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1.
Neuromuscul Disord ; 39: 24-29, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38714145

ABSTRACT

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

2.
J Hazard Mater ; 472: 134466, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38718507

ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.

3.
ACS Biomater Sci Eng ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722544

ABSTRACT

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

4.
J Integr Med ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38714484

ABSTRACT

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, et al. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; Epub ahead of print.

5.
Heliyon ; 10(8): e28543, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38628704

ABSTRACT

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

6.
World J Gastrointest Oncol ; 16(4): 1309-1318, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660663

ABSTRACT

BACKGROUND: Despite continuous changes in treatment methods, the survival rate for advanced hepatocellular carcinoma (HCC) patients remains low, highlighting the importance of diagnostic methods for HCC. AIM: To explore the efficacy of texture analysis based on multi-parametric magnetic resonance (MR) imaging (MRI) in predicting microvascular invasion (MVI) in preoperative HCC. METHODS: This study included 105 patients with pathologically confirmed HCC, categorized into MVI-positive and MVI-negative groups. We employed Original Data Analysis, Principal Component Analysis, Linear Discriminant Analysis (LDA), and Non-LDA (NDA) for texture analysis using multi-parametric MR images to predict preoperative MVI. The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software, with results expressed as the misjudgment rate (MCR). RESULTS: Texture analysis using multi-parametric MRI, particularly the MI + PA + F dimensionality reduction method combined with NDA discrimination, demonstrated the most effective prediction of MVI in HCC. Prediction accuracy in the pulse and equilibrium phases was 83.81%. MCRs for the combination of T2-weighted imaging (T2WI), arterial phase, portal venous phase, and equilibrium phase were 22.86%, 16.19%, 20.95%, and 20.95%, respectively. The area under the curve for predicting MVI positivity was 0.844, with a sensitivity of 77.19% and specificity of 91.67%. CONCLUSION: Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI, portal venous, and equilibrium phases. This study provides an objective, non-invasive method for preoperative prediction of MVI, offering a theoretical foundation for the selection of clinical therapy.

7.
Cytokine ; 179: 156618, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38663252

ABSTRACT

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

8.
Biomicrofluidics ; 18(2): 021301, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38566823

ABSTRACT

Fluid manipulation is an important foundation of microfluidic technology. Various methods and devices have been developed for fluid control, such as electrowetting-on-dielectric-based digital microfluidic platforms, microfluidic pumps, and pneumatic valves. These devices enable precise manipulation of small volumes of fluids. However, their complexity and high cost limit the commercialization and widespread adoption of microfluidic technology. Shape memory polymers as smart materials can adjust their shape in response to external stimuli. By integrating shape memory polymers into microfluidic chips, new possibilities for expanding the application areas of microfluidic technology emerge. These shape memory polymers can serve as actuators or regulators to drive or control fluid flow in microfluidic systems, offering innovative approaches for fluid manipulation. Due to their unique properties, shape memory polymers provide a new solution for the construction of intelligent and automated microfluidic systems. Shape memory microfluidic chips are expected to be one of the future directions in the development of microfluidic technology. This article offers a summary of recent research achievements in the field of shape memory microfluidic chips for fluid and droplet manipulation and provides insights into the future development direction of shape memory microfluidic devices.

