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1.
Small ; : e2406001, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263765

ABSTRACT

Regulating the different growth states of polypyrrole (PPy) is a key strategy for obtaining PPy composites with high electromagnetic wave (EMW) absorption properties. This work finds that the growth states of PPy is regulated by controlling the amount of pyrrole added during the preparation of composites, so as to regulate the development of conductive networks to obtain excellent EMW absorption performance. The POP/PPy-200 composite achieves an effective absorption bandwidth (EAB) of 6.24 GHz (11.76-18.00 GHz) at a thickness of only 2.34 mm, covering 100% of the Ku band. The minimum reflection loss of -73.05 dB can be demonstrated at a thickness of only 2.29 mm, while at the same time showing an EAB of 5.96 GHz to meet the requirements of "thin", "light", "wide", and "strong". Such excellent EMW absorption performance is attributed to the conductive loss caused by the regulation of the growth states of PPy and the polarization loss caused by the heterostructure. This work also addresses the key challenge that porous organic polymers (POPs) cannot be applied to EMW absorption due to poor conductivity and providing new insights into the candidates for EMW absorbing materials.

2.
Quant Imaging Med Surg ; 14(9): 6449-6465, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39281146

ABSTRACT

Background: Low-kiloelectron volt (keV) virtual monochromatic images (VMIs) from low-dose (LD) dual-energy computed tomography (DECT) can enhance lesion contrast but suffer from high image noise. Recently, a deep learning image reconstruction (DLIR) algorithm has been developed and shown significant potential in suppressing image noise and improving image quality. To date, the capacity of LD low-keV thoracic-abdominal-pelvic DECT with DLIR to detect various types of tumor lesions have not been assessed. Hence, this study aimed to evaluate the image quality and lesion detection capabilities of LD VMIs using DLIR with thoracic-abdominal-pelvic DECT versus standard-dose (SD) iterative reconstruction (IR) in oncology patients. Methods: This prospective intraindividual study included 56 oncology patients who received a SD (13.86 mGy) and a consecutive LD (7.15 mGy) thoracic-abdominal-pelvic DECT from April 2022 to July 2023 at The First Affiliated hospital of Zhengzhou University. SD VMIs were reconstructed using IR at 50 keV (SD-IR50 keV), while LD VMIs were processed using DLIR at 50 keV (LD-DL50 keV) and 40 keV (LD-DL40 keV), respectively. Quantitative image parameters [computed tomography (CT) values, image noise, and contrast-to-noise ratios (CNRs)], qualitative metrics (image noise, vessel conspicuity, image contrast, artificial sensation, and overall image quality), and lesion CNRs and conspicuity were compared. The lesion detection rates in the SD-IR50 keV, LD-DL50 keV, and LD-DL40 keV VMIs were assessed according to lesion location (lung, liver, and lymph), type, and size. Repeated measures analysis of variance and the Friedman test were applied for comparing quantitative and qualitative measures, respectively. The Cochran Q test was used for comparing lesion detection rates. Results: Compared to SD-IR50 keV VMIs, LD-DL50 keV VMIs showed similar CT values and image noise (P>0.05), similar (P>0.05) or higher(P<0.05) CNRs, similar (P>0.05) or superior (P<0.05) perceptual image quality, and similar (P>0.05) or higher (P<0.001) lesion CNR and conspicuity. LD-DL40 keV VMIs exhibited higher CT values (by 40.4-47.1%) and CNRs (by 21.8-39.8%) (P<0.001), equivalent image noise, similar (P>0.05) or superior (P<0.05) perceptual image quality except for artificial sensation, and similar (P>0.05) or higher (P<0.001) lesion CNRs (by 16.5-46.3%) and conspicuity. The VMIs of LD-DL50 keV and LD-DL40 keV were consistent with those of SD-IR50 keV in terms of lesion detection capability in pulmonary nodules [SD-IR50 keV vs. LD-DL50 keV vs. LD-DL40 keV: 88/88 (100.0%) vs. 88/88 (100.0%) vs. 88/88 (100.0%); P>0.99], for lymph nodes [125/126 (99.2%) vs. 123/126 (97.6%) vs. 124/126 (98.4%); P>0.05], and high-contrast liver lesions [12/12 (100.0%) vs. 12/12 (100.0%) vs. 12/12 (100.0%); P>0.05], but not for small liver lesions (≤0.5 cm) [63/65 (96.9%) vs. 43/65 (66.2%) vs. 51/65 (78.5%); P<0.05] or low-contrast liver lesions [198/200 (99.0%) vs. 174/200 (87.0%) vs. 183/200 (91.5%); P<0.05]. Conclusions: VMIs at 40 keV with DLIR enables a 50% decrease in the radiation dose while largely maintaining diagnostic capabilities for multidetection of pulmonary nodules, lymph nodes, and liver lesions in oncology patients.

