Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.080
Filter
1.
Clin Rheumatol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961031

ABSTRACT

The burden of osteoarthritis (OA) is rapidly increasing with population aging, but there are still no approved disease-modifying drugs available. Accumulating evidence has shown that OA is a heterogeneous disease with multiple phenotypes, and it is unlikely to respond to one-size-fits-all treatments. Inflammation is recognized as an important phenotype of OA and is associated with worse pain and joint deterioration. Therefore, it is believed that anti-inflammatory treatments may be more effective for OA with an inflammatory phenotype. In this review, we summarized clinical trials that evaluated anti-inflammatory treatments for OA and discussed whether these treatments are more effective in inflammatory OA phenotypes compared to general OA patients.

2.
Adv Mater ; : e2407433, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38973089

ABSTRACT

Interface-induced nonradiative recombination losses at the perovskite/electron transport layer (ETL) are an impediment to improving the efficiency and stability of inverted (p-i-n) perovskite solar cells (PSCs). Tridecafluorohexane-1-sulfonic acid potassium (TFHSP) is employed as a multifunctional dipole molecule to modify the perovskite surface. The solid coordination and hydrogen bonding efficiently passivate the surface defects, thereby reducing nonradiative recombination. The induced positive dipole layer between the perovskite and ETLs improves the energy band alignment, enhancing interface charge extraction. Additionally, the strong interaction between TFHSP and the perovskite stabilizes the perovskite surface, while the hydrophobic fluorinated moieties prevent the ingress of water and oxygen, enhancing the device stability. The resultant devices achieve a power conversion efficiency (PCE) of 24.6%. The unencapsulated devices retain 91% of their initial efficiency after 1000 h in air with 60% relative humidity, and 95% after 500 h under maximum power point (MPP) tracking at 35 °C. The utilization of multifunctional dipole molecules opens new avenues for high-performance and long-term stable perovskite devices.

3.
Vet Sci ; 11(6)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38922021

ABSTRACT

The continuously evolving PRRSV has been plaguing pig farms worldwide for over 30 years, with conventional vaccines suffering from insufficient protection and biosecurity risks. To address these challenges, we identified 10 PRRSV-specific CTL epitopes through enzyme-linked immunospot assay (ELISPOT) and constructed a multi-epitope peptide (PTE) by linking them in tandem. This PTE was then fused with a modified porcine Fc molecule to create the recombinant protein pFc-PTE. Our findings indicate that pFc-PTE effectively stimulates PRRSV-infected specific splenic lymphocytes to secrete high levels of interferon-gamma (IFN-γ) and is predicted to be non-toxic and non-allergenic. Compared to PTE alone, pFc-PTE not only induced a comparable cellular immune response in mice but also extended the duration of the immune response to at least 10 weeks post-immunization. Additionally, pFc-PTE predominantly induced a Th1 immune response, suggesting its potential advantage in enhancing cellular immunity. Consequently, pFc-PTE holds promise as a novel, safe, and potent candidate vaccine for PRRSV and may also provide new perspectives for vaccine design against other viral diseases.

4.
Skeletal Radiol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877110

ABSTRACT

Osteoarthritis (OA) is a leading cause of pain, functional impairment, and disability in older adults. However, there are no effective treatments to delay and reverse OA. Magnetic resonance imaging (MRI) can assess structural abnormalities of OA by directly visualizing damage and inflammatory reactions within the tissues and detecting abnormal signals in the subchondral bone marrow region. While some studies have shown that bone marrow lesions (BMLs) are one of the early signs of the development of OA and predict structural and symptomatic progression of OA, others claimed that BMLs are prevalent in the general population and have no role in the progression of OA. In this narrative review, we screened and summarized studies with different designs that evaluated the association of BMLs with joint symptoms and structural abnormalities of OA. We also discussed whether BMLs may serve as an imaging biomarker and a treatment target for OA based on existing clinical trials.

