Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 645
Filter
1.
Endocrine ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969908

ABSTRACT

PURPOSE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO). METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for "unresponsiveness" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model's discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis. RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model's consistent and reliable ability to distinguish between responsive and non-responsive TAO patients. CONCLUSION: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

2.
JAMA Ophthalmol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958962

ABSTRACT

Importance: Exotropia and myopia are commonly coexistent. However, evidence is limited regarding atropine interventions for myopia control in children with myopia and intermittent exotropia (IXT). Objective: To evaluate the efficacy and safety of 0.01% atropine eye drops on myopia progression, exotropia conditions, and binocular vision in individuals with myopia and IXT. Design, Setting, and Participants: This placebo-controlled, double-masked, randomized clinical trial was conducted from December 2020 to September 2023. Children aged 6 to 12 years with basic-type IXT and myopia of -0.50 to -6.00 diopters (D) after cycloplegic refraction in both eyes were enrolled. Intervention: Participants were randomly assigned in a 2:1 ratio to 0.01% atropine or placebo eye drops administered in both eyes once at night for 12 months. Main Outcomes and Measures: The primary outcome was change in cycloplegic spherical equivalent from baseline at 1 year. Secondary outcomes included change in axial length (AL), accommodative amplitude (AA), exotropia conditions, and binocular vision at 1 year. Results: Among 323 screened participants, 300 children (mean [SD] age, 9.1 [1.6] years; 152 male [50.7%]) were included in this study. A total of 200 children (66.7%) were in the atropine group, and 100 (33.3%) were in the placebo group. At 1 year, the 0.01% atropine group had slower spherical equivalent progression (-0.51 D vs -0.75 D; difference = 0.24 D; 95% CI, 0.11-0.37 D; P < .001) and AL elongation (0.31 mm vs 0.42 mm; difference = -0.11 mm; 95% CI, -0.17 to -0.06 mm; P < .001) than the placebo group. The mean AA change was -3.06 D vs 0.12 D (difference = -3.18 D; 95% CI, -3.92 to -2.44 D; P < .001) in the atropine and placebo groups, respectively. The 0.01% atropine group had a decrease in near magnitude of exodeviation whereas the placebo group had an increase (-1.25 prism diopters [PD] vs 0.74 PD; difference = -1.99 PD; 95% CI, -3.79 to -0.19 PD; P = .03). In the atropine vs placebo group, respectively, the incidence of study drug-related photophobia was 6.0% (12 of 200 participants) vs 8.0% (8 of 100 participants; difference = -2.0%; 95% CI, -9.4% to 3.7%; P = .51) and for blurred near vision was 6.0% (12 of 200 participants) vs 7.0% (7 of 100 participants) (difference = -1.0%; 95% CI, -8.2% to 4.5%; P = .74). Conclusions and Relevance: The findings of this randomized clinical trial support use of 0.01% atropine eye drops, although compromising AA to some extent, for slowing myopia progression without interfering with exotropia conditions or binocular vision in children with myopia and IXT. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000039827.

3.
Front Immunol ; 15: 1395513, 2024.
Article in English | MEDLINE | ID: mdl-39011035

ABSTRACT

Background: Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran's Q statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy. Results: In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032-1.250, p = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086-1.477, p = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630-0.833, p < 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823-0.969, p = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28- CD127- CD25++ CD8+ T cell AC, CD28- CD25++ CD8+ T cell AC, CD28- CD8+ T cell/CD8+ T cell, CD28- CD8+ T cell AC, and CD45 RA- CD28- CD8+ T cell AC. Conclusion: Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.


Subject(s)
Cholangitis, Sclerosing , Mendelian Randomization Analysis , Humans , Cholangitis, Sclerosing/immunology , Cholangitis, Sclerosing/genetics , Genetic Predisposition to Disease , T-Lymphocytes, Regulatory/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Polymorphism, Single Nucleotide
4.
Sci Data ; 11(1): 773, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003335

ABSTRACT

Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998-2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED's monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944-0.995), Bias (-0.68-0.53), and Root Mean Square Error (5.50-15.59 mm). Additionally, TPRED's monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED's annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

5.
Molecules ; 29(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38999010

ABSTRACT

Hypochlorite (ClO-) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to develop mitochondria-targeting fluorescent probes for the dual sensing of ClO- and viscosity. Herein, we have explored a new fluorescent probe, XTAP-Bn, which responds sensitively to ClO- and viscosity with off-on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP-Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO- and viscosity. In addition, XTAP-Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP-Bn is successfully employed to monitor the dynamic change in ClO- and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.


