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1.
Cell ; 185(25): 4788-4800.e13, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36413996

RESUMO

The TOC and TIC complexes are essential translocons that facilitate the import of the nuclear genome-encoded preproteins across the two envelope membranes of chloroplast, but their exact molecular identities and assembly remain unclear. Here, we report a cryoelectron microscopy structure of TOC-TIC supercomplex from Chlamydomonas, containing a total of 14 identified components. The preprotein-conducting pore of TOC is a hybrid ß-barrel co-assembled by Toc120 and Toc75, while the potential translocation path of TIC is formed by transmembrane helices from Tic20 and YlmG, rather than a classic model of Tic110. A rigid intermembrane space (IMS) scaffold bridges two chloroplast membranes, and a large hydrophilic cleft on the IMS scaffold connects TOC and TIC, forming a pathway for preprotein translocation. Our study provides structural insights into the TOC-TIC supercomplex composition, assembly, and preprotein translocation mechanism, and lays a foundation to interpret the evolutionary conservation and diversity of this fundamental translocon machinery.


Assuntos
Proteínas de Algas , Chlamydomonas , Cloroplastos , Cloroplastos/metabolismo , Microscopia Crioeletrônica , Membranas Intracelulares/metabolismo , Transporte Proteico , Chlamydomonas/química , Chlamydomonas/citologia , Complexos Multiproteicos/metabolismo , Proteínas de Algas/metabolismo
2.
Nature ; 611(7935): 365-373, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36323783

RESUMO

Cells respond to physical stimuli, such as stiffness1, fluid shear stress2 and hydraulic pressure3,4. Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer5. However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity are unknown. Here we demonstrate that elevated viscosity counterintuitively increases the motility of various cell types on two-dimensional surfaces and in confinement, and increases cell dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed by elevated viscosity induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, which enhances Na+/H+ exchanger 1 (NHE1) polarization through its actin-binding partner ezrin. NHE1 promotes cell swelling and increased membrane tension, which, in turn, activates transient receptor potential cation vanilloid 4 (TRPV4) and mediates calcium influx, leading to increased RHOA-dependent cell contractility. The coordinated action of actin remodelling/dynamics, NHE1-mediated swelling and RHOA-based contractility facilitates enhanced motility at elevated viscosities. Breast cancer cells pre-exposed to elevated viscosity acquire TRPV4-dependent mechanical memory through transcriptional control of the Hippo pathway, leading to increased migration in zebrafish, extravasation in chick embryos and lung colonization in mice. Cumulatively, extracellular viscosity is a physical cue that regulates both short- and long-term cellular processes with pathophysiological relevance to cancer biology.


Assuntos
Movimento Celular , Líquido Extracelular , Metástase Neoplásica , Neoplasias , Viscosidade , Animais , Embrião de Galinha , Camundongos , Actinas/metabolismo , Líquido Extracelular/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Trocadores de Sódio-Hidrogênio/metabolismo , Canais de Cátion TRPV , Peixe-Zebra/metabolismo , Metástase Neoplásica/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Via de Sinalização Hippo , Esferoides Celulares/patologia , Complexo 2-3 de Proteínas Relacionadas à Actina , Proteína rhoA de Ligação ao GTP , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pulmão/patologia
3.
Nature ; 595(7869): 746-750, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34225353

RESUMO

The cation channel of sperm (CatSper) is essential for sperm motility and fertility1,2. CatSper comprises the pore-forming proteins CATSPER1-4 and multiple auxiliary subunits, including CATSPERß, γ, δ, ε, ζ, and EFCAB91,3-9. Here we report the cryo-electron microscopy (cryo-EM) structure of the CatSper complex isolated from mouse sperm. In the extracellular view, CATSPER1-4 conform to the conventional domain-swapped voltage-gated ion channel fold10, following a counterclockwise arrangement. The auxiliary subunits CATSPERß, γ, δ and ε-each of which contains a single transmembrane segment and a large extracellular domain-constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. Our EM map reveals several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. We name this channel-transporter ultracomplex the CatSpermasome. The assembly and organization details of the CatSpermasome presented here lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives.


