摘要：
Van der Hoeve's syndrome, also known as osteogenesis imperfecta (OI), is a genetic connective tissue disorder characterized by fragile, fracture-prone bone and hearing loss. The disease is caused by a gene mutation in one of the two type I collagen genes COL1A1 or COL1A2. In this study, we identified a novel frameshift mutation of the COL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in the COL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in the COL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ability to differentiate into osteoblasts. Using a CRISPR-based homology-directed repair strategy, we corrected the OI disease-causing COL1A1 novel mutations in iPSCs generated from an affected individual. Our results demonstrated that the diminished expression of type I collagen and osteogenic potential were enhanced in OB induced from corrected OI-iPSCs compared to those from OI-iPSCs. Overall, our results provide new insights into the genetic basis of Van der Hoeve's syndrome and highlight the potential of iPSC technology for disease modeling and therapeutic development.
摘要：
This study utilizes both experimental and computational approaches to investigate the performance of Lu(2)Ti(2)O(7)(LTO) and Lu(1.5)Ce(0.5)Ti(2)O(7+x)(LCTO) pyrochlores under high pressure. The structural changes of LTO and LCTO pyrochlores were characterized usingin-situsynchrotron x-ray diffraction (SXRD) andin-situRaman spectroscopy at pressures up to 44.6 GPa. The kinks inP-aandP-Vcurves at around 5 GPa are mainly attributed to the interaction between the pressure medium and the isostructural changes. The onset pressures for transitioning from the cubic pyrochlore phase (Fd-3 m) to the monoclinic phase (P2(1)) are observed at 32.5 GPa and 38.1 GPa, respectively. It is important to note that at the highest measured pressures, the phase transition remains incomplete. This partial transition is likely the result of oriented disorder among cations and anions under high pressure. In addition, introducing Ce as a dopant significantly enhances structural stability. This can be explained by the larger ionic radius of Ce, which hinders the disordering process.
摘要：
center dot PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. center dot DESIGN: Subanalysis of prospective cohort study data. center dot METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income [LIC], lower-middle income [LMIC], upper-middle income [UMIC], and high income [HIC]) of 491 treatment-naive retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. center dot RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval [CI] 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients > 4 years of age (vs <= 4 years, HR = 0.45 [95% CI 0.27-0.78], P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 x 109 [95% CI 1.25 x 109 -1.72 x 10(10)], P < .001) and females (vs males, HR = 1.98 [95% CI 1.27-3.10], P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 [95% CI 2.36-10.5], P < .001). center dot CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs. (Am J Ophthalmol 2024;260: 91-101. (c) 2023 Elsevier Inc. All rights reserved.)
摘要：
BACKGROUND: We previously revealed that hydrogen sulfide (H(2)S) attenuates chronic stress-induced cognitive impairment, but the underlying mechanism needs to be further clarified. Growth differentiation factor 11 (GDF11) plays an important regulatory role in cognitive function and that hippocampal NLRP3/caspase-1-mediated pyroptosis contributes to the pathogenesis of cognitive impairment. Hence, this research aimed to explore whether promoting GDF11 levels and suppressing hippocampal NLRP3/caspase-1-mediated pyroptosis mediate H(2)S to alleviate chronic stress-induced cognitive impairment. METHODS: Sprague-Dawley rats were subjected to unpredictable chronic mild stress lasting four weeks to establish an animal model of chronic stress-induced cognitive impairment. Behavioral performance was assessed by the Y-maze test and the novel object recognition test. The expression levels of proteins were analyzed by Western blot analysis. The levels of IL-1β and IL-18 in the hippocampus were measured by ELISA. RESULTS: NaHS upregulated the expression of GDF11 in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed rats. Silencing GDF11 blocked NaHS-improved cognitive impairment in CUMS-exposed rats, according to the Y-maze test and the novel object recognition test. Furthermore, NaHS mitigated NLRP3/caspase-1-mediated pyroptosis in the hippocampus of CUMS-exposed rats and this effect was reversed by silencing GDF11. Moreover, overexpression of GDF11 alleviated CUMS-induced cognitive impairment and NLRP3/caspase-1-mediated hippocampal pyroptosis. CONCLUSIONS: GDF11 mediates H(2)S to attenuate chronic stress-induced cognitive impairment via inhibiting hippocampal NLRP3/caspase-1-mediated pyroptosis.
