Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 30
Filter
1.
Sci Total Environ ; 945: 173927, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901584

ABSTRACT

The ubiquity and persistence of organophosphate esters (OPEs) and heavy metal (HMs) pose global environmental risks. This study explored tris(2-chloroisopropyl)phosphate (TCPP) biomineralization coupled to lead (Pb2+) biostabilization driven by denitrifying bacteria (DNB). The domesticated DNB achieved synergistic bioremoval of TCPP and Pb2+ in the batch bioreactor (efficiency: 98 %).TCPP mineralized into PO43- and Cl-, and Pb2+ precipitated with PO43-. The TCPP-degrading/Pb2+-resistant DNB: Achromobacter, Pseudomonas, Citrobacter, and Stenotrophomonas, dominated the bacterial community, and synergized TCPP biomineralization and Pb2+ biostabilization. Metagenomics and metaproteomics revealed TCPP underwent dechlorination, hydrolysis, the TCA cycle-based dissimilation, and assimilation; Pb2+ was detoxified via bioprecipitation, bacterial membrane biosorption, EPS biocomplexation, and efflux out of cells. TCPP, as an initial donor, along with NO3-, as the terminal acceptor, formed a respiratory redox as the primary energy metabolism. Both TCPP and Pb2+ can stimulate phosphatase expression, which established the mutual enhancements between their bioconversions by catalyzing TCPP dephosphorylation and facilitating Pb2+ bioprecipitation. TCPP may alleviate the Pb2+-induced oxidative stress by aiding protein phosphorylation. 80 % of Pb2+ converted into crystalized pyromorphite. These results provide the mechanistic foundations and help develop greener strategies for synergistic bioremediation of OPEs and HMs.

2.
Aging Dis ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38913050

ABSTRACT

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

3.
iScience ; 27(6): 109979, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38832007

ABSTRACT

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

4.
World J Gastroenterol ; 30(19): 2612-2614, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38817654

ABSTRACT

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.


Subject(s)
Gastroesophageal Reflux , Heartburn , Pepsin A , Saliva , Humans , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/microbiology , Saliva/microbiology , Heartburn/diagnosis , Heartburn/etiology , Pepsin A/analysis , Pepsin A/metabolism , Diagnosis, Differential , Biomarkers/analysis , Biomarkers/metabolism
5.
Environ Sci Technol ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316131

ABSTRACT

China's online food delivery (OFD) services consume enormous amounts of disposable plastics. Here, we investigated and modeled the national mass inventories and environmental release of plastics and chemical additives in the plastic. The extra-tree regression identified six key descriptors in determining OFD sales in Chinese cities. Approximately 847 kt of OFD plastic waste was generated in 2021 (per capita 1.10 kg/yr in the megacities and 0.39 kg/yr in other cities). Various additives were extensively detected, with geomean concentrations of 140.96, 4.76, and 0.25 µg/g for ∑8antioxidants, ∑21phthalates, and bisphenol A (BPA), respectively. The estimated mass inventory of these additives in the OFD plastics was 164.7 t, of which 51.1 t was released into the atmosphere via incineration plants and 51.0 t was landfilled. The incineration also released 8.07 t of polycyclic aromatic hydrocarbons and 39.1 kt of particulate matter into the atmosphere. Takeout food may increase the dietary intake of phthalates and BPA by 30% to 50% and raise concerns about considerable exposure to antioxidant transformation products. This study provides profound environmental implications for plastic waste in the Chinese OFD industry. We call for a sustainable circular economy action plan for waste disposal, but mitigating the hazardous substance content and their emissions is urgent.

6.
J Transl Med ; 22(1): 15, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172946

ABSTRACT

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.