Assuntos
Canais de Cálcio/química , Canais Iônicos/química , Proteínas de Plasma Seminal/química , Espermatozoides , Animais , Microscopia Crioeletrônica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estrutura Quaternária de Proteína , Motilidade dos Espermatozoides
4.
Proc Natl Acad Sci U S A ; 120(11): e2215553120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36877839

RESUMO

Mounting evidence implicates the giant, cytoskeletal protein obscurin (720 to 870 kDa), encoded by the OBSCN gene, in the predisposition and development of breast cancer. Accordingly, prior work has shown that the sole loss of OBSCN from normal breast epithelial cells increases survival and chemoresistance, induces cytoskeletal alterations, enhances cell migration and invasion, and promotes metastasis in the presence of oncogenic KRAS. Consistent with these observations, analysis of Kaplan-Meier Plotter datasets reveals that low OBSCN levels correlate with significantly reduced overall and relapse-free survival in breast cancer patients. Despite the compelling evidence implicating OBSCN loss in breast tumorigenesis and progression, its regulation remains elusive, limiting any efforts to restore its expression, a major challenge given its molecular complexity and gigantic size (~170 kb). Herein, we show that OBSCN-Antisense RNA 1 (OBSCN-AS1), a novel nuclear long-noncoding RNA (lncRNA) gene originating from the minus strand of OBSCN, and OBSCN display positively correlated expression and are downregulated in breast cancer biopsies. OBSCN-AS1 regulates OBSCN expression through chromatin remodeling involving H3 lysine 4 trimethylation enrichment, associated with open chromatin conformation, and RNA polymerase II recruitment. CRISPR-activation of OBSCN-AS1 in triple-negative breast cancer cells effectively and specifically restores OBSCN expression and markedly suppresses cell migration, invasion, and dissemination from three-dimensional spheroids in vitro and metastasis in vivo. Collectively, these results reveal the previously unknown regulation of OBSCN by an antisense lncRNA and the metastasis suppressor function of the OBSCN-AS1/OBSCN gene pair, which may be used as prognostic biomarkers and/or therapeutic targets for metastatic breast cancer.


Assuntos
RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , RNA Longo não Codificante/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Recidiva Local de Neoplasia , Biópsia , Proteínas Serina-Treonina Quinases , Fatores de Troca de Nucleotídeo Guanina Rho
5.
Proc Natl Acad Sci U S A ; 120(46): e2220300120, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37948584

RESUMO

Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.


Assuntos
Sobrecarga de Ferro , Traumatismos da Medula Espinal , Humanos , Recém-Nascido , Neurônios , Neurogênese , Traumatismos da Medula Espinal/terapia , Hidrogéis , Ferro , Polifenóis , Homeostase , Medula Espinal
6.
Plant J ; 118(2): 405-422, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38163320

RESUMO

Cell polarity is the foundation of cell development and tissue morphogenesis. The investigation of polarized growth provides opportunities to gain profound insights into morphogenesis and tissue functionality in organisms. Currently, there are still many mysteries surrounding the mechanisms that regulate polarized cell growth. Cotton fiber cells serve as an excellent model for studying polarized growth, and provide important clues for unraveling the molecular mechanisms, signaling pathways, and regulatory networks of polarized growth. In this study, we characterized two functional genes, GhMDHAR1AT/DT and GhDHAR2AT/DT with predominant expression during fiber elongation. Loss of function of both genes contributed to a significant increase in fiber length. Transcriptomic data revealed up-regulated expression of antioxidant genes in CRISPR mutant lines, along with delayed expression of secondary wall-related genes and temporally prolonged expression of primary wall-related genes. Experimental evidence demonstrated that the increase in GSH content and glutathione peroxidase (GPX) enzyme activity led to enhanced total antioxidant capacity (T-AOC), resulting in reduced H2O2 levels, which contributed to the extension of fiber elongation stage in CRISPR mutant lines. Moreover, the increased polysaccharide synthesis in CRISPR mutant lines was found to provide an abundant supply of raw materials for fiber cell wall elongation, suggesting that synergistic interplay between redox homeostasis and polysaccharide synthesis in fiber cells may facilitate cell wall remodeling and fiber elongation. This study provides valuable insights for deciphering the mechanisms of cell polarized growth and improving cotton fiber quality.