作者机构：
[Chen, Alex F.; Zhang, Zhen; Yu, Fan] Cent South Univ, Dept Cardiol, Xiangya Hosp 3, Changsha, Peoples R China.;[Yu, Fan] Zhejiang Univ, Res Ctr Life Sci & Human Hlth, Binjiang Inst, Hangzhou, Zhejiang, Peoples R China.;[Leng, Yiping] Univ South China, Affiliated Changsha Cent Hosp, Res Ctr PhaseClin Trials 1, Hengyang Med Sch, Changsha, Hunan, Peoples R China.;[Chen, Alex F.] Shanghai Jiao Tong Univ, Inst Cardiovasc Dev & Regenerat Med, Dept Cardiol, Sch Med,Xinhua Hosp, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China.
通讯机构：
[Chen, AF ] C;Cent South Univ, Dept Cardiol, Xiangya Hosp 3, Changsha, Peoples R China.;Shanghai Jiao Tong Univ, Inst Cardiovasc Dev & Regenerat Med, Dept Cardiol, Sch Med,Xinhua Hosp, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China.
关键词：
GSDMD;O-GlcNAc;Sepsis;Endothelial;Pyroptosis
摘要：
OBJECTIVE: Increased O-linked β-N-acetylglucosamine (O-GlcNAc) stimulation has been reported to protect against sepsis associated mortality and cardiovascular derangement. Previous studies, including our own research, have indicated that gasdermin-D(GSDMD)-mediated endothelial cells pyroptosis contributes to sepsis-associated endothelial injury. This study explored the functions and mechanisms of O-GlcNAc modification on lipopolysaccharide (LPS)-induced pyroptosis and its effects on the function of GSDMD. METHODS: A LPS-induced septic mouse model administrated with O-GlcNAcase (OGA) inhibitor thiamet-G (TMG) was used to assess the effects of O-GlcNAcylation on sepsis-associated vascular dysfunction and pyroptosis. We conducted experiments on human umbilical vein endothelial cells (HUVECs) by challenging them with LPS and TMG to investigate the impact of O-GlcNAcylation on endothelial cell pyroptosis and implications of GSDMD. Additionally, we identified potential O-GlcNAcylation sites in GSDMD by utilizing four public O-GlcNAcylation site prediction database, and these sites were ultimately established through gene mutation. RESULTS: Septic mice with increased O-GlcNAc stimulation exhibited reduced endothelial injury, GSDMD cleavage (a marker of pyroptosis). O-GlcNAc modification of GSDMD mitigates LPS-induced pyroptosis in endothelial cells by preventing its interaction with caspase-11 (a human homologous of caspases-4/5). We also identified GSDMD Serine 338 (S338) as a novel site of O-GlcNAc modification, leading to decreased association with caspases-4 in HEK293T cells. CONCLUSIONS: Our findings identified a novel post-translational modification of GSDMD and elucidated the O-GlcNAcylation of GSDMD inhibits LPS-induced endothelial injury, suggesting that O-GlcNAc modification-based treatments could serve as potential interventions for sepsis-associated vascular endothelial injury.