9.
Plant Dis ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568791

ABSTRACT

Chrysanthemum (Chrysanthemum morifolium cv. Fubaiju) is used as medicinal herb (Chen et al. 2020). In October 2021, a leaf spot disease was observed on leaves of C. morifolium in Huanggang, Hubei province. Disease incidence was approximately 40%. Leaf lesions manifested as necrotic spots, coalesced, and expanded to form brown-black spots, leading to wilting of the leaves. On stems, the lesions manifested as dark brown necrotic spots. To identify the pathogen, 29 pieces (5 × 5 mm) from lesion margins were surface sterilized in 1% NaOCl and rinsed three times with sterile water. The pieces were transferred onto potato dextrose agar (PDA) for incubation at 25℃ for 3 d in the dark. Fifteen fungal colonies were successfully isolated. The colony morphology with flat wavy edge, sparse aerial mycelia, and surface olivaceous black were observed at 7 days post incubation. Subglobular pycnidia were brown with a short beak, and pycnidia diameters were thick (212 to 265 × 189 to 363 µm, n = 20). Ovoid conidia were aseptate and hyaline, conidia diameters were thick (4.0 to 9.8 × 1.8 to 4.7 µm, n = 100). The morphological characters of these isolates were consistent with those of Stagonosporopsis chrysanthemi (Zhao et al. 2021). Pure culture of representative HGNU2021-18 isolated from the diseased leaves subjected to molecular identification. Sequences of the rDNA internal transcribed spacer (ITS) region, 28S large subunit ribosomal RNA (LSU), ß-tubulin (TUB2), actin (ACT), and partial RNA polymerase II largest subunit (RPB2) genes were amplified from genomic DNA of isolate HGNU2021-18 using the following primer pairs: ITS1/ITS4 (White et al. 1990), LR0R/LR5 (Rehner et al. 1994), Btub2Fd/Btub4Rd (Woudenberg et al. 2009), ACT512F/ACT783R (Carbone et al.1999), and RPB2-5F2 (Sung et al. 2007)/fRPB2-7cR (Liu et al. 1999), respectively. The PCR products were purified and then sequenced by Sangon Biotech (China). Nucleotide sequences of ITS (544 bp, OM346748), LSU (905 bp, OM758418), TUB2 (563 bp, OM945724), ACT (294 bp, OM793715), and RPB2 (957 bp, OM793716) amplified from the isolate HGNU2021-18 were subjected to BLASTn analysis. The results showed that ITS, LSU, TUB2, ACT, and RPB2 shared 100.00%, 99.45%, 99.20%, 100.00%, and 100.00% sequence identity to the five published sequences (MW810272.1, MH869953.1, MW815129.1, JN251973.1, and MT018012.1, respectively) of the S. chrysanthemi isolate CBS 500.63. Phylogenetic analysis of the multilocus sequences of ITS, LSU, RPB2, ACT, and TUB2 belonging to different Stagonosporopsis species was performed in MEGA 7.0 (Chen et al. 2015). Isolate HGNU2021-18 was placed in a clade with S. chrysanthemi with 99% bootstrap support. Thus, the results of morphological and molecular analyses indicated that the disease symptoms on chrysanthemum plants were caused by S. chrysanthemi. Under conditions of 25°C and 85% relative humidity, pathogenicity test was performed on 2-month-old healthy plants using isolate HGNU2021-18. The leaves were inoculated with 5 mm diameter mycelial plugs or with sterile agar plugs (control). Six plants were used in each treatment. Disease symptoms were observed on treated plants at 2 weeks post inoculation which were those previously observed in the field, while the control plants remained symptomless. The pathogen was re-isolated from the diseased plants, and S. chrysanthemi was confirmed as the causal pathogen. This is the first report of S. chrysanthemi causing stem and foliage blight of chrysanthemum in China.

10.
Opt Express ; 32(7): 12601-12608, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571078

ABSTRACT

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

13.
Biomed Environ Sci ; 37(3): 242-253, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38582989

ABSTRACT

Objective: This study aimed to evaluate the associations of serum folate and/or vitamin B 12 concentrations with obesity among Chinese children and adolescents. Methods: A cross-sectional study was conducted including 3,079 Chinese children and adolescents, aged 6 to 17 years, from Jiangsu, China. Anthropometric indices, such as, children's body mass index (BMI), BMI z-scores, waist circumference, and waist-to-height ratio were utilized. Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B 12 levels with anthropometric indices and odds of obesity. Results: We observed that serum vitamin B 12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity [odds ratio ( OR) = 0.68; 95% confidence interval ( CI) = 0.59, 0.78] and abdominal obesity ( OR = 0.68; 95% CI = 0.60, 0.77). When compared to participants with both serum vitamin levels in the two middle quartiles, those with both serum folate and vitamin B 12 levels in the highest quartile were less prone to general ( OR = 0.31, 95% CI = 0.19, 0.50) or abdominal obesity ( OR = 0.46, 95% CI = 0.31, 0.67). Conversely, participants with vitamin B 12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity ( OR = 2.06, 95% CI = 1.09, 3.91). Conclusion: Higher serum vitamin B 12 concentrations, but not serum folate concentrations, were associated with lower odds of childhood obesity. Children and adolescents with high levels of vitamin B 12 and folate were less likely to be obese.


Subject(s)
Pediatric Obesity , Vitamin B 12 , Humans , Child , Adolescent , Obesity, Abdominal , Cross-Sectional Studies , Pediatric Obesity/epidemiology , Risk Factors , Body Mass Index , Folic Acid , Vitamins
14.
BMC Med Genomics ; 17(1): 116, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684994

ABSTRACT

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.


Subject(s)
Histone-Lysine N-Methyltransferase , Sotos Syndrome , Humans , Histone-Lysine N-Methyltransferase/genetics , Sotos Syndrome/genetics , Male , Female , Child, Preschool , Child , Infant , Intracellular Signaling Peptides and Proteins/genetics , Exome Sequencing , Mutation , Karyotyping , Histone Methyltransferases/genetics , Nuclear Proteins/genetics
15.
Chem Sci ; 15(11): 4106-4113, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38487231

