presence mediated the restorative environment on the recovery from anxiety and depression; (3) the environmental settings, the complexity of interaction, human factors, and maturity of VR devices and technology were also key factors that influenced the effects of interactive VR scenario experience and intervention. These studies revealed VR psychological intervention scenarios could be designed with comprehensive factors. Moreover, they might help pave the way for future study in exploring the physiology and psychology mode in virtual and real spaces, enhancing intervention effectiveness.


Subject(s)
Depression , Virtual Reality , Anxiety/therapy , Anxiety Disorders , Depression/therapy , Humans
12.
Cell Rep ; 39(9): 110880, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35649354

ABSTRACT

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.


Subject(s)
Antiviral Restriction Factors , Cathelicidins , Immunity, Innate , Interferons , Antiviral Restriction Factors/immunology , Cathelicidins/immunology , Humans , Interferons/immunology , Membrane Proteins/metabolism , Nucleotides, Cyclic
13.
Clin Interv Aging ; 17: 825-835, 2022.
Article in English | MEDLINE | ID: mdl-35620020

ABSTRACT

Introduction: Research on preoperative blood management in older patients with delayed surgery for intertrochanteric fracture is scarce, especially regarding hematopoiesis and hemostasis. We assessed the effectiveness of optimized blood management programs in older patients undergoing delayed surgery for intertrochanteric fractures. Methods: This retrospective study included 456 patients who underwent delayed surgery for intertrochanteric fractures. According to the optimized blood management plan, the patients were divided into four groups: group A was the control group; group B received 1 g of tranexamic acid (TXA) intravenously at admission; group C underwent sequential TXA treatment after admission until 1 day before surgery (1 g/day); and group D received iron supplements (200 mg/day) in addition to the treatment administered to group C, with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). The primary outcomes were preoperative hidden blood loss (HBL), preoperative allogeneic blood transfusion (ABT) rate, hemoglobin (Hb) change, and actual Hb drop. Results: The Hb reduction, calculated HBL, and hospitalization duration in groups C and D were significantly lower than those in groups A and B. The preoperative ABT rates in groups C and D were significantly lower than those in groups A and B, with no significant difference between groups C and D. Discussion: The results of this study suggested that iron supplementation (with or without rHuEPO) combined with the sequential IV TXA scheme did not show a better clinical effect than the sequential IV TXA scheme in the management of patients undergoing delayed surgery for intertrochanteric fractures. Therefore, further evaluation is needed before recommending iron supplements and rHuEPO in older patients.


Subject(s)
Erythropoietin , Hip Fractures , Tranexamic Acid , Aged , Blood Loss, Surgical/prevention & control , Erythropoietin/therapeutic use , Hip Fractures/surgery , Humans , Iron/therapeutic use , Retrospective Studies , Tranexamic Acid/therapeutic use
14.
Nat Commun ; 13(1): 1787, 2022 04 04.
Article in English | MEDLINE | ID: mdl-35379834

ABSTRACT

Macropinocytosis, an evolutionarily conserved mechanism mediating nonspecific bulk uptake of extracellular fluid, has been ascribed diverse functions. How nascent macropinosomes mature after internalization remains largely unknown. By searching for proteins that localize on macropinosomes during the Rab5-to-Rab7 transition stage in Dictyostelium, we uncover a complex composed of two proteins, which we name PripA and TbcrA. We show that the Rab5-to-Rab7 conversion involves fusion of Rab5-marked early macropinosomes with Rab7-marked late macropinosomes. PripA links the two membrane compartments by interacting with PI(3,4)P2 and Rab7. In addition, PripA recruits TbcrA, which acts as a GAP, to turn off Rab5. Thus, the conversion to Rab7 is linked to inactivation of the upstream Rab5. Consistently, disruption of either pripA or tbcrA impairs Rab5 inactivation and macropinocytic cargo processing. Therefore, the PripA-TbcrA complex is the central component of a Rab GAP cascade that facilitates programmed Rab switch and efficient cargo trafficking during macropinosome maturation.


Subject(s)
Dictyostelium , Biological Transport , Dictyostelium/genetics , Dictyostelium/metabolism , Endosomes/metabolism , Pinocytosis , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
15.
Bioengineered ; 13(3): 5262-5276, 2022 03.
Article in English | MEDLINE | ID: mdl-35170378