摘要：
Objectives: This study aimed to evaluate the therapeutic effects and mechanism of genistein on dextran sulfate sodium-induced mouse model of ulcerative colitis (UC).Materials and Methods: A DSS-induced mouse model for UC was used in this study. Mice were then treated with genistein or a combination of genistein and the G protein-coupled estrogen receptor (GPER) antagonist G15. Colon length, disease activity index (DAI), spleen index (SI), histopathological alterations, and integrity of the colonic barrier were evaluated. The expression of inflammatory cytokines and antioxidant capacity were detected. Populations of T helper 17 cells (Th17) and Regulatory T cells (Treg) in the mesenteric lymph nodes (MLN) were analyzed. The expression of a transcription factor for Th17 and Treg in the colonic tissues was detected.Results: Genistein treatment significantly alleviated DSS-induced colitis, summarized as increased colonic length, decreased DAI, SI, improved histopathological alterations, and colonic barrier integrity. Genistein treatment restrained pro-inflammatory cytokines and oxidative enzyme release while promoting anti-inflammatory and anti-oxidative enzyme release. Flow cytometry indicated that genistein significantly reduced the Th17 population while boosting Treg populations. Furthermore, genistein inhibited the expression of transcription factors associated with Th17 and promoted the expression of transcription factors associated with Treg in the colonic tissue. Intriguingly, these observed effects of genistein were abolished when UC mice were treated with a combination of genistein and GPER antagonist G15.Conclusion: This study suggests that genistein is potent in protecting against DSS-induced colonic injuries by rebalancing Th17/Treg and that GPER may be a vital target for genistein-mediated immunomodulatory effects in UC.
摘要：
To explore the influence of lithology on the failure behavior of layered tunnel, true triaxial compression experiments were undertaken on cubical phyllite and yellow sandstone samples containing a "D" shaped hole. The failure progress of the hole sidewalls was monitored and captured using a miniature camera. The results reveal that the initial vertical failure stress of the phyllite samples presents a "U" shaped change as the bedding angle increases. At the bedding angle of 45 degrees, compared with the initial vertical failure stress of the yellow sandstone tunnel, that of the phyllite tunnel is lower, resulting in larger rock fragments and deeper V-shaped grooves. The failure pattern of the phyllite tunnel is primarily manifested as extensive shear sliding failure, and the failure is more severe. The failure of the yellow sandstone tunnel is primarily characterized by the sequential laminar fracturing along the maximum principal stress direction, predominantly manifesting as tensile failure. The primary factors influencing the failure of two types of layered rocks are the significant variations in the clay mineral content within the rocks. For the phyllite, it contains nearly one-third of montmorillonite (a clay mineral). This results in the formation of weak bedding planes within surrounding rocks, which induces shear slip failures along these bedding planes. In contrast, the yellow sandstone has a lower clay mineral content, leading to the absence of distinct weak bedding planes within the surrounding rock. In this case, bedding planes present ignorable effect on the surrounding rock.
摘要：
BACKGROUND: With the burgeoning advancements in disease modeling, drug development, and precision medicine, organ-on-a-chip has risen to the forefront of biomedical research. Specifically in tumor research, this technology has exhibited exceptional potential in elucidating the dynamics of metastasis within the tumor microenvironment. Recognizing the significance of this field, our study aims to provide a comprehensive bibliometric analysis of global scientific contributions related to organ-on-a-chip. METHODS: Publications pertaining to organ-on-a-chip from 2014 to 2023 were retrieved at the Web of Science Core Collection database. Rigorous analyses of 2305 articles were conducted using tools including VOSviewer, CiteSpace, and R-bibliometrix. RESULTS: Over the 10-year span, global publications exhibited a consistent uptrend, anticipating continued growth. The United States and China were identified as dominant contributors, characterized by strong collaborative networks and substantial research investments. Predominant institutions encompass Harvard University, MIT, and the Chinese Academy of Sciences. Leading figures in the domain, such as Dr. Donald Ingber and Dr. Yu Shrike Zhang, emerge as pivotal collaboration prospects. Lab on a Chip, Micromachines, and Frontiers in Bioengineering and Biotechnology were the principal publishing journals. Pertinent keywords encompassed Microfluidic, Microphysiological System, Tissue Engineering, Organoid, In Vitro, Drug Screening, Hydrogel, Tumor Microenvironment, and Bioprinting. Emerging research avenues were identified as "Tumor Microenvironment and Metastasis," "Application of organ-on-a-chip in drug discovery and testing" and "Advancements in personalized medicine applications". CONCLUSION: The organ-on-a-chip domain has demonstrated a transformative impact on understanding disease mechanisms and drug interactions, particularly within the tumor microenvironment. This bibliometric analysis underscores the ever-increasing importance of this field, guiding researchers and clinicians towards potential collaborative avenues and research directions.
