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1.
Nat Commun ; 15(1): 4702, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830878

ABSTRACT

Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]- anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10-4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α31 component (~89 mV Oe-1 cm-1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

2.
Arthritis Res Ther ; 26(1): 92, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725078

ABSTRACT

OBJECTIVE: The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. METHODS: We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. RESULTS: Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5-25%), normal (25-75%), high (75-95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. CONCLUSION: Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.


Subject(s)
Lupus Erythematosus, Systemic , Machine Learning , Macrophage Activation Syndrome , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Female , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/etiology , Retrospective Studies , Male , Adult , Middle Aged , Early Diagnosis , ROC Curve
3.
Sci Data ; 11(1): 548, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811659

ABSTRACT

A well-designed educational programming dataset is a valuable asset for students and educators. Such a dataset enables students to improve their programming performances continuously, provides researchers with significant data sources to identify students' learning behaviours and enhance the quality of programming education. Several existing datasets for programming education are either limited by a small number of participating students or a short span of learning records, bringing great challenges to investigate students' learning patterns in programming. We present a graph-based large-scale dataset specialized in programming learning on Online Judge (OJ) platform. The dataset, named ACcoding, was built by a university teaching group. As of the submission date of the initial manuscript of this paper (May 6, 2022), the dataset contains 4,046,652 task-solving records submitted by 27,444 students on 4,559 programming tasks over a span of 6 years. The large size of the dataset, combined with rich functional features, empowers educators to trace students' programming progress and choose appropriate programming tasks for specific training purposes. We also presents examples of applications used by the dataset.

4.
Chemphyschem ; : e202400297, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797706

ABSTRACT

Materials that integrate magnetism, electricity and luminescence can not only improve the operational efficiency of devices, but also potentially generate new functions through their coupling. Therefore, multifunctional synergistic effects have broad application prospects in fields such as optoelectronic devices, information storage and processing, and quantum computing. However, in the research field of molecular materials, there are few reports on the synergistic multifunctional properties. The main reason is that there is insufficient awareness of how to obtain such material. In this brief review, we summarized the molecular materials with this characteristic. The structural phase transition of substances will cause changes in their physical properties, as the electronic configurations of the active unit in different structural phases are different. Therefore, we will classify and describe the multifunctional synergistic complexes based on the structural factors that cause the first-order phase transition of the complexes. This enables us to quickly screen complexes with synergistic responses to these properties through structural phase transitions, providing ideas for studying the synergistic response of physical properties in molecular materials.

5.
Proc Natl Acad Sci U S A ; 121(18): e2310283121, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38669183

ABSTRACT

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.


Subject(s)
Carrier Proteins , Cell Polarity , Membrane Proteins , Spine , Zebrafish , Animals , Zebrafish/genetics , Zebrafish/embryology , Humans , Mice , Cell Polarity/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Spine/abnormalities , Spine/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , Scoliosis/genetics , Scoliosis/congenital , Scoliosis/metabolism , Wnt Signaling Pathway/genetics , Genetic Predisposition to Disease , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Female
6.
Toxicol Sci ; 199(1): 108-119, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38445754

ABSTRACT

Carbamazepine (CBZ) has been identified in the aquatic environment as an emerging contaminant. Its immune effect across generations at environmentally relevant concentrations is little known. We aim to elucidate the effects of CBZ on the immune system in zebrafish (Danio rerio), hypothesizing the effects caused by CBZ exposure in the parental generation can be passed on to its offspring, leading to impairment of innate immune function and defense against pathogen weakened. A suite of bioassays (including a test with added lipopolysaccharide) was used to measure the effects of environmentally relevant levels of CBZ (1, 10, and 100 µg/l) on zebrafish at multiple biological levels, and across 2 successive generations (21 days exposure for F0; 5 and 21 days exposure or nonexposure for F1). The results showed that CBZ affected homeostasis in the immune system, caused liver vacuolization, increased the inflammation-related microbiota proportion in gut, and decreased reproduction, by induction of oxidative stress and modulation of Toll-like receptors (TLR) signaling pathway on gut-liver axis. The effects of exposure to CBZ over 21 days in F0 could be passed to the next generation. Intergenerational effects on TLR and antioxidant defense system were also observed in nonexposed F1 at 5 days post-fertilization (5 dpf), but diminished at 21 dpf. The finding provided evidence to unravel immune response by gut-liver axis mediated and oxidative stress under 4 test conditions. The study has raised a potential concern about the multigenerational immune effects of environmental pollutants and calls for a focus on the risk of synergetic pathogen infection.


