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1.
Article in English | MEDLINE | ID: mdl-39394730

ABSTRACT

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.

2.
Plant Cell Environ ; 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39403855

ABSTRACT

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

3.
J Inflamm Res ; 17: 6743-6764, 2024.
Article in English | MEDLINE | ID: mdl-39345892

ABSTRACT

Purpose: Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types. Patients and Methods: The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU's influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples. Results: This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers. Conclusion: This comprehensive pan-cancer analysis underscores CALU's critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.

4.
Sci Rep ; 14(1): 22058, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39333264

ABSTRACT

LiDAR systems that rely on classical signals are susceptible to intercept-and-recent spoofing attacks, where a target attempts to avoid detection. To address this vulnerability, we propose a quantum-secured LiDAR protocol that utilizes Gaussian modulated coherent states for both range determination and spoofing attack detection. By leveraging the Gaussian nature of the signals, the LiDAR system can accurately determine the range of the target through cross-correlation analysis. Additionally, by estimating the excess noise of the LiDAR system, the spoofing attack performed by the target can be detected, as it can introduce additional noise to the signals. We have developed a model for target ranging and security check, and conducted numerical simulations to evaluate the Receiver Operating Characteristic (ROC) of the LiDAR system. The results indicate that an intercept-and-recent spoofing attack can be detected with a high probability at a low false-alarm rate. Furthermore, the proposed method can be implemented using currently available technology, highlighting its feasibility and practicality in real-world applications.

5.
Ear Nose Throat J ; : 1455613241271635, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39331956

ABSTRACT

Objectives: To explore the risk factors of early postoperative taste disturbance (EPTD) after type I endoscopic tympanoplasty and operative modification strategies to improve taste disturbance. Methods: This was a controlled study. One hundred and twenty-four patients who underwent type I endoscopic tympanoplasty with tragal cartilage graft were separated evenly into control and modified groups. The full-thickness tragus cartilage graft was placed close to the bony annulus to ensure drum integrity in the control group, and in the modified group, the cartilage graft was not in contact with the posterior-superior bony annulus, and the inferior-posterior of the scutum. Univariate and multivariate models were used to analyze the possible factors affecting EPTD and the prognosis of taste recovery. Results: The incidence of EPTD was significantly lower in the modification group (24.19%) than in the control group (56.45%) (OR: 4.24, 95% CI: 1.93-9.33, P < .001). Surgical manipulation of the chorda tympani nerve resulted in a higher incidence of EPTD (OR: 2.43; 95% CI: 1.06-5.57, P = .035). The size of the graft did not affect taste disturbance. No difference in the taste recovery rate was observed between the control and test groups (Z = -1.57, P = .116) after 3 months. The recovery rate of patients with manipulated chorda tympani nerves was still lower than that of patients without at 3 months (Z = -2.74, P = .006). Conclusion: Modified surgery and reduced manipulation of the chorda tympani nerve effectively reduce EPTD. Manipulated chorda tympani nerves may have a persistent effect on taste recovery.

6.
Molecules ; 29(18)2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39339344

ABSTRACT

The traditional Mongolian medicine Erdun-Uril is a conventional combination of 29 herbs commonly used for the treatment of cerebrovascular ailments. It has the effects of reducing inflammation, counteracting oxidative stress, and averting strokes caused by persistent cerebral hypoperfusion. Prior research on Erdun-Uril has predominantly concentrated on its pharmacodynamics and mechanism of action; however, there has been a lack of systematic and comprehensive investigation into its chemical constituents. Therefore, it is crucial to establish an efficient and rapid method for evaluating the chemical constituents of Erdun-Uril. In this study, Erdun-Uril was investigated using UHPLC-Q-Exactive Orbitrap MS combined with parallel reaction monitoring for the first time. Eventually, a total of 237 compounds, including 76 flavonoids, 68 phenolic compounds, 19 alkaloids, 7 amino acids, etc., were identified based on the chromatographic retention time, bibliography data, MS/MS2 information, neutral loss fragments (NLFs), and diagnostic fragment ions (DFIs). And of these, 225 were reported for the first time in this study. This new discovery of these complex components would provide a reliable theoretical basis for the development of pharmacodynamics and quality standards of the Mongolian medicine Erdun-Uril.


Subject(s)
Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods , Medicine, Mongolian Traditional , Flavonoids/analysis , Flavonoids/chemistry , Alkaloids/analysis , Alkaloids/chemistry , Phenols/analysis , Phenols/chemistry , Tandem Mass Spectrometry/methods
7.
Front Immunol ; 15: 1419126, 2024.
Article in English | MEDLINE | ID: mdl-39234248

ABSTRACT

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.


