Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 961
Filter
2.
Respir Med ; : 107663, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38763445

ABSTRACT

BACKGROUND: Few evidence exists for the effect of frailty on the patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). OBJECTIVE: We explored the link of frailty and in-hospital death, and whether laboratory indicators mediate this association. METHODS: This was a real-world prospective cohort study including older patients with AECOPD, consisting of two cohorts, training set (n=1356) and validation set (n=478). The independent prognostic factors including frail status were determined by multivariate logistic regression analysis. The relationship between frailty and in-hospital mortality was estimated by multivariable Cox regression. A nomogram was developed to provide the clinician with a quantitative tool to predict the risk of in-hospital death. Mediation analyses for frailty and in-hospital death were conducted. RESULTS: The training set included 1356 patients(aged 86.7±6.6), and 25.0% of them were frail. A nomogram model was created, including ten independent variables: age, sex, frailty, chronic obstructive pulmonary disease grades (COPD grades), severity of exacerbation, mean arterial pressure (MAP), Charlson Comorbidity Index (CCI), Interleukin-6 (IL-6), albumin, and troponin T (TPN-T). The area under the receiver operating characteristic curve (ROCs) was 0.862 and 0.845 for the training set and validation set, respectively. Patients with frailty had higher risk of in-hospital death than those without frailty (HR,1.83, 95%CI: 1.14-2.94; p=0.013). Furthermore, CRP and albumin mediated the associations between frailty with in-hospital death. CONCLUSIONS: Frailty may be an adverse prognostic factor for older patients admitted with an AECOPD. CRP and albumin may be parts of the immunoinflammatory mechanism between frailty and in-hospital death.

4.
Phytomedicine ; 130: 155704, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38759316

ABSTRACT

BACKGROUND: Dysregulation of vascular smooth muscle cell (VSMC) function leads to a variety of diseases such as atherosclerosis and hyperplasia after injury. However, antiproliferative drug targeting VSMC exhibits poor specificity. Therefore, there is an urgent to develop highly specific antiproliferative drugs to prevention and treatment VSMC dedifferentiation associated arteriosclerosis. Kanglexin (KLX), a new anthraquinone compound designed by our team, has potential to regulate VSMC phenotype according to the physicochemical properties. PURPOSE: This project aims to evaluate the therapeutic role of KLX in VSMC dedifferentiation and atherosclerosis, neointimal formation and illustrates the underlying molecular mechanism. METHODS: In vivo, the ApoE-/- mice were fed with high-fat diet (HFD) for a duration of 13 weeks to establish the atherosclerotic model. And rat carotid artery injury model was performed to establish the neointimal formation model. In vitro, PDGF-BB was used to induce VSMC dedifferentiation. RESULTS: We found that KLX ameliorated the atherosclerotic progression including atherosclerotic lesion formation, lipid deposition and collagen deposition in aorta and aortic sinus in atherosclerotic mouse model. In addition, The administration of KLX effectively ameliorated neointimal formation in the carotid artery following balloon injury in SD rats. The findings derived from molecular docking and surface plasmon resonance (SPR) experiments unequivocally demonstrate that KLX had potential to bind PDGFR-ß. Mechanism research work proved that KLX prevented VSMC proliferation, migration and dedifferentiation via activating the PDGFR-ß-MEK -ERK-ELK-1/KLF4 signaling pathway. CONCLUSION: Collectively, we demonstrated that KLX effectively attenuated the progression of atherosclerosis in ApoE-/- mice and carotid arterial neointimal formation in SD rats by inhibiting VSMC phenotypic conversion via PDGFR-ß-MEK-ERK-ELK-1/KLF4 signaling. KLX exhibits promising potential as a viable therapeutic agent for the treatment of VSMC phenotype conversion associated arteriosclerosis.

