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1.
Anaerobe ; : 102863, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38718918

RESUMEN

This paper reports a case of Bacteroides fragilis induced spondylitis. Diagnosis was confirmed through blood culture and metagenomic sequencing of pus for pathogen detection. Due to persistent lumbar pain, surgical intervention became imperative, resulting in favorable postoperative outcomes. A detailed patient history revealed a severe episode of oral ulceration two weeks before symptom onset, although a direct link to the infection remained elusive. Leveraging insights from this case, we conducted a comprehensive literature review on B. fragilis spondylitis, elucidating clinical manifestations, diagnostic methodologies, and therapeutic strategies.

2.
Sci Rep ; 14(1): 9179, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649459

RESUMEN

Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, ß = - 0.051, 95% CI - 0.072, - 0.031, p = 7.325 × 10-07). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (ß = - 0.054, 95% CI - 0.092, - 0.015, p = 0.006). Further, MVMR analyses determined a predominant role of ferritin (ß = - 0.068, 95% CI - 0.12, - 0.017, p = 9.658 × 10-03) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.


Asunto(s)
Ferritinas , Hierro , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Sarcopenia , Humanos , Sarcopenia/genética , Sarcopenia/sangre , Hierro/metabolismo , Hierro/sangre , Ferritinas/sangre , Masculino
3.
J Environ Manage ; 358: 120886, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38648726

RESUMEN

Intercropping-driven changes in nitrogen (N)-acquiring microbial genomes and functional expression regulate soil N availability and plant N uptake. However, present data seem to be limited to a specific community, obscuring the viewpoint of entire N-acquiring microbiomes and functions. Taking maize intercropped with legumes (peanut and soybean) and non-legumes (gingelly and sweet potato) as models, we studied the effects of intercropping on N transformations and N-acquiring microbiomes in rhizosphere soil across four maize growth stages. Meanwhile, we compiled promising strategies such as random forest analysis and structural equation model for the exploitation of the associations between microbe-driven N dynamics and soil-plant N trade-offs and maize productivity. Compared with monoculture, maize intercropping significantly increased the denitrification rate of rhizosphere soils across four maize growth stages, net N mineralization in the elongation and flowering stages, and the nitrification rate in the seedling and mature stages. The abundance of most N-acquiring microbial populations was influenced significantly by intercropping patterns and maize growth stages. Soil available N components (NH4+-N, NO3--N, and dissolved organic N content) showed a highly direct effect on plant N uptake, which mainly mediated by N transformations (denitrification rate) and N-acquiring populations (amoB, nirK3, and hzsB genes). Overall, the adaptation of N-acquiring microbiomes to changing rhizosphere micro-environments caused by intercropping patterns and maize development could promote soil N transformations and dynamics to meet demand of maize for N nutrient. This would offer another unique perspective to manage the benefits of the highly N-effective and production-effective intercropping ecosystems.


Asunto(s)
Nitrógeno , Rizosfera , Suelo , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Nitrógeno/metabolismo , Suelo/química , Microbiología del Suelo , Microbiota , Agricultura/métodos
4.
Toxics ; 12(2)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38393209

RESUMEN

Although the ecological risk of emerging contaminants is currently a research hotspot in China and abroad, few studies have investigated the ecological risk of pesticide pollutants in Chinese coastal sediments. In this study, nine pesticide pollutants included in the "List of New Key Pollutants for Control (2023 Edition)" issued by the Chinese government were used as the research objects, and the environmental exposure of pesticide pollutants in China's coastal sediments was analyzed. The baseline sediment quality criteria were deduced using the balanced distribution method, and a multi-level ecological risk assessment of pesticides in sediment was performed. The results showed that the nine pesticide pollutants were widespread in Chinese coastal sediments, with concentrations ranging from 0.01 ng·g-1 to 330 ng·g-1. The risk quotient assessment showed that endosulfan and DDT posed medium environmental risks to the Chinese coastal sediment environment, and PCBs posed medium risks in some bays of the East China Sea. The semi-probabilistic, optimized semi-probability evaluation and joint probability curve (JPC) assessments all show that endosulfan and DDT pose a certain degree of risk to the environment.