5.
BMC Cancer ; 24(1): 744, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890593

ABSTRACT

BACKGROUND: Tumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical trials. A better understanding of the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia is needed for future clinical application. Here, we investigated the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia in patients with localized PCa, in order to apply PIMO as a prognostic tool and to identify potential biomarkers for future clinical translation. METHODS: A total of 39 patients with localized PCa were recruited and administered oral PIMO before undergoing radical prostatectomy (RadP). Immunohistochemical staining for PIMO was performed on 37 prostatectomy specimens with staining patterns evaluated and clinical association analyzed. Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative tumor areas. A hypoxia related methylation molecular signature was generated by integrating the differentially methylated regions with previously established RNA-seq datasets. RESULTS: Three PIMO staining patterns were distinguished: diffuse, focal, and comedo-like. The comedo-like staining pattern was more commonly associated with adverse pathology. PIMO-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology. The generated DNA methylation signature was found to be a robust hypoxia biomarker, which could risk-stratify PCa patients across multiple clinical datasets, as well as be applicable in other cancer types. CONCLUSIONS: Oral PIMO unveiled clinicopathologic features of disease aggressiveness in localized PCa. The generated DNA methylation signature is a novel and robust hypoxia biomarker that has the potential for future clinical translation.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Nitroimidazoles , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/metabolism , Aged , Middle Aged , Tumor Hypoxia/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Administration, Oral
6.
Phys Chem Chem Phys ; 26(23): 16821-16828, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38828761

ABSTRACT

Sulfur compounds (SO2, CS2, H2S and OCS) are common toxic pollutants in the atmospheric environment, and the absorption spectroscopy technique can indeed help to realize online monitoring of their concentrations. However, nonlinear effects that occur during absorption spectroscopy measurements have a serious impact on the measurement of the absorption cross-sections (ACSs) of sulfur compounds, leading to serious deviations in both the substance absorption properties and concentrations obtained based on ACS analysis. In this paper, the maximum effective ACSs of sulfur compounds in the linear region are obtained by considering the influence of nonlinear effects and eliminating interference factors such as oxygen and photolysis. In addition, the nonlinear effects are found to be greatly attenuated in spectra with broad band absorption characteristics by comparing the oscillatory absorption spectra before and after the differential treatment and by comparing the change in the oscillatory ACS with the broad band ACS. The experimental results show that the effective ACSs of SO2, CS2, H2S, and OCS with a resolution of 0.23 nm are 14.15 × 10-18 cm2 per molecule, 5.61 × 10-16 cm2 per molecule, 7.09 × 10-18 cm2 per molecule, and 3.20 × 10-19 cm2 per molecule, respectively. So far, it is the largest ACS obtained at room temperature and atmospheric pressure, which is of great significance for online measurement of sulfur compounds.

7.
Int Wound J ; 21(2): e14710, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38838072

ABSTRACT

To explore the knowledge, attitudes and practice (KAP) status of preventing pressure injury among clinical nurses working in paediatric ICU, and to examine factors affecting nurses' KAP. A questionnaire survey was conducted among 1906 paediatric ICU nurses in 18 children's hospitals by convenience sampling method. The survey tools were self-designed general data questionnaire, KAP questionnaire for the prevention of pressure injury and the influencing factors were analysed. A total of 1906 valid questionnaires were collected. The scores of overall KPA, knowledge, attitudes, and practice were 101.24 ± 17.22, 20.62 ± 9.63, 54.93 ± 5.81and 25.67 ± 6.76, respectively. The results of multiple linear regression analysis showed that education background, professional title, age and specialist nurse were the main influencing factor of nurses' knowledge of preventing PI; education background and specialist nurse were the main influencing factors of nurses' attitudes of preventing PI; knowledge, attitudes and education background were the main influencing factors of nurses' practice of preventing PI. Paediatric ICU nurses have a positive attitude towards the prevention of PI, but their knowledge and practice need to be improved. According to different characteristics of nurses, nursing managers should carry out training on the knowledge of prevention of PI to establish a positive attitude, so as to drive the change of nursing practice and improve the nursing practice level of ICU nurses to prevent of PI.