5.
J Environ Manage ; 360: 121088, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38735070

ABSTRACT

Residue returning (RR) was widely implemented to increase soil organic carbon (SOC) in farmland. Extensive studies concentrated on the effects of RR on SOC quantity instead of SOC fractions at aggregate scales. This study investigated the effects of 20-year RR on the distribution of labile (e.g., dissolved, microbial biomass, and permanganate oxidizable organic) and stable (e.g., microbial necromass) carbon fractions at aggregate scales, as well as their contribution to SOC accumulation and mineralization. The findings indicated a synchronized variation in the carbon content of bacterial and fungal necromass. Residue retention (RR) notably elevated the concentration of bacterial and fungal necromass carbon, while it did not amplify the microbial necromass carbon (MNC) contribution to SOC when compared to residue removal (R0) in the topsoil (0-5 cm). In the subsoil (5-15 cm), RR increased the MNC contribution to SOC concentration by 21.2%-33.4% and mitigated SOC mineralization by 12.6% in micro-aggregates (P < 0.05). Besides, RR increased soil ß-glucosidase and peroxidase activities but decreased soil phenol oxidase activity in micro-aggregates (P < 0.05). These indicated that RR might accelerate cellulose degradation and conversion to stable microbial necromass C, and thus RR improved SOC stability because SOC occluded in micro-aggregates were more stable. Interestingly, SOC concentration was mainly regulated by MNC, while SOC mineralization was by dissolved organic carbon under RR, both of which were affected by soil carbon, nitrogen, and phosphorus associated nutrients and enzyme activities. The findings of this study emphasize that the paths of RR-induced SOC accumulation and mineralization were different, and depended on stable and labile C, respectively. Overall, long-term RR increased topsoil carbon quantity and subsoil carbon quality.

6.
BMJ Open ; 14(5): e082484, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760047

ABSTRACT

PURPOSE: The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted. METHODS: Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. RESULTS: A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively. CONCLUSIONS: Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.


Subject(s)
Glomerular Filtration Rate , Immune Checkpoint Inhibitors , Nomograms , Humans , Male , Female , Retrospective Studies , Immune Checkpoint Inhibitors/adverse effects , Middle Aged , Case-Control Studies , Aged , Risk Factors , Logistic Models , Neoplasms/drug therapy , Renal Insufficiency/chemically induced , Renal Insufficiency/epidemiology , Kidney Diseases/chemically induced , Kidney Diseases/epidemiology
7.
Brain Sci ; 14(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38790448

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental disorder that affects approximately 5-10% of school-aged children worldwide. Early diagnosis and intervention are essential to improve the quality of life of patients and their families. In this study, we propose ConvMixer-ECA, a novel deep learning architecture that combines ConvMixer with efficient channel attention (ECA) blocks for the accurate diagnosis of ADHD using electroencephalogram (EEG) signals. The model was trained and evaluated using EEG recordings from 60 healthy children and 61 children with ADHD. A series of experiments were conducted to evaluate the performance of the ConvMixer-ECA. The results showed that the ConvMixer-ECA performed well in ADHD recognition with 94.52% accuracy. The incorporation of attentional mechanisms, in particular ECA, improved the performance of ConvMixer; it outperformed other attention-based variants. In addition, ConvMixer-ECA outperformed state-of-the-art deep learning models including EEGNet, CNN, RNN, LSTM, and GRU. t-SNE visualization of the output of this model layer validated the effectiveness of ConvMixer-ECA in capturing the underlying patterns and features that separate ADHD from typically developing individuals through hierarchical feature learning. These outcomes demonstrate the potential of ConvMixer-ECA as a valuable tool to assist clinicians in the early diagnosis and intervention of ADHD in children.

