ABSTRACT
The challenges generated by insufficient T cell activation and infiltration have constrained the application of immunotherapy. Making matters worse, the complex tumor microenvironment (TME), resistance to apoptosis collectively poses obstacles for cancer treatment. The carrier-free small molecular self-assembly strategy is a current research hotspot to overcome these challenges. This strategy can transform multiple functional agents into sustain-released hydrogel without the addition of any excipients. Herein, a coordination and hydrogen bond mediated tricomponent hydrogel (Cel hydrogel) composed of glycyrrhizic acid (GA), copper ions (Cu2+) and celastrol (Cel) was initially constructed. The hydrogel can regulate TME by chemo-dynamic therapy (CDT), which increases reactive oxygen species (ROS) in conjunction with GA and Cel, synergistically expediting cellular apoptosis. What's more, copper induced cuproptosis also contributes to the anti-tumor effect. In terms of regulating immunity, ROS generated by Cel hydrogel can polarize tumor-associated macrophages (TAMs) into M1-TAMs, Cel can induce T cell proliferation as well as activate DC mediated antigen presentation, which subsequently induce T cell proliferation, elevate T cell infiltration and enhance the specific killing of tumor cells, along with the upregulation of PD-L1 expression. Upon co-administration with aPD-L1, this synergy mitigated both primary and metastasis tumors, showing promising clinical translational value.
Subject(s)
Copper , Hydrogels , Immune Checkpoint Inhibitors , Immunotherapy , Lymphocyte Activation , Pentacyclic Triterpenes , Reactive Oxygen Species , T-Lymphocytes , Tumor Microenvironment , Pentacyclic Triterpenes/pharmacology , Hydrogels/chemistry , Animals , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Immunotherapy/methods , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Mice , Lymphocyte Activation/drug effects , Copper/chemistry , Tumor Microenvironment/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Humans , Mice, Inbred C57BL , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/chemistry , Female , Triterpenes/pharmacology , Triterpenes/chemistryABSTRACT
OBJECTIVE: To investigate the therapeutic efficacy and prognostic factors of combined administration of estriol valerate tablets and progesterone for the prevention of intrauterine adhesions (IUA) in patients with early missed abortion (EMA) after dilation and curettage. METHODS: Clinical data of 120 EMA patients undergoing dilation and curettage at Ganzhou People's Hospital from July 2021 to June 2023 were collected for this retrospective study. The 120 enrolled patients were divided into two groups, with 70 patients in the study group receiving both estriol valerate tablets and progesterone for the prevention of IUA, and 50 in the control group undergoing no such treatments at all. The therapeutic efficacy of IUA prevention in patients was compared between the two groups. Subsequently, patients who developed IUA were categorized into the adhesion group (n = 23) and those who did not into the non-adhesion group (n = 97). The clinical data of patients were compared between the adhesion group and the non-adhesion group. Both univariate and multivariate logistic regression analyses were performed to identify the risk factors of IUA in patients with EMA after dilation and curettage. Receiver Operating Characteristic (ROC) curves were drawn to analyze the predictive value of independent risk factors for IUA in patients with EMA after dilation and curettage. RESULTS: The study group showed a notably higher excellent and good response rate than the control group in IUA prevention (92.00% vs. 82.00%, P = 0.035). Logistic regression analysis revealed that a history of multiple previous miscarriages (P: 0.018; OR: 0.120; 95% CI: 0.02-2.119), relatively small endometrial volume (P: 0.001; OR: 0.026; 95% CI: 0.003-0.210), relatively thin endometrial thickness (P: 0.001; OR: 32.123; 95% CI: 4.339-237.807) and lack of preventive treatment (P: 0.051; OR: 0.211; 95% CI: 0.048-0.935) were independent risk factors for the occurrence of IUA in patients with EMA after dilation and curettage. ROC curve-based analysis showed that these risk factors; encompassing, the number of previous miscarriages, endometrial volume, endometrial thickness and preventive treatment, had a notably higher efficacy in jointly predicting the occurrence of IUA in EMA patients following dilation and curettage in comparison to an individual risk factor alone. CONCLUSION: The occurrence of IUA in patients with EMA following dilation and curettage is influenced by several factors, including the number of previous miscarriages, the volume and thickness of the endometrium, and preventive treatments. To minimize the risk of IUA, it is crucial to implement proactive interventions prior to uterine surgeries. It was found that a combination therapy involving estriol valerate tablets and progesterone could effectively prevent the development of IUA in patients with EMA after dilation and curettage.