Subject(s)
Fluorescent Dyes , Hypochlorous Acid , Mitochondria , Zebrafish , Hypochlorous Acid/analysis , Fluorescent Dyes/chemistry , Animals , Mitochondria/metabolism , Viscosity , Humans , Optical Imaging/methods , HeLa Cells
6.
Article in English | MEDLINE | ID: mdl-39023781

ABSTRACT

Objective: To examine if METTL5 promotes the proliferation of nonsmall cell lung cancer (NSCLC) cells by interacting with IGF2BP3. Methods: The expression patterns of METTL5 and IGF2BP3 in NSCLC tissues, their relationship with survival rate, and their correlation were analyzed using bioinformatics and clinical sample analyses. The effects of METTL5 overexpression and IGF2BP3 knockdown, as well as those of METTL5 knockdown and IGF2BP3 overexpression, on the proliferation of NSCLC cells were analyzed by transfecting appropriate constructs. The interaction between METTL5 and IGF2BP3 was verified using the co-immunoprecipitation (Co-IP) assay. The in vivo effects of METTL5 and IGF2BP3 on NSCLC growth were analyzed using the tumor-bearing nude mouse model. Results: METTL5 and IGF2BP3 expression levels were positively correlated and were associated with poor clinical prognosis. The METTL5 and IGF2BP3 expression levels were upregulated in the clinical NSCLC samples. IGF2BP3 expression did not affect METTL5 expression but was regulated by METTL5. IGF2BP3 overexpression mitigated the METTL5 knockdown-induced impaired cell proliferation. Meanwhile, IGF2BP3 knockdown suppressed METTL5-mediated NSCLC cell proliferation. The Co-IP assay results revealed the interaction between METTL5 and IGF2BP3 in NSCLC cells. IGF2BP3 knockdown suppressed tumor growth, whereas IGF2BP3 overexpression enhanced tumor volume and quality. Conclusion: METTL5 induces NSCLC cell proliferation by interacting with IGF2BP3. Thus, METTL5 is a potential biomarker and a therapeutic target for NSCLC.

7.
Article in English | MEDLINE | ID: mdl-38980998

ABSTRACT

Conductive hydrogels (CHs) are emerging materials for next generation sensing systems in flexible electronics. However, the fabrication of competent CHs with excellent stretchability, adhesion, self-healing, photothermal conversion, multisensing, and environmental stability remains a huge challenge. Herein, a nanocomposite organohydrogel with the above features is constructed by in situ copolymerization of zwitterionic monomer and acrylamide in the existence of carboxylic cellulose nanofiber-carrying reduced graphene oxide (rGO) plus a solvent displacement strategy. The synergy of abundant dipole-dipole interactions and intermolecular hydrogen bonds enables the organohydrogel to exhibit high stretchability, strong adhesion, and good self-healing. The presence of glycerol weakens the formation of hydrogen bonds between water molecules, endowing the organohydrogel with excellent environmental stability (-40 to 60 °C) to adapt to different application scenarios. Importantly, the multimodal organohydrogel presents excellent sensing behavior, including a high gauge factor of 16.3 at strains of 400-1440% and a reliable thermal coefficient of resistance (-4.2 °C-1) over a wide temperature widow (-40 to 60 °C). Moreover, the organohydrogel displays a highly efficient and reliable photothermal conversion ability due to the favorable optical absorbing behavior of rGO. Notably, the organohydrogel can detect accurate human activities at ambient temperature, demonstrating potential applications in flexible intelligent electronics.

