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1.
Int Immunopharmacol ; 142(Pt A): 113069, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39241520

ABSTRACT

Schisandra chinensis, a traditional Chinese medicine, has been widely applied in China to treat diabetes and its complications. The aim of this study was to discover the active compounds and explain related molecular mechanism contributing to the anti-diabetic effect of Schisandra chinensis. Herein, the therapeutic effects of Schisandra chinensis extracts on type 2 diabetes mellitus (T2DM) were firstly confirmed in vivo. Subsequently, various lignans were isolated from Schisandra chinensis and tested for hypoglycemic activity in palmitic acid-induced insulin-resistant HepG2 (IR-HepG2) cells. Among these lignans, R-biar-(7S,8R)-6,7,8,9-tetrahydro-1,2,3,12,13,14-hexamethoxy-7,8-dimethyl-7-dibenzo [a, c] cyclooctenol (compound 2) and Gomisin A (compound 4) were identified significantly increased the glucose consumption in IR-HepG2 cells. Meanwhile, compounds 2 and 4 activated the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Ak strain transforming (AKT) pathway, which regulates glucose transporter 2 (GLUT2) and glucose-6-phosphatase (G6Pase), essential for gluconeogenesis and glucose uptake. These compounds also inhibited the nuclear factor-κB (NF-κB) signaling pathway, reducing interleukin-6 (IL-6) levels. Importantly, the hypoglycemic effects of compounds 2 and 4 were diminished after Toll-like receptor 4 (TLR4) knockdown. Cellular thermal shift assays confirmed increased TLR4 protein stability upon treatment with these compounds, indicating direct binding to TLR4. Furthermore, TLR4 knockdown reversed the effects of compounds 2 and 4 on the NF-κB and IRS-1/PI3K/AKT pathways. Taken together, compounds 2 and 4 alleviate IR by targeting TLR4, thereby modulating the NF-κB and IRS-1/PI3K/AKT pathways. These findings suggest that compounds 2 and 4 could be developed as therapeutic agents for T2DM.

2.
Chem Sci ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39296993

ABSTRACT

A C-H functionalizing annulation reaction of boron-doped polycyclic aromatic hydrocarbons (PAHs) with alkynes is described. This metal-free π-extension provides a new synthetic route to fusion atom B-doped polycyclic aromatic hydrocarbons (PAHs) that is demonstrated with the synthesis of a family of new, functionalized, structurally constrained 6a,15a-diborabenzo[tuv]naphtho[2,1-b]picenes. These annulation products exhibit deep LUMO energy levels, strong visible-range absorptions, and sterically accessible π-systems that can adopt herringbone or π-stacked solid-state structures based on choice of substituents. From regioselectivity and DFT calculations, we propose an annulation mechanism involving intramolecular electrophilic aromatic substitution of a zwitterionic intermediate.

3.
J Cell Mol Med ; 28(15): e18589, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39135202

ABSTRACT

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.


Subject(s)
Endoplasmic Reticulum Stress , Inflammation , Lipopolysaccharides , Protein Serine-Threonine Kinases , Signal Transduction , Solute Carrier Family 12, Member 2 , Humans , Protein Serine-Threonine Kinases/metabolism , Endoplasmic Reticulum Stress/drug effects , A549 Cells , Inflammation/drug therapy , Inflammation/pathology , Inflammation/metabolism , Solute Carrier Family 12, Member 2/metabolism , Solute Carrier Family 12, Member 2/genetics , Signal Transduction/drug effects , Apoptosis/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Plant Extracts/pharmacology , Cell Survival/drug effects , Cytokines/metabolism , Anti-Inflammatory Agents/pharmacology
4.
Materials (Basel) ; 17(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39124357