ABSTRACT
Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.
Subject(s)
Autoantibodies , Interferon-gamma , Humans , Prospective Studies , Male , Female , Middle Aged , Autoantibodies/blood , Autoantibodies/immunology , Interferon-gamma/blood , Interferon-gamma/immunology , Aged , Adult , Glucocorticoids/therapeutic use , Opportunistic Infections/immunology , Opportunistic Infections/drug therapy , Syndrome , Immunoglobulin G/blood , Immunoglobulin G/immunologyABSTRACT
The longan pericarp turns brown dramatically after harvesting, but the mechanism is not well understood. In this work, two peroxidases were purified from longan pericarp and found to be identical to the class III peroxidases PRX53-2 and PRX53-3. In vitro, PRX53-2/3 catalyzed the browning of several pericarp abundant proanthocyanidin and lignin monomers, such as (-)-epicatechin (EC), (+)-catechin (CT) and coniferyl alcohol (ConA). PRX53-2 was upregulated and highly-expressed, while PRX53-3 was expressed at low levels after harvesting; thus, PRX53-2 was considered a browning-related gene. The reaction with both proanthocyanidin and lignin presented a greater degree of brown coloration compared to the single substrate reactions. Several procyanidins isomers, EC-ConA and CT-ConA were detected in the double-substrate reaction. These results not only demonstrate that the effects of PRX53-2 on proanthocyanidin and lignin polymerization may be crucial for longan pericarp browning, but also help in developing new strategies or preservatives to delay pericarp browning.
ABSTRACT
BACKGROUND: Patients in late-stage Parkinson's disease (PDLS) are caregiver-dependent, have low quality of life, and higher healthcare costs. OBJECTIVE: To estimate the prevalence of PDLS patients in the current US healthcare system. METHODS: We downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 US healthcare sites. PD was identified using standard diagnosis codes, and PDLS was identified by the usage of wheelchair dependence, personal care assistance, and/or presence of diagnoses of dementia. Age of PDLS identification and survival information were obtained and stratified by demographic and the disability subgroups. RESULTS: We identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fitted our definition of PDLS (n = 194,297), and 10.2% met two or more late-stage criteria. Among all PDLS, the mean age of PDLS identification was 78.1 (±7.7) years, and 49% were already reported as deceased. PDLS patients were predominantly male (58.5%) with similar distribution across PDLS subgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information >90% (n = 53,162) were White, 8.2% (n = 5121) Hispanic/Latino, 7.8% (n = 4557) Black, and <0.01% (n = 408) Asian. Of the PDLS cohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair-bound. CONCLUSIONS: Late-stage patients are a significant part of the PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
ABSTRACT
Plant pollen tubes and root hairs typical polarized tip growth. It is well established that calcium ions (Ca2+) play essential roles in maintaining cell polarity and guiding cell growth orientation. Ca2+ signals are encoded by Ca2+ channels and transporters and are decoded by a variety of Ca2+-binding proteins often called Ca2+ sensors, in which calcineurin B-like protein (CBL) proteins function by interacting with and activating a group of kinases, activate CBL-interacting protein kinases (CIPKs). Some CBL-CIPK complexes, such as CBL2/3-CIPK12/19, act as crucial regulators of pollen tube growth. Whether these calcium decoding components regulate the growth of root hairs, another type of plant cell featuring Ca2+-regulated polarized growth, remains unknown. In this study, we identified CIPK13 and CIPK18 as genes specifically expressed in Arabidopsis (Arabidopsis thaliana) root hairs. The cipk13 cipk18 double mutants showed reduced root hair length and lower growth rates. The calcium oscillations at the root hair tip were attenuated in the cipk13 cipk18 mutants as compared to the wild-type plants. Through yeast two-hybrid screens, CBL2 and CBL3 were identified as interacting with CIPK13 and CIPK18. cbl2 cbl3 displayed a shortened root hair phenotype similar to cipk13 cipk18. This genetic analysis, together with biochemical assays showing activation of CIPK13/18 by CBL2/3, supported the conclusion that CBL2/3 and CIPK13/18 may work as Ca2+-decoding modules in controlling root hair growth. Thus, the findings that CIPK12/19 and CIPK13/18 function in pollen tube and root hair growth, respectively, illustrate a molecular mechanism in which the same CBLs recruit distinct CIPKs in regulating polarized tip growth in different types of plant cells.
