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1.
Clin Interv Aging ; 19: 891-900, 2024.
Article in English | MEDLINE | ID: mdl-38779379

ABSTRACT

Purpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT. Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve. Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk. Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.


Subject(s)
Endovascular Procedures , Ischemic Stroke , Humans , Male , Female , Aged , Retrospective Studies , Middle Aged , Triglycerides/blood , Tomography, X-Ray Computed , Aged, 80 and over , Lipids/blood , ROC Curve , Logistic Models , Cholesterol, HDL/blood , Cerebral Hemorrhage , Cholesterol/blood , Risk Factors
2.
Sci Rep ; 14(1): 11299, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760436

ABSTRACT

The relationship between the Systemic Inflammatory Response Index (SIRI) and the Fibrinogen-to-albumin ratio (FAR) has not been extensively investigated. The objective of this study was to determine the independent relationship between FAR and SIRI in people with osteoporotic fractures (OPF). A cross-sectional study was conducted using retrospective data from 3431 hospitalized OPF patients. The exposure variable in this study was the baseline FAR, while the outcome variable was the SIRI. Covariates, including age, gender, BMI, and other clinical and laboratory factors, were adjusted. Cross-correlation analysis and linear regression models were applied. The generalized additive model (GAM) investigated non-linear relationships. Adjusted analysis revealed an independent negative association between FAR and SIRI in OPF patients (ß = - 0.114, p = 0.00064, 95% CI - 0.180, - 0.049). A substantial U-shaped association between FAR and SIRI was shown using GAM analysis (p < 0.001). FAR and SIRI indicated a negative association for FAR below 6.344% and a positive correlation for FAR over 6.344%. The results of our study revealed a U-shaped relationship between SIRI and FAR. The lowest conceivable FAR for a bone-loose inflammatory disease might be 6.344%, suggesting that this has particular significance for the medical diagnosis and therapy of persons with OPF. Consequently, the term "inflammatory trough" is proposed. These results offer fresh perspectives on controlling inflammation in individuals with OPF and preventing inflammatory osteoporosis.


Subject(s)
Fibrinogen , Osteoporotic Fractures , Humans , Female , Fibrinogen/metabolism , Fibrinogen/analysis , Male , Osteoporotic Fractures/blood , Osteoporotic Fractures/epidemiology , Aged , Cross-Sectional Studies , Retrospective Studies , Middle Aged , Inflammation/blood , Aged, 80 and over , Serum Albumin/analysis
3.
Osteoporos Int ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771526

ABSTRACT

This large-scale prospective study showed that a significant association between longer duration of daily outdoor walking and reduced osteoporosis risk was found among older adults, particularly among those with a low genetic predisposition to osteoporosis, which highlighted the importance of outdoor walking as a simple, cost-effective adjunct for preventing osteoporosis. PURPOSE: The available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis. METHODS: 24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms. RESULTS: 4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3 months. Those who walked outside for > 30 but ≤ 60 min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72-0.95) for incident osteoporosis, whereas those who walked outside for > 60 min per day had an HR of 0.60 (95% CI: 0.39-0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60 min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk. CONCLUSIONS: A significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

4.
ChemSusChem ; : e202400552, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622064

ABSTRACT

We represent a segmented flow surfactant-free microfluidic strategy for continuous synthesis of Prussian blue analogues (PBAs) with high dispersity and high crystallization. Representative zinc hexacyanoferrate (ZnHCF) nanocubes were successfully synthesized in a microfluidic reactor within a few minutes via the cooperation method and possessed lower contents of crystal water and Fe(CN)6 3- vacancies than that of synthesis in bulk solution. The nucleation and particle growth process can be precisely controlled by the exploration of different flow rates and reaction temperatures during the formation of ZnHCF nanocubes in segmented flow microfluidic reactors. High crystallinity, low crystal water and vacancies in the ZnHCF structure were presented at relatively high temperatures for the crystal growth process. High-quality ZnHCF with a low content of crystal water showed excellent electrochemical activity and stability towards zinc-ion storage. The continuous and scalable synthesis approach can be extended to the fabrication of other PBAs such as NiHCF, CoHCF, MnHCF, and CuHCF with high dispersity without using any surfactants. The controllable construction of PBAs with tunable properties in microfluidic reactors provides a promising direction to minimize the gap between commercial reality and laboratory research.

