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1.
J Colloid Interface Sci ; 673: 444-452, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38878378

RESUMEN

Electrocatalytic water splitting (EWS) for hydrogen production is considered an ideal strategy for utilizing renewable energy, reducing fossil fuel consumption, and addressing environmental pollution issues. Traditional noble metal electrocatalysts have excellent performance, but their cost is high. Developing efficient, stable, and relatively inexpensive dual functional electrocatalysts is crucial for promoting large-scale EWS hydrogen production processes. Herein, a simple one-step electrodeposition method was used to grow nickel-iron phosphorus-sulfides (NiFePS) on the surface of hydrophilic treated carbon cloth (CC). The resultant NiFePS/CC with a phosphorus to sulfur ratio of 1:4 exhibited the best electrocatalytic performance, requiring only -91 mV and 216 mV overpotentials to generate the current densities of 10 mA·cm-2 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. When it was used as a bifunctional electrocatalyst to overall water splitting (OWS), a voltage of 1.536 V can generate a current density of 10 mA·cm-2. The excellent electrocatalytic performance can be ascribed to two factors: 1) the CC with excellent conductivity serves as a growth substrate, reducing the impedance of charge transfer from the electrode to the electrolyte and accelerating the electron transfer rate; 2) The large number of ultra-thin nanosheets formed on the surface of the catalyst increase the electrochemical specific surface area, expose more reaction sites, and thus improve the electrocatalytic reaction performance. This work provides a new approach for designing efficient non-noble metal electrocatalysts for water splitting.

2.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1101-1111, 2024 Apr 18.
Artículo en Chino | MEDLINE | ID: mdl-38884245

RESUMEN

The accurate identification and monitoring of urban green space is of great significance in urban planning and ecological management. In view of the complex background of urban green space, the traditional remote sensing classification technology is prone to the problem of misalignment and adhesion. Taking Yuhua District of Changsha City as the research area and Gaofen-2 (GF-2) remote sensing image as the data source, we proposed a remote sensing classification method for urban green space based on the LA-UNet model, which was based on the UNet model. We introduced the DWTCA channel attention mechanism module to improve the attention of the network to green space information, and used the CARAFE module to up sample the extracted features to achieve accurate classification of trees, shrubs and other land types in the complex background of the city. The results showed that the LA-UNet model had the best classification effect of urban green space when using standard false color remote sensing images. The overall accuracy and mean intersection over union were 96.3% and 90.9%, which were 2.8% and 6.1% higher than the UNet model, respectively. In the Potsdam public dataset, the overall accuracy and mean intersection over union of the LA-UNet model were also better than those of the UNet model, which increased by 0.9% and 1.8%, respectively, indicating that the LA-UNet model had good robustness and versatility. In summary, the proposed LA-UNet model could effectively alleviate the problems of misalignment and adhesion of urban green space, with advantages in the remote sensing classification of urban green space. The improved LA-UNet model had a smaller parameter volume than the UNet model, which could effectively improve the classification accuracy of urban green space. This study would provide a methodological reference for the accurate classification and understanding the spatial distribution of urban green space.


Asunto(s)
Ciudades , Planificación de Ciudades , Ecosistema , Modelos Teóricos , Tecnología de Sensores Remotos , Tecnología de Sensores Remotos/métodos , China , Planificación de Ciudades/métodos , Monitoreo del Ambiente/métodos , Árboles/clasificación , Árboles/crecimiento & desarrollo , Conservación de los Recursos Naturales/métodos
3.
Hematology ; 29(1): 2365596, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38864494

RESUMEN

OBJECTIVES: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6. METHODS: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy. RESULTS: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/µL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/µL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow. CONCLUSIONS: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.


Asunto(s)
Reacción en Cadena de la Polimerasa , Talasemia alfa , Talasemia alfa/genética , Talasemia alfa/diagnóstico , Talasemia alfa/sangre , Humanos , Reacción en Cadena de la Polimerasa/métodos , Femenino , Asia Sudoriental , Eliminación de Secuencia , Pueblo Asiatico/genética , Pueblos del Este de Asia
4.
Nat Commun ; 15(1): 4688, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824144

RESUMEN

Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas for efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of organic transformations that copper nanoclusters can catalyze remain limited to date. Herein, we report a structurally well-defined anionic Cu40 nanocluster that emits in the second near-infrared region (NIR-II, 1000-1700 nm) after photoexcitation and can conduct single-electron transfer with fluoroalkyl iodides without the need for external ligand activation. This photoredox-active copper nanocluster efficiently catalyzes the three-component radical couplings of alkenes, fluoroalkyl iodides, and trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety of fluorine-containing electrophiles and a cyanide nucleophile can be added onto an array of alkenes, including styrenes and aliphatic olefins. Our current work demonstrates the viability of using readily accessible metal nanoclusters to establish photocatalytic systems with a high degree of practicality and reaction complexity.