Subject(s)
Health Knowledge, Attitudes, Practice , Intensive Care Units, Pediatric , Pressure Ulcer , Humans , Pressure Ulcer/prevention & control , Female , Male , Surveys and Questionnaires , Adult , Attitude of Health Personnel , Nursing Staff, Hospital/psychology , Critical Care Nursing/methods , Middle Aged , Young Adult , Clinical Competence/statistics & numerical data
8.
Maturitas ; 187: 108057, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908060

ABSTRACT

OBJECTIVE: To describe the association of handgrip strength asymmetry and weakness with cognitive function among Chinese middle-aged and older adults. STUDY DESIGN: We used data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study. Handgrip strength was measured at baseline. Handgrip strength asymmetry was defined on the basis of the ratio of handgrip strength of the non-dominant hand to that of the dominant hand (i.e. non-dominant/dominant): a ratio of <0.9 defined as dominant handgrip strength asymmetry and >1.1 as non-dominant handgrip strength asymmetry. Weakness was defined as a handgrip strength of <28 kg for males or <18 kg for females. MAIN OUTCOME MEASURES: Cognitive function with its two core dimensions (episodic memory and mental status) at each wave was assessed and standardized. RESULTS: 9333 participants (48.3 % female, age 58.2 ± 9.0 years) were included. Non-dominant but not dominant handgrip strength asymmetry was significantly associated with poorer cognitive function at baseline (ß = -0.121, -0.092, and -0.132 for mental status, episodic memory, and global cognition, respectively). In longitudinal analyses over 2 years, dominant handgrip strength asymmetry significantly slowed cognitive decline (ß = -0.078 and -0.069 for mental status and global cognition, respectively), and non-dominant handgrip strength asymmetry accelerated cognitive decline (ß = 0.053 and 0.043 for episodic memory and global cognition, respectively). Weakness was associated with poorer cognitive function at baseline and cognitive decline over 2, 4, and 7 years (all P < 0.05). CONCLUSIONS: In middle-aged and older adults, non-dominant handgrip strength asymmetry and weakness were associated with poorer cognitive function and predicted accelerated cognitive decline. Dominant handgrip strength asymmetry may be beneficial for maintaining cognitive function.

9.
Discov Oncol ; 15(1): 228, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874871

ABSTRACT

The prognosis for Cutaneous Melanoma (CM), a skin malignant tumor that is extremely aggressive, is not good. A recently identified type of controlled cell death that is intimately related to immunotherapy and the development of cancer is called cuproptosis. Using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we developed and validated a DNA-methylation located in cuproptosis death-related gene prognostic signature (CRG-located DNA-methylation prognostic signature) to predict CM's prognosis. Kaplan-Meier analysis of our TCGA and GEO cohorts showed that high-risk patients had a shorter overall survival. The area under the curve (AUC) for the TCGA cohort was 0.742, while for the GEO cohort it was 0.733, according to the receiver operating characteristic (ROC) analysis. Furthermore, this signature was discovered as an independent prognostic indicator over CM patients based on Cox-regression analysis. Immunogenomic profiling indicated that majority immune-checkpoints got an opposite relationship with the signature, and patients in the group at low risk got higher immunophenoscore. Several immune pathways were enriched, according to functional enrichment analysis. In conclusion, a prognostic methylation signature for CM patients was established and confirmed. Because of its close relationship to the immune landscape, this signature may help clinicians make more accurate and individualized choices regarding therapy.