5.
Sci Bull (Beijing) ; 69(4): 473-482, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38123429

RESUMEN

The growth of data and Internet of Things challenges traditional hardware, which encounters efficiency and power issues owing to separate functional units for sensors, memory, and computation. In this study, we designed an α-phase indium selenide (α-In2Se3) transistor, which is a two-dimensional ferroelectric semiconductor as the channel material, to create artificial optic-neural and electro-neural synapses, enabling cutting-edge processing-in-sensor (PIS) and computing-in-memory (CIM) functionalities. As an optic-neural synapse for low-level sensory processing, the α-In2Se3 transistor exhibits a high photoresponsivity (2855 A/W) and detectivity (2.91 × 1014 Jones), facilitating efficient feature extraction. For high-level processing tasks as an electro-neural synapse, it offers a fast program/erase speed of 40 ns/50 µs and ultralow energy consumption of 0.37 aJ/spike. An AI vision system using α-In2Se3 transistors has been demonstrated. It achieved an impressive recognition accuracy of 92.63% within 12 epochs owing to the synergistic combination of the PIS and CIM functionalities. This study demonstrates the potential of the α-In2Se3 transistor in future vision hardware, enhancing processing, power efficiency, and AI applications.

6.
Mol Biol Evol ; 40(10)2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37804524

RESUMEN

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.


Asunto(s)
Áfidos , Hemípteros , Animales , Ferredoxinas/metabolismo , Plantas/metabolismo , Hemípteros/genética , Nicotiana/genética , Nicotiana/metabolismo , Áfidos/metabolismo , Proteínas y Péptidos Salivales/genética
7.
Radiat Oncol ; 18(1): 153, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37723540

RESUMEN

OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. RESULTS: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040). CONCLUSION: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.


Asunto(s)
Neoplasias Nasofaríngeas , Sinusitis , Humanos , Carcinoma Nasofaríngeo/radioterapia , Estudios Retrospectivos , Sinusitis/diagnóstico por imagen , Sinusitis/etiología , Imagen por Resonancia Magnética , Neoplasias Nasofaríngeas/radioterapia
8.
Genes (Basel) ; 14(8)2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37628691

RESUMEN

The whitefly Bemisia tabaci is one of the most destructive pests worldwide, and causes tremendous economic losses. Tobacco Nicotiana tabacum serves as a model organism for studying fundamental biological processes and is severely damaged by whiteflies. Hitherto, our knowledge of how tobacco perceives and defends itself against whiteflies has been scare. In this study, we analyze the gene expression patterns of tobacco in response to whitefly infestation. A total of 244 and 2417 differentially expressed genes (DEGs) were identified at 12 h and 24 h post whitefly infestation, respectively. Enrichment analysis demonstrates that whitefly infestation activates plant defense at both time points, with genes involved in plant pattern recognition, transcription factors, and hormonal regulation significantly upregulated. Notably, defense genes are more intensely upregulated at 24 h post infestation than at 12 h, indicating an increased immunity induced by whitefly infestation. In contrast, genes associated with energy metabolism, carbohydrate metabolism, ribosomes, and photosynthesis are suppressed, suggesting impaired plant development. Taken together, our study provides comprehensive insights into how plants respond to phloem-feeding insects, and offers a theoretical basis for better research on plant-insect interactions.


Asunto(s)
Hemípteros , Nicotiana , Animales , Nicotiana/genética , Hemípteros/genética , Transcriptoma/genética , Metabolismo Energético , Miedo
9.
Small ; 19(40): e2302961, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37264718

RESUMEN

Constructing the adjustable surface conductive networks is an innovation that can achieve a balance between enhanced attenuation and impedance mismatch according to the microwave absorption mechanism. However, the traditional design strategies remain significant challenges in terms of rational selection and controlled growth of conductive components. Herein, a hierarchical construction strategy and quantitative construction technique are employed to introduce conductive metal-organic frameworks (MOFs) derivatives in the classic yolk-shell structure composed of electromagnetic components and the cavity for remarkable optimized performance. Specifically, the surface conductive networks obtained by carbonized ZIF-67 quantitative construction, together with the Fe3 O4 magnetic core and dielectric carbon layer linked by the cavity, achieve the cooperative enhancement of impedance matching optimization and synergistic attenuation in the Fe3 O4 @C@Co/N-Doped C (FCCNC) absorber. This interesting design is further verified by experimental results and simulation calculations. The products FCCNC-2 yield a distinguished minimum reflection loss of -66.39 dB and an exceptional effective absorption bandwidth of 6.49 GHz, indicating that moderate conduction excited via hierarchical and quantitative design can maximize the absorption capability. Furthermore, the proposed versatile methodology of surface assembly paves a new avenue to maximize beneficial conduction effect and manipulate microwave attenuation in MOFs derivatives.