8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 449-457, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953270

ABSTRACT

Long-term treatment of anemia involving frequent blood transfusions and intravenous iron administration increases the risks of hepatic iron overload and steatosis in the patients undergoing hemodialysis.Pathological accumulation of iron damages hepatocytes,not only elevating the risks of progressive hepatic fibrosis and cirrhosis but also potentially accelerating the process of hepatic steatosis.Iron overload and steatosis may interact with each other,exacerbating liver damage and ultimately leading to further deterioration of hepatic fibrosis and cirrhosis.MRI characterized by non-invasiveness and high repeatability,enables the simultaneous quantitative assessment of hepatic iron and fat content,providing crucial information for early diagnosis and intervention of liver diseases.In recent years,researchers have achieved significant advances in the application of MRI in the diagnosis and treatment of liver diseases.MRI can accurately reflect the extent of hepatic iron overload and steatosis in patients and predict the risk of liver diseases.This article reviews the latest advances,challenges,and perspectives in the application of MRI in assessing hepatic iron overload and steatosis in the patients undergoing hemodialysis,aiming to offer valuable references for clinical practice.


Subject(s)
Fatty Liver , Iron Overload , Magnetic Resonance Imaging , Renal Dialysis , Humans , Iron Overload/diagnostic imaging , Magnetic Resonance Imaging/methods , Fatty Liver/diagnostic imaging , Fatty Liver/metabolism , Liver/diagnostic imaging , Liver/metabolism , Liver/pathology
9.
Opt Express ; 32(10): 16629-16644, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38858864

ABSTRACT

Differential phase contrast (DPC) imaging relies on computational analysis to extract quantitative phase information from phase gradient images. However, even modest noise level can introduce errors that propagate through the computational process, degrading the quality of the final phase result and further reducing phase sensitivity. Here, we introduce the noise-corrected DPC (ncDPC) to enhance phase sensitivity. This approach is based on a theoretical DPC model that effectively considers most relevant noise sources in the camera and non-uniform illumination in DPC. In particular, the dominating shot noise and readout noise variance can be jointly estimated using frequency analysis and further corrected by block-matching 3D (BM3D) method. Finally, the denoised images are used for phase retrieval based on the common Tikhonov inversion. Our results, based on both simulated and experimental data, demonstrate that ncDPC outperforms the traditional DPC (tDPC), enabling significant improvements in both phase reconstruction quality and phase sensitivity. Besides, we have demonstrated the broad applicability of ncDPC by showing its performance in various experimental datasets.

10.
Food Res Int ; 190: 114581, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945601

ABSTRACT

Microplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.


Subject(s)
Microplastics , Muscle, Skeletal , Polystyrenes , Thrombospondin 1 , Animals , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Thrombospondin 1/metabolism , Swine , Meat/analysis , Neovascularization, Physiologic/drug effects , Carnosine/pharmacology , Animal Feed , Food Quality , Food Contamination/analysis , Male , Angiogenesis
11.
Sci Total Environ ; 937: 173412, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38797405

ABSTRACT

Lakes are important sources of methane (CH4), and understanding the influence of environmental factors on CH4 concentration in lake water is crucial for accurately assessing CH4 emission from lakes. In this study, we investigated CH4 concentration in two connected Tibetan Plateau lakes, Lake Keluke (an open freshwater lake) and Lake Tuosu (a closed saline lake), through in-situ continuous measurements taken in different months from 2021 to 2023. The results show substantial spatial and seasonal variations in CH4 concentrations in the two lakes, while the CH4 concentrations in Lake Keluke are consistently higher than those in Lake Tuosu for each month. Despite sharing similar environmental conditions due to connected (e.g. pH, water temperature, dissolved oxygen content, and total organic carbon content), the critical difference between the two lakes is their salinity. This implies that salinity is the critical factor contributing to the decrease in CH4 concentrations in Lake Tuosu, possibly due to the changes in microbial species between freshwater and brackish/saline lakes. Additionally, to further validate the effect of salinity on CH4 concentrations in lake water, we compared the CH4 concentrations of 33 lakes (including 5 saline lakes and 28 freshwater lakes) from the Tibetan Plateau, Chinese Loess Plateau, and Yangtze Plain, and found that saline lakes consistently exhibit lower CH4 concentrations (avg. 0.08 µmol/L), while freshwater lakes generally display higher CH4 concentrations (avg. 1.25 µmol/L) with considerable fluctuations. Consequently, freshwater and saline lakes exhibit distinct CH4 emissions, which could be used for more accurate estimation of global CH4 emission from lakes.