10.
Article in English | MEDLINE | ID: mdl-38909686

ABSTRACT

OBJECTIVES: Invasive lumbar puncture (LP) is the conventional method for diagnosing neurosyphilis (NS). We investigated a noninvasive alternative method to detect serum Treponema pallidum specific antibodies against highly immunogenic antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) by using luciferase immunosorbent assay (LISA). METHODS: 816 HIV-negative patients suspected of NS from Beijing and Guangzhou cohort were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibody. Two diagnostic prediction models were developed using stepwise logistic regression in Beijing cohort, and evaluated in Guangzhou cohort for external validation. RESULTS: Serum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in Beijing cohort and the corresponding AUCs were 0.722 (95% CI: 0.680-0.762), 0.780 (95% CI: 0.741-0.817), and 0.774 (95% CI: 0.734-0.811), respectively. An expanded NS prediction model integrated with anti-TP17 and anti-TP47 antibodies showed better performance than the base NS diagnostic model without anti-TP17 and anti-TP47 antibodies with the AUC of 0.874 (95% CI: 0.841-0.906) vs 0.845 (95% CI: 0.809-0.881) (p = 0.007) in the development cohort, and 0.934 (95% CI: 0.909-0.960) vs 0.877 (95% CI: 0.840-0.914) (p<0.001) in validation cohort, respectively. Decision curve analysis (DCA) revealed that the net benefit of the expanded model exceeded that of the base model when the threshold probability was between 0.10 and 0.95 in both the development and external validation cohorts. CONCLUSIONS: Serum antibodies against TP17 and TP47 exhibited promising diagnostic capability for NS and significantly enhanced predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a noninvasive method for NS diagnosis to substitute invasive LP in NS diagnosis.

11.
Int J Mol Sci ; 25(12)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38928450

ABSTRACT

Abnormal cell proliferation and growth leading to cancer primarily result from cumulative genome mutations. Single gene mutations alone do not fully explain cancer onset and progression; instead, clustered mutations-simultaneous occurrences of multiple mutations-are considered to be pivotal in cancer development and advancement. These mutations can affect different genes and pathways, resulting in cells undergoing malignant transformation with multiple functional abnormalities. Clustered mutations influence cancer growth rates, metastatic potential, and drug treatment sensitivity. This summary highlights the various types and characteristics of clustered mutations to understand their associations with carcinogenesis and discusses their potential clinical significance in cancer. As a unique mutation type, clustered mutations may involve genomic instability, DNA repair mechanism defects, and environmental exposures, potentially correlating with responsiveness to immunotherapy. Understanding the characteristics and underlying processes of clustered mutations enhances our comprehension of carcinogenesis and cancer progression, providing new diagnostic and therapeutic approaches for cancer.


Subject(s)
Carcinogenesis , Mutation , Neoplasms , Humans , Neoplasms/genetics , Neoplasms/pathology , Carcinogenesis/genetics , Genomic Instability , Cell Transformation, Neoplastic/genetics , DNA Repair/genetics , Animals
12.
Med Eng Phys ; 129: 104189, 2024 07.
Article in English | MEDLINE | ID: mdl-38906572

ABSTRACT

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.


Subject(s)
Cell Survival , Compressive Strength , Finite Element Analysis , Glucose , Intervertebral Disc , Tensile Strength , Glucose/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/cytology , Models, Biological , Biomechanical Phenomena , Stress, Mechanical
13.
J Biol Chem ; 300(6): 107374, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38762180

ABSTRACT

The pre-integration steps of the HIV-1 viral cycle are some of the most valuable targets of recent therapeutic innovations. HIV-1 integrase (IN) displays multiple functions, thanks to its considerable conformational flexibility. Recently, such flexible proteins have been characterized by their ability to form biomolecular condensates as a result of Liquid-Liquid-Phase-Separation (LLPS), allowing them to evolve in a restricted microenvironment within cells called membrane-less organelles (MLO). The LLPS context constitutes a more physiological approach to study the integration of molecular mechanisms performed by intasomes (complexes containing viral DNA, IN, and its cellular cofactor LEDGF/p75). We investigated here if such complexes can form LLPS in vitro and if IN enzymatic activities were affected by this LLPS environment. We observed that the LLPS formed by IN-LEDGF/p75 functional complexes modulate the in vitro IN activities. While the 3'-processing of viral DNA ends was drastically reduced inside LLPS, viral DNA strand transfer was strongly enhanced. These two catalytic IN activities appear thus tightly regulated by the environment encountered by intasomes.


