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1.
Int J Rheum Dis ; 27(6): e15204, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831528

ABSTRACT

BACKGROUND: Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study. METHODS: Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively. RESULTS: The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs. CONCLUSION: We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.


Subject(s)
Dermatomyositis , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Vitamin D , Humans , Vitamin D/analogs & derivatives , Vitamin D/blood , Dermatomyositis/genetics , Dermatomyositis/blood , Dermatomyositis/diagnosis , Dermatomyositis/epidemiology , Risk Factors , Genetic Predisposition to Disease , Biomarkers/blood , Risk Assessment , Vitamin D Deficiency/blood , Vitamin D Deficiency/genetics , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiology , Case-Control Studies , Phenotype , Databases, Genetic
2.
Acta Pharm Sin B ; 14(6): 2505-2519, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828154

ABSTRACT

The nucleocapsid protein (NP) plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life. Despite its vital role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assembly and host inflammatory response, it remains an unexplored target for drug development. In this study, we identified a small-molecule compound (ciclopirox) that promotes NP degradation using an FDA-approved library and a drug-screening cell model. Ciclopirox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation. Ciclopirox induced abnormal NP aggregation through indirect interaction, leading to the formation of condensates with higher viscosity and lower mobility. These condensates were subsequently degraded via the autophagy-lysosomal pathway, ultimately resulting in a shortened NP half-life and reduced NP expression. Our results suggest that NP is a potential drug target, and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.

3.
Aging (Albany NY) ; 162024 May 31.
Article in English | MEDLINE | ID: mdl-38829771

ABSTRACT

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

4.
J Child Orthop ; 18(3): 277-286, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831861

ABSTRACT

Purpose: Pediatric pelvic fractures are uncommon. This study aimed to investigate the clinical characteristics of pediatric pelvic fractures requiring hospitalization and analyze their correlation with associated injuries and complications. Methods: Data from 315 pediatric pelvic fracture patients admitted to our hospital from January 2006 to December 2021 were retrospectively analyzed. Sex, age, modified Torode-Zieg classification, abbreviated injury scale score, injury severity score, mortality, and concomitant injuries were analyzed. Results: Of the 285 (90.5%) cases of combined injuries, most injuries occurred in the abdomen (64.8%) and lower extremities (47.6%), followed by the chest (45.4%) and head (34.6%). A total of 78 patients (24.8%) were transferred to the intensive care unit. In total, 94 patients (29.8%) had complications during hospitalization. There were differences based on injury mechanism (p = 0.001), with the highest complication rate in the fall injury group (32 cases (46.4%)). Approximately 51.4% of patients received surgical treatment for problems that were not related to pelvic fractures. Among these, 30.2% necessitated surgical intervention on the lower limbs. Abdominal surgery was necessary in 19.0% of patients. Conclusions: Children who have pelvic fractures frequently require hospitalization due to the presence of severe injuries in other areas of their bodies. IIIB pelvic fractures frequently occur in conjunction with more severe abdominal injuries; therefore, the prompt management of cavity and organ injuries is of particular importance. Blood transfusion and injury severity score were associated risk factors for intensive care unit admission.