5.
Mol Biol Evol ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842255

RESUMEN

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100-200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

6.
China CDC Wkly ; 6(20): 463-468, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38846361

RESUMEN

Introduction: In order to enhance the effectiveness of resource allocation, regions must tailor their responses to their specific epidemiological and economic situations. Methods: Utilizing Spectrum software, we projected the cost-effectiveness of 10 chosen HIV interventions in six cities in eastern China from 2019 to 2028. We assessed three scenarios - Base, Achievable, and Idealized - for each city. The analysis included the projected number of HIV infections and deaths averted, as well as the incremental cost-effectiveness ratios for each intervention in the six cities. Results: In Shijiazhuang, Wuxi, Yantai, and Zhenjiang, cities with initially low antiretroviral therapy (ART) coverage, ART showed significant effectiveness, especially for males. Conversely, in Foshan and Ningbo, where ART coverage was notably high, oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) proved effective in the Idealized scenario. MSM outreach, ART for males, and ART for females demonstrated cost-effectiveness across all six cities in both Achievable and Idealized scenarios at the predefined thresholds for each city. Discussion: Maintaining an appropriate coverage rate for outreach to MSM can lead to cost-effectiveness. In cities with low ART coverage, scaling up ART remains a crucial intervention. In regions with high ART coverage, consideration may be given to the utilization of oral PrEP for MSM individuals, requiring budget allocation.

7.
Tob Induc Dis ; 222024.
Artículo en Inglés | MEDLINE | ID: mdl-38835514

RESUMEN

INTRODUCTION: The controversial relationship between smoking and prostate cancer (PCa) risk prompted us to conduct a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database and apply Mendelian randomization (MR) analyses in order to clarify the possible causal effect of smoking on PCa risk. METHODS: Using univariate and multivariate logistic regression methods, a secondary analysis of the pooled 2003-2018 NHANES dataset was performed to explore the association between smoking and PCa risk. Propensity-score matching was used to reduce selection bias. Then, we conducted subsequent MR analysis study to investigate the potential causal effect of smoking on PCa risk, with genetic variants of four exposure factors including the lifetime smoking index, light smoking, smoking initiation, and the amount of smoking per day obtained from genome-wide association studies, and PCa summary statistics obtained from three database populations. Inverse-variance weighting was the primary analytical method, and weighted median and MR-Egger regression were used for sensitivity analyses. The MR results for the three PCa databases were combined using meta-analysis. RESULTS: The study included 16073 NHANES subjects, comprising 554 with PCa and 15519 without PCa. Logistic regression before and after matching did not reveal any significant association. Meta-analysis of the MR results also did not support an association of PCa risk with lifetime smoking index (OR=0.95; 95% CI: 0.83-1.09), light smoking (OR=1.00; 95% CI: 0.95-1.06), smoking initiation (OR=0.99, 95% CI=0.99-1.00), or the amount of smoking per day (OR=1.00; 95% CI: 0.99-1.00) and PCa risk. CONCLUSIONS: There was no evidence for an association between smoking and the risk of PCa. Further studies are needed to determine if there are any associations of other forms of smoking with the risk of PCa at different stages.

9.
Sci China Life Sci ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38874712
10.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1932-1946, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38812206