ABSTRACT

Autophagy occurs throughout the development and maturation of bone tissues and various types of bone cells and plays a vital role in osteoporosis progression. This study aimed to explore the role of runt-related transcription factor 2 (RUNX2) in osteoblast autophagy and its related molecular mechanisms. MC3T3-E1 cells were treated with different concentrations of rapamycin, and their viability was determined using a cell counting Kit-8 (CCK-8). The cells were then transfected with si-RUNX2 and RUNX2 overexpression plasmids, and the viability of these rapamycin-treated cells was measured using CCK-8, while the expression of autophagy-related genes/proteins and osteoblast differentiation-related genes was determined using Western blotting and RT-qPCR. Finally, Alizarin red staining was used to observe osteoblast mineralization, and transmission electron microscopy was employed to detect autophagosomes in cells administered different treatments. Rapamycin significantly inhibited cell viability and promoted cell autophagy compared with the control (P < 0.05). Cells with RUNX2 knockdown and overexpression were successfully established. Further, RUNX2 overexpression was found to significantly enhance the viability and osteoblast mineralization of rapamycin-treated cells and suppress cell autophagy. RUNX2 overexpression also increased p-p38MAPK/p38MAPK levels and ALP, OCN, and OSX expression, and markedly downregulated Beclin-1, LC3-II/LC3-I, p62, ATG1, p-Beclin-1, and ATG5 levels (P < 0.05). However, the trends after RUNX2 knockdown opposed those observed after RUNX2 overexpression. RUNX2 may regulate osteoblast differentiation and autophagy by mediating autophagy-related and osteoblast differentiation-related genes/proteins, as well as the p38MAPK signaling pathway.


Subject(s)
Core Binding Factor Alpha 1 Subunit , Sirolimus , Autophagy/genetics , Beclin-1/genetics , Beclin-1/metabolism , Beclin-1/pharmacology , Cell Differentiation/genetics , Cell Line , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Osteoblasts , Sirolimus/pharmacology
16.
Toxics ; 11(1)2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36668752

ABSTRACT

Using styrene as a proxy for VOCs, a new method was developed to remove styrene gas in nitrogen atmospheres. The effect on the styrene removal efficiency was explored by varying parameters within the continuum dynamic experimental setup, such as ferrous ion concentration, hydrogen peroxide concentration, and pH values. The by-products are quantized by a TOC analyzer. The optimal process conditions were hydrogen peroxide at 20 mmol/L, ferrous ions at 0.3 mmol/L and pH 3, resulting in an average styrene removal efficiency of 96.23%. In addition, in this study, we construct a BAS-BP neural network model with experimental data as a sample training set, which boosts the goodness-of-fit of the BP neural network and is able to tentatively predict styrene gas residuals for different front-end conditions.

17.
BMC Musculoskelet Disord ; 22(1): 940, 2021 Nov 10.
Article in English | MEDLINE | ID: mdl-34758790

ABSTRACT

BACKGROUND: Simultaneous bilateral distal tibial tubercle high tibial osteotomy (SBDTT-HTO) can result in increased blood loss. The aim of this study is to evaluate the actual hemostatic effect of different tranexamic acid (TXA) treatment regimen in SBDTT-HTO. METHODS: We conducted a retrospective case-control study including 54 patients who underwent SBDTT-HTO. The single-dose group (n = 18) received 1 g of intravenous TXA 15-30 min before surgery, the two-dose group (n = 18) received an additional 1 g of intravenous TXA 6 h after surgery, and the multiple-dose group (n = 18) received an additional 1 g intravenous TXA per-day until discharge. Blood loss, hemoglobin levels, occurrence of any adverse events,functional analysis, quality of life, and pain assessmentswere compared among the three groups. RESULTS: The total blood loss, hidden blood loss, drainage volumes, and haemoglobin level in the multiple-dose group all occupy a significant advantage.(p < 0.05). In addition, better quality of life were observed in patients belonging to the multiple-dose group then single-dose group.(p < 0.05). CONCLUSIONS: Based on our results, for patients undergoing SBDTT-HTO, sequential intravenous TXA administration can effectively and safely reduce blood loss,maintain postoperative Hb levels,and with the advantage of accelerating recovery.


Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Administration, Intravenous , Antifibrinolytic Agents/therapeutic use , Blood Loss, Surgical/prevention & control , Case-Control Studies , Humans , Osteotomy , Postoperative Hemorrhage/prevention & control , Quality of Life , Retrospective Studies
18.
J Orthop Surg Res ; 16(1): 602, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34654453

ABSTRACT

BACKGROUND: Linear blisters (LBs) often occur around dressings when negative-pressure wound therapy (NPWT) is used to cover open wounds. Tension blisters may increase the wound infection incidence rate, delay the start of operation, and prolong the duration of hospital stay. Currently, there are no established methods for the prevention of LB formation around dressings, which remains to be a major concern in clinical applications. Therefore, we developed a novel, simple, reproducible, and convenient method for preventing LB formation around NPWT dressings. METHOD: Fifty-three cases of Gustilo type II and III open fractures under NPWT were considered. NPWT was used on every wound after debridement. All patients were divided into a conventional group (27 cases, 33 wounds) and a novel group (26 cases, 27 wounds) based on the difference in the NPWT dressing appearance. A healthy volunteer with intact skin was also included to perform the detailed process of NPWT. LBs occurring on intact skin around the dressings were observed and recorded when the dressing was removed 3 days after the operation. The occurrence of LB formation and wound infection was considered as categorical data and compared between the two groups using a chi-square test. The duration of hospital stay was considered as numerical data and compared between the two groups using two independent t tests. RESULTS: The percentage of occurrence of LB formation around dressings in the conventional group was 27.3%, whereas it was merely 3.7% in the novel group (P = 0.037). The infection incidence rate in the conventional group was 30.3%, whereas that in the novel group was 25.9%; however, no statistical difference was observed between the two groups (P = 0.708). The average duration of hospital stay in the conventional group was 14.39 ± 4.55 days, whereas that in the novel group was 11.04 ± 3.47 days (P = 0.003). CONCLUSION: Thus, changing the NPWT dressing appearance can prevent LB formation around dressings, providing an effective method to improve NPWT application. Modified NPWT dressings also shorten the duration of hospital stay, but do not significantly decrease the incidence of wound infection.