ABSTRACT

In this study, to improve the fatigue strength of the LDED (laser-directed energy deposition) 316L stainless steel, an in situ ultrasonic rolling technology is developed to assist the laser-directed energy deposition process (LDED-UR). The microstructural characteristics and fatigue behavior are comprehensively discussed. The results show that the average size of pores of the LDED-UR alloy is about 10.2 µm, which is much smaller than that of the LDED alloy (34.1 µm). Meanwhile, the density of the LDED alloy is also enhanced from 98.26% to 99.27% via the in situ ultrasonic rolling. With the application of the in situ ultrasonic rolling, the grains are transformed into fully equiaxed grains, and their average grain size is greatly reduced from 84.56 µm to 26.93 µm. The fatigue limit of the LDED-UR alloy is increased by 29% from 210 MPa (LDED alloy) to 270 MPa, which can be ascribed to the decreased porosity and the fine grains. In particular, the crack initiation site of the LDED alloy is located at the surfaces, while it is nucleated from the sub-surface for the LDED-UR alloy. This is mainly attributed to the compression residual stress induced by the in situ ultrasonic rolling. This research offers a valuable understanding of the failure mechanisms in additively manufactured metals, guiding the development of effective strategies to improve their fatigue threshold under severe operating conditions.

5.
J Neurosci Methods ; 411: 110251, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39151656

ABSTRACT

BACKGROUND: Electroencephalography (EEG) and electrocorticography (ECoG) recordings have been used to decode finger movements by analyzing brain activity. Traditional methods focused on single bandpass power changes for movement decoding, utilizing machine learning models requiring manual feature extraction. NEW METHOD: This study introduces a 3D convolutional neural network (3D-CNN) model to decode finger movements using ECoG data. The model employs adaptive, explainable AI (xAI) techniques to interpret the physiological relevance of brain signals. ECoG signals from epilepsy patients during awake craniotomy were processed to extract power spectral density across multiple frequency bands. These data formed a 3D matrix used to train the 3D-CNN to predict finger trajectories. RESULTS: The 3D-CNN model showed significant accuracy in predicting finger movements, with root-mean-square error (RMSE) values of 0.26-0.38 for single finger movements and 0.20-0.24 for combined movements. Explainable AI techniques, Grad-CAM and SHAP, identified the high gamma (HG) band as crucial for movement prediction, showing specific cortical regions involved in different finger movements. These findings highlighted the physiological significance of the HG band in motor control. COMPARISON WITH EXISTING METHODS: The 3D-CNN model outperformed traditional machine learning approaches by effectively capturing spatial and temporal patterns in ECoG data. The use of xAI techniques provided clearer insights into the model's decision-making process, unlike the "black box" nature of standard deep learning models. CONCLUSIONS: The proposed 3D-CNN model, combined with xAI methods, enhances the decoding accuracy of finger movements from ECoG data. This approach offers a more efficient and interpretable solution for brain-computer interface (BCI) applications, emphasizing the HG band's role in motor control.


Subject(s)
Electrocorticography , Fingers , Movement , Neural Networks, Computer , Humans , Fingers/physiology , Electrocorticography/methods , Movement/physiology , Adult , Male , Female , Epilepsy/physiopathology , Young Adult , Machine Learning , Signal Processing, Computer-Assisted
6.
Drugs R D ; 24(2): 275-283, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39042293

ABSTRACT

BACKGROUND AND OBJECTIVE: Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. METHODS: A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) and the maximum observed concentration (Cmax). RESULTS: A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0-t and Cmax of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80-125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. CONCLUSIONS: Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. CLINICAL TRIALS REGISTRATION: This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.


Subject(s)
Capsules , Cross-Over Studies , Delayed-Action Preparations , Healthy Volunteers , Therapeutic Equivalency , Venlafaxine Hydrochloride , Humans , Venlafaxine Hydrochloride/pharmacokinetics , Venlafaxine Hydrochloride/administration & dosage , Venlafaxine Hydrochloride/adverse effects , Male , Adult , Delayed-Action Preparations/pharmacokinetics , Female , Young Adult , Area Under Curve , Drugs, Generic/pharmacokinetics , Drugs, Generic/administration & dosage , Drugs, Generic/adverse effects , Asian People , China , Middle Aged , East Asian People
7.
Materials (Basel) ; 17(14)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39063779

ABSTRACT

This paper introduces a novel method for preparing high-performance, metal-containing carbon foam wave-absorbing materials. The process involves foaming glucose through catalysis by transition metals followed by high-temperature pyrolysis. The resulting carbon foam materials exhibit a highly porous structure, which is essential for their wave-absorption properties. Notably, at a thickness of 2.0 mm, the glucose-derived carbon foam composite catalyzed by Fe and Co (GCF-CoFe) achieved a minimum reflection loss (RLmin) of -51.4 dB at 15.11 GHz, along with an effective absorption bandwidth (EAB) of 5.20 GHz, spanning from 12.80 GHz to 18.00 GHz. These impressive performance metrics indicate that this approach offers a promising pathway for developing low-density, efficient carbon foam materials for wave-absorption applications. This advancement has significant implications for fields requiring effective electromagnetic interference (EMI) shielding, stealth technology, and other related applications, potentially leading to more efficient and lightweight solutions.

