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1.
Cell ; 178(6): 1478-1492.e20, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31474362

RESUMO

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.


Assuntos
Células Endoteliais/metabolismo , Hepatócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Cirrose Hepática/metabolismo , Fígado/metabolismo , Receptores de TIE/metabolismo , Animais , Biomarcadores/metabolismo , Capilares/metabolismo , Células Endoteliais/citologia , Células Endoteliais/patologia , Células HEK293 , Hepatócitos/citologia , Hepatócitos/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Fígado/irrigação sanguínea , Fígado/patologia , Cirrose Hepática/diagnóstico , Camundongos Endogâmicos C57BL
2.
Nature ; 615(7950): 50-55, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36859583

RESUMO

The newly discovered nickelate superconductors so far only exist in epitaxial thin films synthesized by a topotactic reaction with metal hydrides1. This method changes the nickelates from the perovskite to an infinite-layer structure by deintercalation of apical oxygens1-3. Such a chemical reaction may introduce hydrogen (H), influencing the physical properties of the end materials4-9. Unfortunately, H is insensitive to most characterization techniques and is difficult to detect because of its light weight. Here, in optimally Sr doped Nd0.8Sr0.2NiO2H epitaxial films, secondary-ion mass spectroscopy shows abundant H existing in the form of Nd0.8Sr0.2NiO2Hx (x ≅ 0.2-0.5). Zero resistivity is found within a very narrow H-doping window of 0.22 ≤ x ≤ 0.28, showing unequivocally the critical role of H in superconductivity. Resonant inelastic X-ray scattering demonstrates the existence of itinerant interstitial s (IIS) orbitals originating from apical oxygen deintercalation. Density functional theory calculations show that electronegative H- occupies the apical oxygen sites annihilating IIS orbitals, reducing the IIS-Ni 3d orbital hybridization. This leads the electronic structure of H-doped Nd0.8Sr0.2NiO2Hx to be more two-dimensional-like, which might be relevant for the observed superconductivity. We highlight that H is an important ingredient for superconductivity in epitaxial infinite-layer nickelates.

3.
Nature ; 605(7909): 262-267, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35546188

RESUMO

The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.

4.
Proc Natl Acad Sci U S A ; 120(27): e2301170120, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37364094

RESUMO

Bacterial antimicrobial resistance (AMR) is among the most significant challenges to current human society. Exposing bacteria to antibiotics can activate their self-saving responses, e.g., filamentation, leading to the development of bacterial AMR. Understanding the molecular changes during the self-saving responses can reveal new inhibition methods of drug-resistant bacteria. Herein, we used an online microfluidics mass spectrometry system for real-time characterization of metabolic changes of bacteria during filamentation under the stimulus of antibiotics. Significant pathways, e.g., nucleotide metabolism and coenzyme A biosynthesis, correlated to the filamentation of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) were identified. A cyclic dinucleotide, c-di-GMP, which is derived from nucleotide metabolism and reported closely related to bacterial resistance and tolerance, was observed significantly up-regulated during the bacterial filamentation. By using a chemical inhibitor, ebselen, to inhibit diguanylate cyclases which catalyzes the synthesis of c-di-GMP, the minimum inhibitory concentration of ceftriaxone against ESBL-E. coli was significantly decreased. This inhibitory effect was also verified with other ESBL-E. coli strains and other beta-lactam antibiotics, i.e., ampicillin. A mutant strain of ESBL-E. coli by knocking out the dgcM gene was used to demonstrate that the inhibition of the antibiotic resistance to beta-lactams by ebselen was mediated through the inhibition of the diguanylate cyclase DgcM and the modulation of c-di-GMP levels. Our study uncovers the molecular changes during bacterial filamentation and proposes a method to inhibit antibiotic-resistant bacteria by combining traditional antibiotics and chemical inhibitors against the enzymes involved in bacterial self-saving responses.


Assuntos
Infecções Bacterianas , Infecções por Escherichia coli , Humanos , Escherichia coli , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Bactérias/metabolismo , Nucleotídeos/farmacologia , Infecções por Escherichia coli/microbiologia
5.
Mol Ther ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39233439