5.
J Matern Fetal Neonatal Med ; 37(1): 2345855, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38679588

ABSTRACT

INTRODUCTION: Intraamniotic infection (IAI) and subsequent early-onset neonatal sepsis (EONS) are among the main complications associated with preterm prelabor rupture of membranes (PPROM). Currently used diagnostic tools have been shown to have poor diagnostic performance for IAI. This study aimed to investigate whether the exposure to IAI before delivery is associated with short-term variation of the fetal heart rate in pregnancies with PPROM. METHODS: Observational cohort study of 678 pregnancies with PPROM, delivering between 24 + 0 and 33 + 6 gestational weeks from 2012 to 2019 in five labor units in Stockholm County, Sweden. Electronic medical records were examined to obtain background and exposure data. For the exposure IAI, we used the later diagnosis of EONS in the offspring as a proxy. EONS is strongly associated to IAI and was considered a better proxy for IAI than the histological diagnosis of acute chorioamnionitis, since acute chorioamnionitis can be observed in the absence of both positive microbiology and biochemical markers for inflammation. Cardiotocography traces were analyzed by a computerized algorithm for short-term variation of the fetal heart rate, which was the main outcome measure. RESULTS: Twenty-seven pregnancies were categorized as having an IAI, based on the proxy diagnosis of EONS after birth. Fetuses exposed to IAI had significantly lower short-term variation values in the last cardiotocography trace before birth than fetuses who were not exposed (5.25 vs 6.62 ms; unadjusted difference: -1.37, p = 0.009). After adjustment for smoking and diabetes, this difference remained significant. IAI with a later positive blood culture in the neonate (n = 12) showed an even larger absolute difference in STV (-1.65; p = 0.034), with a relative decrease of 23.5%. CONCLUSION: In pregnancies with PPROM, fetuses exposed to IAI with EONS as a proxy have lower short-term variation of the fetal heart rate than fetuses who are not exposed. Short-term variation might be useful as adjunct surveillance in pregnancies with PPROM.


Subject(s)
Cardiotocography , Fetal Membranes, Premature Rupture , Heart Rate, Fetal , Humans , Female , Pregnancy , Heart Rate, Fetal/physiology , Fetal Membranes, Premature Rupture/diagnosis , Adult , Infant, Newborn , Chorioamnionitis/diagnosis , Cohort Studies , Sweden/epidemiology , Neonatal Sepsis/diagnosis , Pregnancy Complications, Infectious/diagnosis , Gestational Age
6.
BMC Pediatr ; 24(1): 272, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664650

ABSTRACT

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.


Subject(s)
Intensive Care Units, Neonatal , Respiratory Distress Syndrome, Newborn , Humans , Infant, Newborn , China/epidemiology , Retrospective Studies , Female , Male , Respiratory Distress Syndrome, Newborn/therapy , Respiratory Insufficiency/therapy , Pulmonary Surfactants/therapeutic use , Pulmonary Surfactants/administration & dosage , Extracorporeal Membrane Oxygenation , Respiration, Artificial/statistics & numerical data , Treatment Outcome
7.
Biophys Chem ; 310: 107236, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38615538

ABSTRACT

A novel inhibitor, carboxyphenylboronic acid-modified chitosan oligosaccharide (COS-CPBA), was developed by coupling carboxyphenylboronic acid (CPBA) with chitosan oligosaccharide (COS) to inhibit insulin fibrillation. Extensive biophysical assays indicated that COS-CPBA could decelerate insulin aggregation, hinder the conformational transition from α-helix to ß-sheet structure, change the morphology of insulin aggregates and alter fibrillation pathway. A mechanism for the inhibition of insulin fibrillation by COS-CPBA was proposed. It considers that insulin molecules bind to COS-CPBA via hydrophobic interactions, while the positively charged groups in COS-CPBA exert electrostatic repulsion on the bound insulin molecules. These two opposite forces cause the insulin molecules to display extended conformations and hinder the conformational transition of insulin from α-helix to ß-sheet structure necessary for fibrillation, thus decelerating aggregation and altering the fibrillation pathway of insulin. The studies provide novel ideas for the development of more effective inhibitors of amyloid fibrillation.