8.
Nanoscale ; 16(30): 14213-14246, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39021117

ABSTRACT

Cancer is a major health concern due to its high incidence and mortality rates. Advances in cancer research, particularly in artificial intelligence (AI) and deep learning, have shown significant progress. The swift evolution of AI in healthcare, especially in tools like computer-aided diagnosis, has the potential to revolutionize early cancer detection. This technology offers improved speed, accuracy, and sensitivity, bringing a transformative impact on cancer diagnosis, treatment, and management. This paper provides a concise overview of the application of artificial intelligence in the realms of medicine and nanomedicine, with a specific emphasis on the significance and challenges associated with cancer diagnosis. It explores the pivotal role of AI in cancer diagnosis, leveraging structured, unstructured, and multimodal fusion data. Additionally, the article delves into the applications of AI in nanomedicine sensors and nano-oncology drugs. The fundamentals of deep learning and convolutional neural networks are clarified, underscoring their relevance to AI-driven cancer diagnosis. A comparative analysis is presented, highlighting the accuracy and efficiency of traditional methods juxtaposed with AI-based approaches. The discussion not only assesses the current state of AI in cancer diagnosis but also delves into the challenges faced by AI in this context. Furthermore, the article envisions the future development direction and potential application of artificial intelligence in cancer diagnosis, offering a hopeful prospect for enhanced cancer detection and improved patient prognosis.


Subject(s)
Artificial Intelligence , Deep Learning , Nanomedicine , Neoplasms , Humans , Neoplasms/diagnosis , Diagnosis, Computer-Assisted/methods , Neural Networks, Computer
9.
Phytochemistry ; 226: 114209, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38972439

ABSTRACT

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 µM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.


Subject(s)
Gentiana , Glycosides , Hypolipidemic Agents , Glycosides/pharmacology , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Gentiana/chemistry , Hep G2 Cells , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/isolation & purification , Benzoates/pharmacology , Benzoates/chemistry , Benzoates/isolation & purification , Molecular Structure , Oleic Acid/pharmacology , Oleic Acid/chemistry , Structure-Activity Relationship , Dose-Response Relationship, Drug , Triglycerides , Rhizome/chemistry
10.
Materials (Basel) ; 17(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998206

ABSTRACT

The deformation mechanism and static recrystallization (SRX) behavior of an Ni-based single-crystal superalloy are investigated. Indentation tests were performed to investigate the effects of crystal orientation and external stress on SRX behavior. Following solution heat treatment, the depth of the SRX layer below the indentation increases with a deviation angle (ß) from the [001] orientation. The slip analysis indicates that an increased deviation angle leads to an increase in the resolved shear stress on the slip plane and a decrease in the number of active slip systems. In addition, the variation pattern of the SRX layer depth with the deviation angle is consistent for different external stresses. The depth of the SRX layer also increases with external stress. The coarse γ' phases and residual γ/γ' eutectics obviously enhance the pinning effects on the expansion of recrystallized grain boundaries, resulting in slower growth rates of the recrystallized grains in interdendritic regions than those in dendrite core regions.

11.
Article in English | MEDLINE | ID: mdl-39081255

ABSTRACT

Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open-label, single-dose, 2-sequence, and 2-period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography-tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%-125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers.

12.
J Nat Prod ; 87(7): 1754-1762, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-38982404

ABSTRACT

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.