RESUMO

Cardiomyopathy is a prevalent cardiovascular disease that affects individuals of all ages and can lead to life-threatening heart failure. Despite its variety in types, each with distinct characteristics and causes, our understanding of cardiomyopathy at a systematic biology level remains incomplete. Mass spectrometry-based techniques have emerged as powerful tools, providing a comprehensive view of the molecular landscape and aiding in the discovery of biomarkers and elucidation of mechanisms. This review highlights the significant potential of integrating proteomic and metabolomic approaches with specialized databases to identify biomarkers and therapeutic targets across different types of cardiomyopathies. In vivo and in vitro models, such as genetically modified mice, patient-derived or induced pluripotent stem cells, and organ chips, are invaluable in exploring the pathophysiological complexities of this disease. By integrating omics approaches with these sophisticated modeling systems, our comprehension of the molecular underpinnings of cardiomyopathy can be greatly enhanced, facilitating the development of diagnostic markers and therapeutic strategies. Among the promising therapeutic targets are those involved in extracellular matrix remodeling, sarcomere damage, and metabolic remodeling. These targets hold the potential to advance precision therapy in cardiomyopathy, offering hope for more effective treatments tailored to the specific molecular profiles of patients.

6.
Nano Lett ; 24(29): 8818-8825, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38985501

RESUMO

Stationary energy storage infrastructure based on zinc-ion transport and storage chemistry is attracting more attention due to favorable metrics, including cost, safety, and recycling feasibility. However, splitting water and liquid electrolyte fluidity lead to cathode dissolution and Zn corrosion, resulting in rapid attenuation of the capacity and service life. Herein, a new architecture of solid-state electrolytes with high zinc ionic conductivity at room temperature was prepared via solidification of deep eutectic solvents utilizing MXene as nucleation additives. The ionic conductivity of MXene/ZCEs reached 6.69 × 10-4 S cm-1 at room temperature. Dendrite-free Zn plating/stripping with high reversibility can remain for over 2500 h. Subsequently, the fabricated solid-state zinc-ion battery with eliminated HER and suppressed Zn dendrites exhibited excellent cycling performance and could work normally in a range from -10 to 60 °C. This design inspired by eutectic solidification affords new insights into the multivalent solid electrochemistry suffering from slow ion migration.

7.
J Proteome Res ; 23(9): 3837-3846, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39167422

RESUMO

Proteome analysis currently heavily relies on tandem mass spectrometry (MS/MS), which does not fully utilize MS1 features, as many precursors remain unselected for MS/MS fragmentation, especially in the cases of low abundance samples and wide abundance dynamic range samples. Therefore, leveraging MS1 features as a complement to MS/MS has become an attractive option to improve the coverage of feature identification. Herein, we propose MonoMS1, an approach combining deep learning-based retention time, ion mobility, detectability prediction, and logistic regression-based scoring for MS1 feature identification. The approach achieved a significant increase in MS1 feature identification based on an E. coli data set. Application of MonoMS1 to data sets with wide dynamic range, such as human serum proteome samples, and with low sample abundance, such as single-cell proteome samples, enabled substantial complementation of MS/MS-based peptide and protein identification. This method opens a new avenue for proteomic analysis and can boost proteomic research on complex samples.


Assuntos
Aprendizado Profundo , Escherichia coli , Proteoma , Proteômica , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Proteômica/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteoma/análise , Proteínas de Escherichia coli/análise , Modelos Logísticos
8.
J Am Chem Soc ; 146(17): 11719-11725, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636103

RESUMO

The diversity of chemical environments present on unique crystallographic facets can drive dramatic differences in catalytic activity and the reaction mechanism. By coupling experimental investigations of five different IrO2 facets and theory, we characterize the detailed elemental steps of the surface redox processes and the rate-limiting processes for the oxygen evolution reaction (OER). The predicted complex evolution of surface adsorbates and the associated charge transfer as a function of applied potential matches well with the distinct redox features observed experimentally for the five facets. Our microkinetic model from grand canonical quantum mechanics (GC-QM) calculations demonstrates mechanistic differences between nucleophilic attack and O-O coupling across facets, providing the rates as a function of applied potential. These GC-QM calculations explain the higher OER activity observed on the (100), (001), and (110) facets and the lower activity observed for the (101) and (111) facets. This combined study with theory and experiment brings new insights into the structural features that either promote or hinder the OER activity of IrO2, which are expected to provide parallels in structural effects on other oxide surfaces.