作者机构：
[Lu, Jibu; Song, Cailu; Xie, Xiaoming; Liu, Lingrui; Tang, HL; Tang, Hailin; Mo, Yunxian; Wu, Song] Sun Yat Sen Univ, Canc Ctr, Guangdong Prov Clin Res Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Peoples R China.;[Li, YH; Zhu, Hongbo; Li, Yuehua; Xie, Liming] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang, Peoples R China.;[Wu, Feiyue] Guizhou Prov Peoples Hosp, Guiyang, Peoples R China.;[Lin, Huan; Tang, Hailin] Guangzhou Med Univ, Affiliated TCM Hosp, Guangzhou, Peoples R China.
通讯机构：
[Tang, HL ] S;[Li, YH ] U;[Lin, H ] G;Sun Yat Sen Univ, Canc Ctr, Guangdong Prov Clin Res Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang, Peoples R China.
关键词：
Autophagy;Circular RNAs;Competitive endogenous RNAs;Triple-negative breast cancer;circKIF4A
摘要：
Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases. Inhibition of circKIF4A impaired the ability of TNBC to proliferate, migrate, and cause brain metastasis. Luciferase reporter assays confirmed that circKIF4A competed for binding to miR-637 with STAT3 3' UTR. Western blot analysis revealed that inhibition of circKIF4A decreased STAT3 and p62 expression, while increased the LC3B-II/LC3B-I ratio and the expression of Beclin, indicating that downregulation of circKIF4A induced autophagy by competing with STAT3 for binding to miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, the circKIF4A-miR-637-STAT3 axis coordinates brain metastasis in TNBC. circKIF4A can therefore be used as a prognostic biomarker for brain metastasis in TNBC and as a therapeutic target.
期刊：
JOURNAL OF MATERIALS CHEMISTRY B,2024年12(6):1530-1537 ISSN：2050-750X
通讯作者：
Cheng, D;He, Longwei
作者机构：
[Cheng, Dan; He, Longwei; He, LW; Jiang, Renfeng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.;[Cheng, Dan; Zhang, Hongshuai; Yang, Xuefeng] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Gastroenterol, Hengyang 421002, Hunan Prov, Peoples R China.;[Cheng, Dan; Liu, Qian; Zhang, Hongshuai; Yang, Xuefeng; Xia, Yuqing] Univ South China, Affiliated Nanhua Hosp, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.
通讯机构：
[Cheng, D ; He, LW] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Gastroenterol, Hengyang 421002, Hunan Prov, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hunan Prov Clin Res Ctr Metab Associated Fatty Liv, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421002, Hunan, Peoples R China.
摘要：
Carboxylesterases (CESs) are critical for metabolizing ester-containing biomolecules and are specifically important in liver metabolic disorders. The modulation of CESs is also an important issue in pharmacology and clinical applications. Herein, we present a near-infrared (NIR) CES fluorescent probe (NCES) based on the protection-deprotection of the hydroxyl group for monitoring CES levels in living systems. The NCES probe has good selectivity and sensitivity for CESs with a limit of detection (LOD) of 5.24 mU mL-1, which allows for tracing the fluctuation of cellular CES after treatment with anticancer drugs and under inflammation and apoptosis states. Furthermore, NCES can be successfully applied for guiding liver cancer surgery with high-contrast in vivo imaging and detecting clinical serum samples from liver cancer patients. This work showed that the NCES probe has great potential in drug development, imaging applications for medical diagnosis, and early-stage detection for clinical liver diseases. A carboxylesterase-activated near-infrared fluorescent probe with high sensitivity and selectivity was developed to guide surgical resection of liver tumors and monitor clinical serum samples from liver cancer patients.