8.
Clin Nutr ; 43(6): 1524-1531, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38744096

ABSTRACT

BACKGROUND: Cachexia is prevalent in cancer patients. The conventional diagnostic criteria for cachexia are often based on Western evidence, lacking consensus for Asian populations. This study aims to compare Asian Working Group for Cachexia (AWGC) criteria with Fearon's criteria, assessing their differences in population characteristics and prognostic impact. METHODS: The clinical data of patients who underwent radical gastrectomy between 2013 and 2019 were prospectively collected. Cachexia diagnosis involves the utilization of either AWGC criteria and the previous international consensus proposed by Fearon et al. A scoring model is established based on the optional criteria according to the AWGC criteria. Univariate and multivariate logistic and Cox regression analysis were conducted to determine the independent effect factors for postoperative complications and overall survival. RESULTS: In a total of 1330 patients, 461 met AWGC cachexia criteria and 311 met Fearon's criteria. Excluding 262 overlapping cases, those diagnosed solely with AWGC-cachexia had higher age and lower BMI, albumin, hemoglobin, and handgrip strength compared to those by Fearon's criteria alone. AWGC-cachexia independently increased the risk of postoperative complications, whereas Fearon's criteria did not. Patients with AWGC-cachexia also exhibited shorter overall survival than Fearon's criteria. The AWGC-based cachexia grading system effectively stratifies the risks of postoperative complications and mortality. CONCLUSIONS: The AWGC criteria is more effective in diagnosing cancer cachexia in the Asian population and provide better prognostic indicators.

9.
Int J Biol Macromol ; 268(Pt 2): 131868, 2024 May.
Article in English | MEDLINE | ID: mdl-38677690

ABSTRACT

Phenotype transformation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Asprosin is a newly discovered adipokine, which is critical in regulating metabolism. However, the relationship between asprosin and phenotype transformation of VSMCs in atherosclerosis remains unclear. The aim of this study is to investigate whether asprosin affects the progression of atherosclerosis by inducing phenotype transformation of VSMCs. We established an atherosclerosis model in ApoE-/- mice and administered asprosin recombinant protein and asprosin antibody to mice. Knocking down asprosin was also as an intervention. Interestingly, we found a correlation between asprosin levels and atherosclerosis. Asprosin promoted plaque formation and phenotype transformation of VSMCs. While, AspKD or asprosin antibody reduced the plaque lesion and suppressed vascular stiffness in ApoE-/- mice. Mechanistically, asprosin induced phenotype transformation of MOVAs by binding to GPR54, leading to Gαq/11 recruitment and activation of the PLC-PKC-ERK1/2-STAT3 signaling pathway. Si GPR54 or GPR54 antagonist partially inhibited the action of asprosin in MOVAs. Mutant GPR54-(267, 307) residue cancelled the binding of asprosin and GPR54. In summary, this study confirmed asprosin activated GPR54/Gαq/11-dependent ERK1/2-STAT3 signaling pathway, thereby promoting VSMCs phenotype transformation and aggravating atherosclerosis, thus providing a new target for the treatment of atherosclerosis.


Subject(s)
Atherosclerosis , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Phenotype , Animals , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/genetics , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Mice , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Fibrillin-1/metabolism , Fibrillin-1/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Male , Signal Transduction , Disease Models, Animal , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Humans , Extracellular Matrix Proteins/metabolism , Extracellular Matrix Proteins/genetics , Mice, Knockout
10.
World J Clin Cases ; 12(12): 2065-2073, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38680258

ABSTRACT

BACKGROUND: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS). CASE SUMMARY: We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD. CONCLUSION: In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.

11.
Pestic Biochem Physiol ; 201: 105849, 2024 May.
Article in English | MEDLINE | ID: mdl-38685233

ABSTRACT

Beta-cypermethrin (ß-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of ß-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17ß-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of ß-CYP and its specific isomers. Our results showed that ß-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 µM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and ß-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 µM 1R-trans-αS. Scratch assays revealed that ß-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor ß (ERß), ß-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of ß-CYP, its isomers, and E2 for PDE3A than for ERα or ERß. Consequently, ß-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.