9.
Anal Chem ; 96(3): 1029-1037, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38180447

RESUMO

Metaproteomics offers a direct avenue to identify microbial proteins in microbiota, enabling the compositional and functional characterization of microbiota. Due to the complexity and heterogeneity of microbial communities, in-depth and accurate metaproteomics faces tremendous limitations. One challenge in metaproteomics is the construction of a suitable protein sequence database to interpret the highly complex metaproteomic data, especially in the absence of metagenomic sequencing data. Herein, we present a high-abundance protein-guided hybrid spectral library strategy for in-depth data independent acquisition (DIA) metaproteomic analysis (HAPs-hyblibDIA). A dedicated high-abundance protein database of gut microbial species is constructed and used to mine the taxonomic information on microbiota samples. Then, a sample-specific protein sequence database is built based on the taxonomic information using Uniprot protein sequence for subsequent analysis of the DIA data using hybrid spectral library-based DIA analysis. We evaluated the accuracy and sensitivity of the method using synthetic microbial community samples and human gut microbiome samples. It was demonstrated that the strategy can successfully identify taxonomic compositions of microbiota samples and that the peptides identified by HAPs-hyblibDIA overlapped greatly with the peptides identified using a metagenomic sequencing-derived database. At the peptide and species level, our results can serve as a complement to the results obtained using a metagenomic sequencing-derived database. Furthermore, we validated the applicability of the HAPs-hyblibDIA strategy in a cohort of human gut microbiota samples of colorectal cancer patients and controls, highlighting its usability in biomedical research.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Proteômica/métodos , Proteínas/análise , Peptídeos
10.
Anal Chem ; 96(36): 14621-14629, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39189349

RESUMO

Macrophage-derived foam cells play a crucial role in plaque formation and rupture during the progression of atherosclerosis. Traditional studies have often overlooked the heterogeneity of foam cells, focusing instead on populations of cells. To address this, we have developed time-resolved, single-cell metabolomics and lipidomics approaches to explore the heterogeneity of macrophages during foam cell formation. Our dynamic metabolomic and lipidomic analyses revealed a dual regulatory axis involving inflammation and ferroptosis. Further, single-cell metabolomics and lipidomics have delineated a continuum of macrophage states, with varied susceptibilities to apoptosis and ferroptosis. Single-cell transcriptomic profiling confirmed these divergent fates, both in established cell lines and in macrophages derived from peripheral blood monocytes. This research has uncovered the complex molecular interactions that dictate these divergent cell fates, providing crucial insights into the pathogenesis of atherosclerosis.


Assuntos
Apoptose , Ferroptose , Células Espumosas , Lipidômica , Metabolômica , Análise de Célula Única , Células Espumosas/metabolismo , Lipidômica/métodos , Metabolômica/métodos , Humanos , Animais , Camundongos , Macrófagos/metabolismo , Macrófagos/citologia
11.
BMC Plant Biol ; 24(1): 319, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38654176

RESUMO

Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat worldwide. Identification of new and elite Pst-resistance loci or genes has the potential to enhance overall resistance to this pathogen. Here, we conducted an integrated genome-wide association study (GWAS) and transcriptomic analysis to screen for loci associated with resistance to stripe rust in 335 accessions from Yunnan, including 311 landraces and 24 cultivars. Based on the environmental phenotype, we identified 113 protein kinases significantly associated with Pst resistance using mixed linear model (MLM) and generalized linear model (GLM) models. Transcriptomic analysis revealed that 52 of 113 protein kinases identified by GWAS were up and down regulated in response to Pst infection. Among these genes, a total of 15 receptor kinase genes were identified associated with Pst resistance. 11 candidate genes were newly discovered in Yunnan wheat germplasm. Our results revealed that resistance alleles to stripe rust were accumulated in Yunnan wheat germplasm, implying direct or indirect selection for improving stripe rust resistance in elite wheat breeding programs.


Assuntos
Resistência à Doença , Estudo de Associação Genômica Ampla , Doenças das Plantas , Puccinia , Triticum , Triticum/genética , Triticum/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Resistência à Doença/genética , China , Puccinia/fisiologia , Perfilação da Expressão Gênica , Basidiomycota/fisiologia , Genes de Plantas , Proteínas Quinases/genética , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
12.
Small ; 20(13): e2308084, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38243883

RESUMO

Ammonia is an essential commodity in the food and chemical industry. Despite the energy-intensive nature, the Haber-Bosch process is the only player in ammonia production at large scales. Developing other strategies is highly desirable, as sustainable and decentralized ammonia production is crucial. Electrochemical ammonia production by directly reducing nitrogen and nitrogen-based moieties powered by renewable energy sources holds great potential. However, low ammonia production and selectivity rates hamper its utilization as a large-scale ammonia production process. Creating effective and selective catalysts for the electrochemical generation of ammonia is critical for long-term nitrogen fixation. Single-atom alloys (SAAs) have become a new class of materials with distinctive features that may be able to solve some of the problems with conventional heterogeneous catalysts. The design and optimization of SAAs for electrochemical ammonia generation have recently been significantly advanced. This comprehensive review discusses these advancements from theoretical and experimental research perspectives, offering a fundamental understanding of the development of SAAs for ammonia production.