Subject(s)
Biomarkers, Tumor , DNA Ligase ATP , Machine Learning , Single-Cell Analysis , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Humans , Single-Cell Analysis/methods , Biomarkers, Tumor/genetics , DNA Ligase ATP/genetics , DNA Ligase ATP/metabolism , Prognosis , Male , Gene Expression Regulation, Neoplastic , Female , Gene Regulatory Networks , Protein Interaction Maps , Middle Aged , Gene Expression Profiling , Computational Biology/methods , Cell Line, Tumor , Aged
8.
Eur J Pharmacol ; 983: 176905, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39154828

ABSTRACT

The gut microbiome-metabolites-kidney axis is a potential target for treating diabetic kidney disease (DKD). Our previous study found that Liraglutide attenuated DKD in rats by decreasing renal tubular ectopic lipid deposition (ELD) and serum metabolites levels, including L-5-Oxoproline (5-OP). However, the response of gut microbiome-metabolites-kidney axis to Liraglutide in DKD rats and the effect of 5-OP on ELD remain unknown. In this study, Sprague-Dawley rats were used as an animal model of DKD. They were subjected to a high fat diet, streptozotocin and uninephrectomy, followed by Liraglutide treatment (0.4 mg/kg d). Additionally, HK-2 cells were incubated with 30 mM glucose and 200 µM palmitate for 24h, and exposed to different concentrations of 5-OP. In DKD rats, Liraglutide dramatically improved the renal tubule structure. It increased the Simpson index (F = 4.487, p = 0.035) and reduced the Actinobacteria-to-Bacteroidetes ratio (F = 6.189, p = 0.014). At the genus level, Liraglutide increased the relative abundance of Clostridium, Oscillospira, Sarcina, SMB53, and 02d06 while decreasing that of Allobaculum. Meanwhile, 13 metabolites were significantly altered after Liraglutide treatment. Multi-omics analysis found that 5-OP levels were positively correlated with Clostridium abundance but negatively correlated with renal injury related indicators. In HK-2 cells, 5-OP significantly reduced the ELD in a dose-dependent manner through inhibiting the expression of SREBP1 and FAS. Overall, the renoprotective effect of Liraglutide in DKD rats is linked to the improvement of the gut microbiota composition and increased serum 5-OP levels, which may reduce ELD in renal tubular cells by lowering lipid synthesis.


Subject(s)
Diabetic Nephropathies , Gastrointestinal Microbiome , Liraglutide , Rats, Sprague-Dawley , Animals , Liraglutide/pharmacology , Liraglutide/therapeutic use , Gastrointestinal Microbiome/drug effects , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/pathology , Male , Rats , Humans , Cell Line , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Kidney Tubules/drug effects , Kidney Tubules/pathology , Kidney Tubules/metabolism
9.
Emerg Microbes Infect ; 13(1): 2389095, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39101691

ABSTRACT

Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Disulfides , Hemagglutinin Glycoproteins, Influenza Virus , Influenza Vaccines , Mice, Inbred BALB C , Orthomyxoviridae Infections , Animals , Influenza Vaccines/immunology , Influenza Vaccines/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Antibodies, Viral/immunology , Mice , Disulfides/chemistry , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Antibodies, Neutralizing/immunology , Female , Cross Protection/immunology , Cross Reactions , Humans , Influenza, Human/prevention & control , Influenza, Human/immunology , Influenza, Human/virology , Epitopes/immunology , Epitopes/genetics , Epitopes/chemistry , Protein Multimerization , Influenza B virus/immunology , Influenza B virus/genetics , Influenza B virus/chemistry
10.
Natl Sci Rev ; 11(8): nwae237, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39206180

ABSTRACT

An increase in atmospheric pO2 has been proposed as a trigger for the Cambrian Explosion at ∼539-514 Ma but the mechanistic linkage remains unclear. To gain insights into marine habitability for the Cambrian Explosion, we analysed excess Ba contents (Baexcess) and isotope compositions (δ138Baexcess) of ∼521-Myr-old metalliferous black shales in South China. The δ138Baexcess values vary within a large range and show a negative logarithmic correlation with Baexcess, suggesting a major (>99%) drawdown of oceanic Ba inventory via barite precipitation. Spatial variations in Baexcess and δ138Baexcess indicate that Ba removal was driven by sulfate availability that was ultimately derived from the upwelling of deep seawaters. Global oceanic oxygenation across the Ediacaran-Cambrian transition may have increased the sulfate reservoir via oxidation of sulfide and concurrently decreased the Ba reservoir by barite precipitation. The removal of both H2S and Ba that are deleterious to animals could have improved marine habitability for early animals.