ABSTRACT
Studies have confirmed that the spatial arrangement of chiral molecules has a decisive influence on supramolecular assembly. However, the effect of epimerization caused by the change of a single chiral center on the self-assembly of chiral molecules has not been reported. Herein, we explored a pair of epimers 18 α-glycyrrhetinic acid and 18 ß-glycyrrhetinic acid from Glycyrrhiza uralensis Fisch, which had completely different medicinal activities. In this study, we found that these epimers of glycyrrhetinic acid showed distinct self-assembly properties under the condition of the deionized water and a small amount of DMSO solution. Interestingly, the cis-configured 18 ß-GA could form a 'head-to-tail' interlaced structure and further self-assembled to form nanoparticles, while trans-configured 18 α-GA was connected in a "head-to-head" manner, and due to the excessive steric hindrance that made it difficult to assemble. This work not only clearly demonstrates the impact of epimerization due to changes in a single chiral center on the self-assembly of chiral molecules as well as biological activity, but also provides new insights into the self-assembly of natural organic molecules in the development of nanomedicines and biofunctional materials.
Subject(s)
Anti-Bacterial Agents , Glycyrrhetinic Acid , Glycyrrhetinic Acid/chemistry , Glycyrrhetinic Acid/pharmacology , Glycyrrhetinic Acid/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Stereoisomerism , Microbial Sensitivity Tests , Nanoparticles/chemistry , Glycyrrhiza uralensis/chemistry , Escherichia coli/drug effects , Particle Size , Staphylococcus aureus/drug effectsABSTRACT
The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from â¼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.
ABSTRACT
Alpha-synuclein seed amplification assays (αSyn-SAAs) have emerged as promising diagnostic tools for Parkinson's disease (PD) by detecting misfolded αSyn and amplifying the signal through cyclic shaking and resting in vitro. Recently, our group and others have shown that multiple biospecimens, including CSF, skin, and submandibular glands (SMGs), can be used to seed the aggregation reaction and robustly distinguish between patients with PD and non-disease controls. The ultrasensitivity of the assay affords the ability to detect minute quantities of αSyn in peripheral tissues, but it also produces various technical challenges of variability. To address the problem of variability, we present a high-yield αSyn protein purification protocol for the efficient production of monomers with a low propensity for self-aggregation. We expressed wild-type αSyn in BL21 Escherichia coli, lysed the cells using osmotic shock, and isolated αSyn using acid precipitation and fast protein liquid chromatography (FPLC). Following purification, we optimized the ionic strength of the reaction buffer to distinguish the fluorescence maximum (Fmax) separation between disease and healthy control tissues for enhanced assay performance. Our protein purification protocol yielded high quantities of αSyn (average: 68.7 mg/mL per 1 L of culture) and showed highly precise and robust αSyn-SAA results using brain, skin, and SMGs with inter-lab validation.