Subject(s)
Apoptosis , Pyrethrins , Humans , Pyrethrins/toxicity , Pyrethrins/pharmacology , Apoptosis/drug effects , Cell Line , Molecular Docking Simulation , Estradiol/pharmacology , Cell Proliferation/drug effects , Insecticides/toxicity , Insecticides/pharmacology , Insecticides/chemistry , Isomerism , Cell Movement/drug effects , Benzoates/pharmacology , Benzoates/chemistry , Stereoisomerism , Cell Survival/drug effects , Estrogen Receptor alpha/metabolism , Cell Cycle Checkpoints/drug effects
12.
Plants (Basel) ; 13(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38674484

ABSTRACT

Trait-based approaches are increasingly used to understand crop yield improvement, although they have not been widely applied to anatomical traits. Little is known about the relationships between root and leaf anatomy and yield in wheat. We selected 20 genotypes that have been widely planted in Luoyang, in the major wheat-producing area of China, to explore these relationships. A field study was performed to measure the yields and yield components of the genotypes. Root and leaf samples were collected at anthesis to measure the anatomical traits relevant to carbon allocation and water transport. Yield was negatively correlated with cross-sectional root cortex area, indicating that reduced root cortical tissue and therefore reduced carbon investment have contributed to yield improvement in this region. Yield was positively correlated with root xylem area, suggesting that a higher water transport capacity has also contributed to increased yields in this study. The area of the leaf veins did not significantly correlate with yield, showing that the high-yield genotypes did not have larger veins, but they may have had a conservative water use strategy, with tight regulation of water loss from the leaves. This study demonstrates that breeding for higher yields in this region has changed wheat's anatomical traits, reducing the roots' cortical tissue and increasing the roots' xylem investment.

13.
Nanomaterials (Basel) ; 14(8)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38668184

ABSTRACT

It is usually difficult to realize high mobility together with a low threshold voltage and good stability for amorphous oxide thin-film transistors (TFTs). In addition, a low fabrication temperature is preferred in terms of enhancing compatibility with the back end of line of the device. In this study, α-IGZO TFTs were prepared by high-power impulse magnetron sputtering (HiPIMS) at room temperature. The channel was prepared under a two-step deposition pressure process to modulate its electrical properties. X-ray photoelectron spectra revealed that the front-channel has a lower Ga content and a higher oxygen vacancy concentration than the back-channel. This process has the advantage of balancing high mobility and a low threshold voltage of the TFT when compared with a conventional homogeneous channel. It also has a simpler fabrication process than that of a dual active layer comprising heterogeneous materials. The HiPIMS process has the advantage of being a low temperature process for oxide TFTs.

14.
Dalton Trans ; 53(17): 7350-7357, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38616717

ABSTRACT

Near-infrared (NIR) emissive probes are becoming increasingly popular in biological sensing and imaging due to the advantages of non-invasiveness and deep tissue-penetrating ability. Herein, a series of complexes of trivalent lanthanide ions (Ln = Yb, Er, and Gd) with the commercially available azo dye chromophore 2R (Na2H2C2R) as ligand and featuring respectively H2O and dimethylsulfoxide (DMSO) as ancillary ligands have been prepared. Formulated as [Ln2(HC2R)2(H2O)10]·8H2O (1-3, Ln = Yb, Er, Gd) and [Ln2(HC2R)2(DMSO)10]·2DMSO (4-6, Ln = Yb, Er, Gd), their structures have been determined by single-crystal X-ray diffraction studies. Photophysical property studies revealed NIR emissions of the DMSO complexes characteristic of Yb(III) and Er(III), effectively sensitized by the dye ligand arising mainly from the π-π* transition of the chromophore. The long-wavelength excitation of the complexes, covering the whole visible-light range and extending into the NIR region, portends the potential applications of such complexes for flexible bioimaging and sensing.

15.
J Clin Lab Anal ; 38(8): e25033, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38563457

ABSTRACT

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.


Subject(s)
Immunoglobulin G , Luminescent Measurements , Humans , Immunoglobulin G/blood , Female , Male , Middle Aged , Immunoassay/methods , Luminescent Measurements/methods , Adult , ROC Curve , Nephelometry and Turbidimetry/methods , Case-Control Studies , China , Aged , Sjogren's Syndrome/blood , Sjogren's Syndrome/diagnosis , Asian People , Immunoglobulin G4-Related Disease/blood , Immunoglobulin G4-Related Disease/diagnosis , East Asian People
16.
Angew Chem Int Ed Engl ; : e202404244, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639067