期刊：
EUROPEAN JOURNAL OF MEDICAL RESEARCH,2024年29(1):1-21 ISSN：0949-2321
通讯作者：
Liu, T;Zhu, GH
作者机构：
[Liu, Tang; Wang, Lifan; Lin, Zhengjun; Wang, Mingrui; Ji, Yuqiao; Yang, Jing; Zhou, Ziting; Yang, Yaocheng] Cent South Univ, Xiangya Hosp 2, Dept Orthoped, Changsha 410011, Hunan, Peoples R China.;[Zhu, Guanghui] Hunan Childrens Hosp, Dept Pediat Orthoped, Hunan Prov Key Lab Pediat Orthoped, Changsha 410007, Hunan, Peoples R China.;[Zhu, Guanghui] Furong Lab, Changsha, Hunan, Peoples R China.;[Zhu, Guanghui] Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;[Wang, Mingrui] Cent South Univ, Sch Basic Med Sci, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Zhu, GH ] H;[Liu, T ] C;Cent South Univ, Xiangya Hosp 2, Dept Orthoped, Changsha 410011, Hunan, Peoples R China.;Hunan Childrens Hosp, Dept Pediat Orthoped, Hunan Prov Key Lab Pediat Orthoped, Changsha 410007, Hunan, Peoples R China.;Furong Lab, Changsha, Hunan, Peoples R China.
摘要：
BACKGROUND: The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. METHODS: The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by theapplication of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors,utilizingdata extracted from the GEO database. RESULTS: PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. CONCLUSIONS: Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.
摘要：
Radon exhaled from building materials infiltrates the indoor atmosphere and is transported into the indoor space by buoyancy-driven airflow. This paper investigated the dynamic coupling of radon concentration in the building wall area and indoor space. An indoor radon migration model under natural convection caused by temperature gradient was established. The radon exhalation rate, average Nusselt number, and average Sherwood number at the building wall and indoor space interface were quantified. The mechanism of radon migration from building materials into the indoor atmosphere was elucidated. Results show that natural convection influences the flow of indoor air and the radon concentration distribution, which increases with the increase of temperature gradient.
期刊：
Qualitative Theory of Dynamical Systems,2024年23(2):1-17 ISSN：1575-5460
通讯作者：
Hu, SL
作者机构：
[Pan, Chaohong] Hunan First Normal Univ, Sch Math & Stat, Changsha 410205, Hunan, Peoples R China.;[Hu, Shulin; Pan, Chaohong; Wang, Hongyong] Univ South China, Sch Math & Phys, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Hu, SL ] U;Univ South China, Sch Math & Phys, Hengyang 421001, Hunan, Peoples R China.
摘要：
In this paper, we investigate the speed selection mechanism of traveling wave solutions for a reaction–diffusion–advection equation with high-order terms in a cylindrical domain. The study focuses the problem under two cases for Neumann boundary condition and Dirichlet boundary condition. By using the upper and lower solutions method, general conditions for both linear and nonlinear selections are obtained. When the equation is expanded to higher dimensions, literature examining this particular topic is scarce. In light of this, new results have been obtained for both linear and nonlinear speed selections of the equation with high-order terms. For different power exponents m and n, specific sufficient conditions for linear and nonlinear selections with the minimal wave speed are derived by selecting suitable upper and lower solutions. The impact of the power exponents m and n on speed selection is analyzed.