12.
Chem Biodivers ; 21(7): e202400792, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38738487

ABSTRACT

In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA-seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF-κB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML-099. Moreover, pretreatment of ML-099 on A549 cells could reverse the grifolin-induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS-mediated multiple signaling pathways.


Subject(s)
Cell Proliferation , Lung Neoplasms , Proto-Oncogene Proteins p21(ras) , Signal Transduction , Humans , Signal Transduction/drug effects , Proto-Oncogene Proteins p21(ras)/metabolism , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/genetics , A549 Cells , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Cell Proliferation/drug effects , Apoptosis/drug effects , Drug Screening Assays, Antitumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Dose-Response Relationship, Drug , Cell Movement/drug effects , Cell Death/drug effects , Terpenes
13.
Zool Res ; 45(3): 679-690, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38766749

ABSTRACT

General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.


Subject(s)
Anesthetics, Inhalation , Mice, Inbred C57BL , Neurotransmitter Agents , Propofol , Sevoflurane , Sevoflurane/pharmacology , Animals , Propofol/pharmacology , Neurotransmitter Agents/metabolism , Mice , Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Male , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism
14.
PeerJ ; 12: e17380, 2024.
Article in English | MEDLINE | ID: mdl-38799063

ABSTRACT

As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in Artemisia capillaris which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.


Subject(s)
Coumarins , Glycerophospholipids , Lipidomics , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Glycerophospholipids/metabolism , Coumarins/pharmacology , Coumarins/therapeutic use , Lipidomics/methods , Mice , Chromatography, Liquid/methods , Male , Disease Models, Animal , Mice, Inbred C57BL , Diet, High-Fat/adverse effects , Mass Spectrometry/methods , Lipid Metabolism/drug effects
15.
EClinicalMedicine ; 72: 102623, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38800802

ABSTRACT

Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18. Interpretation: The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC. Funding: This study was funded by Innovent Biologics and was co-funded by Eli Lilly.

16.
Nanomicro Lett ; 16(1): 195, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743205

ABSTRACT

A lightweight flexible thermally stable composite is fabricated by combining silica nanofiber membranes (SNM) with MXene@c-MWCNT hybrid film. The flexible SNM with outstanding thermal insulation are prepared from tetraethyl orthosilicate hydrolysis and condensation by electrospinning and high-temperature calcination; the MXene@c-MWCNTx:y films are prepared by vacuum filtration technology. In particular, the SNM and MXene@c-MWCNT6:4 as one unit layer (SMC1) are bonded together with 5 wt% polyvinyl alcohol (PVA) solution, which exhibits low thermal conductivity (0.066 W m-1 K-1) and good electromagnetic interference (EMI) shielding performance (average EMI SET, 37.8 dB). With the increase in functional unit layer, the overall thermal insulation performance of the whole composite film (SMCx) remains stable, and EMI shielding performance is greatly improved, especially for SMC3 with three unit layers, the average EMI SET is as high as 55.4 dB. In addition, the organic combination of rigid SNM and tough MXene@c-MWCNT6:4 makes SMCx exhibit good mechanical tensile strength. Importantly, SMCx exhibit stable EMI shielding and excellent thermal insulation even in extreme heat and cold environment. Therefore, this work provides a novel design idea and important reference value for EMI shielding and thermal insulation components used in extreme environmental protection equipment in the future.

17.
Clin Respir J ; 18(6): e13790, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38817043

ABSTRACT

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron. METHOD: In this study, we conducted a follow-up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations. RESULT: We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T-cells, and a negative correlation between EOS count and age, neutrophil, and C-reactive protein. CONCLUSION: Overall, our study contributes to the knowledge of COPD management during the COVID-19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis.


Subject(s)
COVID-19 , Eosinophils , Pulmonary Disease, Chronic Obstructive , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/immunology , COVID-19/blood , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Pulmonary Disease, Chronic Obstructive/blood , Male , Female , Middle Aged , Aged , SARS-CoV-2/immunology , Leukocyte Count , Hospitalization/statistics & numerical data , China/epidemiology , Follow-Up Studies
18.
Int Immunopharmacol ; 133: 112060, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38652970