Subject(s)
Boronic Acids , Chitosan , Hydrophobic and Hydrophilic Interactions , Insulin , Oligosaccharides , Static Electricity , Insulin/chemistry , Insulin/metabolism , Chitosan/chemistry , Boronic Acids/chemistry , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Protein Aggregates/drug effects , Animals , Humans
8.
Heliyon ; 10(8): e29644, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644813

ABSTRACT

As the forest health care in China is still in the early stage of development, the construction standards of forest health care base are not unified yet, resulting in large differences in the evaluation criterion for the ecological environment of forest health care bases. So, it is urgent to develop a new forest health care ecological environment quality assessment method. Yunnan, Guizhou and Sichuan provinces of China were selected as the study area, the previous 6 batches of 165 national forest health care pilot construction bases were selected as the main data source. This study explored the spatial and temporal distribution characteristics of forest health care bases in the study area using standard deviation ellipses, kernel density estimation method and cold and hot spot analysis. Furthermore, this study evaluated the ecological environment quality of the forest health care bases with a new ecological environment quality evaluation index model, which assembled Fraction Vegetation Coverage (FVC), Wetness (WET), Evapotranspiration (ET), Land Surface Temperature (LST) and Normalized Difference Bare Soil Index (NDBSI). The results are as follows: (1) the forest health bases in the study area are mainly located by the east of the Hu Line with a northeast-southwest distribution direction characteristics, and gradually expanded into a shape of "high in the east and low in the west, multi-point development". (2) the area with ecological environment quality in excellent, good and medium grade accounts for about 87.73 % in the study area, indicating that most of the study area is suitable for the construction of forest health care base. These results can provide a practical guidance for the further rational layout and balanced development of forest health care bases in the study area.

9.
PLoS One ; 19(4): e0300192, 2024.
Article in English | MEDLINE | ID: mdl-38578725

ABSTRACT

The current bag filter system used by railway ballast bed coal suction vehicles for cleaning coal dust from railway tunnels has low operational efficiency and generates significant volumes of dust. This paper describes a simulation test unit designed to enhance the dust removal performance in railway tunnels. The flow field inside the simulation test unit is investigated under different operating conditions through numerical simulations, and the variations in air volume and working resistance, total dust collection efficiency, and optimal operating parameters of a pulse cleaning system are identified through a series of experiments. The numerical results show that the pulse cleaning system does not significantly affect the uniformity of the flow field distribution at the bottom of the filter cartridge during the process of operation. The experimental research indicates that the simulation test unit satisfies the design requirements, achieving an average total dust removal efficiency of 99.93%. A field application shows that the total dust mass concentration at the operator position can be reduced from 335.8 mg∙m-3 to 4.2 mg∙m-3, effectively improving the operating environment within the tunnel.


Subject(s)
Coal Mining , Coal , Coal/analysis , Suction , Dust/analysis
10.
Front Neurosci ; 18: 1358998, 2024.
Article in English | MEDLINE | ID: mdl-38445255

ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein-protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