作者机构：
[He, Fang; Yang, Li; Deng, Xiaolu; Peng, Jing; Chen, Chen; Zhang, Ciliu; Wang, Xiaole; Yang, Lifen; Duan, Haolin; Mao, Leilei; Pang, Nan; Wang, Guoli; Zhang, Wen; Yin, Fei] Cent South Univ, Xiangya Hosp, Dept Pediat, Changsha 410008, Peoples R China.;[He, Fang; Yang, Li; Deng, Xiaolu; Peng, Jing; Chen, Chen; Zhang, Ciliu; Wang, Xiaole; Yang, Lifen; Duan, Haolin; Mao, Leilei; Pang, Nan; Wang, Guoli; Zhang, Wen; Yin, Fei] Cent South Univ, Xiangya Hosp, Clin Res Ctr Children Neurodev Disabil Hunan Prov, Changsha, Peoples R China.;[Xia, K; Li, Kuokuo; Chen, Meilin; Tan, Senwei; Guo, Hui; Xia, Kun] Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410078, Hunan, Peoples R China.;[Xia, K; Li, Kuokuo; Chen, Meilin; Tan, Senwei; Guo, Hui; Xia, Kun] Cent South Univ, Sch Life Sci, Hunan Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.;[Li, Kuokuo] Anhui Med Univ, Affiliated Hosp 1, Dept Oncol, Hefei 230022, Peoples R China.
通讯机构：
[Peng, J; Xia, K ; Yin, F ] C;Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410078, Hunan, Peoples R China.;Cent South Univ, Sch Life Sci, Hunan Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Cent South Univ, Xiangya Hosp, Clin Res Ctr Children Neurodev disabil Hunan Prov, Dept Pediat, Changsha, Peoples R China.
关键词：
Autism spectrum disorder;CDKL5;De novo variants;Epilepsy;Intellectual disability;Molecular inversion probes;Neurodevelopmental disorders;SCN1A
摘要：
With the continuous deepening of genetic research on neurodevelopmental disorders (NDDs), more patients have been identified the causal or candidate genes. However, it is still urgent needed to increase the sample size to confirm the associations between variants and clinical manifestations. We previously performed molecular inversion probe sequencing of autism spectrum disorder (ASD) candidate genes in 1543 ASD patients. In this study, we used the same method to detect de novo variants (DNVs) in 665 NDD patients with intellectual disability (ID) and/or epilepsy (EP) for genetic analysis and diagnosis. We compared findings from ID/EP and ASD patients to improve our understanding of different subgroups of NDDs. We identified 72 novel variants and 39 DNVs. A totally of 5.71% (38/665) of the patients were genetically diagnosed by this sequencing strategy. ID/EP patients demonstrated a higher prevalence of likely gene disruptive DNVs in ASD genes than the healthy population. Regarding high-risk genes, SCN1A and CKDL5 were more frequently mutated in ID/EP patients than in ASD patients. Our data provide an overview of the mutation burden in ID/EP patients from the perspective of high risk ASD genes, indicating the differences and association of NDDs subgroups.
摘要：
Chronic, non-healing wounds pose significant challenges for public health, particularly in the context of diabetes, and carry significant economic consequences. This article introduces a new solution in the form of a wireless theranostic patch, developed to meet the critical need for real-time monitoring and targeted treatments to facilitate optimal healing. The patch incorporates advanced materials that are both multifunctional and electro-responsive, leveraging a sophisticated blend of smart hydrogels and wearable bioelectronics to support diabetic wound management with unparalleled efficacy. With electro-responsive multifunctional polymer hydrogels at its core, the patch delivers a stretchable, antimicrobial, and moist environment for the wound, with added benefits such as conductivity and visibility. The materials also allow for continuous and autonomous monitoring of glucose and pH levels, providing precise and personalized treatments like insulin delivery via iontophoresis and electrical stimulation. Animal models have demonstrated that this integrated system is highly adaptable, effectively promoting wound closure and healing. Overall, the wireless theranostic system offers an exciting prospect for personalized healthcare solutions, adopting a patient-centric approach that prioritizes real-time, targeted care for chronic wounds. Its incorporation of advanced materials and electro-controlled treatments paves the way for new and innovative approaches to wound management. A wireless theranostic wound patch is designed to tackle the critical need by continuous monitoring of glucose and pH, on-demand delivering of insulin via iontophoresis, and electrical stimulation. Moreover, integrating wearable bioelectronics with advanced multifunctional and electro-responsive hydrogels provides a stretchable, antimicrobial, and moist environment for wounds, resulting in high efficacy in diabetic wound management. image
作者机构：
[Wang, Jingyu; Bai, Qinqin; Liang, H; Zheng, Yi; Zhao, Fengxia; Liang, Hao; Yan, Hangli; Wu, Linghao; Niu, Xiangheng] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.;[Hu, Hongmei] Hengyang Ctr Dis Control & Prevent, Hengyang 421001, Peoples R China.