Subject(s)
Breast Neoplasms , Phosphatidylinositol 3-Kinase , Humans , Female , Phosphatidylinositol 3-Kinases/metabolism , Breast Neoplasms/pathology , Precision Medicine , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Mutation/genetics , Class I Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolism
7.
World J Stem Cells ; 15(9): 876-896, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37900937

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury (IRI) and regulating immune rejection. However, some studies have indicated that the effects of MSCs are not very significant. Therefore, approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study. AIM: To enhance the therapeutic potential of human menstrual blood-derived stromal cells (MenSCs) in the mouse liver ischemia-reperfusion (I/R) model via interferon-γ (IFN-γ) priming. METHODS: Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γ priming, and indoleamine 2,3-dioxygenase (IDO) levels were measured by quantitative real-time reverse transcription polymerase chain reaction, western blotting, and ELISA to evaluate the efficacy of IFN-γ priming. In vivo, the liver I/R model was established in male C57/BL mice, hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury, and regulatory T cell (Treg) numbers in spleens were determined by flow cytometry to assess immune tolerance potential. Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs. In vitro, we established a hypoxia/reoxygenation (H/R) model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis. Transmission electron microscopy, western blotting, and immunofluorescence were used to analyze autophagy levels. RESULTS: IFN-γ-primed MenSCs secreted higher levels of IDO, attenuated liver injury, and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs. Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers. In the H/R model, autophagy inhibitors increased the level of H/R-induced apoptosis, indicating that autophagy exerted protective effects. In addition, primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy. Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin (mTOR) pathway and activating the AMPK pathway. CONCLUSION: IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels. MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI, and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance. Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

8.
Cell Mol Neurobiol ; 43(7): 3575-3592, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37418138

ABSTRACT

It has been demonstrated that diabetes cause neurite degeneration in the brain and cognitive impairment and neurovascular interactions are crucial for maintaining brain function. However, the role of vascular endothelial cells in neurite outgrowth and synaptic formation in diabetic brain is still unclear. Therefore, present study investigated effects of brain microvascular endothelial cells (BMECs) on high glucose (HG)-induced neuritic dystrophy using a coculture model of BMECs with neurons. Multiple immunofluorescence labelling and western blot analysis were used to detect neurite outgrowth and synapsis formation, and living cell imaging was used to detect uptake function of neuronal glucose transporters. We found cocultured with BMECs significantly reduced HG-induced inhibition of neurites outgrowth (including length and branch formation) and delayed presynaptic and postsynaptic development, as well as reduction of neuronal glucose uptake capacity, which was prevented by pre-treatment with SU1498, a vascular endothelial growth factor (VEGF) receptor antagonist. To analyse the possible mechanism, we collected BMECs cultured condition medium (B-CM) to treat the neurons under HG culture condition. The results showed that B-CM showed the same effects as BMEC on HG-treated neurons. Furthermore, we observed VEGF administration could ameliorate HG-induced neuronal morphology aberrations. Putting together, present results suggest that cerebral microvascular endothelial cells protect against hyperglycaemia-induced neuritic dystrophy and restorate neuronal glucose uptake capacity by activation of VEGF receptors and endothelial VEGF release. This result help us to understand important roles of neurovascular coupling in pathogenesis of diabetic brain, providing a new strategy to study therapy or prevention for diabetic dementia. Hyperglycaemia induced inhibition of neuronal glucose uptake and impaired to neuritic outgrowth and synaptogenesis. Cocultured with BMECs/B-CM and VEGF treatment protected HG-induced inhibition of glucose uptake and neuritic outgrowth and synaptogenesis, which was antagonized by blockade of VEGF receptors. Reduction of glucose uptake may further deteriorate impairment of neurites outgrowth and synaptogenesis.


Subject(s)
Endothelial Cells , Hyperglycemia , Humans , Endothelial Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism , Cells, Cultured , Neurons/metabolism , Vascular Endothelial Growth Factors/metabolism , Vascular Endothelial Growth Factors/pharmacology , Brain/metabolism , Glucose/toxicity , Glucose/metabolism
9.
Acta Pharmacol Sin ; 44(8): 1701-1711, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36932232