Subject(s)
Flowers , Inula , Nitric Oxide , Sesquiterpenes , Flowers/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Inula/chemistry , Mice , Animals , RAW 264.7 Cells , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Dimerization
13.
Int J Surg ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869983

ABSTRACT

BACKGROUND: Calcaneal osteomyelitis (CO) still poses great challenges to orthopaedic surgeons due to unique anatomic and functional features of the calcaneus. This study summarized the current data regarding clinical characteristics, treatment and efficacy of CO, based on an analysis of literature-reported cases. MATERIALS AND METHODS: We searched the PubMed, Embase, and Cochrane Library databases to find English and Chinese studies reporting on CO patients between 2000 and 2021, with available data for synthesis analysis. The quality of the included studies was evaluated by the National Institutes of Health (NIH) assessment scale. Effective data were extracted and pooled for analysis. RESULTS: Altogether 198 studies involving 1118 patients were included, with a male-to-female ratio of 2.3 (724 males and 310 females). The median age at CO diagnosis was 46 years, with a median symptom duration of 3 months. Injury-related infections (524 cases) and diabetic foot infections (336 cases) were the two most common causes, with ulcer (468 cases) and wound sinus or exudation (209 cases) being the predominant symptoms. The overall positive culture rate was 80.2%, with polymicrobial infections accounting for 18.1%. Staphylococcus aureus was the most frequently detected pathogen (42.7%), with fungal-related infections isolated in 17 cases. Although most patients received surgical interventions (96.9%), the recurrence rate was 20.1%. The incidence of infection relapse following partial calcanectomy, total calcanectomy, debridement with implantation of local antibiotics, and debridement with or without flap or skin coverage were 31.7%, 45.0%, 16.8%, and 15.1%, respectively. The overall incidence of limb amputation was 12.4%, with all-cause and CO-related mortalities of 2.8% and 0.2%, separately. CONCLUSIONS: CO shared similar characteristics with extremity chronic osteomyelitis, primarily affecting young males, with trauma and diabetic foot as the leading causes and Staphylococcus aureus as the most frequently detected pathogen. Despite surgery being the primary treatment modality, clinical outcomes remained unsatisfactory, marked by high rates of infection recurrence and limb amputation.

14.
Stem Cell Res Ther ; 15(1): 187, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937829

ABSTRACT

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.


Subject(s)
Staphylococcus aureus , Humans , Animals , Inflammation/therapy , Staphylococcal Infections/therapy , Signal Transduction , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism
15.
BMC Geriatr ; 24(1): 413, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730354

ABSTRACT

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.


Subject(s)
Accidental Falls , Osteoporosis , Humans , Male , Aged , Osteoporosis/epidemiology , Osteoporosis/diagnosis , Retrospective Studies , Aged, 80 and over , Incidence , Risk Assessment/methods , Risk Factors , Comorbidity , China/epidemiology , Age Factors
16.
Front Mol Neurosci ; 17: 1375925, 2024.
Article in English | MEDLINE | ID: mdl-38807922

ABSTRACT

Zinc transporter 3 (ZnT3) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT3 knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT3 deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT3 deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT3 knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT3 knockout mice. We hypothesize that the ZnT3 deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.

17.
Front Psychol ; 15: 1276968, 2024.
Article in English | MEDLINE | ID: mdl-38659671

ABSTRACT

Introduction: Despite the numerous potential benefits of health chatbots for personal health management, a substantial proportion of people oppose the use of such software applications. Building on the innovation resistance theory (IRT) and the prototype willingness model (PWM), this study investigated the functional barriers, psychological barriers, and negative prototype perception antecedents of individuals' resistance to health chatbots, as well as the rational and irrational psychological mechanisms underlying their linkages. Methods: Data from 398 participants were used to construct a partial least squares structural equation model (PLS-SEM). Results: Resistance intention mediated the relationship between functional barriers, psychological barriers, and resistance behavioral tendency, respectively. Furthermore, The relationship between negative prototype perceptions and resistance behavioral tendency was mediated by resistance intention and resistance willingness. Moreover, negative prototype perceptions were a more effective predictor of resistance behavioral tendency through resistance willingness than functional and psychological barriers. Discussion: By investigating the role of irrational factors in health chatbot resistance, this study expands the scope of the IRT to explain the psychological mechanisms underlying individuals' resistance to health chatbots. Interventions to address people's resistance to health chatbots are discussed.

18.
Heliyon ; 10(7): e28957, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601682

ABSTRACT

Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.

19.
RSC Adv ; 14(15): 10714-10725, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38567330

ABSTRACT

Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the in situ generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells in vitro. In vivo, the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.

20.
Curr Issues Mol Biol ; 46(3): 1921-1923, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38534741

ABSTRACT

As a physiological defense mechanism, inflammation is a complex response to harmful stimuli [...].

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