Subject(s)
Carbamazepine , Liver , Signal Transduction , Toll-Like Receptors , Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/immunology , Carbamazepine/toxicity , Toll-Like Receptors/metabolism , Signal Transduction/drug effects , Liver/drug effects , Liver/immunology , Liver/metabolism , Water Pollutants, Chemical/toxicity , Oxidative Stress/drug effects , Female , Immunity, Innate/drug effects , Gastrointestinal Microbiome/drug effects , Male , Dose-Response Relationship, Drug , Reproduction/drug effects
7.
J Multidiscip Healthc ; 17: 937-947, 2024.
Article in English | MEDLINE | ID: mdl-38455274

ABSTRACT

Background: This study aims to investigate the knowledge, attitudes, and practices (KAP) among patients with systemic lupus erythematosus (SLE) toward disease management and biologic therapy. Methods: This cross-sectional study was conducted between April 20, 2023, and May 5, 2023, among patients with SLE at Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. A self-designed questionnaire was developed to collect demographic information of SLE patients and assess their KAP. Results: A total of 463 SLE patients participated. The mean scores for knowledge, attitudes, and practices were 8.52 ± 2.36 (possible range: 0-11), 39.40 ± 3.38 (possible range: 11-55), and 27.10 ± 6.29 (possible range: 8-40), respectively. The path analysis demonstrated a significant and positive association between knowledge and attitudes, as indicated by a path coefficient of 0.455 (p < 0.001), and a significant and positive relationship between knowledge and practices, with a path coefficient of 0.709 (p < 0.001). Conclusion: Patients with SLE exhibited insufficient knowledge, negative attitudes, and poor practices.

8.
Br J Radiol ; 97(1156): 812-819, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38366622

ABSTRACT

OBJECTIVE: To demonstrate that a T2 periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique using deep learning reconstruction (DLR) will provide better image quality and decrease image noise. METHODS: From December 2020 to March 2021, 35 patients examined cervical spine MRI were included in this study. Four sets of images including fast spin echo (FSE), original PROPELLER, PROPELLER DLR50%, and DLR75% were quantitatively and qualitatively reviewed. We calculated the signal-to-noise ratio (SNR) of the spinal cord and sternocleidomastoid (SCM) muscle and the contrast-to-noise ratio (CNR) of the spinal cord by applying region-of-interest at the spinal cord, SCM muscle, and background air. We evaluated image noise with regard to the spinal cord, SCM, and back muscles at each level from C2-3 to C6-7 in the 4 sets. RESULTS: At all disc levels, the mean SNR values for the spinal cord and SCM muscles were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE and original PROPELLER images (P < .0083). The mean CNR values of the spinal cord were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE at the C3-4 and 4-5 levels and PROPELLER DLR75% compared to FSE at the C6-7 level (P < .0083). Qualitative analysis of image noise on the spinal cord, SCM, and back muscles showed that PROPELLER DLR50% and PROPELLER DLR75% images showed a significant denoising effect compared to the FSE and original PROPELLER images. CONCLUSION: The combination of PROPELLER and DLR improved image quality with a high SNR and CNR and reduced noise. ADVANCES IN KNOWLEDGE: Motion-insensitive imaging technique (PROPELLER) increased the image quality compared to conventional FSE images. PROPELLER technique with a DLR reduced image noise and improved image quality.


Subject(s)
Deep Learning , Humans , Image Enhancement/methods , Artifacts , Magnetic Resonance Imaging/methods , Cervical Vertebrae/diagnostic imaging , Treatment Outcome
9.
Nat Commun ; 15(1): 1838, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418810

ABSTRACT

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3-(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg-1 K-1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.

10.
Elife ; 122024 Jan 26.
Article in English | MEDLINE | ID: mdl-38277211

ABSTRACT

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.