ABSTRACT

Eriocalyxin B (EB), 17-hydroxy-jolkinolide B (HJB), parthenolide (PN), xanthatin (XT) and andrographolide (AG) are terpenoid natural products with a variety of promising antitumor activities, which commonly bear electrophilic groups (α,ß-unsaturated carbonyl groups and/or epoxides) capable of covalently modifying protein cysteine residues. However, their direct targets and underlying molecular mechanisms are still largely unclear, which limits the development of these compounds. In this study, we integrated activity-based protein profiling (ABPP) and quantitative proteomics approach to systematically characterize the covalent targets of these natural products and their involved cellular pathways. We first demonstrated the anti-proliferation activities of these five compounds in triple-negative breast cancer cell MDA-MB-231. Tandem mass tag (TMT)-based quantitative proteomics showed all five compounds commonly affected the ubiquitin mediated proteolysis pathways. ABPP platform identified the preferentially modified targets of EB and PN, two natural products with high anti-proliferation activity. Biochemical experiments showed that PN inhibited the cell proliferation through targeting ubiquitin carboxyl-terminal hydrolase 10 (USP10). Together, this study uncovered the covalently modified targets of these natural products and potential molecular mechanisms of their antitumor activities.


Subject(s)
Biological Products , Biological Products/pharmacology , Biological Products/chemistry , Proteomics , Proteins/metabolism , Ubiquitins
10.
BMC Oral Health ; 22(1): 464, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36329463

ABSTRACT

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.


Subject(s)
Carcinoma, Squamous Cell , Esthetics, Dental , Humans , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Operative Time , Survival Rate , Treatment Outcome
11.
Chemosphere ; 307(Pt 1): 135670, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35839992

ABSTRACT

Organophosphate esters (OPEs) and phthalic acid esters (PAEs) are widespread contaminants in the environment. The variations of these chemicals in plants throughout their life cycle is little known. In this study, OPEs, OPE metabolites, and PAEs in peanut and corn grown under field conditions, soil, and air were measured to understand the uptake and translocation, distributions in the plant compartments, and metabolism in the plants. The soil concentrations showed an enrichment effect of OPEs onto the rhizosphere soil but a depletion effect of PAEs on rhizosphere soils. The PAE concentrations between peanut (with a mean of 1295 ng/g dw) and corn (3339 ng/g dw) were significantly different, but the OPE concentrations were not significantly different (with means of 15.6 and 19.2 ng/g dw, respectively). OPE metabolites were also detected in the plants, with lower concentrations and detection rates. Similarities and differences in the temporal variations of the concentrations of traditional OPEs, novel OPEs, and PAEs in plants during their growth were observed. The variations were dependent on both plant species and particular tissues. The leaf compartment is the most important reservoir of OPEs and PAEs (but not OPE metabolites) for both species, highlighting the importance of an aerial uptake pathway. The chemicals have a low potential to be translocated into peanut and corn kernels, reducing their risks via food consumption. Less hydrophobic compounds have higher root concentration factors in this study. These observations differ from those of previous hydroponic experiments.


Subject(s)
Flame Retardants , Organophosphates , Animals , China , Environmental Monitoring , Esters , Flame Retardants/analysis , Life Cycle Stages , Phthalic Acids , Soil/chemistry
12.
Environ Res ; 214(Pt 1): 113840, 2022 11.
Article in English | MEDLINE | ID: mdl-35810804

ABSTRACT

Combustion of domestic solid fuels is a significant source of polycyclic aromatic hydrocarbons (PAHs). Some oxygenated PAHs (o-PAHs) and PAHs with molecular weight of 302 (MW302 PAHs) are more toxic than the traditional 16 priority PAHs, whereas their emissions were much less elucidated. This study characterized the size-dependent emissions of parent PAHs (p-PAHs), o-PAHs, and MW302 PAHs from various combustion sources. The estimated emission factors (eEFs) from biomass burning sources were highest for most of the PAHs (391-8928 µg/kg), much higher than that of anthracite coal combustion (43.0-145 µg/kg), both which were operated in an indoor stove. Cigarette smoking had a high eEF of o-PAHs (240 ng/g). MW302 PAHs were not found in the emissions of smoking, cooking, and vehicular exhausts. Particle-size distributions of PAHs were compound- and source-dependent, and the tendency to associate with smaller particles was observed especially in biomass burning and cigarette smoking sources. Furthermore, the inter-source differences in PAH eEFs were associated with their dominance in fine particles. PAH composition profiles also varied with the particle size, showing increasing contributions of large-molecule PAHs with decreasing sizes in most cases. The size distributions of p-PAHs are much more significantly dependent on their n-octanol/air partition coefficients and vapor pressures than those of o-PAHs, suggesting differences in mechanisms governing their distributions. Several molecular diagnostic ratios (MDRs), including two based on MW302 PAHs, specific to these combustion scenarios were identified. However, the MDRs within some sources are also strongly size-dependent, providing a new explanation for the uncertainty in their application for source identification of PAHs. This work also highlights the necessity for understanding the size-resolved atmospheric behaviors and fate of PAHs after their emission.