5.
Heart Lung ; 67: 53-61, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38701700

ABSTRACT

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

6.
Int J Ophthalmol ; 17(3): 528-536, 2024.
Article in English | MEDLINE | ID: mdl-38721515

ABSTRACT

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

8.
Article in English | MEDLINE | ID: mdl-38779737

ABSTRACT

AIMS: The machine learning-based QSAR modeling procedure, molecular generations, and molecular dynamic simulations were applied to virtually screen the DNA polymerase theta inhibitors. BACKGROUND: The DNA polymerase theta (Polθ or POLQ) is an attractive target for treatments of homologous recombination deficient (such as BRCA deficient) cancers. There are no approved drugs for targeting POLQ, and only one inhibitor is in Phase Ⅱclinical trials; thus, it is necessary to develop novel POLQ inhibitors. OBJECTIVES: To build machine learning models that predict the bioactivities of POLQ inhibitors. To build molecular generation models that generate diverse molecules. To virtually screen the generated molecules by the machine learning models. To analyze the binding modes of the screening results by molecular dynamic simulations. METHODS: In the present work, 325 inhibitors with POLQ polymerase domain bioactivities were Collected. Two machine learning methods, random forest and deep neural network, were used for building the ligand- and structure-based quantitative structure-activity relationship (QSAR) models. The substructure replacement-based method and transfer learning-based deep recurrent neural network method were used for molecular generations. Molecular docking and consensus QSAR models were carried out for virtual screening. The molecular dynamic simulations and MM/GBSA binding free energy calculation and decomposition were used to further analyze the screening results. RESULTS: The MCC values of the best ligand- and structure-based consensus QSAR models reached 0.651 and 0.361 for the test set, respectively. The machine learning-based docking scores had better-predicted ability to distinguish the highly and weakly active poses than the original docking scores. The 96490 molecules were generated by both molecular generation methods, and 10 molecules were retained by virtual screening. Four favorable interactions were concluded by molecular dynamic simulations. CONCLUSION: We hope that the screening results and the binding modes are helpful for designing the highly active POLQ polymerase inhibitors and the models of the molecular design workflow can be used as reliable tools for drug design.

9.
Comput Biol Med ; 177: 108569, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38781640

ABSTRACT

Accurate segmentation of polyps in colonoscopy images has gained significant attention in recent years, given its crucial role in automated colorectal cancer diagnosis. Many existing deep learning-based methods follow a one-stage processing pipeline, often involving feature fusion across different levels or utilizing boundary-related attention mechanisms. Drawing on the success of applying Iterative Feedback Units (IFU) in image polyp segmentation, this paper proposes FlowICBNet by extending the IFU to the domain of video polyp segmentation. By harnessing the unique capabilities of IFU to propagate and refine past segmentation results, our method proves effective in mitigating challenges linked to the inherent limitations of endoscopic imaging, notably the presence of frequent camera shake and frame defocusing. Furthermore, in FlowICBNet, we introduce two pivotal modules: Reference Frame Selection (RFS) and Flow Guided Warping (FGW). These modules play a crucial role in filtering and selecting the most suitable historical reference frames for the task at hand. The experimental results on a large video polyp segmentation dataset demonstrate that our method can significantly outperform state-of-the-art methods by notable margins achieving an average metrics improvement of 7.5% on SUN-SEG-Easy and 7.4% on SUN-SEG-Hard. Our code is available at https://github.com/eraserNut/ICBNet.

10.
Cancer Lett ; 592: 216953, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38729557

ABSTRACT

TGFBR2, a key regulator of the TGFß signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin ß5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFß signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFß signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies.


Subject(s)
Endosomes , Epithelial-Mesenchymal Transition , Receptor, Transforming Growth Factor-beta Type II , Signal Transduction , Stomach Neoplasms , Receptor, Transforming Growth Factor-beta Type II/genetics , Receptor, Transforming Growth Factor-beta Type II/metabolism , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Humans , Endosomes/metabolism , Animals , Cell Line, Tumor , Integrin beta Chains/metabolism , Integrin beta Chains/genetics , Sorting Nexins/genetics , Sorting Nexins/metabolism , Mice , Neoplasm Metastasis , Gene Expression Regulation, Neoplastic , Transforming Growth Factor beta/metabolism
11.
J Colloid Interface Sci ; 669: 275-282, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38718581