Subject(s)
Parkinson Disease , alpha-Synuclein , alpha-Synuclein/genetics , alpha-Synuclein/chemistry , alpha-Synuclein/isolation & purification , alpha-Synuclein/metabolism , Humans , Parkinson Disease/metabolism , Parkinson Disease/genetics , Osmolar Concentration , Reproducibility of Results , Escherichia coli/genetics , Escherichia coli/metabolismABSTRACT
INTRODUCTION: The substantia nigra pars compacta (SNc) is the key pathologic locus in neurodegenerative parkinsonian disorders. Recently, in vivo susceptibility MRI metrics were associated with postmortem glial cell density and tau burden in the SNc of parkinsonism subjects. This study investigated the red nucleus (RN), another iron-rich region adjacent to the SNc and a potential site of higher functionality in parkinsonisms. METHODS: In vivo MRI and postmortem data were obtained from 34 parkinsonism subjects and 3 controls. Neuron density, glial cell density, and percentages of area occupied by α-synuclein and tau were quantified using digitized midbrain slides. R2* and quantitative susceptibility mapping (QSM) metrics in the RN and SNc were derived from multi-gradient echo images. Histopathology data were compared between the RN and SNc using paired t-tests. MRI-histology associations were analyzed using partial Pearson correlations. RESULTS: The RN had greater neuron (t23 = 3.169, P = 0.004) and glial cell densities (t23 = 2.407, P = 0.025) than the SNc, whereas the SNc had greater α-synuclein (t28 = 4.614, P < 0.0001) and tau burden (t24 = 4.513, P = 0.0001). In both the RN (R2*: r = 0.47, P = 0.043; QSM: r = 0.52, P = 0.024) and SNc (R2*: r = 0.57, P = 0.01; QSM: r = 0.58, P = 0.009), MRI values were associated with glial cell density but not neuron density or α-synuclein (Ps > 0.092). QSM associated with tau burden (r = 0.49, P = 0.038) in the SNc, but not the RN. CONCLUSIONS: The RN is resilient to parkinsonian-related pathological processes compared to the SNc, and susceptibility MRI captured glial cell density in both regions. These findings help to further our understanding of the underlying pathophysiological processes in parkinsonisms.
Subject(s)
Magnetic Resonance Imaging , Parkinsonian Disorders , Pars Compacta , Red Nucleus , Substantia Nigra , Humans , Red Nucleus/diagnostic imaging , Red Nucleus/pathology , Red Nucleus/metabolism , Male , Aged , Female , Pars Compacta/diagnostic imaging , Pars Compacta/pathology , Pars Compacta/metabolism , Aged, 80 and over , Middle Aged , Parkinsonian Disorders/diagnostic imaging , Parkinsonian Disorders/pathology , Parkinsonian Disorders/metabolism , Substantia Nigra/diagnostic imaging , Substantia Nigra/pathology , Substantia Nigra/metabolism , tau Proteins/metabolism , Neuroglia/pathology , Neuroglia/metabolism , alpha-Synuclein/metabolism , Neurons/pathology , Neurons/metabolismABSTRACT
Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2) has been related to transcriptional inhibition and chromatin compaction. Nevertheless, the biological functions and mechanisms of L3MBTL2 are undefined in breast cancer (BRCA). Here, we revealed that L3MBTL2 is responsible for the decline of Nischarin (NISCH), a well-known tumor suppressor, in BRCA, and explored the detailed mechanism. Knockdown of L3MBTL2 reduced monoubiquitination of histone H2A at lysine-119 (H2AK119ub), leading to reduced binding to the NISCH promoter and increased expression of NISCH. Meanwhile, the knockdown of L3MBTL2 decreased proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BRCA cells, and increased apoptosis, which were abated by NISCH knockdown. Nucleolar transcription factor 1 (UBTF) induced the transcription of L3MBTL2 in BRCA, and the suppressing effects of UBTF silencing on EMT in BRCA cells were also reversed by NISCH knockdown. Knockdown of UBTF slowed tumor progression and attenuated lung tumor infiltration, whereas simultaneous knockdown of NISCH accelerated EMT and increased tumor lung metastasis. Taken together, our results show that L3MBTL2, transcriptionally activated by UBTF, exerts oncogenic functions in BRCA, by catalyzing H2AK119Ub and reducing expression of NISCH.