ABSTRACT

The modulation of two-dimensional metal-organic framework (2-D MOF) nanosheet stacking is an effective means to improve the properties and promote the application of nanosheets in various fields. Here, we employed a series of alcohol guest molecules (MeOH, EtOH and PrOH) to modulate Zr-BTB (BTB = benzene-1,3,5-tribenzoate) nanosheets and to generate untwisted stacking. The distribution of stacking angles was statistically analyzed from high-angle annular dark-field (HAADF) and fast Fourier transform (FFT) images. The ratios of untwisted stacking were calculated, such as 77.01% untwisted stacking for MeOH, 83.45% for EtOH, and 85.61% for PrOH. The obtained untwisted Zr-BTB showed good separation abilities for different substituted benzene isomers, superior para selectivity and excellent column stability and reusability. Control experiments of 2-D Zr-TCA (TCA = 4,4',4''-tricarboxytriphenylamine) and Zr-TATB (TATB = 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid) nanosheets with similar pore sizes and stronger polarity regulated by the alcohol guests exhibited moderate separation performance. The electron microscopy images revealed that polar alcohol regulation dominantly generated the twisted stacking of Zr-TCA and Zr-TATB with various Moiré patterns. Polar guest molecules, such as alcohols, provide strong host-guest interactions during the regulation of MOF nanosheet stacking, providing an opportunity to design new porous Moiré materials with application prospects.

16.
Ying Yong Sheng Tai Xue Bao ; 35(2): 480-488, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38523106

ABSTRACT

The construction of urban ecological green wedges, which can mitigate the heat island effect through cooling and ventilation effects, is an important way to enhance the adaptation of cities to climate change. Dynamic monitoring and periodic assessment of both the conservation status and cooling effect of ecological green wedges is a key to ensure the heat mitigation benefits. Based on multi-source remote sensing data, we systematically analyzed the land use changes of six ecological green wedges in Wuhan in 2013 and 2020 using the methods of Markov transfer matrix, land use dynamics, and comprehensive index of land use degree, and evaluated the changes in surface temperature of the ecological green wedges and their cooling island effect. Results showed that the ecological green wedges in Wuhan generally had a large amount of construction land encroaching on ecological land from 2013 to 2020, with the water decreased the most. With the continuous deterioration of ecological green wedges, their land surface temperatures showed rising trends, together with significant weakening trends in cooling island effects. Among all the six wedges, the Dadonghu, Tangxun, and Wuhu exhibited relatively better ecological conservation, slighter land use change and lower overall development degree. Qinglinghu and Houguanhu demonstrated average levels of conservation. Fuhe experienced the most severe change under the significant influence of the westward policy of Wuhan City, with the proportion of water decreasing by 7.1%, warming up by 3.00 ℃, and the largest reduction in cooling distance for the cooling island effect, amounting to about 210 m. The results provided scientific evidence for the urban heat island mitigation-oriented planning and management of ecological green wedges for Wuhan City.


Subject(s)
Hot Temperature , Water , Cities , Temperature , China , Environmental Monitoring/methods
17.
Science ; 383(6689): 1302-1303, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38513007
18.
Trials ; 25(1): 200, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509589

ABSTRACT

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.


Subject(s)
Parkinson Disease , Transcranial Direct Current Stimulation , Humans , Middle Aged , Aged , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Parkinson Disease/complications , Transcranial Direct Current Stimulation/adverse effects , Transcranial Direct Current Stimulation/methods , Quality of Life , Exercise Therapy/methods , Double-Blind Method , Randomized Controlled Trials as Topic
19.
J Agric Food Chem ; 72(12): 6372-6388, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38471112

ABSTRACT

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.


Subject(s)
Calcium Oxalate , Edible Seaweeds , Kidney Calculi , Porphyra , Rats , Animals , Kelch-Like ECH-Associated Protein 1/metabolism , Calcium Oxalate/metabolism , Calcium Oxalate/pharmacology , Antioxidants/metabolism , NF-E2-Related Factor 2/metabolism , Kidney/metabolism , Kidney Calculi/metabolism , Oxidative Stress , Oxalates/metabolism , Oxalates/pharmacology , Polysaccharides/metabolism
20.
Appl Opt ; 63(4): 982-989, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38437395

ABSTRACT

In underwater wireless optical communication (UWOC), vortex beams carrying orbital angular momentum (OAM) can improve channel capacity but are vulnerable to oceanic turbulence (OT), leading to recognition errors. To mitigate this issue, we propose what we believe to be a novel method that combines the Gerchberg-Saxton (GS) algorithm-based recovery with convolutional neural network (CNN)-based recognition (GS-CNN). Our experimental results demonstrate that superposed Laguerre-Gaussian (LG) beams with small topological charge are ideal information carriers, and the GS-CNN remains effective even when OT strength C n2 is high up to 10-11 K 2 m -2/3. Furthermore, we use 16 kinds of LG beams to transmit a 256-grayscale digital image, giving rise to an increase in recognition accuracy from 0.75 to 0.93 and a decrease in bit error ratio from 3.98×10-2 to 6.52×10-3 compared to using the CNN alone.

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