Assuntos
Antioxidantes , Fibra de Algodão , Peróxido de Hidrogênio , Perfilação da Expressão Gênica , Oxirredução , Homeostase , Polissacarídeos , Gossypium/genética , Regulação da Expressão Gênica de Plantas
7.
Neuroimage ; 285: 120493, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38086496

RESUMO

Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.


Assuntos
Esquizofrenia , Recém-Nascido , Humanos , Adulto Jovem , Adulto , Criança , Adolescente , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Imageamento por Ressonância Magnética , Encéfalo , Córtex Pré-Frontal , Lobo Occipital
8.
Br J Haematol ; 204(4): 1402-1413, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38327115

RESUMO

To investigate the clinical characteristics and risk factors of specific human leukocyte antigen loss (HLA loss) in relapsed acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS) patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and compare the responses of patients with HLA loss relapse with those without HLA loss (non-HLA loss) to different treatment regimens. Clinical data of traceable patients with AML/MDS after myeloablative allo-HSCT in our centre between January 2010 and June 2021, who experienced disease relapse after the transplantation, were collected. The patients were divided into the HLA loss relapse group and the non-HLA loss relapsed group based on HLA loss gene test findings by next-generation sequencing. The patients' median overall survival (OS) after the relapse were compared, and univariate and multivariate analyses were performed using the Kaplan-Meier survival curve and Cox proportional hazard model to explore the responses to different treatments after relapse. A total of 2359 patients were selected. Retrospective HLA gene loss gene detection was performed for the deoxyribonucleic acid in 179 relapsed patients, including 47 patients in the HLA loss group (27.2%), 126 patients in the non-HLA loss group (72.8%) and 6 patients were excluded due to a lack of confirmed results. There was no significant statistical difference in the baseline characteristics of patients between the two groups, but as to transplantation-related characteristics, the donor-recipient relationship and HLA mismatched loci were statistically different between the two groups (both p < 0.001). Multivariate Cox analysis showed that more HLA mismatched loci ≥3 (HR = 3.66; 95% CI: 1.61-8.31; p = 0.002), time (≤6 months) from HSCT to relapse (HR = 7.92; 95% CI: 3.35-18.74; p < 0.001) and donor chimerism (CD3) in bone marrow at relapse (HR = 1.02; 95% CI: 1.00-1.03; p = 0.036) were independent factors affecting HLA loss relapse. The ratio of negative conversion of FLT3-ITD or CEBPA mutation was significantly lower in patients with post-transplantation HLA loss relapse than in the non-HLA loss group (0.0% vs. 45.5%, p = 0.003; 0.0% vs. 80.0%, p = 0.035), with none of the patients with FLT3-ITD or CEBPA mutation turned negative in the HLA loss group. The number of gene mutations turned negative when relapse in the non-HLA loss group was remarkably higher than that in the HLA loss group (p = 0.001). Using donor lymphocyte infusion (DLI) could not prolong OS for the HLA loss group (p = 0.42). Nevertheless, second transplantation had a significant positive impact on OS in the HLA loss group (p = 0.017), although only five patients in the HLA loss group underwent second transplantation. However, patients in the non-HLA loss group using DLI had a relatively longer OS time than those without DLI (p = 0.017). Second transplantation could also prolong OS in the non-HLA loss group, but the effect was not as significant as in the HLA loss group (p = 0.053). In summary, HLA loss detection is essential for patients with recurrence after transplantation, especially for those with more HLA mismatched loci and non-sibling donor. Furthermore, the detection of HLA loss has a guiding role in choosing subsequent therapy when relapsed, as secondary transplantation is more suitable than DLI for those with HLA loss.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Antígenos HLA/genética , Fatores de Risco , Antígenos de Histocompatibilidade Classe II , Modelos de Riscos Proporcionais , Recidiva
9.
Anal Chem ; 96(15): 5852-5859, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38556977

RESUMO

A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.