11.
Front Med (Lausanne) ; 11: 1284207, 2024.
Article in English | MEDLINE | ID: mdl-38549874

ABSTRACT

Introduction: To develop and validate a comprehensive prognostic model for the mid-to-long term mortality risk among ≥50-year-old osteoporotic fracture (OPF) surgical patients. Methods: Our retrospective investigation included data from the Osteoporotic Fracture Registration System established by the Affiliated Kunshan Hospital of Jiangsu University, and involved 1,656 patients in the development set and 675 patients in the validation set. Subsequently, we employed a multivariable Cox regression model to establish a 3-year mortality predicting nomogram, and the model performance was further evaluated using C-index and calibration plots. Decision curve analysis (DCA) was employed to assess feasibility of the clinical application of this model. Results: Using six prognostic indexes, namely, patient age, gender, the American Society of Anesthesiologists (ASA) score, the Charlson comorbidity index (CCI), fracture site, and fracture liaison service (FLS), we generated a simple nomogram. The nomogram demonstrated satisfactory discrimination within the development (C-index = 0.8416) and validation (C-index = 0.8084) sets. Using calibration plots, we also revealed good calibration. The model successfully classified patients into different risk categories and the results were comparable in both the development and validation sets. Finally, a 1-70% probability threshold, according to DCA, suggested that the model has promise in clinical settings. Conclusion: Herein, we offer a robust tool to estimating the 3-year all-cause mortality risk among elderly OPF surgical patients. However, we recommend further assessments of the proposed model prior to widespread clinical implementation.

12.
Funct Integr Genomics ; 24(2): 62, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38514486

ABSTRACT

Long-wave sensitive (LWS) is a G protein-coupled receptor expressed in the retina, and zebrafish is a better model organism for studying vision, but the role of LWS1 in vision-guided behavior of larvae fish has rarely been reported. In this study, we found that zebrafish lws1 and lws2 are tandemly replicated genes, both with six exons, with lws1 being more evolutionarily conserved. The presence of Y277F in the amino acid sequence of lws2 may have contributed to the shift of λmax to green light. We established a lws1 knockout zebrafish model using CRISPR/Cas9 technology. Lws1-/- larvae showed significantly higher levels of feeding and appetite gene (agrp) expression than WT, and significantly lower levels of anorexia gene (pomc, cart) expression. In addition, green light gene compensation was observed in lws1-/- larvae with significantly increased expression levels of rh2-1. The light-dark movement test showed that lws1-/- larvae were more active under light-dark transitions or vibrational stimuli, and the expression of phototransduction-related genes was significantly up-regulated. This study reveals the important role of lws1 gene in the regulation of vision-guided behavior in larvae.


Subject(s)
Cone Opsins , Zebrafish , Animals , Amino Acid Sequence , Zebrafish/genetics , Zebrafish/metabolism , Cone Opsins/genetics , Feeding Behavior , Vision, Ocular/genetics
13.
J Pain ; : 104504, 2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38442838

ABSTRACT

The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 (Nmur2+) as critical elements for mechanical itch. We found that spinal Nmur2+ neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2+ neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2+ neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2+ neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. PERSPECTIVE: Excitatory Nmur2+ neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2+ neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2+ neurons may play different roles in pain signal processing.

14.
Sci Rep ; 14(1): 6574, 2024 03 19.
Article in English | MEDLINE | ID: mdl-38503865

ABSTRACT

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Protein Kinases , Cyclin-Dependent Kinases/metabolism , Prognosis , Carcinogenesis , Biomarkers, Tumor/metabolism , Immunomodulation/genetics
15.
Chem Sci ; 15(12): 4581-4589, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38516097

ABSTRACT

The realization of high energy is of great importance to unlock the practical potential of zinc-iodine batteries. However, significant challenges, such as low iodine loading (mostly less than 50 wt%), restricted iodine reutilization, and severe structural pulverization during cycling, compromise its intrinsic features. This study introduces an optimized, fully zincified zinc iodide loaded onto a hierarchical carbon scaffold with high active component loading and content (82 wt%) to prepare a thick cathode for enabling high-energy Zn-I2 batteries. The synergistic interactions between nitrogen heteroatoms and cobalt nanocrystals within the porous matrix not only provide forceful chemisorption to lock polyiodide intermediates but also invoke the electrocatalytic effects to manipulate efficient iodine conversion. The ZnI2 cathode could effectively alleviate continuous volumetric expansion and maximize the utilization of active species. The electrochemical examinations confirm the thickness-independent battery performance of assembled Zn-I2 cells due to the ensemble effect of composite electrodes. Accordingly, with a thickness of 300 µm and ZnI2 loading of up to 20.5 mg cm-2, the cathode delivers a specific capacity of 92 mA h gcathode-1 after 2000 cycles at 1C. Moreover, the Zn-I2 pouch cell with ZnI2 cathode has an energy density of 145 W h kgcathode-1 as well as a stable long cycle life.