3.
Gene ; 933: 148939, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39278373

ABSTRACT

BACKGROUND AND OBJECTIVES: Genome-wide association studies (GWASs) have identified numerous candidate genes for human brain-imaging phenotypes; however, the biological relevance of many of these genes remains unconfirmed. This study aimed to investigate the causal relationships among tescalcin (TESC) (a GWAS-indicated gene), hippocampal volume, Alzheimer's disease (AD), and the underlying biological mechanisms. METHODS: Human transcriptional data were analyzed to confirm relative TESC expression in the hippocampus. In cell experiments, RNA-seq analysis was used to identify the potential biological pathways for TESC overexpression, and immunofluorescence imaging and cell viability assays were used to evaluate the effect of TESC overexpression on neuronal structure and survival. In animal experiments, the effects of TESC overexpression on hippocampal volume and cognitive function in normal mice and amyloid-ß (Aß)-induced AD mice were investigated by 9.4 T magnetic resonance imaging and behavioral tests. Underlying mechanisms were further assessed via western blotting and electrophysiological recordings. RESULTS: Human transcriptional data demonstrated that TESC is primarily expressed in the hippocampus and neurons. TESC overexpression enhanced the viability of HT22 cells and reduced Aß-induced cell death. In mouse models, Tesc-overexpressing mice revealed increased hippocampal volume, likely owing to enhanced cell viability and long-term potentiation (LTP), and reducing apoptotic- and oxidation-induced hippocampal damage. TESC overexpression could significantly mitigate Aß-induced hippocampal atrophy and memory impairment, potentially by reducing Aß-induced neuronal apoptosis and LTP weakening. CONCLUSION: This study exemplifies the translation of GWAS findings into actionable biological knowledge and suggests that upregulation of TESC may offer a promising therapeutic strategy for AD.

4.
Front Endocrinol (Lausanne) ; 15: 1416234, 2024.
Article in English | MEDLINE | ID: mdl-39145313

ABSTRACT

Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P< 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported. Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938. Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance.


Subject(s)
Coronary Disease , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Male , Female , Aged , Coronary Disease/epidemiology , Coronary Disease/blood , Middle Aged , Aging, Premature/epidemiology , Risk Factors , Aging , Triglycerides/blood , China/epidemiology , Adenosine Deaminase/metabolism , Urea/blood
6.
J Int Med Res ; 52(8): 3000605241272532, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39192614

ABSTRACT

Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.


Subject(s)
Cervix Uteri , Uterine Cervical Dysplasia , Vagina , Humans , Female , Cervix Uteri/abnormalities , Cervix Uteri/surgery , Cervix Uteri/pathology , Vagina/abnormalities , Vagina/surgery , Uterine Cervical Dysplasia/surgery , Uterine Cervical Dysplasia/complications , Uterine Cervical Dysplasia/pathology , Fallopian Tubes/surgery , Fallopian Tubes/abnormalities , Fallopian Tubes/pathology , Congenital Abnormalities
7.
Article in English | MEDLINE | ID: mdl-39160775

ABSTRACT

INTRODUCTION: Cardioneuroablation (CNA) has proven effectiveness in addressing hypervagotonia symptoms, such as neurocardiogenic syncope. METHODS AND RESULTS: In this case, we present the first-time application of CNA in a case of vago-glossopharyngeal neuralgia (VGPN). A 59-year-old female with near-syncope, sinus bradycardia, and sinus pauses triggered by recurrent right-sided neck pain was diagnosed with VGPN. The patient underwent successful treatment with carbamazepine and CNA. Subsequent follow-up revealed the sustained absence of sinus bradycardia or pauses, even upon neck pain resurgence after discontinuing carbamazepine. CONCLUSION: In this patient, CNA successfully prevented pauses associated with VGPN, avoiding permanent pacemaker implantation.