ABSTRACT
BACKGROUND: Asiaticoside (AS) has been reported to improve the changes induced by high glucose stimulation, and it may have potential therapeutic effects on gestational diabetes mellitus (GDM). This study aims to explore the effect of AS on the cell model of GDM and the action mechanism of the PI3K/AKT pathway. METHODS: The GDM model was established in HTR-8/Svneo cells with a high glucose (HG) medium. After the cytotoxicity assay of AS, cells were divided into the control group, HG group and HG + AS group to conduct control experiment in cells. The cell proliferation and migration were detected by CCK-8 assay and scratch test, respectively. The mRNA levels of PI3K, AKT2, mTORC1, and GLUT4 in PI3K/AKT signalling pathway were measured by RT-PCR, and the protein expressions of these signalling molecules were monitored by western blot. RESULTS: AS showed a promotion effect on the cell proliferation rate of HTR-8/Svneo cells, and 80 µmol/L AS with a treatment time of 48 h had no cytotoxicity. The cell proliferation rate, migration rate, mRNA levels and protein expressions of PI3K, AKT2, mTORC1, and GLUT4 in the HG group were significantly lower than those in the control group, which were significantly increased in the HG + AS group (p < 0.05). CONCLUSIONS: AS can facilitate the cell proliferation and migration in the cell model of GDM, and might play a role in GDM treatment via PI3K/AKT pathway.
Asiaticoside possesses various pharmacological effects and has been reported to show a beneficial effect on the treatment of diabetes mellitus. This research firstly investigated the effect and mechanism of asiaticoside on gestational diabetes mellitus, and found that asiaticoside could facilitate the cell proliferation and migration of HTR-8/Svneo cells treated with high glucose, and affect the signalling molecules of PI3K/AKT pathway. Therefore, asiaticoside may be a novel useful therapeutic drug in the treatment of gestational diabetes mellitus.
Subject(s)
Cell Movement , Cell Proliferation , Diabetes, Gestational , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Triterpenes , Humans , Diabetes, Gestational/metabolism , Female , Pregnancy , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation/drug effects , Triterpenes/pharmacology , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Cell Movement/drug effects , Cell Line , Trophoblasts/drug effects , Trophoblasts/metabolism , Glucose/pharmacology , Mechanistic Target of Rapamycin Complex 1/metabolismABSTRACT
Baicalein has been implicated in the chemotherapy overcoming triple-negative breast cancer (TNBC). However, many unanswered questions remain regarding its role in treating TNBC. Here, we sought to demonstrate the molecular pathway mediated by baicalein in TNBC. Lysine-specific demethylase 4E (KDM4E), reduced in TNBC cells, was identified as a target protein of baicalein, and baicalein enhanced the protein expression and stability of KDM4E in TNBC cells. Knockdown of KDM4E attenuated the inhibitory effect of baicalein on TNBC cell activity, as demonstrated by intensified mobility, viability, and apoptosis resistance in TNBC cells. KDM4E activated protein bicaudal D homolog 1 (BICD1) expression by reducing the deposition of histone H3 lysine 9 trimethylation (H3K9me3) in its promoter, whereas BICD1 promoted protease-activated receptor-1 (PAR1) endocytosis and blocked PAR1 signaling through physical interaction with PAR1. Knockdown of KDM4E strengthened the PAR1-dependent activity of TNBC cells in response to thrombin activation, whereas TNBC progression activated by PAR1 signaling was blocked by combined overexpression of BICD1. Taken together, our data indicate that baicalein-promoted KDM4E enhanced the expression of BICD1 and activated the inhibitory effect of BICD1 on PAR1 signaling, thereby inhibiting TNBC progression.