13.
Expert Rev Proteomics ; 21(7-8): 271-280, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39152734

RESUMO

INTRODUCTION: Metaproteomics offers insights into the function of complex microbial communities, while it is also capable of revealing microbe-microbe and host-microbe interactions. Data-independent acquisition (DIA) mass spectrometry is an emerging technology, which holds great potential to achieve deep and accurate metaproteomics with higher reproducibility yet still facing a series of challenges due to the inherent complexity of metaproteomics and DIA data. AREAS COVERED: This review offers an overview of the DIA metaproteomics approaches, covering aspects such as database construction, search strategy, and data analysis tools. Several cases of current DIA metaproteomics studies are presented to illustrate the procedures. Important ongoing challenges are also highlighted. Future perspectives of DIA methods for metaproteomics analysis are further discussed. Cited references are searched through and collected from Google Scholar and PubMed. EXPERT OPINION: Considering the inherent complexity of DIA metaproteomics data, data analysis strategies specifically designed for interpretation are imperative. From this point of view, we anticipate that deep learning methods and de novo sequencing methods will become more prevalent in the future, potentially improving protein coverage in metaproteomics. Moreover, the advancement of metaproteomics also depends on the development of sample preparation methods, data analysis strategies, etc. These factors are key to unlocking the full potential of metaproteomics.


Assuntos
Espectrometria de Massas , Proteômica , Proteômica/métodos , Espectrometria de Massas/métodos , Humanos , Microbiota
14.
J Org Chem ; 89(8): 5883-5895, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38600052

RESUMO

By creating an unsymmetric double Michael acceptor 1, we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-b]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile 2d (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)2AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings. Beyond providing a synthetic approach, this work illustrated the compounds' possible use in antitumor activity.

15.
J Org Chem ; 89(14): 9958-9971, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38981120

RESUMO

Herein, a versatile highly regioselective three-component annulation of simple aromatic ketones and methylamines using a hypervalent iodine reagent for polyarylated 1-pyrrolines has been described in good to excellent yields. Meanwhile, unsymmetrical 1-pyrroline isomers could be realized and synthesized. Such an intriguing one-pot two-step tandem assembly strategy with green conditions and high regioselectivity shows predictable inspiration in related annulation reactions.

16.
Cell Biol Int ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39099163

RESUMO

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

17.
Anal Bioanal Chem ; 416(8): 1833-1842, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367041

RESUMO

The frequent mutations in SARS-CoV-2 significantly increase the virus's pathogenicity and transmissibility while also diminishing the effectiveness of vaccines. Consequently, assays capable of rapidly and simultaneously identifying multiple SARS-CoV-2 variants are essential for large-scale applications that aim to monitor the evolution of the virus. In this work, we propose a method combining duplex-specific nuclease (DSN)-assisted cyclic amplification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detection, enabling the simultaneous identification of multiple SARS-CoV-2 variants at high-throughput. Due to the high specificity of DSN, single-base mutations can be resolved by the method. With ultra-sensitive detection by MALDI-TOF MS, a limit of detection of 100 pM viral RNA fragment was demonstrated. The assay was used for simultaneous identification and typing of SARS-CoV-2 Alpha, Beta, and Delta variants. The whole assay can be accomplished within 3 h, and the amplification is performed under constant temperature, making the technique simple in operation and efficient. It is also feasible to extend the technique to the detection of many other variants of the virus. We expect that the method can add value to the rapid screening of viral variants and can play an important role in pandemic control.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , SARS-CoV-2/genética , COVID-19/diagnóstico
18.
Plant Cell Rep ; 43(3): 67, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38341832

RESUMO

KEY MESSAGE: In this study, genome-wide association studies combined with transcriptome data analysis were utilized to reveal potential candidate genes for stripe rust resistance in wheat, providing a basis for screening wheat varieties for stripe rust resistance. Wheat stripe rust, which is caused by the wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst) is one of the world's most devastating diseases of wheat. Genetic resistance is the most effective strategy for controlling diseases. Although wheat stripe rust resistance genes have been identified to date, only a few of them confer strong and broad-spectrum resistance. Here, the resistance of 335 wheat germplasm resources (mainly wheat landraces) from southwestern China to wheat stripe rust was evaluated at the adult stage. Combined genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) based on RNA sequencing from stripe rust resistant accession Y0337 and susceptible accession Y0402, five candidate resistance genes to wheat stripe rust (TraesCS1B02G170200, TraesCS2D02G181000, TraesCS4B02G117200, TraesCS6A02G189300, and TraesCS3A02G122300) were identified. The transcription level analyses showed that these five genes were significantly differentially expressed between resistant and susceptible accessions post inoculation with Pst at different times. These candidate genes could be experimentally transformed to validate and manipulate fungal resistance, which is beneficial for the development of the wheat cultivars resistant to stripe rust.