Subject(s)
HIV Integrase , HIV-1 , Virus Integration , HIV Integrase/metabolism , HIV Integrase/chemistry , HIV Integrase/genetics , HIV-1/metabolism , HIV-1/physiology , Humans , DNA, Viral/metabolism , DNA, Viral/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/chemistry
14.
Med Eng Phys ; 128: 104169, 2024 06.
Article in English | MEDLINE | ID: mdl-38789212

ABSTRACT

Despite the fact that lower back pain caused by degenerative lumbar spine pathologies seriously affects the quality of life, however, there is a paucity of research on the biomechanical properties of different auxiliary fixation systems for its primary treatment (oblique lumbar interbody fusion) under vibratory environments. In order to study the effects of different fixation systems of OLIF surgery on the vibration characteristics of the human lumbar spine under whole-body vibration (WBV), a finite element (FE) model of OLIF surgery with five different fixation systems was established by modifying a previously established model of the normal lumbar spine (L1-S1). In this study, a compressive follower load of 500 N and a sinusoidal axial vertical load of ±40 N at the frequency of 5 Hz with a duration of 0.6 s was applied. The results showed that the bilateral pedicle screw fixation model had the highest resistance to cage subsidence and maintenance of disc height under WBV. In contrast, the lateral plate fixation model exerted very high stresses on important tissues, which would be detrimental to the patient's late recovery and reduction of complications. Therefore, this study suggests that drivers and related practitioners who are often in vibrating environments should have bilateral pedicle screws for OLIF surgery, and side plates are not recommended to be used as a separate immobilization system. Additionally, the lateral plate is not recommended to be used as a separate fixation system.


Subject(s)
Finite Element Analysis , Lumbar Vertebrae , Spinal Fusion , Vibration , Spinal Fusion/instrumentation , Lumbar Vertebrae/surgery , Humans , Biomechanical Phenomena , Pedicle Screws
15.
Biomed Pharmacother ; 175: 116734, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754264

ABSTRACT

Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced ferroptosis and provide a novel insight for treating SCI.


Subject(s)
Arachidonate 15-Lipoxygenase , Down-Regulation , Ferroptosis , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord Injuries , alpha-Tocopherol , Animals , Ferroptosis/drug effects , alpha-Tocopherol/pharmacology , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Recovery of Function/drug effects , Down-Regulation/drug effects , Rats , Arachidonate 15-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/genetics , Lipid Peroxidation/drug effects , Male , Reactive Oxygen Species/metabolism , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 12-Lipoxygenase/genetics , Disease Models, Animal , Molecular Docking Simulation
16.
J Hazard Mater ; 474: 134666, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38815389

ABSTRACT

The Hartman Park community in Houston, Texas-USA, is in a highly polluted area which poses significant risks to its predominantly Hispanic and lower-income residents. Surrounded by dense clustering of industrial facilities compounds health and safety hazards, exacerbating environmental and social inequalities. Such conditions emphasize the urgent need for environmental measures that focus on investigating ambient air quality. This study estimated benzene, one of the most reported pollutants in Hartman Park, using machine learning-based approaches. Benzene data was collected in residential areas in the neighborhood and analyzed using a combination of five machine-learning algorithms (i.e., XGBR, GBR, LGBMR, CBR, RFR) through a newly developed ensemble learning model. Evaluations on model robustness, overfitting tests, 10-fold cross-validation, internal and stratified validation were performed. We found that the ensemble model depicted about 98.7% spatial variability of benzene (Adj. R2 =0.987). Through rigorous validations, stability of model performance was confirmed. Several predictors that contribute to benzene were identified, including temperature, developed intensity areas, leaking petroleum storage tank, and traffic-related factors. Analyzing spatial patterns, we found high benzene spread over areas near industrial zones as well as in residential areas. Overall, our study area was exposed to high benzene levels and requires extra attention from relevant authorities.