Assuntos
Técnicas Biossensoriais , Neoplasias da Próstata , Masculino , Humanos , Medições Luminescentes/métodos , Fotometria , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , DNA , Técnicas Biossensoriais/métodos , Eletrodos , Técnicas Eletroquímicas/métodos
10.
BMC Plant Biol ; 24(1): 329, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664610

RESUMO

BACKGROUND: Advancement in agricultural biotechnology has resulted in increasing numbers of commercial varieties of genetically modified (GM) crops worldwide. Though several databases on GM crops are available, these databases generally focus on collecting and providing information on transgenic crops rather than on screening strategies. To overcome this, we constructed a novel tool named, Genetically Modified Organisms Identification Tool (GMOIT), designed to integrate basic and genetic information on genetic modification events and detection methods. RESULTS: At present, data for each element from 118 independent genetic modification events in soybean, maize, canola, and rice were included in the database. Particularly, GMOIT allows users to customize assay ranges and thus obtain the corresponding optimized screening strategies using common elements or specific locations as the detection targets with high flexibility. Using the 118 genetic modification events currently included in GMOIT as the range and algorithm selection results, a "6 + 4" protocol (six exogenous elements and four endogenous reference genes as the detection targets) covering 108 events for the four crops was established. Plasmids pGMOIT-1 and pGMOIT-2 were constructed as positive controls or calibrators in qualitative and quantitative transgene detection. CONCLUSIONS: Our study provides a simple, practical tool for selecting, detecting, and screening strategies for a sustainable and efficient application of genetic modification.


Assuntos
Produtos Agrícolas , Glycine max , Oryza , Plantas Geneticamente Modificadas , Produtos Agrícolas/genética , Plantas Geneticamente Modificadas/genética , Oryza/genética , Glycine max/genética , Zea mays/genética , Transgenes , Brassica napus/genética
11.
Breast Cancer Res Treat ; 203(2): 397-406, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37851289

RESUMO

PURPOSE: Mastectomy, breast reconstruction (BR) and breast conserving therapy (BCT) are core components of the treatment paradigm for early-stage disease but are differentially associated with significant financial burdens. Given recent price transparency regulations, we sought to characterize rates of disclosure for breast cancer-related surgery, including mastectomy, BCT, and BR (oncoplastic reconstruction, implant, pedicled flap and free flap) and identify associated factors. METHODS: For this cross-sectional analysis, cost reports were obtained from the Turquoise Health price transparency platform for all U.S. hospitals meeting national accreditation standards for breast cancer care. The Healthcare Cost Report Information System was used to collect facility-specific data. Addresses were geocoded to identify hospital referral and census regions while data from CMS was also used to identify the geographic practice cost index. We leveraged a Poisson regression model and relevant Medicare billing codes to analyze factors associated with price disclosure and the availability of an OOP price estimator. RESULTS: Of 447 identified hospitals, 221 (49.4%) disclosed prices for mastectomy and 188 42.1%) disclosed prices for both mastectomy and some form of reconstruction including oncoplastic reduction (n = 184, 97.9%), implants (n = 187, 99.5%), pedicled flaps (n = 89, 47.3%), and free flaps (n = 81, 43.1%). Non-profit status and increased market competition were associated with price nondisclosure. 121 hospitals (27.1%) had an out-of-pocket price estimator that included at least one breast surgery. CONCLUSIONS: Most eligible hospitals did not disclose prices for breast cancer surgery. Distinct hospital characteristics were associated with price disclosure. Breast cancer patients face persistent difficulty in accessing costs.