8.
Sci Total Environ ; 946: 174463, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-38964385

ABSTRACT

The increasingly urgent issue of climate change is driving the development of carbon dioxide (CO2) capture and separation technologies in flue gas after combustion. The monolithic adsorbent stands out in practical adsorption applications for its simplified powder compaction process while maintaining the inherent balance between energy consumption for regeneration and selectivity for adsorption. However, optimizing the adsorption capacity and selectivity of CO2 separation materials remains a significant challenge. Herein, we synthesized monolithic polymer networks (N-CMPs) with triphenylamine adsorption sites, acid-base environment tolerance, and precise narrow microchannel pore systems for the selective sieving of CO2 and particulate matter (PM) in flue gas. The inherent continuous covalent bonding of N-CMPs, along with their highly delocalized π-π conjugated porous framework, ensures the stability of the monolithic polymer network's adsorption and separation capabilities under wet and acid-base conditions. Specifically, under the conditions of 1 bar at 273 K, the CO2 adsorption capacity of N-CMP-1 is 3.35 mmol/g. Attributed to the highly polar environment generated by triphenylamine and the inherent high micropore/mesopore ratio, N-CMPs exhibit an excellent ideal adsorbed solution theory (IAST) selectivity for CO2/N2 under simulated flue gas conditions (CO2/N2 = 15:85). Dynamic breakthrough experiments further visualize the high separation efficiency of N-CMPs in practical adsorption applications. Moreover, under acid-base conditions, N-CMPs achieve a capture efficiency exceeding 99.76 % for PM0.3, enabling the selective separation of CO2 and PM in flue gas. In fact, the combined capture of hazardous PM and CO2 from the exhaust gases produced by the combustion of fossil fuels will play a pivotal role in mitigating climate change and environmental issues until low-carbon and alternative energy technologies are widely adopted.

9.
World J Clin Cases ; 12(18): 3395-3402, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38983409

ABSTRACT

BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124676, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-38909400

ABSTRACT

Five series of cyanostilbene-based rod-like liquid crystals containing one different terminal atom (H, F, Cl, Br and I) at one end and one terminal aliphatic chain with different numbers of carbon atoms at the other end were reported by Suzuki coupling and Knoevenagel reactions. The influence of terminal halogen atoms and terminal chain length on the self-assembly, AIE behavior, temperature-dependent emission and mechanochromism behavior was explored by POM, DSC, XRD, SEM, absorption spectra and emission spectra. All the compounds are enantiotropic liquid crystals. The lowest non-halogen substituted homologue exhibited solo N phase, but the higher non-halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature. All the lowest halogen substituted homologues exhibited mesogenic transition from SmA phase to N phase upon rising temperature and all the higher homologues only exhibited SmA. The distinct mesogenic phase transition could be attributed to the intermolecular interaction produced by terminal halogen and the rigidity of the terminal aliphatic chain. All the non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom) exhibited AIE behaviors, whereas the iodinated compounds exhibited extremely weak emission in solution and aggregated states due to the heavy atoms effect. These compounds also exhibited distinct solid-state emission with blue or cyan fluorescence, which could be quenched by increasing temperature. The reversible mechanochromism behavior was also achieved in all the compounds. The mechanical force induced quench in emission in non-halogen substituted compounds and halogen substituted compounds with smaller terminal halogen atom (F, Cl and Br atom), whereas enhancement in iodinated compounds. The reversible mechanochromism behavior endowed these compounds with potential applications in rewritable paper and anti-counterfeiting. The interesting properties in these liquid crystals would be attributed to the balance of the halogen-halogen interactions, heavy atom effect, steric-hindrance effect and chain length. These investigations would be helpful to understand the relationship between chemical structures and properties.

11.
J Colloid Interface Sci ; 671: 751-769, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38824748

ABSTRACT

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Catechin , Copper , Nanocomposites , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Copper/chemistry , Copper/pharmacology , Nanocomposites/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Mice , Humans , Catechin/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Microbial Sensitivity Tests , Drug Resistance, Bacterial/drug effects , Photochemotherapy , Wound Infection/drug therapy , Wound Infection/pathology , Wound Infection/microbiology , Drug Screening Assays, Antitumor , Staphylococcus aureus/drug effects , Photothermal Therapy , Particle Size , Escherichia coli/drug effects , Cell Survival/drug effects , Cell Line, Tumor , Surface Properties , Cell Proliferation/drug effects
12.
Adv Sci (Weinh) ; 11(29): e2309889, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38838096

ABSTRACT

Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS-C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue-specific enrichment analysis indicate that the protective effect of PGS-C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high-cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS-C.


Subject(s)
Cognitive Dysfunction , Humans , Cognitive Dysfunction/genetics , Male , Aged , Female , Personality/genetics , Protective Factors , Multifactorial Inheritance/genetics , Cognition/physiology , Magnetic Resonance Imaging/methods , Aged, 80 and over , Brain/diagnostic imaging
13.
Gigascience ; 132024 01 02.
Article in English | MEDLINE | ID: mdl-38837945

ABSTRACT

BACKGROUND: Traditional Chinese medicine has used Peucedanum praeruptorum Dunn (Apiaceae) for a long time. Various coumarins, including the significant constituents praeruptorin (A-E), are the active constituents in the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies have attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and thus the development of better breeding strategies. RESULTS: A telomere-to-telomere (T2T) genome was assembled for P. praeruptorum by combining PacBio HiFi, ONT ultra-long, and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes with genome completeness >98%. Comparative genomic analysis suggested that P. praeruptorum experienced 2 whole-genome duplication events. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the COSY and cytochrome P450 genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins. CONCLUSIONS: A T2T genome for P. praeruptorum was obtained, providing molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds.