RESUMEN

This study investigated the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules based on metabonomics, network pharmacology, and molecular docking. The aging mice model was induced by intraperitoneal injection of D-galactose(D-gal). Mice were randomly divided into a control group, model group, melatonin group(MT group), and low, medium, and high dose groups of Xiyangshen Sanqi Danshen Granules(XSD-L, XSD-M, and XSD-H). An open-field experiment was conducted, and the expression of cell cycle arrest proteins(p16) and phosphorylated histone family 2A variant(γH2AX) in the brain tissue was detected by immunofluorescence. The expression of interleukin-1ß(IL-1ß) and interleukin-6(IL-6) in the brain tissue was detected by enzyme-linked immunosorbent assay(ELISA). Metabolomics analysis was performed on the serum of mice in control, model, and XSD-H groups to obtain metabolic processes and metabolites. The effective chemical components and potential targets of Xiyangshen Sanqi Danshen Granules were predicted through network pharmacology, and the network diagram of "drug-effective chemical components-key targets" was constructed. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were carried out, and a protein-protein interaction(PPI) network was constructed to clarify the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules. The results showed that the Xiyangshen Sanqi Danshen Granules could significantly improve the aging degree of D-gal mice, significantly improve the total motion distance and the mean motion speed of D-gal mice, and reduce the rest time. In addition, Xiyangshen Sanqi Danshen Granules could significantly reduce the protein levels of IL-6 and IL-1ß and the expression of p16 and γH2AX in D-gal mice. Compared with the model group, 66 differential metabolites(DMs) were significantly up-regulated, and 91 DMs were down-regulated in the XSD-H group. Moreover, four key metabolic pathways(tryptophan metabolism, glycerophospholipid metabolism, pyrimidine metabolism, and lysine degradation) and 16 biomarkers(lysine, tryptophan, indoleacetaldehyde, PCs, LysoPCs, 3-hydroxyanthranilic acid, melatonin, etc) were screened out. 58 main active components and 62 key targets of Xiyangshen Sanqi Danshen Granules were screened by network pharmacology. The GO functional enrichment analysis found the positive regulation of gene expression, drug response, etc. KEGG pathway enrichment screening involved diabetic complications-related AGE-RAGE signaling pathway, hypoxia inducible factor-1 signaling pathway, etc. Through the PPI network and molecular docking, six potential core targets of STAT3, MAPK1, MAPK14, EGFR, FOS, and STAT1 were screened.


Asunto(s)
Envejecimiento , Biología Computacional , Medicamentos Herbarios Chinos , Metabolómica , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Masculino , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Simulación del Acoplamiento Molecular , Salvia miltiorrhiza/química , Interleucina-1beta/genética , Interleucina-1beta/metabolismo
11.
DNA Cell Biol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700464

RESUMEN

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

12.
Eur J Pharm Biopharm ; 199: 114309, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38704102

RESUMEN

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.


Asunto(s)
Alginatos , Quitosano , Colitis Ulcerosa , Sistemas de Liberación de Medicamentos , Geles , Microesferas , Saponinas , Colitis Ulcerosa/tratamiento farmacológico , Animales , Ratas , Alginatos/química , Quitosano/química , Sistemas de Liberación de Medicamentos/métodos , Masculino , Saponinas/farmacología , Saponinas/administración & dosificación , Saponinas/química , Tamaño de la Partícula , Humanos , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Ratas Sprague-Dawley , Polímeros/química , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Administración Oral
13.
Infect Agent Cancer ; 19(1): 25, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802946

RESUMEN

This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

14.
Org Biomol Chem ; 22(20): 4179-4189, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38716654

RESUMEN

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.


Asunto(s)
Aspergillus , Inhibidores de Glicósido Hidrolasas , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores , Policétidos , alfa-Glucosidasas , Aspergillus/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Policétidos/farmacología , Policétidos/química , Policétidos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Células PC12 , Animales , Ratas , alfa-Glucosidasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Estructura Molecular
15.
Sci Total Environ ; 935: 173343, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38777069

RESUMEN

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.


Asunto(s)
Altitud , Biodiversidad , Bosques , Árboles , China , Filogenia , Ecosistema , Clima Tropical
16.
Oncogene ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744953

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.

17.
Sensors (Basel) ; 24(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38793942

RESUMEN

Autonomous driving, as a pivotal technology in modern transportation, is progressively transforming the modalities of human mobility. In this domain, vehicle detection is a significant research direction that involves the intersection of multiple disciplines, including sensor technology and computer vision. In recent years, many excellent vehicle detection methods have been reported, but few studies have focused on summarizing and analyzing these algorithms. This work provides a comprehensive review of existing vehicle detection algorithms and discusses their practical applications in the field of autonomous driving. First, we provide a brief description of the tasks, evaluation metrics, and datasets for vehicle detection. Second, more than 200 classical and latest vehicle detection algorithms are summarized in detail, including those based on machine vision, LiDAR, millimeter-wave radar, and sensor fusion. Finally, this article discusses the strengths and limitations of different algorithms and sensors, and proposes future trends.