17.
J Neuroimmunol ; 391: 578367, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38735091

ABSTRACT

BACKGROUND: Sepsis-associated encephalopathy (SAE) presents a significant clinical challenge, associated with increased mortality and healthcare expenses. Hyperbaric oxygen therapy (HBOT), involving inhaling pure or highly concentrated oxygen under pressures exceeding one atmosphere, has demonstrated neuroprotective effects in various conditions. However, the precise mechanisms underlying its protective actions against sepsis-associated brain injury remain unclear. This study aimed to determine whether HBOT protects against SAE and to elucidate the impact of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway on SAE. METHODS: The experiment consisted of two parts. In the first part, C57BL/6 J male mice were divided into five groups using a random number table method: control group, sham surgery group, sepsis group, HBOT + sepsis group, and HBOT + sham surgery group. In the subsequent part, C57BL/6 J male mice were divided into four groups: sepsis group, HBOT + sepsis group, HIF-1α + HBOT + sepsis group, and HIF-1α + sepsis group. Sepsis was induced via cecal ligation and puncture (CLP). Hyperbaric oxygen therapy was administered at 1 h and 4 h post-CLP. After 24 h, blood and hippocampal tissue were collected for cytokine measurements. HIF-1α, TNF-α, IL-1ß, and IL-6 expression were assessed via ELISA and western blotting. Microglial expression was determined by immunofluorescence. Blood-brain barrier permeability was quantified using Evans Blue. Barnes maze and fear conditioning were conducted 14 days post-CLP to evaluate learning and memory. RESULTS: Our findings reveal that CLP-induced hippocampus-dependent cognitive deficits coincided with elevated HIF-1α and increased TNF-α, IL-1ß, and IL-6 levels in both blood and hippocampus. Observable activation of microglial cells in the hippocampus and increased blood-brain barrier (BBB) permeability were also evident. HBOT mitigated HIF-1α, TNF-α, IL-1ß, and IL-6 levels, attenuated microglial activation in the hippocampus, and significantly improved learning and memory deficits in CLP-exposed mice. Additionally, these outcomes were corroborated by injecting a lentivirus that overexpressed HIF-1α into the hippocampal region of the mice. CONCLUSION: HIF-1α escalation induced peripheral and central inflammatory factors, promoting microglial activation, BBB impairment, and cognitive dysfunction. However, HBOT ameliorated these effects by reducing HIF-1α levels in Sepsis-Associated Encephalopathy.


Subject(s)
Disease Models, Animal , Hyperbaric Oxygenation , Hypoxia-Inducible Factor 1, alpha Subunit , Mice, Inbred C57BL , Neuroinflammatory Diseases , Sepsis-Associated Encephalopathy , Signal Transduction , Animals , Hyperbaric Oxygenation/methods , Male , Mice , Sepsis-Associated Encephalopathy/metabolism , Sepsis-Associated Encephalopathy/therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Signal Transduction/physiology , Neuroinflammatory Diseases/etiology , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/therapy , Sepsis/complications , Sepsis/therapy , Sepsis/metabolism
18.
J Mater Chem B ; 12(22): 5439-5454, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38726947