Assuntos
Neoplasias da Mama , Retalhos de Tecido Biológico , Mamoplastia , Humanos , Idoso , Estados Unidos/epidemiologia , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Mastectomia , Revelação , Estudos Transversais , Medicare
12.
Appl Environ Microbiol ; 90(2): e0202523, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38259074

RESUMO

Marine bacteria play important roles in the degradation and cycling of algal polysaccharides. However, the dynamics of epiphytic bacterial communities and their roles in algal polysaccharide degradation during kelp decay are still unclear. Here, we performed metagenomic analyses to investigate the identities and predicted metabolic abilities of epiphytic bacterial communities during the early and late decay stages of the kelp Saccharina japonica. During kelp decay, the dominant epiphytic bacterial communities shifted from Gammaproteobacteria to Verrucomicrobia and Bacteroidetes. In the early decay stage of S. japonica, epiphytic bacteria primarily targeted kelp-derived labile alginate for degradation, among which the gammaproteobacterial Vibrionaceae (particularly Vibrio) and Psychromonadaceae (particularly Psychromonas), abundant in alginate lyases belonging to the polysaccharide lyase (PL) families PL6, PL7, and PL17, were key alginate degraders. More complex fucoidan was preferred to be degraded in the late decay stage of S. japonica by epiphytic bacteria, predominantly from Verrucomicrobia (particularly Lentimonas), Pirellulaceae of Planctomycetes (particularly Rhodopirellula), Pontiellaceae of Kiritimatiellota, and Flavobacteriaceae of Bacteroidetes, which depended on using glycoside hydrolases (GHs) from the GH29, GH95, and GH141 families and sulfatases from the S1_15, S1_16, S1_17, and S1_25 families to depolymerize fucoidan. The pathways for algal polysaccharide degradation in dominant epiphytic bacterial groups were reconstructed based on analyses of metagenome-assembled genomes. This study sheds light on the roles of different epiphytic bacteria in the degradation of brown algal polysaccharides.IMPORTANCEKelps are important primary producers in coastal marine ecosystems. Polysaccharides, as major components of brown algal biomass, constitute a large fraction of organic carbon in the ocean. However, knowledge of the identities and pathways of epiphytic bacteria involved in the degradation process of brown algal polysaccharides during kelp decay is still elusive. Here, based on metagenomic analyses, the succession of epiphytic bacterial communities and their metabolic potential were investigated during the early and late decay stages of Saccharina japonica. Our study revealed a transition in algal polysaccharide-degrading bacteria during kelp decay, shifting from alginate-degrading Gammaproteobacteria to fucoidan-degrading Verrucomicrobia, Planctomycetes, Kiritimatiellota, and Bacteroidetes. A model for the dynamic degradation of algal cell wall polysaccharides, a complex organic carbon, by epiphytic microbiota during kelp decay was proposed. This study deepens our understanding of the role of epiphytic bacteria in marine algal carbon cycling as well as pathogen control in algal culture.


Assuntos
Algas Comestíveis , Flavobacteriaceae , Kelp , Laminaria , Microbiota , Phaeophyceae , Humanos , Metagenoma , Kelp/metabolismo , Polissacarídeos/metabolismo , Alginatos/metabolismo , Flavobacteriaceae/genética , Flavobacteriaceae/metabolismo , Carbono/metabolismo
13.
J Hum Genet ; 69(7): 321-327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565611

RESUMO

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.


Assuntos
Sequenciamento do Exoma , Humanos , Feminino , Feto/anormalidades , Gravidez , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Mutação , Meningomielocele/genética , Meningomielocele/diagnóstico por imagem , Variações do Número de Cópias de DNA , Povo Asiático/genética , População do Leste Asiático , Hérnia Diafragmática
14.
J Exp Bot ; 75(10): 2994-3008, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38436737