11.
ACS Appl Mater Interfaces ; 15(19): 23573-23582, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37141554

RESUMEN

Artificial synapse networks capable of massively parallel computing and mimicking biological neural networks can potentially improve the processing efficiency of existing information technologies. Semiconductor devices functioning as excitatory and inhibitory synapses are crucial for developing intelligence systems, such as traffic control systems. However, achieving reconfigurability between two working modes (inhibitory and excitatory) and bilingual synaptic behavior in a single transistor remains challenging. This study successfully mimics a bilingual synaptic response using an artificial synapse based on an ambipolar floating gate memory comprising tungsten selenide (WSe2)/hexagonal boron nitride (h-BN)/ molybdenum telluride (MoTe2). In this WSe2/h-BN/MoTe2 structure, ambipolar semiconductors WSe2 and MoTe2 are inserted as channel and floating gates, respectively, and h-BN serves as the tunneling barrier layer. Using either positive or negative pulse amplitude modulations at the control gate, this device with bipolar channel conduction produced eight distinct resistance states. Based on this, we experimentally projected that we could achieve 490 memory states (210 hole-resistance states + 280 electron-resistance states). Using the bipolar charge transport and multistorage states of WSe2/h-BN/MoTe2 floating gate memory, we mimicked reconfigurable excitatory and inhibitory synaptic plasticity in a single device. Furthermore, the convolution neural network formed by these synaptic devices can recognize handwritten digits with an accuracy of >92%. This study identifies the unique properties of heterostructure devices based on two-dimensional materials as well as predicts their applicability in advanced recognition of neuromorphic computing.

12.
Cell Death Dis ; 14(4): 249, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024487

RESUMEN

Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is indispensable in organ development because it maintains intracellular cholesterol homeostasis. The vessel is not widely conceived of as a cholesterol-sensitive tissue, so the specific role of SCAP in angiogenesis has not been paid attention to. As an important component of the vascular mesoderm, vascular smooth muscle cells (VSMCs) are widely involved in each step of angiogenesis. Here, we report for the first time that VSMC-specific ablation of SCAP inhibits VSMC proliferation and migration, interacting with endothelial cells (ECs), and finally causes defective embryonic angiogenesis in mice. Mechanistically, we demonstrated that SCAP ablation in VSMCs leads to the upregulation of KISS-1 protein, consequently resulting in suppressed activation of the MAPK/ERK signaling pathway and downregulation of matrix metalloproteinase 9 (MMP9) and vascular endothelial-derived growth factor (VEGF) expression to prevent angiogenesis. Importantly, we found that SCAP promotes the cleavage and nuclear translocation of SREBP2, which acts as a negative transcription regulator, regulating KISS-1 expression. Our findings suggest that SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice and provide a new point of view for therapeutic targets of vascular development.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Kisspeptinas , Animales , Ratones , Colesterol/metabolismo , Células Endoteliales/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Kisspeptinas/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo
13.
Chemosphere ; 324: 138293, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36870619