Subject(s)
Negative-Pressure Wound Therapy , Bandages , Blister , Humans , Skin Transplantation , Soft Tissue Injuries , Wound Healing , Wound Infection
19.
Article in English | MEDLINE | ID: mdl-34501643

ABSTRACT

In this study, restorative environment theory and virtual reality (VR) technology were combined to build different 3D dynamic VR interactive scenes. We discuss the effects of a VR restorative environment on the emotional and cognitive recovery of individuals with mild-to-moderate anxiety and depression. First, we built a VR restorative garden scene, divided into four areas: forest, lawn, horticultural planting, and water features. The scene was verified to have a good recovery effect in 26 participants. Then, 195 participants with mild-to-moderate anxiety and depression were selected as experimental subjects. Through psychological testing and EMG (Electromyography) and EEG (Electroencephalography) data feedback, we further explored the differences in the sense of presence in VR restorative scenes and their effect on individual emotional and cognitive recovery. The results showed that (1) both the restorative environment images and the VR scenes had a healing effect (the reduction in negative emotions and the recovery of positive emotions and cognition), with no difference in the subjective feeling of recovery among the different scenes, but the recovery score of the VR urban environment was higher than that of the natural environment (differing from the results in real environments); (2) a high sense of presence can be experienced in different VR scenes, and interactive activities in VR scenes can provide a great presence experience; (3) the recovery effects of VR restorative environment on emotion and self-efficacy are realized through the presence of VR scenes; (4) a VR restorative environment is helpful for the emotional improvement and cognitive recovery of individuals with mild-to-moderate anxiety and depression. VR urban scenes also have good recovery effects. In terms of cognitive recovery, self-efficacy improved significantly. In addition, from the perspective of EEG indicators, the VR restorative scene experience activated the prefrontal lobe, which is conducive to cognitive recovery in individuals with mild-to-moderate anxiety and depression. In terms of emotional improvement, negative emotions were significantly reduced in the different VR scene groups. In conclusion, we further explored ways to help individuals with mild-to-moderate anxiety and depression, in order to promote the development and application of mental health.


Subject(s)
Virtual Reality , Anxiety , Cognition , Depression , Emotions , Humans
20.
Medicine (Baltimore) ; 100(32): e26884, 2021 Aug 13.
Article in English | MEDLINE | ID: mdl-34397908

ABSTRACT

ABSTRACT: High tibial osteotomy (HTO) is a promising surgery that can treat osteoarthritis of the medial septum of the knee. However, the extensive release of soft tissue and the osteotomy gap may produce intraoperative and postoperative bone bleeding. Tranexamic acid (TXA) is an effective blood management strategy, as it competitively inhibits the activation process of plasminogen and prevents fibrinolytic enzymes from degrading fibrin. Therefore, we compared the operative bone bleeding of patients who underwent HTO who received either intravenous (IV) or topical TXA in this research.The medical records of a total of 191 patients (including 72 who received IV TXA, 64 who received topical TXA and 55 control patients) who received open-wedge HTO were retrospectively reviewed from January 2016 to August 2019. There were no obvious demographic differences between the groups. Here, we used independent parameters to assess the efficacy of topical and IV TXA in reducing blood loss.Compared with the IV TXA group, patients receiving topical TXA therapy had greater blood loss (622 ±â€Š231 ml versus 451 ±â€Š231 ml, mean difference 171 mL [95% CI, 87-254]; p < 0.001). The hemoglobin concentration of the IV TXA group was obviously higher than that of the topical medication group. No patients had thromboembolic complications during the entire study period.In our study, it seemed that either IV or topical use of TXA might reduce blood loss after open-wedge HTO, and the blood loss and amount of drainage in the IV TXA group showed huge decreases compared to those in the topical group.


Subject(s)
Blood Loss, Surgical/prevention & control , Osteotomy/methods , Postoperative Hemorrhage/prevention & control , Tibia/surgery , Tranexamic Acid/administration & dosage , Administration, Topical , Adult , Aged , Antifibrinolytic Agents/administration & dosage , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Male , Middle Aged , Retrospective Studies , Treatment Outcome
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