Subject(s)
Apiaceae , Coumarins , Genome, Plant , Telomere , Coumarins/metabolism , Apiaceae/genetics , Apiaceae/metabolism , Telomere/genetics , Telomere/metabolism , Evolution, Molecular , Phylogeny , Genomics/methods , Biosynthetic Pathways/genetics
14.
Nat Commun ; 15(1): 4897, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851742

ABSTRACT

DNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.e., T-to-C or T-to-G) and C-to-G conversions, respectively. Furthermore, we conduct parallel comparison of gTBE/gCBE with those recently developed using other protein engineering strategies, and find gTBE/gCBE show the outperformance. Thus, we provide several base editors, gTBEs and gCBEs, with corresponding engineered UNG variants, broadening the targeting scope of base editors.


Subject(s)
CRISPR-Associated Protein 9 , Gene Editing , Protein Engineering , Uracil-DNA Glycosidase , Humans , Gene Editing/methods , Uracil-DNA Glycosidase/metabolism , Uracil-DNA Glycosidase/genetics , Protein Engineering/methods , CRISPR-Associated Protein 9/metabolism , CRISPR-Associated Protein 9/genetics , Cytosine/metabolism , Thymine/metabolism , CRISPR-Cas Systems , HEK293 Cells , Mutagenesis , Guanine/metabolism , DNA/metabolism , DNA/genetics
15.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38836287

ABSTRACT

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.


Subject(s)
Insulin Receptor Substrate Proteins , MAP Kinase Signaling System , Mutation , Humans , Insulin Receptor Substrate Proteins/genetics , Insulin Receptor Substrate Proteins/metabolism , MAP Kinase Signaling System/genetics , Animals , Malformations of Cortical Development, Group I/genetics , Malformations of Cortical Development, Group I/metabolism , Brain/metabolism , Brain/pathology , Neurons/metabolism , Neurons/pathology , Cell Movement/genetics , HEK293 Cells , Female , Focal Cortical Dysplasia , Epilepsy
16.
BMC Pregnancy Childbirth ; 24(1): 384, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778289

ABSTRACT

OBJECTIVE: We sought to investigate the impact of individualized exercise guidance during pregnancy on the incidence of macrosomia and the mediating effect of gestational weight gain (GWG). DESIGN: A prospective randomized clinical trial. SETTING: A Hospital in Xingtai District, Hebei Province. POPULATION: Older than 20 years of age, mid-pregnancy, and singleton pregnant women without contraindications to exercise during pregnancy. METHODS: A randomized clinical trial was conducted from December 2021 to September 2022 to compare the effects of standard prenatal care with individualized exercise guidance on the incidence of macrosomia. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: In all, 312 singleton women were randomized into an intervention group (N = 162) or a control group (N = 150). Participants who received individualized exercise guidance had a significantly lower incidence of macrosomia (3.73% vs. 13.61%, P = 0.002) and infants large for gestational age (9.94% vs. 19.73%, P = 0.015). However, no differences were observed in the rate of preterm birth (1.86% vs. 3.40%, P = 0.397) or the average gestational age at birth (39.14 ± 1.51 vs. 38.69 ± 1.85, P = 0.258). Mediation analysis revealed that GWG mediated the effect of exercise on reducing the incidence of macrosomia. CONCLUSION: Individualized exercise guidance may be a preventive tool for macrosomia, and GWG mediates the effect of exercise on reducing the incidence of macrosomia. However, evidence does not show that exercise increases the rate of preterm birth or affects the average gestational age at birth. TRIAL REGISTRATION: The trial is registered at www.clinicaltrails.gov [registration number: NCT05760768; registration date: 08/03/2023 (retrospectively registered)].


Subject(s)
Exercise , Fetal Macrosomia , Gestational Weight Gain , Prenatal Care , Humans , Female , Fetal Macrosomia/prevention & control , Pregnancy , Adult , Prenatal Care/methods , Prospective Studies , Incidence , China/epidemiology , Infant, Newborn
17.
Diabetes Metab Syndr Obes ; 17: 1911-1921, 2024.
Article in English | MEDLINE | ID: mdl-38711675

ABSTRACT

Purpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester. Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester. Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (ß 0.010, 95% CI 0.001, 0.019) and fetal body weight (ß 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively). Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.