ABSTRACT

Powder-based hemostatic technology has offered unprecedented opportunities in surgical sealing and repair of irregularly shaped and noncompressible wounds. Despite their routine use, existing clinical hemostatic powders are challenged either by poor mechanical properties or inadequate adhesion to bleeding tissues in biological environments. Here, inspired by the mussel foot proteins' fusion assembly strategy, a novel silk fibroin-based hemostatic powder (named as SF/PEG/TA) with instant and robust adhesion performance is developed. Upon absorbing interfacial liquids, the SF/PEG/TA powders rapidly swell into micro-gels and subsequently contact with each other to transform into a macroscopically homogeneous hydrogel in situ, strengthening its interfacial bonding with various substrates in fluidic environments. The in vitro and in vivo results show that the SF/PEG/TA powder possesses ease of use, good biocompatibility, strong antibacterial activities, and effective blood clotting abilities. The superior hemostatic sealing capability of the SF/PEG/TA powder is demonstrated in the rat liver, heart, and gastrointestinal injury models. Moreover, in vivo investigation of rat skin incision and gastrointestinal perforation models validates that the SF/PEG/TA powder promotes wound healing and tissue regeneration. Taken together, compared to existing clinical hemostatic powders, the proposed SF/PEG/TA powder with superior wound treatment capabilities has high potential for clinical hemostasis and emergency rescue.


Subject(s)
Fibroins , Hemostatics , Powders , Rats, Sprague-Dawley , Fibroins/chemistry , Fibroins/pharmacology , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Rats , Wound Healing/drug effects , Male , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Humans , Polyethylene Glycols/chemistry
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124295, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38703407

ABSTRACT

Surface-enhanced Raman Spectroscopy (SERS) is extensively implemented in drug detection due to its sensitivity and non-destructive nature. Deep learning methods, which are represented by convolutional neural network (CNN), have been widely applied in identifying the spectra from SERS for powerful learning ability. However, the local receptive field of CNN limits the feature extraction of sequential spectra for suppressing the analysis results. In this study, a hybrid Transformer network, TMNet, was developed to identify SERS spectra by integrating the Transformer encoder and the multi-layer perceptron. The Transformer encoder can obtain precise feature representations of sequential spectra with the aid of self-attention, and the multi-layer perceptron efficiently transforms the representations to the final identification results. TMNet performed excellently, with identification accuracies of 99.07% for the spectra of hair containing drugs and 97.12% for those of urine containing drugs. For the spectra with additive white Gaussian, baseline background, and mixed noises, TMNet still exhibited the best performance among all the methods. Overall, the proposed method can accurately identify SERS spectra with outstanding noise resistance and excellent generalization and holds great potential for the analysis of other spectroscopy data.

20.
ACS Appl Mater Interfaces ; 16(19): 25246-25255, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38696547

ABSTRACT

Ion transportation via the mixed mechanisms of hydrogels underpins ultrafast biological signal transmission in nature, and its application to the rapid and sensitive sensing detection of human specific ions is of great interest for the field of medical science. However, current research efforts are still unable to achieve transmission results that are comparable to those of bioelectric signals. Herein, 3D interconnected nanochannels based on poly(pyrrole-co-dopamine)/poly(vinyl alcohol) (P(Py-co-DA)/PVA) supernetwork conductive hydrogels are designed and fabricated as stimuli-responsive structures for K+ ions. Distinct from conventional configurations, which exhibit rapid electron transfer and permeability to biosubstrates, interconnected nanofluidic nanochannels collaborated with the P(Py-co-DA) conductive polymer in the supernetwork conductive hydrogel significantly improve conductivity (88.3 mS/cm), ion transport time (0.1 s), and ion sensitivity (74.6 mV/dec). The faster ion response time is attributed to the synergism of excellent conductivity originating from the P(Py-co-DA) polymer and the electronic effect in the interconnected nanofluidic channels. Furthermore, the supernetwork conductive hydrogel demonstrates K+ ion selectivity relative to other cations in biofluids such as Na+, Mg2+, and Ca2+. The DFT calculation indicates that the small solvation energy and low chemical transfer resistance are the main reasons for the excellent K+ ion selectivity. Finite element analysis (FEA) simulations further support these experimental results. Consequently, the P(Py-co-DA)/PVA supernetwork conductive hydrogels enriched with the 3D interconnected nanofluidic channels developed in this work possess excellent sensing of K+ ions. This strategy provides great insight into efficient ion sensing in traditional biomedical sensing that has not been explored by previous researchers.

SELECTION OF CITATIONS
SEARCH DETAIL
...