ABSTRACT

Acute respiratory distress syndrome (ARDS) is characterized by lung tissue oedema and inflammatory cell infiltration, with limited therapeutic interventions available. Receptor-interacting protein kinase 1 (RIPK1), a critical regulator of cell death and inflammation implicated in many diseases, is not fully understood in the context of ARDS. In this study, we employed RIP1 kinase-inactivated (Rip1K45A/K45A) mice and two distinct RIPK1 inhibitors to investigate the contributions of RIP1 kinase activity in lipopolysaccharide (LPS)-induced ARDS pathology. Our results indicated that RIPK1 kinase inactivation, achieved through both genetic and chemical approaches, significantly attenuated LPS-induced ARDS pathology, as demonstrated by reduced polymorphonuclear neutrophil percentage (PMN%) in alveolar lavage fluid, expression of inflammatory and fibrosis-related factors in lung tissues, as well as histological examination. Results by tunnel staining and qRT-PCR analysis indicated that RIPK1 kinase activity played a role in regulating cell apoptosis and inflammation induced by LPS administration in lung tissue. In summary, employing both pharmacological and genetic approaches, this study demonstrated that targeted RIPK1 kinase inactivation attenuates the pathological phenotype induced by LPS inhalation in an ARDS mouse model. This study enhances our understanding of the therapeutic potential of RIPK1 kinase modulation in ARDS, providing insights for the pathogenesis of ARDS.


Subject(s)
Lipopolysaccharides , Protein Kinase Inhibitors , Receptor-Interacting Protein Serine-Threonine Kinases , Respiratory Distress Syndrome , Animals , Humans , Male , Mice , Apoptosis/drug effects , Disease Models, Animal , Lung/pathology , Lung/drug effects , Lung/immunology , Mice, Inbred C57BL , Neutrophils/immunology , Neutrophils/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/immunology
19.
ACS Appl Mater Interfaces ; 16(14): 17838-17845, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38556984

ABSTRACT

Changeable substituent groups of organic molecules can provide an opportunity to clarify the antibacterial mechanism of organic molecules by tuning the electron cloud density of their skeleton. However, understanding the antibacterial mechanism of organic molecules is challenging. Herein, we reported a molecular view strategy for clarifying the antibacterial switch mechanism by tuning electron cloud density of cinnamaldehyde molecule skeleton. The cinnamaldehyde and its derivatives were self-assembled into nanosheets with excellent water solubility, respectively. The experimental results show that α-bromocinnamaldehyde (BCA) nanosheets exhibits unprecedented antibacterial activity, but there is no antibacterial activity for α-methylcinnamaldehyde nanosheets. Therefore, the BCA nanosheets and α-methylcinnamaldehyde nanosheets achieve an antibacterial switch. Theoretical calculations further confirmed that the electron-withdrawing substituent of the bromine atom leads to a lower electron cloud density of the aldehyde group than that of the electron-donor substituent of the methyl group at the α-position of the cinnamaldehyde skeleton, which is a key point in elucidating the antimicrobial switch mechanism. The excellent biocompatibility of BCA nanosheets was confirmed by CCK-8. The mouse wound infection model, H&E staining, and the crawling ability of drosophila larvae show that as-prepared BCA nanosheets are safe and promising for wound healing. This study provides a new strategy for the synthesis of low-cost organic nanomaterials with good biocompatibility. It is expected to expand the application of natural organic small molecule materials in antimicrobial agents.


Subject(s)
Acrolein/analogs & derivatives , Nanostructures , Mice , Animals , Anti-Bacterial Agents/pharmacology , Acrolein/pharmacology , Skeleton
20.
Heliyon ; 10(8): e29522, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38644815

ABSTRACT

Rhizopus stolonifer is one of the main pathogens in postharvest storage logistics of more than 100 kinds of fruit, such as strawberries, tomatoes and melons. In this paper, the research on the morphology and detection, pathogenicity and infection mechanism of Rhizopus stolonifer was reviewed. The control methods of Rhizopus stolonifer in recent years was summarized from three dimensions of physics, chemistry and biology, including the nanomaterials, biological metabolites, light control bacteria, etc. Future direction of postharvest Rhizopus stolonifer infection control was analyzed from two aspects of pathogenic mechanism research and new composite technology. The information provided in this review will help researchers and technicians to deepen their understanding of the pathogenicity of Rhizopus stolonifer, and develop more effective control methods in the future.

SELECTION OF CITATIONS
SEARCH DETAIL