ABSTRACT

The triboelectric nanogenerator (TENG) of natural biomaterials is a new type of energy harvesting device and can be used as a self-powered sensor, which has received extensive research and attention. In this paper, based on the biocompatibility of chitosan and chondroitin sulfate, ZnO-modified chitosan/chondroitin sulfate/ZnO TENG was prepared for research on wearable devices and sustainable power supply devices. This study employs molecular dynamics to compute the interaction energy between chitosan and ZnO molecules. Theoretical calculations have unequivocally substantiated the occurrence of a binding interaction between these two molecular entities. The effect of ZnO on chitosan/chondroitin sulfate morphology was investigated by atomic force microscopy. The chitosan/chondroitin sulfate/ZnO TENG has high flexibility and electrical output performance. It can reach 105 V and 3.3 µA of open-circuit voltage and short-circuit current. Chitosan/chondroitin Sulfate/ZnO TENG successfully converts the mechanical energy of human motion into electrical energy. Strong electrical signals are exhibited when making fists and waving fingers and wrists. The TENG is a self-powered source and lights up 70 blue light-emitting diodes (LEDs). The chitosan/chondroitin sulfate/ZnO TENG has demonstrated its capabilities in energy harvesting and wearable self-powered sensors.

12.
BMC Musculoskelet Disord ; 25(1): 389, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762453

ABSTRACT

BACKGROUND: Several methods have been used for the treatment of pediatric distal femoral fractures, such as elastic stable intramedullary nail (ESIN), external fixator (EF) and plate osteosynthesis, but there has been no consensus about the optimal method. The purpose of this study was to compare the clinical outcome between EF and ESIN techniques used in metaphyseal-diaphyseal junction (MDJ) fractures of the pediatric distal femur. METHODS: We retrospectively analyzed operatively treated MDJ fractures of pediatric distal femur between January 2015 and January 2022. Patient charts were reviewed for demographics, injury and data of radiography. All of the patients were divided into EF and ESIN groups according to the operation techniques. Malalignment was defined as more than 5 degrees of angular deformity in either plane. Clinical outcomes were measured by Flynn scoring system. RESULTS: Thirty-eight patients were included in this study, among which, 23 were treated with EF, and 15 with ESIN. The mean follow-up time was 18 months (12-24 months). At the final follow-up, all of the fractures were healed. Although there were no statistical differences between the two groups in demographic data, length of stay, estimated blood loss (EBL), rate of open reduction, time to fracture healing and Flynn score, the EF was superior to ESIN in operative time, fluoroscopic exposure and time to partial weight-bearing. The EF group had a significantly higher rate of skin irritation, while the ESIN had a significantly higher rate of malalignment. CONCLUSION: EF and ESIN are both effective methods in the treatment of MDJ fractures of the pediatric distal femur. ESIN is associated with lower rates of skin irritation. However, EF technique has the advantages of shorter operative time, reduced fluoroscopic exposure, and shorter time to partial weight-bearing, as well as lower incidence of malalignment. LEVEL OF EVIDENCE: Level III.


Subject(s)
Bone Nails , External Fixators , Femoral Fractures , Fracture Fixation, Intramedullary , Humans , Female , Male , Retrospective Studies , Femoral Fractures/surgery , Femoral Fractures/diagnostic imaging , Child , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/methods , Treatment Outcome , Case-Control Studies , Fracture Healing , Diaphyses/injuries , Diaphyses/surgery , Diaphyses/diagnostic imaging , Child, Preschool , Follow-Up Studies , Adolescent , Femur/surgery , Femur/diagnostic imaging
13.
Cancer Cell ; 42(5): 727-731, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38701791

ABSTRACT

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/immunology , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Immunotherapy/methods , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Biomarkers, Tumor/genetics , Neoadjuvant Therapy/methods , Clinical Trials as Topic
14.
EMBO J ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806659

ABSTRACT

Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.