18.
Nature ; 629(8014): 1118-1125, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38778102

RESUMEN

Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how plants monitor water availability during rehydration is unknown. Although increases in hypo-osmolarity-induced cytosolic Ca2+ concentration (HOSCA) have long been postulated to be the mechanism for sensing hypo-osmolarity in rehydration1,2, the molecular basis remains unknown. Because osmolarity triggers membrane tension and the osmosensing specificity of osmosensing channels can only be determined in vivo3-5, these channels have been classified as a subtype of mechanosensors. Here we identify bona fide cell surface hypo-osmosensors in Arabidopsis and find that pollen Ca2+ spiking is controlled directly by water through these hypo-osmosensors-that is, Ca2+ spiking is the second messenger for water status. We developed a functional expression screen in Escherichia coli for hypo-osmosensitive channels and identified OSCA2.1, a member of the hyperosmolarity-gated calcium-permeable channel (OSCA) family of proteins6. We screened single and high-order OSCA mutants, and observed that the osca2.1/osca2.2 double-knockout mutant was impaired in pollen germination and HOSCA. OSCA2.1 and OSCA2.2 function as hypo-osmosensitive Ca2+-permeable channels in planta and in HEK293 cells. Decreasing osmolarity of the medium enhanced pollen Ca2+ oscillations, which were mediated by OSCA2.1 and OSCA2.2 and required for germination. OSCA2.1 and OSCA2.2 convert extracellular water status into Ca2+ spiking in pollen and may serve as essential hypo-osmosensors for tracking rehydration in plants.


Asunto(s)
Arabidopsis , Señalización del Calcio , Calcio , Germinación , Concentración Osmolar , Polen , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Calcio/metabolismo , Canales de Calcio/genética , Canales de Calcio/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Germinación/genética , Mutación , Polen/genética , Polen/metabolismo , Agua/metabolismo , Células HEK293 , Humanos , Deshidratación
19.
Artículo en Inglés | MEDLINE | ID: mdl-38734235

RESUMEN

OBJECTIVES: The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a major global public threat. we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant Pseudomonas aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity. METHODS: An XDR Pseudomonas aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing and phylogenetic analysis was performed. Predictions were fulfilled using curated bioinformatics tools. RESULTS: The assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1791 (ST1791) and the O11 serogroup. Nine prophage regions, three CRISPR arrays, and two Cas clusters were identified. However, no plasmids were predicted. Antibiotic susceptibility tests showed that CRPA190 was resistant to all the tested antibiotics, including carbapenem, polymyxin B and ceftazidime-avibactam. Forty antimicrobial resistance genes were predicted in CRPA190, including several carbapenemase genes such as blaPDC-142, blaPME-1, blaNDM-1 and blaOXA-902. The isolate was predicted to be pathogenic and possess strong biofilm-forming ability. It harbors virulence genes that are associated with an arsenal of virulence determinants involved in adherence, motility, exotoxins, exoenzymes, immune modulation, biofilms, nutritional/metabolic factors and effector delivery systems. CONCLUSION: These findings enhance our understanding of the resistance and pathogenicity of the ST1791 Pseudomonas aeruginosa strain which is unique in China and provide a broader perspective on the global epidemiological landscape, suggesting the emergence of P. aeruginosa ST1971, which requires control measures to limit its dissemination.

20.
Br J Haematol ; 204(6): 2429-2441, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38665119

RESUMEN

Primary immune thrombocytopenia (ITP) is linked to specific pathogenic mechanisms, yet its relationship with mitophagy and ferroptosis is poorly understood. This study aimed to identify new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Techniques such as differential analysis, Mfuzz expression pattern clustering, machine learning, gene set enrichment analysis, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to investigate the molecular pathways of pivotal genes. Two-sample Mendelian randomization (TSMR) assessed the causal effects in ITP. Key genes identified in the training set included GABARAPL1, S100A8, LIN28A, and GDF9, which demonstrated diagnostic potential in validation sets. Functional analysis indicated these genes' involvement in ubiquitin phosphorylation, PPAR signalling pathway and T-cell differentiation. Immune infiltration analysis revealed increased macrophage presence in ITP, related to the critical genes. scRNA-seq indicated reduced GABARAPL1 expression in ITP bone marrow macrophages. TSMR linked S100A8 with ITP diagnosis, presenting an OR of 0.856 (95% CI = 0.736-0.997, p = 0.045). The study pinpointed four central genes, GABARAPL1, S100A8, LIN28A, and GDF9, tied to mitophagy and ferroptosis in ITP. It posits that diminished GABARAPL1 expression may disrupts ubiquitin phosphorylation and PPAR signalling, impairing mitophagy and inhibiting ferroptosis, leading to immune imbalance.


Asunto(s)
Ferroptosis , Mitofagia , Púrpura Trombocitopénica Idiopática , Humanos , Ferroptosis/genética , Púrpura Trombocitopénica Idiopática/genética , Masculino , Femenino , Biomarcadores , Persona de Mediana Edad
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