RESUMO

Triose phosphate utilization (TPU) limitation is one of the three biochemical limitations of photosynthetic CO2 assimilation rate in C3 plants. Under TPU limitation, abrupt and large transitions in light intensity cause damped oscillations in photosynthesis. When plants are salt-stressed, photosynthesis is often down-regulated particularly under dynamic light intensity, but how salt stress affects TPU-related dynamic photosynthesis is still unknown. To elucidate this, tomato (Solanum lycopersicum) was grown with and without sodium chloride (NaCl, 100 mM) stress for 13 d. Under high CO2 partial pressure, rapid increases in light intensity caused profound photosynthetic oscillations. Salt stress reduced photosynthetic oscillations in leaves initially under both low- and high-light conditions and reduced the duration of oscillations by about 2 min. Besides, salt stress increased the threshold for CO2 partial pressure at which oscillations occurred. Salt stress increased TPU capacity without affecting Rubisco carboxylation and electron transport capacity, indicating the up-regulation of end-product synthesis capacity in photosynthesis. Thus salt stress may reduce photosynthetic oscillations by decreasing leaf internal CO2 partial pressure and/or increasing TPU capacity. Our results provide new insights into how salt stress modulates dynamic photosynthesis as controlled by CO2 availability and end-product synthesis.


Assuntos
Fotossíntese , Estresse Salino , Solanum lycopersicum , Solanum lycopersicum/fisiologia , Solanum lycopersicum/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Trioses/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Fosfatos/metabolismo , Luz , Cloreto de Sódio/farmacologia
15.
Environ Res ; 251(Pt 2): 118696, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493860

RESUMO

The accumulation of heavy metals (HMs) in soil caused by mineral resource exploitation and its ancillary industrial processes poses a threat to ecology and public health. Effective risk control measures require a quantification of the impacts and contributions to health risks from individual sources of soil HMs. Based on high-density sampling, soil contamination risk indexes, positive matrix factorization (PMF) model, Monte Carlo simulation and human health risk analysis model were applied to investigate the risk of HMs in a typical mining town in North China. The results showed that As was the most dominant soil pollutant factor, Cd and Hg were the most dominant soil ecological risk factors, and Cr and Ni were the most dominant health risk factors in the study area. Overall, both pollution and ecological risks were at low levels, while there were still some higher hazard areas located in the central and south-central part of the region. According to the probabilistic health risk assessment (HRA), children suffered greater health risks than adults, with 21.63% of non-carcinogenic risks and 53.24% of carcinogenic risks exceeding the prescribed thresholds (HI > 1 and TCR>1E-4). The PMF model identified five potential sources: fuel combustion (FC), processing of building materials with limestone as raw materials (PBML), industry source (IS), iron ore mining combined with garbage (IOG), and agriculture source (AS). PBML is the primary source of soil HM contamination, as well as the major anthropogenic source of carcinogenic risk for all populations. Agricultural inputs associated with As are the major source of non-carcinogenic risk. This study offers a good example of probabilistic HRA using specific sources, which can provide a valuable reference for strategy establishment of pollution remediation and risk prevention and control.


Assuntos
Metais Pesados , Mineração , Método de Monte Carlo , Poluentes do Solo , China , Medição de Risco , Metais Pesados/análise , Poluentes do Solo/análise , Humanos , Adulto , Criança , Monitoramento Ambiental/métodos
16.
Biosci Biotechnol Biochem ; 88(6): 630-636, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38553959

RESUMO

N-Methylisothiazolinone (MIT) is a thiol group modifier and antimicrobial agent. Arthrobacter sarcosine oxidase (SoxA), a diagnostic enzyme for assaying creatinine, loses its activity upon the addition of MIT, and its inactivation mechanism remains unclear. In this study, SoxA was chemically modified using MIT (mo-SoxA), and its structural and chemical properties were characterized. Spectral analysis data, oxygen consumption rates, and reactions were compared between intact SoxA and mo-SoxA. These demonstrate that the oxidative half-reaction toward oxygen is inhibited by MIT modification. The oxidase activity of mo-SoxA was approximately 2.1% of that of intact SoxA, and its dehydrogenase activity was approximately 4.2 times higher. The C-to-S mutants revealed that cooperative modification of 2 specific cysteine residues caused a drastic change in the enzyme reaction mode. Based on the modeled tertiary structures, the putative entrance for oxygen uptake is predicted to be blocked by the chemical modification of the 2 cysteine residues.