15.
Nanomicro Lett ; 16(1): 198, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758464

ABSTRACT

Vertically oriented carbon structures constructed from low-dimensional carbon materials are ideal frameworks for high-performance thermal interface materials (TIMs). However, improving the interfacial heat-transfer efficiency of vertically oriented carbon structures is a challenging task. Herein, an orthotropic three-dimensional (3D) hybrid carbon network (VSCG) is fabricated by depositing vertically aligned carbon nanotubes (VACNTs) on the surface of a horizontally oriented graphene film (HOGF). The interfacial interaction between the VACNTs and HOGF is then optimized through an annealing strategy. After regulating the orientation structure of the VACNTs and filling the VSCG with polydimethylsiloxane (PDMS), VSCG/PDMS composites with excellent 3D thermal conductive properties are obtained. The highest in-plane and through-plane thermal conductivities of the composites are 113.61 and 24.37 W m-1 K-1, respectively. The high contact area of HOGF and good compressibility of VACNTs imbue the VSCG/PDMS composite with low thermal resistance. In addition, the interfacial heat-transfer efficiency of VSCG/PDMS composite in the TIM performance was improved by 71.3% compared to that of a state-of-the-art thermal pad. This new structural design can potentially realize high-performance TIMs that meet the need for high thermal conductivity and low contact thermal resistance in interfacial heat-transfer processes.

16.
Ann Transplant ; 29: e943281, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38803088

ABSTRACT

BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.


Subject(s)
Anesthetics, Inhalation , Dexmedetomidine , Emergence Delirium , Remifentanil , Sevoflurane , Humans , Dexmedetomidine/administration & dosage , Dexmedetomidine/therapeutic use , Remifentanil/administration & dosage , Remifentanil/therapeutic use , Sevoflurane/administration & dosage , Female , Male , Anesthetics, Inhalation/administration & dosage , Anesthetics, Inhalation/adverse effects , Child, Preschool , Emergence Delirium/prevention & control , Emergence Delirium/etiology , Emergence Delirium/epidemiology , Prospective Studies , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/therapeutic use , Infant , Child , Psychomotor Agitation/prevention & control , Psychomotor Agitation/etiology , Liver/surgery , Anesthesia Recovery Period , Piperidines/administration & dosage , Piperidines/therapeutic use , Piperidines/adverse effects , Double-Blind Method , Drug Therapy, Combination , Methyl Ethers/administration & dosage , Methyl Ethers/adverse effects , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use
17.
Sci Rep ; 14(1): 12419, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816461

ABSTRACT

This article conducts a comprehensive study on the activation characteristics of faults in the mine and analyzes the distribution patterns of the original rock stress field. Through quantitative research and analysis, we determine the partitioning characteristics of tectonic stress in the mine field under the dual effects of fault activation and original rock stress. The study also reveals the significant impact of different fault activation characteristics and different tectonic stress partitions on the stability of roadway surrounding rock. Using the Mohr-Coulomb strength criterion as a foundation, we investigate the mechanisms of fault activation and establish a mathematical model for fuzzy comprehensive evaluation. This model enables us to determine the strength level of fault activation in coal seam 9 of the Limin coal mine and construct a geological structure model. It has realized the transformation of fault activation degree from qualitative evaluation to quantitative evaluation. The stress state analysis software is used to draw the division of tectonic stress dangerous areas under the synergistic effect of fault activation and original rock stress. We then analyze the impact on the stability of roadway surrounding rock in these different hazardous areas. Utilizing the fuzzy comprehensive evaluation method, we take into account the impact of faults on the distribution characteristics of stress fields and the stability of roadway surrounding rock. This approach enables us to more accurately and comprehensively determine the hazardous areas of tectonic stress in the mine field under the dual effects of faults and original rock stress.

18.
Sci Rep ; 14(1): 12161, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38802510

ABSTRACT

To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered.


Subject(s)
Nasal Cavity , Humans , Nasal Cavity/physiology , Nasal Cavity/diagnostic imaging , Computer Simulation , Hydrodynamics , Tomography, X-Ray Computed , Male , Adult , Respiration , Airway Resistance/physiology
19.
Article in English | MEDLINE | ID: mdl-38813696

ABSTRACT

BACKGROUND: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. METHODS: We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. RESULTS: Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 and SEMA3B were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. CONCLUSIONS: We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.

20.
Front Pharmacol ; 15: 1396975, 2024.
Article in English | MEDLINE | ID: mdl-38725666

ABSTRACT

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

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