通讯机构：
[Liang, H ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
摘要：
The detection of foodborne pathogens is crucial for food hygiene regulation and disease diagnosis. Colorimetry has become one of the main analytical methods in studying foodborne pathogens due to its advantages of visualization, low cost, simple operation, and no complex instrument. However, the low sensitivity limits its applications in early identification and on-site detection for trace analytes. In order to overcome such a limitation, herein we propose a joint strategy featuring dual signal amplification based on the hybridization chain reaction (HCR) and DNA-enhanced peroxidase-like activity of gold nanoparticles (AuNPs) for the sensitive visual detection of Escherichia coli. Target bacteria bound specifically to the aptamer domain in the capture hairpin probe, exposing the trigger domain for HCR and forming the extended double-stranded DNA (dsDNA) structures. The peroxidase-like catalytic capacity of AuNPs can be enhanced significantly by dsDNAs with the sticky ends of dsDNAs being adsorbed on AuNPs and the rigidity of dsDNAs causing the spatial regulation of AuNP concentration. The intensity of the enhancement was linearly related to the number of target bacteria. With the above strategy, the detection limit of our colorimetric method for Escherichia coli was down to 28 CFU mL(-1) within a short analytical time (50 min). This study provides a new perspective for the sensitive and visual detection of early bacterial contamination in foods.
作者机构：
[He, Run-Chao; Hu, YW; Zhang, Ting; Jiang, Min; Li, Shu; Song, Yu; Wu, Jia; Zhang, Ke-Lan; Hu, Yan-Wei; Tang, Mao-Lin; Dong, Xian-Hui] Guangzhou Med Univ, Guangzhou Women & Children Med Ctr, Dept Clin Lab, Guangzhou 510600, Guangdong, Peoples R China.;[Dai, Xiaoyan] Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China.;[Wu, Shao-Guo] Guangzhou Twelfth Peoples Hosp, Dept Clin Lab, Guangzhou, Guangdong, Peoples R China.;[Bei, Yan-Rou] Southern Med Univ, Nanfang Hosp, Lab Med Ctr, Guangzhou, Guangdong, Peoples R China.;[Ma, Xin] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, Guangzhou, Guangdong, Peoples R China.
通讯机构：
[Hu, YW ; Dai, XY ] G;Guangzhou Med Univ, Guangzhou Women & Children Med Ctr, Dept Clin Lab, Guangzhou 510600, Guangdong, Peoples R China.;Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China.
摘要：
BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe(-/-)PSMB8-AS1(KI)) and global Apoe and proteasome subunit-β type-9 (Psmb9) double knockout mice (Apoe(-/-)Psmb9(-/-)). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe(-/-)PSMB8-AS1(KI) mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe(-/-) mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe(-/-)PSMB8-AS1(KI) mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-β type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe(-/-) mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.