Assuntos
Arthrobacter , Oxigênio , Sarcosina Oxidase , Tiazóis , Arthrobacter/enzimologia , Oxigênio/metabolismo , Oxigênio/química , Sarcosina Oxidase/metabolismo , Sarcosina Oxidase/química , Sarcosina Oxidase/genética , Tiazóis/química , Tiazóis/metabolismo , Tiazóis/farmacologia , Oxirredução , Cisteína/química , Cisteína/metabolismo , Modelos Moleculares , Cinética
17.
Mar Drugs ; 22(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38921590

RESUMO

Ichthyotoxic red tide is a problem that the world is facing and needs to solve. The use of antialgal compounds from marine macroalgae to suppress ichthyotoxic red tide is considered a promising biological control method. Antialgal substances were screened and isolated from Bangia fusco-purpurea, Gelidium amansii, Gloiopeltis furcate, Hizikia fusifarme, Laminaria japonica, Palmaria palmata, and Sargassum sp. to obtain new materials for the development of algaecides against ichthyotoxic red tide microalgae using bioactivity-guided isolation methods. The fractions of seven macroalgae exhibited selective inhibitory activities against Amphidinium carterae and Karenia mikimotoi, of which the ethyl acetate fractions had the strongest and broadest antialgal activities for the two tested red tide microalgae. Their inhibitory effects on A. carterae and K. mikimotoi were even stronger than that of potassium dichromate, such as ethyl acetate fractions of B. purpurea, H. fusifarme, and Sargassum sp. Thin-layer chromatography and ultraviolet spectroscopy were further carried out to screen the ethyl acetate fraction of Sargassum sp. Finally, a new glycolipid derivative, 2-O-eicosanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-glycerol, was isolated and identified from Sargassum sp., and it was isolated for the first time from marine macroalgae. The significant antialgal effects of 2-O-eicosanoyl-3-O-(6-amino-6-deoxy)-ß-D-glucopyranosyl-glycerol on A. carterae and K. mikimotoi were determined.


Assuntos
Glicolipídeos , Proliferação Nociva de Algas , Microalgas , Alga Marinha , Alga Marinha/química , Glicolipídeos/farmacologia , Glicolipídeos/isolamento & purificação , Glicolipídeos/química , Proliferação Nociva de Algas/efeitos dos fármacos , Microalgas/química , Dinoflagellida/química
18.
J Shoulder Elbow Surg ; 33(3): 556-563, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37783308

RESUMO

BACKGROUND: Giant cell tumor of bone (GCTB) (Campanacci III) or malignant tumors extend to the epiphyseal region of the proximal radius, and intra-articular resection of the proximal radius is often needed. In the present study, we present the patients who underwent reconstruction of the proximal radius with 3D-printed personalized prosthesis after tumor resection, aiming to describe the prosthesis design and surgical technique and evaluate the clinical outcomes of this method. METHODS: Between November 2018 and January 2021, 9 patients received radial hemiarthroplasty with 3D-printed personalized prostheses after tumor resection. The pathologic diagnosis was GCTB (Campanacci III) in 7 patients, osteosarcoma (IIB) in 1 patient, and synovial sarcoma (IIB) in 1 patient. The range of motion (ROM) and strength in terms of elbow flexion/extension and forearm supination/pronation were evaluated. Pain was assessed by the visual analog scale (VAS) preoperatively and at each follow-up visit. To evaluate the functional outcome, the Mayo Elbow Performance Score (MEPS) system and the Musculoskeletal Tumor Society (MSTS) scoring system were administered at each follow-up visit. Complications and oncological outcomes were recorded. RESULTS: The patients were followed from 24 to 51 months, with a median follow-up of 35 months. No patients were lost to follow-up. During the follow-up, local recurrence and metastasis were not observed. The VAS score improved from a median of 5 points (range 4-7) preoperatively to 1 point (range 0-2) at the last follow-up visit. The mean MEPS score was 88.5% (83-93), and the mean MSTS score was 25.3 (24-27) at the last follow-up visit. No complications such as infection and aseptic loosening were detected. CONCLUSIONS: The implantation of a 3D-printed personalized prosthesis after proximal radial resection showed excellent oncologic outcomes and postoperative function at short-term follow-up and is a viable alternative method for reconstruction of the proximal radius bone defect after tumor resection.