18.
Plant Physiol Biochem ; 211: 108670, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703501

ABSTRACT

Plants would encounter various biotic and abiotic stresses during the growth and development. WRKY transcription factors (TFs) as plant-specific TFs, play an important role in responding to various adverse circumstances. Despite some advances were achieved in functional studies of WRKY TFs in tea plants, systematic analysis of the involvement of CsWRKY TFs when facing cold, salt, drought stresses and pathogen and insect attack was lacked. In present study, a total of 78 CsWRKY TFs were identified following the genomic and transcript databases. The expression patterns of CsWRKYs in various organs of tea plants and the expression profiles in response to biotic and abiotic stresses were investigated by examining representative RNA-seq data. Moreover, the effects of hormone treatments (SA and MeJA) on the transcription levels of WRKY TFs were also investigated. The phylogenetic tree of CsWRKY TFs from different species indicated the functional diversity of WRKY TFs was not closely related to their protein classification. Concurrently, CsWRKY70-2 TF was identified as a positive regulator in response to drought stress. This study provided solid and valuable information, helping us better understand the functional diversity of CsWRKY TFs, and laid the foundation for further research on the function of key WRKY genes in tea plants.


Subject(s)
Camellia sinensis , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Stress, Physiological , Transcription Factors , Camellia sinensis/genetics , Camellia sinensis/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant/drug effects , Droughts , Genome, Plant , Cyclopentanes/metabolism , Cyclopentanes/pharmacology , Salicylic Acid/metabolism , Salicylic Acid/pharmacology , Oxylipins/pharmacology , Oxylipins/metabolism , Acetates/pharmacology
19.
Front Neurol ; 15: 1372168, 2024.
Article in English | MEDLINE | ID: mdl-38651098

ABSTRACT

Peripheral nerve injuries, caused by various reasons, often lead to severe sensory, motor, and autonomic dysfunction or permanent disability, posing a challenging problem in regenerative medicine. Autologous nerve transplantation has been the gold standard in traditional treatments but faces numerous limitations and risk factors, such as donor area denervation, increased surgical complications, and diameter or nerve bundle mismatches. The extracellular matrix (ECM) is a complex molecular network synthesized and released into the extracellular space by cells residing in tissues or organs. Its main components include collagen, proteoglycans/glycosaminoglycans, elastin, laminin, fibronectin, etc., providing structural and biochemical support to surrounding cells, crucial for cell survival and growth. Schwann cells, as the primary glial cells in the peripheral nervous system, play various important roles. Schwann cell transplantation is considered the gold standard in cell therapy for peripheral nerve injuries, making ECM derived from Schwann cells one of the most suitable biomaterials for peripheral nerve repair. To better understand the mechanisms of Schwann cells and the ECM in peripheral nerve regeneration and their optimal application, this review provides an overview of their roles in peripheral nerve regeneration.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 282-288, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38557381

ABSTRACT

OBJECTIVES: To investigate the effects of different concentrations of adapalene on the morphology and functions of neuroblastoma cell line SH-SY5Y, as well as its role in inducing cell differentiation and apoptosis. METHODS: SH-SY5Y cells were divided into control group, low concentration (0.1 µM and 1 µM) adapalene groups, and high concentration (10 µM) adapalene group. Time-lapse microscopy was used to observe the morphological changes of SH-SY5Y cells. Immunofluorescence staining was performed to detect the expression of neuronal specific marker ßIII-tubulin and mature neuronal marker neurofilament heavy polypeptide (NFH). Multi-electrode array was used to record the electrophysiological features of SH-SY5Y cells. Cell apoptosis was evaluated using a cell apoptosis detection kit. RESULTS: Low concentrations of adapalene promoted the formation of neurite outgrowth in SH-SY5Y cells, with the neurites interconnected to form a network. Spontaneous discharge activity was observed in SH-SY5Y cells treated with low concentrations of adapalene. Compared to the control group, the expression of ßIII-tubulin and NFH increased in the 1 µM adapalene group, while the level of cell apoptosis increased in the high concentration adapalene group (P<0.05). CONCLUSIONS: Low concentrations of adapalene can induce differentiation of SH-SY5Y cells into mature functional neurons, while high concentrations of adapalene can induce apoptosis in SH-SY5Y cells.


Subject(s)
Neuroblastoma , Tubulin , Humans , Neurons , Cell Differentiation , Apoptosis , Cell Line, Tumor
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