摘要：
The appearance of recalcitrant organic pollutants such as antibiotics in water bodies has gained a lot of attention owing to their adverse effects on organisms and humans. The current study aims to develop a novel approach to eliminate antibiotic tetracycline (TC) from a synthetic aqueous solution based on the advanced oxidation process triggered by MnSO4-catalyzed NaIO4. Single-factor experiment was performed to observe the impact of pH, NaIO4 concentration, and MnSO4 dosage on TC decomposition, and a three-factor, three-level response surface experiment with TC removal rate as the dependent variable was designed based on the range of factors determined from the single-factor experiment. The single-factor experiment revealed that the ranges of pH, NaIO4 concentration, and MnSO4 dosage need to be further optimized. ANOVA (analysis of variance) results showed that the data from the response surface experiment were consistent with the quadratic model with high R2 (0.9909), and the predicted values were very close to the actual values. After optimization by response surface methodology, the optimal condition obtained was pH = 6.7, [NaIO4] = 0.39 mM, and [MnSO4] = 0.12 mM, corresponding to a TC removal of 96.56%. This optimization condition was fully considered to save the dosage of the high-priced chemical NaIO4. HIGHLIGHTS MnSO4/NaIO4 is a potential advanced oxidative process against antibiotics. The impact of pH, NaIO4 concentration, and MnSO4 dosage on TC decomposition is investigated. Box-Behnken model is adopted to determine the scheme of the experiment. The best experimental condition is optimized using response surface methodology.
关键词：
cancer precision treatment;metal-containing two-dimensional nanomaterials;nanotechnology-based therapy;theranostic platform
摘要：
In recent years, metal-containing two-dimensional (2D) nanomaterials, among various 2D nanomaterials have attracted widespread attention because of their unique physical and chemical properties, especially in the fields of biomedical applications. Firstly, the review provides a brief introduction to two types of metal-containing 2D nanomaterials, based on whether metal species take up the major skeleton of the 2D nanomaterials. After this, the synthetical approaches are summarized, focusing on two strategies similar to other 2D nanomaterials, top-down and bottom-up methods. Then, the performance and evaluation of these 2D nanomaterials when applied to cancer therapy are discussed in detail. The specificity of metal-containing 2D nanomaterials in physics and optics makes them capable of killing cancer cells in a variety of ways, such as photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy and so on. Besides, the integrated platform of diagnosis and treatment and the clinical translatability through metal-containing 2D nanomaterials is also introduced in this review. In the summary and perspective section, advanced rational design, challenges and promising clinical contributions to cancer therapy of these emerging metal-containing 2D nanomaterials are discussed.
作者机构：
[Gong, Junyi; Hou, Jie] Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.
通讯机构：
[Hou, J ] U;Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421001, Peoples R China.
摘要：
Proton-conducting solid oxide fuel cells (H-SOFCs) are expected to be an ideal energy conversion device operating below 600 °C. However, the lack of robust electrodes with high catalytic activity remains a major obstacle to commercialization. Herein, B-site high-entropy modification is first performed on K2NiF4-type oxide to obtain a novel cathode material, La1.2Sr0.8Mn0.2Fe0.2Co0.2Ni0.2Cu0.2O4+δ (LSMFCNC). By harnessing the unique properties of multiple elements, the B-site transition metals in LSMFCNC evolve into various compound states, resulting in crystal structure expansion and a decrease in the bond strength between cations and oxygen ions, thereby promoting the formation of oxygen vacancies and achieving high proton/oxygen diffusion rates with excellent oxygen reduction reaction (ORR) activity. Ultimately, H-SOFCs using the high-entropy LSMFCNC cathode demonstrate an excellent cell performance with power outputs of 1759 mW/cm2 at 700 °C and 1126 mW/cm2 at 600 °C. This performance is superior to La1.2Sr0.8NiO4 (LSNO) and other K2NiF4-type cathodes reported in the literature. The outstanding electrochemical performance and fine operational stability suggest that LSMFCNC could be a potential cathode alternative for low-temperature H-SOFC operation. This study provides a new approach to developing highly active and durable cathodes for H-SOFCs.