Subject(s)
Flavanones , Signal Transduction , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Flavanones/pharmacology , Female , Signal Transduction/drug effects , Cell Line, Tumor , Animals , Receptor, PAR-1/metabolism , Receptor, PAR-1/genetics , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects , Apoptosis/drug effects , Disease Progression , MiceABSTRACT
Endocrine therapy (ET) for breast cancer treatment is associated with cognitive complaints, but their etiology is poorly understood. To address this, we developed and implemented an ambulatory assessment protocol consisting of wearable activity monitors, brief surveys of affect, context, and perceived impairments, and ultra-brief performance-based measures of cognition. Newly diagnosed, ER/PR+, stage 0-III, female breast cancer patients, were recruited. Ambulatory assessments were conducted on smart phones and wearable activity monitors were used to monitor sleep and physical activity. Participants were asked to complete five 7-day measurement bursts (one before starting ET and one each month for 4 consecutive months while on ET). We observed a consent rate of 36%, 27 women completed the study. Of the women that withdrew, 91% dropped prior to the midpoint of follow up. There were no significant differences in demographics, clinical breast cancer characteristics, sleep or physical activity patterns, or measures of cognition between women who completed versus withdrew. Women who did not complete the study provided fewer valid days of baseline data. In conclusion, while some women may be overwhelmed with their cancer diagnosis, we did not identify any predictive characteristics of women whom did not complete the study. This novel method enables the prospective study of psychological changes associated with cancer treatment, capturing a wide array of information about behavior, experience, and cognition, thus providing a picture of the lived experiences of cancer patients before and during exposure to ET.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Feasibility Studies , Prospective Studies , Sleep , CognitionABSTRACT
Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.
Subject(s)
Airway Remodeling , Asthma , Bronchi , Eosinophil Peroxidase , Epithelial Cells , Epithelial-Mesenchymal Transition , Transforming Growth Factor beta1 , Humans , Asthma/metabolism , Asthma/pathology , Asthma/physiopathology , Asthma/immunology , Male , Female , Epithelial Cells/metabolism , Eosinophil Peroxidase/metabolism , Transforming Growth Factor beta1/metabolism , Middle Aged , Adult , Bronchi/pathology , Interleukin-5/metabolism , Chromones/pharmacology , Cytokines/metabolism , Cell Line , Thymic Stromal Lymphopoietin , Cell Proliferation , Cell Movement , Morpholines/pharmacology , ADAM ProteinsABSTRACT
The multifunctional development in the field of face masks and the growing demand for scalable manufacturing have become increasingly prominent. In this study, we utilized high-vacuum magnetron sputtering technology to deposit a 5 nm ultra-thin Ag-Cu film on non-woven fabric and fabricated ultra-thin Ag-Cu film face masks. The antibacterial rates against Escherichia coli and Staphylococcus aureus were 99.996% and 99.978%, respectively, while the antiviral activity against influenza A virus H1N1 was 99.02%. Furthermore, the mask's ability to monitor respiratory system diseases was achieved through color change (from brownish-yellow to grey-white). The low cost and scalability potential of ultra-thin silver-copper film masks offer new possibilities for practical applications of multifunctional masks.