Assuntos
Neoplasias Ósseas , Rádio (Anatomia) , Humanos , Rádio (Anatomia)/cirurgia , Cotovelo/patologia , Neoplasias Ósseas/patologia , Estudos Retrospectivos , Desenho de Prótese , Impressão Tridimensional , Resultado do Tratamento
19.
Environ Geochem Health ; 46(4): 124, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483643

RESUMO

This study analyzed the distribution and content of eight heavy metals (Cu, Pb, Zn, Ni, Cr, As, Cd, and Hg) in 221 surface soil samples from the upper reaches of the Xiaowen River. Environmental geochemical baselines were established for the eight heavy metals, and the pollution status was assessed on the basis of these baselines and the soil background value of Weifang City. The calculation results of Nemerow pollution index and the potential ecological hazard index (PEHI)-Ri showed that the overall pollution degree and ecological hazard in the study area were at a slight level. 49% (calculated by baseline value) and 24% (calculated by background value of Weifang City) samples were at moderate or above pollution level. 9% (calculated by baseline value) and 42% (calculated by background value) samples were at the level of moderate potential ecological hazards or above. According to the calculation results of Igeo and PEHI-Ei, the main pollutant in the study area was Hg, followed by Cd. 3% (calculated by baseline value) and 12% (calculated by background value) of Hg samples were at moderate or above contamination levels. 5% (calculated by baseline value) and 38% (calculated by background value) of Hg samples were at the level of strong potential ecological hazard or above. The western, central, and eastern parts of the study area were mainly the primary areas of pollution and ecological hazards. The non-carcinogenic risk was at an acceptable level, the carcinogenic risk was at a tolerable level, and the main risk pathway was oral intake, with Cr being the main contributor. Source apportionment indicated that soil heavy metals primarily originate from soil parent material, transportation, agricultural fertilization, and industrial emissions (waste gas, waste water and solid waste).


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Solo/química , Monitoramento Ambiental/métodos , Rios/química , Cádmio , Poluentes do Solo/análise , Metais Pesados/análise , Medição de Risco , China
20.
Environ Geochem Health ; 46(5): 152, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578358

RESUMO

The Qinghai-Tibet Plateau has low anthropogenic carbon emissions and large carbon stock in its ecosystems. As a crucial region in terrestrial ecosystems responding to climate change, an accurate understanding of the distribution characteristics of soil carbon density holds significance in estimating the soil carbon storage capacity in forests and grasslands. It performs a crucial role in achieving carbon neutrality goals in China. The distribution characteristics of carbon and carbon density in the surface, middle, and deep soil layers are calculated, and the main influencing factors of soil carbon density changes are analyzed. The carbon density in the surface soil ranges from a minimum of 1.62 kg/m2 to a maximum of 52.93 kg/m2. The coefficient of variation for carbon is 46%, indicating a considerable variability in carbon distribution across different regions. There are substantial disparities, with geological background, land use types, and soil types significantly influencing soil organic carbon density. Alpine meadow soil has the highest carbon density compared with other soil types. The distribution of soil organic carbon density at three different depths is as follows: grassland > bare land > forestland > water area. The grassland systems in the Qinghai-Tibet Plateau have considerable soil carbon sink and storage potential; however, they are confronted with the risk of grassland degradation. The grassland ecosystems on the Qinghai-Tibet Plateau harbor substantial soil carbon sinks and storage potential. However, they are at risk of grassland degradation. It is imperative to enhance grassland management, implement sustainable grazing practices, and prevent the deterioration of the grassland carbon reservoirs to mitigate the exacerbation of greenhouse gas emissions and global warming. This highlights the urgency of implementing more studies to uncover the potential of existing grassland ecological engineering projects for carbon sequestration.


Assuntos
Ecossistema , Solo , Tibet , Carbono/análise , Pradaria
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