RESUMEN

Coupled amendments of biochar and organic fertilizers may be one of the effective practice to ensure high cropland productivity and resource use efficiency, but there is little field-based evidence for this. Herein, we employed a eight-years (2014-2021) field experiment to explore the effectiveness of biochar and organic fertilizer amendments on crop productivity and nutrient runoff losses, as well as to further explored their relationships with the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of soil, microbiome, and enzymes. Experiment treatments include No fertilizer (CK), chemical-only fertilizer (CF), CF + biochar (CF + B), 20% chemical N was replaced by organic fertilizer (OF), and OF + biochar (OF + B). Compared with the CF, the CF + B, OF, and OF + B treatments increased average yield by 11.5%, 13.2%, and 32%, average N use efficiency by 37.2%, 58.6%, and 81.4%, average P use efficiency by 44.8%, 55.1%, and 118.6%, average plant N uptake by 19.7%, 35.6%, and 44.3%, as well as average plant P uptake by 18.4%, 23.1%, and 44.3%, respectively (p ≤ 0.05). Compared with the CF, the CF + B, OF, and OF + B decreased average average total N losses by 65.2%, 97.4%, and 241.2%, and average total P losses by 52.9%, 77.1%, and 119.7%, respectively (p ≤ 0.05). Organic-amended treatments (CF + B, OF, and OF + B) significantly changed soil total and available C, N, and P content, soil microbial C, N, and P content, as well as the potential activities of soil C-, N-, and P-acquiring enzymes. Plant P uptake and P-acquiring enzyme activity were the main drivers of maize yield, which was influenced by the contents and stoichiometric ratios of soil available C, N, and P. These findings suggest that organic fertilizer applications combined with biochar have the potential to maintain high crop yields while reducing nutrient losses by regulating the stoichiometric balance of soil available C and nutrients.


Asunto(s)
Microbiota , Suelo , Suelo/química , Zea mays , Carbón Orgánico/química , Nitrógeno/análisis , Fertilizantes/análisis
14.
Nat Commun ; 14(1): 1756, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36991019

RESUMEN

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following recombination-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.


Asunto(s)
Proteínas F-Box , Neoplasias , Telomerasa , Humanos , Línea Celular , ADN , Homeostasis del Telómero/genética , Telómero/genética , Telómero/metabolismo , Neoplasias/genética , Telomerasa/genética , Cisteína Endopeptidasas/metabolismo , Proteínas F-Box/genética , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo
15.
Front Physiol ; 14: 1092352, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776966

RESUMEN

Background: Sarcopenia is an aging syndrome that increases the risks of various adverse outcomes, including falls, fractures, physical disability, and death. Sarcopenia can be diagnosed through medical images-based body part analysis, which requires laborious and time-consuming outlining of irregular contours of abdominal body parts. Therefore, it is critical to develop an efficient computational method for automatically segmenting body parts and predicting diseases. Methods: In this study, we designed an Artificial Intelligence Body Part Measure System (AIBMS) based on deep learning to automate body parts segmentation from abdominal CT scans and quantification of body part areas and volumes. The system was developed using three network models, including SEG-NET, U-NET, and Attention U-NET, and trained on abdominal CT plain scan data. Results: This segmentation model was evaluated using multi-device developmental and independent test datasets and demonstrated a high level of accuracy with over 0.9 DSC score in segment body parts. Based on the characteristics of the three network models, we gave recommendations for the appropriate model selection in various clinical scenarios. We constructed a sarcopenia classification model based on cutoff values (Auto SMI model), which demonstrated high accuracy in predicting sarcopenia with an AUC of 0.874. We used Youden index to optimize the Auto SMI model and found a better threshold of 40.69. Conclusion: We developed an AI system to segment body parts in abdominal CT images and constructed a model based on cutoff value to achieve the prediction of sarcopenia with high accuracy.

16.
Nat Commun ; 14(1): 737, 2023 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-36759625

RESUMEN

Salivary elicitors secreted by herbivorous insects can be perceived by host plants to trigger plant immunity. However, how insects secrete other salivary components to subsequently attenuate the elicitor-induced plant immunity remains poorly understood. Here, we study the small brown planthopper, Laodelphax striatellus salivary sheath protein LsSP1. Using Y2H, BiFC and LUC assays, we show that LsSP1 is secreted into host plants and binds to salivary sheath via mucin-like protein (LsMLP). Rice plants pre-infested with dsLsSP1-treated L. striatellus are less attractive to L. striatellus nymphs than those pre-infected with dsGFP-treated controls. Transgenic rice plants with LsSP1 overexpression rescue the insect feeding defects caused by a deficiency of LsSP1 secretion, consistent with the potential role of LsSP1 in manipulating plant defenses. Our results illustrate the importance of salivary sheath proteins in mediating the interactions between plants and herbivorous insects.


Asunto(s)
Hemípteros , Oryza , Animales , Oryza/genética , Hemípteros/genética , Herbivoria , Plantas Modificadas Genéticamente , Ninfa
17.
bioRxiv ; 2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36798426

RESUMEN

Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following homology-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.