11.
Zhonghua Nan Ke Xue ; 30(5): 424-429, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-39210491

ABSTRACT

OBJECTIVE: To explore the perioperative nursing methods of autologous dermal transplantation for penile girth enhancement combined with penile lengthening surgery. METHODS: Summarize the perioperative nursing data of 5 patients with small penis who underwent autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery. RESULTS: After comprehensive perioperative nursing, all 5 patients recovered well after the surgery. The preoperative APPSSI scores of the patients were 4.60±0.48, which were all less than 6 points. The postoperative APPSSI scores at 2 months, 6 months, and 12 months were 9-12 (10.6±1.02), 10-12 (11.2±0.98), and 10-12 (11.2±0.98) respectively, showing satisfaction with the surgical outcomes. There was a statistically significant difference compared to the preoperative APPSSI scores (ï¼°<0.05). The preoperative SAS scores were 45-58 (52.2±4.35), and the SAS scores at 2 months, 6 months, and 12 months postoperatively were 31-40 (34.2±3.31), 30-41 (35.8±3.65), and 33-40 (35.6±2.33) respectively, indicating a reduction in anxiety levels after the surgery, with a statistically significant difference compared to the preoperative SAS scores (P<0.05). The preoperative IIEF-5 scores were 7-15 (10.4±2.87), and the IIEF-5 scores at 2 months, 6 months, and 1 year postoperatively were 16-24 (19.8±2.71), 18-25 (21.2±2.48), and 18-24 (20.8±2.39) respectively, showing a significant improvement postoperatively, with statistical significance (P<0.05). The preoperative NPTR examination showed a sustained erection time of 18-25 (21.2±2.59) minutes, and the NPTR examination at 2 months, 6 months, and 1 year postoperatively showed sustained erection times of 18-24 (21.8±2.28), 20-25 (23.4±2.30), and 24-27 (25.4±1.14) minutes respectively. There was no statistically significant difference in the sustained erection time at 2 months and 6 months postoperatively compared to preoperative NPTR examination, but there was a statistically significant difference at 12 months postoperatively (P<0.01). CONCLUSION: Comprehensive perioperative nursing is an important factor in achieving high satisfaction with the surgery, promoting postoperative recovery, and improving the quality of sexual life for patients undergoing autologous groin dermal transplantation for penile girth enhancement combined with penile lengthening surgery.


Subject(s)
Penis , Skin Transplantation , Transplantation, Autologous , Humans , Male , Penis/surgery , Skin Transplantation/methods , Plastic Surgery Procedures/methods , Dermis/transplantation , Treatment Outcome , Adult , Perioperative Care
12.
BMC Bioinformatics ; 25(1): 282, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198740

ABSTRACT

BACKGROUND: Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure-function relationship, and is also of great interest in protein engineering and pharmaceutical design. RESULTS: Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. CONCLUSION: Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.


Subject(s)
Mutation , Protein Stability , Proteins , Proteins/chemistry , Proteins/genetics , Proteins/metabolism , Myoglobin/chemistry , Myoglobin/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/chemistry , Tumor Suppressor Protein p53/metabolism , Computational Biology/methods , Deep Learning , Supervised Machine Learning , Databases, Protein , Protein Conformation
13.
Ear Nose Throat J ; : 1455613241266492, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39183573

ABSTRACT

Objectives: To avoid postoperatively acquired cholesteatoma, whether there was any squamous epithelial tissues residue around the tip of the malleus handle, and the need to remove these tissues were explored. Methods: This prospective study enrolled 197 patients who underwent endoscopic tympanoplasty. A postoperative pathological evaluation of the tissue around the tip of the malleus handle was performed to determine the presence of squamous epithelium. Analyzed correlation of epithelial remnants with exposure of malleus handle and microbial infection of middle ear. Results: The detection rate of squamous epithelial retention around the tip of the malleus handle differed significantly among patients with adhesive otitis media (AdOM), acquired cholesteatoma, and chronic suppurative otitis media (CSOM). The detection rate was significantly higher in the acquired cholesteatoma group than in the AdOM and CSOM groups (P < .001). The rate of squamous epithelial retention around the tip of the malleus handle was not significantly associated with microbial infection of the middle ear, the surgical side (P = .672), dry or wet ear status (P = .702), or exposure of the malleus handle (P = .06). Conclusions: In patients with acquired cholesteatoma, AdOM, or COM with severe tympanic sclerosis, the tissue around the tip of the malleus handle should be removed completely. For patients with simple COM, that is, without tympanic sclerosis or keratinizing stratified squamous epithelium at the edge of the perforation, the tissue can be retained.