Assuntos
Basidiomycota , Estudo de Associação Genômica Ampla , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , China
19.
Anim Genet ; 55(1): 99-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087834

RESUMO

Niemann-Pick disease type C1 (NPC1) is a lysosomal lipid storage disease caused by NPC1 gene mutation. Our previous study found that, compared with wild-type (Npc1+/+ ) mice, the renal volume and weight of Npc1 gene mutant (Npc1-/- ) mice were significantly reduced. We speculate that Npc1 gene mutations may affect the basic structure of the kidneys of Npc1-/- mice, and thus affect their function. Therefore, we randomly selected postnatal Day 28 (P28) and P56 Npc1+/+ and Npc1-/- mice, and observed the renal structure and pathological changes by haematoxylin-eosin staining. The level of renal fibrosis was detected by immunofluorescence histochemical techniques, and western blotting was used to detect the expression levels of apoptosis-related proteins and canonical Wnt signalling pathway related proteins. The results showed that compared with Npc1+/+ mice, the kidneys of P28 and P56 Npc1-/- mice underwent apoptosis and fibrosis; furthermore, there were obvious vacuoles in the cytoplasm of renal tubular epithelial cells of P56 Npc1-/- mice, the cell bodies were loose and foam-like, and the canonical Wnt signalling pathway was abnormally activated. These results showed that Npc1 gene mutation can cause pathological changes in the kidneys of mice. As age increased, vacuoles developed in the cytoplasm of renal tubular epithelial cells, and apoptosis of renal cells, abnormal activation of the Wnt signalling pathway, and promotion of renal fibrosis increased.


Assuntos
Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo C , Animais , Camundongos , Fibrose , Rim/metabolismo , Rim/patologia , Mutação , Proteína C1 de Niemann-Pick/genética , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/metabolismo , Doença de Niemann-Pick Tipo C/patologia
20.
Eur Spine J ; 33(5): 1868-1898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38407614

RESUMO

PURPOSE: As an important treatment for spinal metastasis, surgery has strict applicable conditions. Although various organizations have formulated different guidelines on surgical treatment for spinal metastasis (SM), there are certain differences in the content, standardization and quality of the guidelines and it is necessary to make a critical appraisal of them. We aim to systematically review and appraise the current guidelines on surgical treatments of SM and summarize the related recommendations with the quality evaluation of supporting evidence, as to provide a reference for the standardization of surgical treatment plans, and help clinical front-line medical workers can make safe and effective clinical decisions faster. METHODS: We searched Pubmed, Web of Science, and Embase for three major databases and online guideline databases. According to certain inclusion and exclusion criteria, the latest guidelines on the surgical treatment of SM were sorted out. AGREE II was used to evaluated the guideline's quality, and we extracted and compared the recommended treatment content of each guideline with evaluating by the evidence-grading scale. RESULTS: Eight guidelines from 2013 to 2019 were included. Seven guidelines are comprehensive guidelines and one related to the reconstructive surgery of SM. Five guidelines were evaluated as "recommended," and three guidelines were evaluated as "recommended with modifications." Regarding the indications of surgery with SM, four guidelines, seven guidelines, seven guidelines, three guidelines and three guidelines recommended surgical treatment for patients with SM with intractable pain, mechanical instability, metastatic epidural spinal cord compression (MESCC), recurrent spinal metastasis (RSM), and survival predication, respectively. Regarding the surgical strategies, three guidelines recommended minimally invasive therapy but had strict indications. Six guidelines and five guidelines recommend palliative surgery and with receiving radiation therapy, respectively. For the aggressive surgery, only one guideline recommended to apply to patients in good general conditions who has isolated symptomatic SM. Regarding the surgical reconstructions, one guideline didn't recommend iliac bone graft and three guidelines recommended PMMA bone cement. CONCLUSION: Most of the guidelines do not provide clear criteria for surgical application and provide more of a basic framework. The level of evidence for these surgical recommendations ranges from LOE B to D, and almost all guidelines recommend vertebroplasty and kyphoplasty, but for palliative and more aggressive surgery, which recommended to personalize specific surgical strategies with multidisciplinary collaboration.


Assuntos
Guias de Prática Clínica como Assunto , Neoplasias da Coluna Vertebral , Humanos , Guias de Prática Clínica como Assunto/normas , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia
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