16.
Clin Exp Immunol ; 216(2): 132-145, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38386917

ABSTRACT

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

17.
Angew Chem Int Ed Engl ; 63(19): e202402274, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38415322

ABSTRACT

The high theoretical energy density (1274 Wh kg-1) and high safety enable the all-solid-state Na-S batteries with great promise for stationary energy storage system. However, the uncontrollable solid-liquid-solid multiphase conversion and its associated sluggish polysulfides redox kinetics pose a great challenge in tunning the sulfur speciation pathway for practical Na-S electrochemistry. Herein, we propose a new design methodology for matrix featuring separated bi-catalytic sites that control the multi-step polysulfide transformation in tandem and direct quasi-solid reversible sulfur conversion during battery cycling. It is revealed that the N, P heteroatom hotspots are more favorable for catalyzing the long-chain polysulfides reduction, while PtNi nanocrystals manipulate the direct and full Na2S4 to Na2S low-kinetic conversion during discharging. The electrodeposited Na2S on strongly coupled PtNi and N, P-codoped carbon host is extremely electroreactive and can be readily recovered back to S8 without passivation of active species during battery recharging, which delivers a true tandem electrocatalytic quasi-solid sulfur conversion mechanism. Accordingly, stable cycling of the all-solid-state soft-package Na-S pouch cells with an attractive specific capacity of 876 mAh gS -1 and a high energy of 608 Wh kgcathode -1 (172 Wh kg-1, based on the total mass of cathode and anode) at 60 °C are demonstrated.

18.
Nat Metab ; 6(3): 531-549, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38409606

ABSTRACT

Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-ß-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-ß-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-ß-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid ß (Aß) production through ß-catenin-ß-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αß production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.


Subject(s)
Alzheimer Disease , Humans , Male , Female , Mice , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides/therapeutic use , Amyloid Precursor Protein Secretases/metabolism , Amyloid Precursor Protein Secretases/therapeutic use , Osteocytes/metabolism , Osteocytes/pathology , beta Catenin/metabolism , beta Catenin/therapeutic use , Aspartic Acid Endopeptidases/metabolism , Aspartic Acid Endopeptidases/therapeutic use , Wnt Signaling Pathway , Cognition , Aging
19.
Micromachines (Basel) ; 15(1)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38258259

ABSTRACT

We propose an air gap fiber Bragg grating (g-FBG) sensor that can measure strain and temperature simultaneously. The sensor is made by aligning two fiber Bragg gratings (FBGs), and an air gap exists between these two sub-gratings. This sensor's architecture allows it to form a spectrum with phase-shifted fiber Bragg grating (PSFBG) spectroscopy and Fabry-Perot interference (FPI) spectroscopy. Since the sensitivity of PSFBG and FPI spectra is different for strain and temperature, it is possible to measure both strain and temperature by measuring one of the reflected dips of PSFBG and the interference dip of FPI. The experimental results show that the strain sensitivity is about 11.95 pm/µÎµ via the dip wavelength detection of FPI, and the temperature sensitivity is about 9.64 pm/°C via the dip wavelength detection of PSFBG. The g-FBG sensor demonstrates a resolution of approximately ±3.7 µÎµ within the strain range of 0 to 1000 µÎµ and about ±0.6 °C within the temperature range of 25 °C to 120 °C. The proposed g-FBG sensor, characterized by its simple structure, compact size, and cost-effectiveness, exhibits significant potential in the field of multi-parameter measurements.

20.
Cell Prolif ; : e13600, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38199244

ABSTRACT

Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/ß-catenin signalling and its interaction with other signalling pathways, such as transforming growth factor ß (TGF-ß), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF-κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/ß-catenin signalling in OA pathogenesis and interaction of ß-catenin with other pathways, such as TGF-ß, BMP, Notch, Ihh, NF-κB, and FGF. Understanding of these novel insights into the interaction of ß-catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention.

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