14.
Discov Oncol ; 15(1): 348, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134820

ABSTRACT

This review explores the intricate roles of metal ions-iron, copper, zinc, and selenium-in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

15.
Article in Chinese | MEDLINE | ID: mdl-39212067

ABSTRACT

Objective To investigate the effects of sakuranetin (SK) on motor functions in the mouse model of spinal cord injury (SCI) and decipher the mechanism.Methods Fifty-four C57BL/6J mice were randomized into sham,SCI,and SK groups.The mice in the sham group underwent only laminectomy at T9,while those in the SCI and SK groups were subjected to spinal cord contusion injury at T9.Behavioral tests were conducted at different time points after surgery to evaluate the motor functions of mice in each group.The pathological changes in the tissue were observed to assess the extent of SCI in each group.The role and mechanism of SK in SCI were predicted by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses.Reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence were employed to evaluate the inflammation and activation of microglia in SCI mice.BV2 cells in vitro were classified into control (Con),lipopolysaccharide (LPS),and LPS+SK groups.The effects of SK intervention on the release of inflammatory cytokines and the activation of BV2 cells were evaluated.Furthermore,the phosphatidylinositol-3-kinase(PI3K)/protein kinase B (AKT) signaling pathway activator insulin-like growth factor-1 (IGF-1) was used to treat the SK-induced BV2 cells in vitro (SK+IGF-1 group),and SK was used to treat the IGF-1-induced BV2 cells in vitro (IGF-1+SK group).Western blotting was conducted for molecular mechanism validation.Results Behavioral tests and histological staining results showed that compared with the SCI group,the SK group exhibited improved motor abilities and reduced area of damage in the spinal cord tissue (all P<0.001).The GO enrichment analysis predicted that SK may be involved in the inflammation following SCI.The KEGG enrichment analysis predicted that SK regulated the PI3K/Akt pathway to exert the neuroprotective effect.The results from in vitro and in vivo experiments showed that SK lowered the levels of tumor necrosis factor-α,interleukin-6,and interleukin-1ß and inhibited the activation of microglia (all P<0.05).The results of Western blotting showed that SK down-regulated the phosphorylation levels of PI3K and Akt (all P<0.001) and inhibited the IGF-1-induced elevation of PI3K and Akt phosphorylation levels (all P<0.001).Conversely,IGF-1 had the opposite effects (P=0.001,P<0.001).The results of reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence showed that the SK+IGF-1 group had higher levels of inflammatory cytokines and more activated microglia than the SK group(all P<0.05).Conclusion SK may suppress the activation of the PI3K/Akt pathway to inhibit the inflammation mediated by SCI-induced activation of microglia,ameliorate the pathological damage of the spinal cord tissue,and promote the recovery of motor functions in SCI mice.

16.
Sci Adv ; 10(29): eado8471, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39018410

ABSTRACT

Click chemistry offers various applications through efficient bioorthogonal reactions. In bioimaging, pretargeting strategies have often been used, using click reactions between molecular probes with a click handle and reporter molecules that make them observable. Recent efforts have integrated tissue-clearing techniques with fluorescent labeling through click chemistry, allowing high-resolution three-dimensional fluorescence imaging. Nevertheless, these techniques have faced a challenge in limited staining depth, confining their use to imaging tissue sections or partial organs. In this study, we introduce Click3D, a method for thoroughly staining whole organs using click chemistry. We identified click reaction conditions that improve staining depth with our custom-developed assay. The Click3D protocol exhibits a greater staining depth compared to conventional methods. Using Click3D, we have successfully achieved whole-kidney imaging of nascent RNA and whole-tumor imaging of hypoxia. We have also accomplished whole-brain imaging of hypoxia by using the clickable hypoxia probe, which has a small size and, therefore, has high permeability to cross the blood-brain barrier.


Subject(s)
Click Chemistry , Imaging, Three-Dimensional , Optical Imaging , Click Chemistry/methods , Animals , Imaging, Three-Dimensional/methods , Mice , Optical Imaging/methods , Humans , Brain/diagnostic imaging , Fluorescent Dyes/chemistry , Kidney/diagnostic imaging , Cell Line, Tumor
17.
Mol Inform ; : e202300336, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39031899

ABSTRACT

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

18.
Orthop Surg ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39077885

ABSTRACT

OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.

19.
Nanomicro Lett ; 16(1): 253, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39048856

ABSTRACT

The unique and interesting physical and chemical properties of metal-organic framework (MOF) materials have recently attracted extensive attention in a new generation of photoelectric applications. In this review, we summarized and discussed the research progress on MOF-based photodetectors. The methods of preparing MOF-based photodetectors and various types of MOF single crystals and thin film as well as MOF composites are introduced in details. Additionally, the photodetectors applications for X-ray, ultraviolet and infrared light, biological detectors, and circularly polarized light photodetectors are discussed. Furthermore, summaries and challenges are provided for this important research field.

20.
Heliyon ; 10(12): e32595, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38988518

ABSTRACT

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

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