18.
Environ Sci Pollut Res Int ; 30(6): 14402-14412, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36153419

RESUMEN

Increasing research suggested that green spaces are associated with many health benefits, but evidence for the quantitative relationship between green spaces and mortality attributable to particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) is limited. We collected disease-specific mortality and PM2.5 data for a period of 4 years (2015-2018) along with green space data for an 8-year duration (2010-2017) in 31 provincial-level administrative regions of China. First, this study used the Integrated Exposure-Response model to estimate the mortality of four diseases attributable to PM2.5, including chronic obstructive pulmonary diseases (COPD), lung cancer (LC), ischemic heart disease (IHD), and cerebrovascular disease (CBVD). Then we performed linear regression and mixed-effects model to investigate the counteracting effect of green spaces on death caused by PM2.5 exposure. The differences in impacts among the Eastern, Central, and Western regions were explored using stratified analysis. The most significant results from linear regression analysis indicated that per 100 km2 of green spaces increase, there was a decreased total mortality (10-5) (COPD, LC, IHD, and CBVD) attributable to PM2.5 by - 4.012 [95% confidence interval (CI): - 5.535, - 2.488], while the reduction by mixed-linear regression analysis was - 2.702/105 (95% CI = - 3.645, - 1.759). Of all hysteresis analyses, the effect estimates (ß) at lag3 and lag4 were the largest. The effect of green spaces was more advantageous when targeting CBVD and the Eastern region. We found a negative correlation between green space exposure and mortality attributable to PM2.5, which can provide further support for city planners, government personnel, and others to build a healthier city and achieve national health goals.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Trastornos Cerebrovasculares , Neoplasias Pulmonares , Isquemia Miocárdica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Contaminantes Atmosféricos/análisis , Parques Recreativos , Material Particulado/análisis , China , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/análisis
19.
Genes (Basel) ; 13(11)2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36421824

RESUMEN

SNPs in ABCA7 confer the largest genetic risk for Alzheimer's Disease (AD) in African Americans (AA) after APOE ε4. However, the relationship between ABCA7 and cognitive function has not been thoroughly examined. We investigated the effects of five known AD risk SNPs and 72 CpGs in ABCA7, as well as their interactions, on general cognitive function (cognition) in 634 older AA without dementia from Genetic Epidemiology Network of Arteriopathy (GENOA). Using linear mixed models, no SNP or CpG was associated with cognition after multiple testing correction, but five CpGs were nominally associated (p < 0.05). Four SNP-by-CpG interactions were associated with cognition (FDR q < 0.1). Contrast tests show that methylation is associated with cognition in some genotype groups (p < 0.05): a 1% increase at cg00135882 and cg22271697 is associated with a 0.68 SD decrease and 0.14 SD increase in cognition for those with the rs3764647 GG/AG (p = 0.004) and AA (p = 2 × 10-4) genotypes, respectively. In addition, a 1% increase at cg06169110 and cg17316918 is associated with a 0.37 SD decrease (p = 2 × 10-4) and 0.33 SD increase (p = 0.004), respectively, in cognition for those with the rs115550680 GG/AG genotype. While AD risk SNPs in ABCA7 were not associated with cognition in this sample, some have interactions with proximal methylation on cognition.


Asunto(s)
Enfermedad de Alzheimer , Polimorfismo de Nucleótido Simple , Humanos , Anciano , Negro o Afroamericano/genética , Cognición , Transportadoras de Casetes de Unión a ATP/genética , Enfermedad de Alzheimer/genética
20.
J Clin Invest ; 132(24)2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36282572

RESUMEN

Targeting lineage-defined transcriptional dependencies has emerged as an effective therapeutic strategy in cancer treatment. Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), we identified a set of transcription factors (TFs) including FOXO1, EBF1, PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network reconstruction analysis revealed FOXO1 as a master regulator that acts upstream in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to drive MCL lineage commitment through supporting the lineage-specific transcription programs. We further show that FOXO1, but not its close paralog FOXO3, can reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 inhibitor library, induces a robust cytotoxic response in MCL cells in vitro and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition as a therapeutic strategy targeting lineage-driven transcriptional addiction in MCL.


Asunto(s)
Linfoma de Células del Manto , Humanos , Adulto , Linfoma de Células del Manto/genética , Redes Reguladoras de Genes , Proteína Forkhead Box O1/genética
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