Subject(s)
Air Pollutants , Polycyclic Aromatic Hydrocarbons , China , Coal , Environmental Monitoring , Particle Size , Vehicle Emissions
13.
Environ Sci Pollut Res Int ; 29(25): 37737-37747, 2022 May.
Article in English | MEDLINE | ID: mdl-35075556

ABSTRACT

Plasticizers are ubiquitous pollutants in the environment, whereas few efforts have been made to elucidate their emission sources in the atmosphere. In this research, the spatioseasonal variations and sources of particle-bound (PM2.5) phthalates (PAEs) and their substitutes (APs) at residential sites in seven districts and at four potential point-source sites across a megacity in South China were revealed. The total concentrations of PAEs ranging from 10.7 to 528 ng/m3 were substantially higher than those of APs (1.45.58.5 ng/m3). Significant spatial variations in the concentrations of the pollutants were observed, which were generally higher at the sites with intensive industrial activities and the point-source sites. Most atmospheric plasticizer levels peaked in summer, probably due to the temperature-promoted volatilization. Seven sources of plasticizers were identified by the positive matrix factorization (PMF) model. The sources in less industrialized districts are mainly associated with domestic and commercial emissions and with industry in the industrialized districts. Specifically, plastics and personal care products together contributed 60% of the plasticizers in the atmosphere of this city, followed by solvents and polyester industry sources. The incremental lifetime cancer risk of inhalation exposure to bis(2-ethylhexyl) phthalate in the study city is below the acceptable level. Relatively higher risks were found for residents living around sites with intensive industrial activities and around wastewater treatment plant.


Subject(s)
Air Pollutants , Particulate Matter , Air Pollutants/analysis , China , Environmental Monitoring , Particulate Matter/analysis , Phthalic Acids , Plasticizers , Risk Assessment , Seasons
14.
Sci Rep ; 11(1): 20974, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34697383

ABSTRACT

Our lab has previously demonstrated Riluzole to be an effective drug in inhibiting proliferation and inducing apoptosis in both human and mouse osteosarcoma. Yes-associated protein is a transcription co-activator, known to be involved in cell proliferation or apoptosis depending on its protein partner. In the present study we investigated the role of YAP in apoptosis in osteosarcoma, we hypothesized that YAP may be activated by Riluzole to induce apoptosis in osteosarcoma. By knocking down the expression of YAP, we have demonstrated that Riluzole failed to induce apoptosis in YAP deficient osteosarcoma cells. Riluzole caused translocation of YAP from the cytoplasm to the nucleus, indicating YAP's role in apoptosis. Both Riluzole-induced phosphorylation of YAP at tyrosine 357 and Riluzole-induced apoptosis were blocked by inhibitors of c-Abl kinase. In addition, knockdown of c-Abl kinase prevented Riluzole-induced apoptosis in LM7 cells. We further demonstrated that Riluzole promoted interaction between YAP and p73, while c-Abl kinase inhibitors abolished the interaction. Subsequently, we demonstrated that Riluzole enhanced activity of the Bax promoter in a luciferase reporter assay and enhanced YAP/p73 binding on endogenous Bax promoter in a ChIP assay. Our data supports a novel mechanism in which Riluzole activates c-Abl kinase to regulate pro-apoptotic activity of YAP in osteosarcoma.