Adolescent idiopathic scoliosis (AIS) is a twisting deformity of the spine that occurs during periods of rapid growth in children worldwide. Children with severe cases of AIS require surgery to stop it from getting worse, presenting a significant financial burden to health systems and families. Although AIS is known to cluster in families, its genetic causes and its inheritance pattern have remained elusive. Additionally, AIS is known to be more prevalent in females, a bias that has not been explained. Advances in techniques to study the genetics underlying diseases have revealed that certain variations that increase the risk of AIS affect cartilage and connective tissue. In humans, one such variation is near a gene called Pax1, and it is female-specific. The extracellular matrix is a network of proteins and other molecules in the space between cells that help connect tissues together, and it is particularly important in cartilage and other connective tissues. One of the main components of the extracellular matrix is collagen. Yu, Kanshour, Ushiki et al. hypothesized that changes in the extracellular matrix could affect the cartilage and connective tissues of the spine, leading to AIS. To show this, the scientists screened over 100,000 individuals and found that AIS is associated with variants in two genes coding for extracellular matrix proteins. One of these variants was found in a gene called Col11a1, which codes for one of the proteins that makes up collagen. To understand the relationship between Pax1 and Col11a1, Yu, Kanshour, Ushiki et al. genetically modified mice so that they would lack the Pax1 gene. In these mice, the activation of Col11a1 was reduced in the mouse spine. They also found that the form of Col11a1 associated with AIS could not suppress the activation of a gene called Mmp3 in mouse cartilage cells as effectively as unmutated Col11a1. Going one step further, the researchers found that lowering the levels of an estrogen receptor altered the activation patterns of Pax1, Col11a1, and Mmp3 in mouse cartilage cells. These findings suggest a possible mechanism for AIS, particularly in females. The findings of Yu, Kanshour, Ushiki et al. highlight that cartilage cells in the spine are particularly relevant in AIS. The results also point to specific molecules within the extracellular matrix as important for maintaining proper alignment in the spine when children are growing rapidly. This information may guide future therapies aimed at maintaining healthy spinal cells in adolescent children, particularly girls.


Subject(s)
Scoliosis , Male , Animals , Child , Mice , Humans , Female , Adolescent , Scoliosis/genetics , Matrix Metalloproteinase 3/genetics , Spine , Transcription Factors/genetics , Collagen/genetics , Genetic Variation , Collagen Type XI/genetics
11.
Elife ; 132024 Jan 19.
Article in English | MEDLINE | ID: mdl-38240312

ABSTRACT

Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.


Subject(s)
Nucleolus Organizer Region , RNA Precursors , Humans , Animals , Nucleolus Organizer Region/genetics , Nucleolus Organizer Region/metabolism , RNA Precursors/genetics , RNA Precursors/metabolism , Cell Nucleolus/genetics , Cell Nucleolus/metabolism , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , Chromosomes, Human/metabolism , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Mammals/genetics
12.
J Leukoc Biol ; 115(4): 633-646, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38066571

ABSTRACT

Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in situ vaccinia virotherapy recruited primarily polymorphonuclear MDSCs (PMN-MDSCs) into the TME, where they exhibited strong suppression of cytotoxic T lymphocytes in a reactive oxygen species-dependent way. Single-cell RNA sequencing analysis confirmed the suppressive profile of PMN-MDSCs at the transcriptomic level and identified CXCR2 as a therapeutic target expressed on PMN-MDSCs. Abrogating PMN-MDSC trafficking by CXCR2-specific small molecule inhibitor during the vaccinia virotherapy exhibited enhanced antitumor efficacy in 3 syngeneic cancer models, through increasing CD8+/MDSC ratios in the TME, activating cytotoxic T lymphocytes, and skewing suppressive TME into an antitumor environment. Our results warrant clinical development of CXCR2 inhibitor in combination with oncolytic virotherapy.


Subject(s)
Myeloid-Derived Suppressor Cells , Oncolytic Virotherapy , Vaccinia , Animals , Mice , Cell Line, Tumor , Myeloid-Derived Suppressor Cells/pathology , T-Lymphocytes, Cytotoxic , Tumor Microenvironment , Vaccinia/pathology , Vaccinia virus
13.
J Clin Invest ; 134(2)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-37962965

ABSTRACT

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.


Subject(s)
Scoliosis , Animals , Humans , Adolescent , Scoliosis/genetics , Scoliosis/diagnosis , Scoliosis/surgery , Glycine/genetics , Zebrafish , Synaptic Transmission
14.
J Comput Biol ; 31(1): 41-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38010500

ABSTRACT

Intratumoral heterogeneity and the presence of cancer stem cells are challenging issues in cancer therapy. An appropriate quantification of the stemness of individual cells for assessing the potential for self-renewal and differentiation from the cell of origin can define a measurement for quantifying different cell states, which is important in understanding the dynamics of cancer evolution, and might further provide possible targeted therapies aimed at tumor stem cells. Nevertheless, it is usually difficult to quantify the stemness of a cell based on molecular information associated with the cell. In this study, we proposed a stemness definition method with one-class Hadamard kernel support vector machine (OCHSVM) based on single-cell RNA sequencing (scRNA-seq) data. Applications of the proposed OCHSVM stemness are assessed by various data sets, including preimplantation embryo cells, induced pluripotent stem cells, or tumor cells. We further compared the OCHSVM model with state-of-the-art methods CytoTRACE, one-class logistic regression, or one-class SVM methods with different kernels. The computational results demonstrate that the OCHSVM method is more suitable for stemness identification using scRNA-seq data.