ABSTRACT

Ratiometric afterglow luminescent (AGL) probes are attractive for in vivo imaging due to their high sensitivity and signal self-calibration function. However, there are currently few ratiometric AGL probes available for imaging enzymatic activity in living organisms. Here, we present an energy diversion (ED) strategy that enables the design of an enzyme-activated ratiometric AGL probe (RAG-RGD) for in vivo afterglow imaging. The ED process provides RAG-RGD with a radiative transition for an 'always on' 520-nm AGL signal (AGL520) and a cascade three-step energy transfer (ET) process for an 'off-on' 710-nm AGL signal (AGL710) in response to a specific enzyme. Using matrix metalloproteinase-2 (MMP-2) as an example, RAG-RGD shows a significant ~11-fold increase in AGL710/AGL520 toward MMP-2. This can sensitively detect U87MG brain tumors through ratiometric afterglow imaging of MMP-2 activity, with a high signal-to-background ratio and deep imaging depth. Furthermore, by utilizing the self-calibration effect of ratiometric imaging, RAG-RGD demonstrated a strong negative correlation between the AGL710/AGL520 value and the size of orthotopic U87MG tumor, enabling accurate monitoring of orthotopic glioma growth in vivo. This ED process may be applied for the design of other enzyme-activated ratiometric afterglow probes for sensitive afterglow imaging.

17.
J Control Release ; 370: 95-109, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38642859

ABSTRACT

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

18.
Front Neurosci ; 18: 1349059, 2024.
Article in English | MEDLINE | ID: mdl-38560046

ABSTRACT

Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.

19.
NPJ Genom Med ; 9(1): 27, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582909

ABSTRACT

Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains: (I) Development, cognition, and mental health; (II) Feeding and growth; (III) Medication use and treatment history; (IV) Pain, sleep, and quality of life; (V) Adulthood; and (VI) Epilepsy. For a subset of articles, all subsequent published follow-up case descriptions were identified and assessed in a similar manner. A modified Delphi approach was used to develop consensus reporting guidelines, with input from content experts across four countries. In total, 200 of 3243 screened publications met inclusion criteria. Relevant phenotypic details across each of the 6 domains were rated superficial or deficient in >87% of papers. For example, less than 10% of publications provided details regarding neuropsychiatric diagnoses and "behavioural issues", or about the type/nature of feeding problems. Follow-up reports (n = 95) rarely contributed this additional phenotype data. In summary, phenotype information relevant to clinical management, genetic counselling, and the stated priorities of patients and families is lacking for many newly described genetic diseases. The PHELIX (PHEnotype LIsting fiX) reporting guideline checklists were developed to improve phenotype reporting in the genomic era.

20.
Insect Sci ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38571329

ABSTRACT

The silkworm, a crucial model organism of the Lepidoptera, offers an excellent platform for investigating the molecular mechanisms underlying the innate immune response of insects toward pathogens. Over the years, researchers worldwide have identified numerous immune-related genes in silkworms. However, these identified silkworm immune genes are not well classified and not well known to the scientific community. With the availability of the latest genome data of silkworms and the extensive research on silkworm immunity, it has become imperative to systematically categorize the immune genes of silkworms with different database IDs. In this study, we present a meticulous organization of prevalent immune-related genes in the domestic silkworm, using the SilkDB 3.0 database as a reliable source for updated gene information. Furthermore, utilizing the available data, we classify the collected immune genes into distinct categories: pattern recognition receptors, classical immune pathways, effector genes and others. In-depth data analysis has enabled us to predict some potential antiviral genes. Subsequently, we performed antiviral experiments on selected genes, exploring their impact on Bombyx mori nucleopolyhedrovirus replication. The outcomes of this research furnish novel insights into the immune genes of the silkworm, consequently fostering advancements in the field of silkworm immunity research by establishing a comprehensive classification and functional understanding of immune-related genes in the silkworm. This study contributes to the broader understanding of insect immune responses and opens up new avenues for future investigations in the domain of host-pathogen interactions.

SELECTION OF CITATIONS
SEARCH DETAIL
...