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Radiative cooling is the process to dissipate heat to the outer space through an atmospheric window (8-13 µm), which has great potential for energy savings in buildings. However, the traditional "static" spectral characteristics of radiative cooling materials may result in overcooling during the cold season or at night, necessitating the development of dynamic spectral radiative cooling for enhanced energy saving potential. In this study, we showcase the realization of dynamic radiative cooling by modulating the heat transfer process using a tunable transmittance convection shield (TTCS). The transmittance of the TTCS in both solar spectrum and atmospheric window can be dynamically adjusted within ranges of 28.8-72.9 and 27.0-80.5%, with modulation capabilities of ΔTsolar = 44.1% and ΔT8-13 µm = 53.5%, respectively. Field measurements demonstrate that through the modulation, the steady-state temperature of the TTCS architecture is 0.3 °C lower than that of a traditional radiative cooling architecture during the daytime and 3.3 °C higher at nighttime, indicating that the modulation strategy can effectively address the overcooling issue, offering an efficient way of energy saving through dynamic radiative cooling.
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BACKGROUND: A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices. METHODS: Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared. RESULTS: In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons' performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p < 0.005). During the training period, the Group B2 takes 6 trails to achieve gripping force of 0.635 N, which is lower than the threshold line, whereas the Group A2 needs 11 trails, meaning that the learning curve of Group B2 was significantly shorter than that of Group A2. Additionally, during the follow-up period, there was no significant decline in force learning, and Group B2 demonstrated better control of gripping operations. The training with force feedback received positive evaluations. CONCLUSION: Our study shows that using a grasper providing force feedback in laparoscopic training can help to control the gripping force and shorten the learning curve. It is anticipated that the laparoscopic grasper equipped with FBG sensor is promising to provide force feedback during laparoscopic training, which ultimately shows great potential in laparoscopic surgery.
Subject(s)
Laparoscopy , Learning Curve , Humans , Feedback , Laparoscopy/education , Hand Strength , Clinical CompetenceABSTRACT
Purpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section. Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥4) and control group (<4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia. Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P<0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913-19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356-0.604), extraversion (OR=0.667, 95% CI=0.513-0.866), neuroticism (OR=1.427, 95% CI=1.104-1.844), and PCS (OR=7.718, 95% CI=0.657-0.783) were factors affecting postoperative analgesia. Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.
ABSTRACT
BACKGROUND: Air pollutants may contribute to the development of Parkinson's disease (PD), but empirical evidence is limited and inconsistent. OBJECTIVES: This study aimed to prospectively investigate the associations of PD with ambient exposures to fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and nitrogen dioxide (NO2). METHODS: We analyzed data from 47,108 US women from the Sister Study, enrolled from 2003-2009 (35-80 years of age) and followed through 2018. Exposures of interest included address-level ambient PM2.5 and NO2 in 2009 and their cumulative averages from 2009 to PD diagnosis with varying lag-years. The primary outcome was PD diagnosis between 2009 and 2018 (n=163). We used multivariable Cox proportional hazards and time-varying Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: NO2 exposure in 2009 was associated with PD risk in a dose-response manner. The HR and 95% CI were 1.22 (95% CI: 1.03, 1.46) for one interquartile [4.8 parts per billion (ppb)] increment in NO2, adjusting for age, race and ethnicity, education, smoking status, alcohol drinking, caffeine intake, body mass index, physical activity, census region, residential area type, area deprivation index (ADI), and self-reported health status. The association was confirmed in secondary analyses with time-varying averaged cumulative exposures. For example, the multivariable adjusted HR for PD per 4.8 ppb increment in NO2 was 1.25 (95% CI: 1.05, 1.50) in the 2-year lag analysis using cumulative average exposure. Post hoc subgroup analyses overall confirmed the association. However, statistical interaction analyses found that the positive association of NO2 with PD risk was limited to women in urban, rural, and small town areas and women with ≥50th percentile ADI but not among women from suburban areas or areas with <50th percentile ADI. In contrast, PM2.5 exposure was not associated with PD risk with the possible exception for women from the Midwest region of the US (HRinterquartile-range=2.49, 95% CI: 1.20, 5.14) but not in other census regions. DISCUSSION: In this nationwide cohort of US women, higher level exposure to ambient NO2 is associated with a greater risk of PD. This finding needs to be independently confirmed and the underlying mechanisms warrant further investigation. https://doi.org/10.1289/EHP13009.