Subject(s)
Neoplasms , Support Vector Machine , Humans , Neoplasms/genetics , Cell Differentiation , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1111-1117, 2023 Dec 18.
Article in Chinese | MEDLINE | ID: mdl-38101797

ABSTRACT

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.


Subject(s)
Anemia , Lupus Erythematosus, Systemic , Lupus Vasculitis, Central Nervous System , Macrophage Activation Syndrome , Humans , Female , Adult , Rituximab/therapeutic use , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/drug therapy , Macrophage Activation Syndrome/etiology , Retrospective Studies , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Methylprednisolone/therapeutic use , Fever/drug therapy , Erythema/complications , Erythema/drug therapy , Hormones/therapeutic use , Alopecia/complications , Alopecia/drug therapy , Triglycerides/therapeutic use , Ferritins/therapeutic use
18.
Mar Environ Res ; 191: 106170, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37708617

ABSTRACT

In context of testing, screening and monitoring of endocrine-disrupting (ED) type of environmental pollutants, tunicates could possibly represent a particularly interesting group of bioindicator organisms. These primitive chordates are already important model organisms within developmental and genomics research due to their central position in evolution and close relationship to vertebrates. The solitary ascidians, such as the genus Ciona spp. (vase tunicates), could possibly be extra feasible as ED bioindicators. They have a free-swimming, tadpole-like larval stage that develops extremely quickly (<20 h under favorable conditions), has a short life cycle (typically 2-3 months), are relatively easy to maintain in laboratory culture, have fully sequenced genomes, and transgenic embryos with 3D course data of the embryo ontogeny are available. In this article, we discuss possible roles of Ciona spp. (and other solitary ascidians) as ecotoxicological bioindicator organisms in general but perhaps especially for effect studies of contaminants with presumed endocrine disrupting modes of action.


Subject(s)
Ciona intestinalis , Ciona , Endocrine Disruptors , Animals , Environmental Biomarkers , Endocrine Disruptors/toxicity
19.
Chemistry ; 29(66): e202301771, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37665775

ABSTRACT

Qubits are the basic unit of quantum information and computation. To realize quantum computing and information processing, the decoherence times of qubits must be long enough. Among the studies of molecule-based electron spin qubits, most of the work focused on the ions with the spin S=1/2, where only single-bit gates can be constructed. However, quantum operations require the qubits to interact with each other, so people gradually carry out relevant research in ions or systems with S>1/2 and multilevel states. In this work, a two-dimensional (2D) oxygen-coordinated GdIII NaI -based oxamato supramolecular coordination framework, Na[Gd(4-HOpa)4 (H2 O)] ⋅ 2H2 O (1, 4-HOpa=N-4-hydroxyphenyloxamate), was selected as a possible carrier of qubit. The field-induced slow magnetic relaxation shows this system has phonon bottleneck (PB) effect at low temperatures with a very weak magnetic anisotropy. The pulse electron paramagnetic resonance studies show the spin-lattice and spin-spin relaxation times are T1 =1.66 ms at 4 K and Tm =4.25 µs at 8 K for its diamagnetically diluted sample (1Gd0.12 %). It suggested that the relatively long decoherence time is mainly ascribed to its near isotropic and the PB effect from resonance phonon trapped for pure sample, while the dilution further improves its qubit performance.

20.
Mater Today Bio ; 23: 100793, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37766900

ABSTRACT

A pillar dishe for subculture of 3D cultured cells on hydrogel spots (Matrigel and alginate) have been developed. Cells cultured in 3D in an extracellular matrix (ECM) can retain their intrinsic properties, but cells cultured in 2D lose their intrinsic properties as the cells stick to the bottom of the well. Previously, cells and ECM spots were dispensed on a conventional culture dish for 3D cultivation. However, as the spot shape and location depended on user handling, pillars were added to the dish to realize uniform spot shape and stable subculture, supporting 3D cell culture-based high-throughput screening (HTS). Matrigel and alginate were used as ECMs during 6-passage subculture. The growth rate of lung cancer cell (A549) was higher on Matrigel than on alginate. Cancer cell was subcultured in three dimensions in the proposed pillar dish and used for drug screening and differential gene expression analysis. Interestingly, stemness markers, which are unique characteristics of lung cancer cells inducing drug resistance, were upregulated in 3D-subcultured cells compared with those in 2D-subcultured cells. Additionally, the PI3K/Akt/mTOR, VEGFR1/2, and Wnt pathways, which are promising therapeutic targets for lung cancer, were activated, showing high drug sensitivity under 3D-HTS using the 3D-subcultured cells.

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