Subject(s)
Bone Neoplasms/genetics , Osteosarcoma/genetics , Proto-Oncogene Proteins c-abl/metabolism , Riluzole/pharmacology , YAP-Signaling Proteins/genetics , Apoptosis , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , Cell Survival/drug effects , Cytoplasm/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Humans , Osteosarcoma/metabolism , Phosphorylation , Protein Transport , Tumor Protein p73/metabolism , YAP-Signaling Proteins/metabolism , bcl-2-Associated X Protein/genetics
15.
Sci Rep ; 11(1): 8637, 2021 04 21.
Article in English | MEDLINE | ID: mdl-33883588

ABSTRACT

Eradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein-ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.


Subject(s)
Antiviral Agents/pharmacology , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/metabolism , N-Acetylneuraminic Acid/antagonists & inhibitors , Animals , Binding Sites/physiology , Dogs , Madin Darby Canine Kidney Cells , Protein Binding/physiology
16.
Am J Med Genet A ; 182(6): 1321-1328, 2020 06.
Article in English | MEDLINE | ID: mdl-32220041

ABSTRACT

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.


Subject(s)
Genetic Predisposition to Disease , Piebaldism/genetics , Pigmentation Disorders/genetics , Proto-Oncogene Proteins c-kit/genetics , Child, Preschool , Female , Humans , Mutation/genetics , Pedigree , Piebaldism/pathology , Pigmentation Disorders/pathology , Exome Sequencing
17.
BMC Pediatr ; 20(1): 34, 2020 01 27.
Article in English | MEDLINE | ID: mdl-31987033

ABSTRACT

BACKGROUND: Acrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations. CASE PRESENTATION: Here, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreported SLC39A4 mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys' parents were heterozygous carriers of these two mutations. CONCLUSION: We identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.


Subject(s)
Acrodermatitis/genetics , Cation Transport Proteins/genetics , Diseases in Twins/genetics , Mutation , Zinc/deficiency , Acrodermatitis/drug therapy , Female , Heterozygote , Humans , Infant , Male , Pedigree , Zinc/therapeutic use
18.
Opt Lett ; 41(17): 4056-9, 2016 Sep 01.
Article in English | MEDLINE | ID: mdl-27607971

ABSTRACT

We report the coexistence of high-order harmonic soliton molecules and rectangular noise-like pulses (NLP) in a figure-eight fiber laser mode-locked by a nonlinear amplifying loop mirror. The harmonic soliton molecule has a repetition rate of 936.6 MHz, corresponding to the 466th harmonics of the fundamental cavity repetition rate, with soliton separation of 16.5 ps. Meanwhile, the rectangular NLP operates at the fundamental repetition rate. In addition, these two types of pulses could be generated independently by manipulating the polarization controllers. The experimental results demonstrate an interesting operation regime of the fiber laser and contribute to enriching the dynamics of mode-locked pulses in fiber lasers.

19.
Opt Express ; 24(15): 17285-91, 2016 Jul 25.
Article in English | MEDLINE | ID: mdl-27464177

ABSTRACT

We propose and numerically investigate a photonic crystal fiber (PCF) based on As2S3 for supporting the orbital angular momentum (OAM) modes up to 26. The designed PCF is composed of four well-ordered air hole rings in the cladding and an air hole at the center. The OAM modes can be well separated due to the large effective index difference of above 10-4 between the eigenmodes and maintain single-mode condition radially. In addition, the dispersions of the modes increase slowly with wavelengths, while the confinement loss keeps as low as 10-9 dB/m. The proposed PCF increases the supported OAM modes which could have some potential applications in short-distance, high-capacity transmission.

20.
Opt Express ; 24(7): 7356-63, 2016 Apr 04.
Article in English | MEDLINE | ID: mdl-27137025

ABSTRACT

We report on the generation of versatile patterns of multiple rectangular noise-like pulses (NLPs) in a fiber laser mode-locked by nonlinear amplifying loop mirror (NALM). Benefiting from the strengthened nonlinear effect of a segment of highly nonlinear fiber (HNLF) in the loop, multiple rectangular NLPs with various patterns are formed depending on the cavity parameter settings. In particular, the multiple rectangular NLPs could possess unequal packet durations, which is different from the conventional multi-soliton patterns. The experimental results contribute to further understanding the characteristics of the rectangular NLP and the dynamics of multi-pulse patterns.

SELECTION OF CITATIONS
SEARCH DETAIL
...