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1.
Sleep Breath ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115598

RESUMO

BACKGROUND: Sympathetic nerve activation followed by obstructive sleep apnea (OSA) accounts for blood pressure elevation. The effectiveness of renal denervation (RDN) in controlling blood pressure in patients with OSA remains controversial. In this systematic review, we tried to pool currently available data to assess the effects of RDN therapy on blood pressure in OSA patients. METHODS: We retrieved Pubmed, EMbase and Cochrane Library through 17 May 2023, using the following key words: "renal denervation" and"obstructive sleep apnea". Full articles reporting the change of blood pressure after RDN procedure were included. RESULTS: A total of five studies were included in the meta-analysis. Pooled analysis showed that RDN markedly reduced both 24-h ambulatory systolic blood pressure (24 h-SBP) (Mean difference (MD): -7.54mmHg; 95%Cl: -10.16 to -4.91mmHg; I2 = 0%) and 24-h ambulatory diastolic blood pressure (24 h-DBP) (MD: -5.28mmHg; 95%Cl: -7.35 to -3.22mmHg; I2=0%). Daytime systolic blood pressure (dSBP) was reduced after RDN (MD: -7.54mmHg; 95%Cl: -10.82 to -4.57mmHg; I2 = 54%). With regards to nocturnal blood pressure, we found that RDN resulted in a significant reduction in nighttime systolic blood pressure (nSBP) (MD: -6.91mmHg; 95%Cl: -10.69 to -2.85mmHg; I2=0%). Subgroup analysis showed that dSBP was reduced by 12.00 mmHg, 12.00 mmHg, and 7.25 mmHg at 1 month, 3 months and 6 months, respectively. Our pooled analysis showed that AHI was not significantly changed by RDN. No major compilations were associated with RDN. CONCLUSIONS: RDN exerts a considerable blood pressure-lowering effect in hypertensive patients with OSA, which was sustained at least 6 months.

2.
Heredity (Edinb) ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138378

RESUMO

Arid ecosystems, characterized by severe water scarcity, play a crucial role in preserving Earth's biodiversity and resources. The Tarim Basin in Northwestern China, a typical arid region isolated by the Tianshan Mountains and expansive deserts, provides a special study area for investigating how plant response and adaptation to such environments. Tamarix hispida, a species well adapted to saline-alkaline and drought conditions, dominates in the saline-alkali lands of the Tarim Basin. This study aims to examine the genetic diversity and environmental adaptation of T. hispida in the Tarim Basin. Genomic SNPs for a total of 160 individuals from 17 populations were generated using dd-RAD sequencing approach. Population genetic structure and genetic diversity were analyzed by methods including ADMIXTURE, PCA, and phylogenetic tree. Environmental association analysis (EAA) was performed using LFMM and RDA analyses. The results revealed two major genetic lineages with geographical substitution patterns from west to east, indicating significant gene flow and hybridization. Environmental factors such as Precipitation Seasonality (bio15) and Topsoil Sand Fraction (T_SAND) significantly shaped allele frequencies, supporting the species' genetic adaptability. Several genes associated with environmental adaptation were identified and annotated, highlighting physiological and metabolic processes crucial for survival in arid conditions. The study highlights the role of geographical isolation and environmental factors in shaping genetic structure and adaptive evolution. The identified adaptive genes related to stress tolerance emphasize the species' resilience and highlight the importance of specific physiological and metabolic pathways.

3.
New Phytol ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075808

RESUMO

Catalase (CAT) is the main reactive oxygen species (ROS)-scavenging enzyme in plants and insects. However, it remains elusive whether and how insect saliva CAT suppresses ROS-mediated plant defense, thereby promoting initial virus transmission by insect vectors. Here, we investigated how leafhopper Recilia dorsalis catalase (RdCAT) was secreted from insect salivary glands into rice phloem, and how it was perceived by rice chaperone NO CATALASE ACTIVITY1 (OsNCA1) to scavenge excessive H2O2 during insect-to-plant virus transmission. We found that the interaction of OsNCA1 with RdCAT activated its enzymatic activity to decompose H2O2 in rice plants during leafhopper feeding. However, initial insect feeding did not significantly change rice CATs transcripts. Knockout of OsNCA1 in transgenic lines decreased leafhopper feeding-activated CAT activity and caused higher H2O2 accumulation. A devastating rice reovirus activated RdCAT expression and promoted the cosecretion of virions and RdCAT into leafhopper salivary cavities and ultimately into the phloem. Virus-mediated increase of RdCAT secretion suppressed excessive H2O2, thereby promoting host attractiveness to insect vectors and initial virus transmission. Our findings provide insights into how insect saliva CAT is secreted and perceived by plant chaperones to suppress the early H2O2 burst during insect feeding, thereby facilitating viral transmission.

4.
Mitochondrial DNA B Resour ; 9(7): 915-919, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39077056

RESUMO

Tamarix hispida Willd. 1816, a crucial native plant species in the arid desert region of northwestern China, plays a significant role in maintaining ecological stability. It is instrumental in addressing soil salinity-alkalinity and heavy metal pollution. This research aims to analyze the phylogenetic divergence pattern and evolutionary history of T. hispida by comparing chloroplast genome structures across different populations. Despite the minimal differences in chloroplast genome structure due to conserved genes and junction regions, sequencing was conducted using the Illumina NovaSeq platform to verify the historical evolutionary processes between different populations, followed by assembly and annotation. The results revealed that the T. hispida chloroplast genome is approximately 156,164-156,186 bp in length, with a quadripartite structure and 131 annotated genes. Phylogenetic analysis indicated two lineages within T. hispida, with a divergence time of 3.15 Ma. These findings emphasize the low genetic diversity in T. hispida and offer valuable insights into its evolutionary past. To effectively protect and manage this species, increased scientific research and monitoring of its genetic diversity are necessary. This study underscores the importance of comprehending the genetic mechanisms behind species divergence to develop informed conservation strategies.

5.
Nat Commun ; 15(1): 6231, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39043649

RESUMO

The geodynamic processes that formed Earth's earliest continents are intensely debated. Particularly, the transformation from ancient crustal nuclei into mature Archaean cratons is unclear, primarily owing to the paucity of well-preserved Eoarchaean-Palaeoarchaean 'protocrust'. Here, we report a newly identified Palaeoarchaean continental fragment-the Baishanhu nucleus-in northeastern North China Craton. U-Pb geochronology shows that this nucleus preserves five major magmatic events during 3.6-2.5 Ga. Geochemistry and zircon Lu-Hf isotopes reveal ancient 4.2-3.8 Ga mantle extraction ages, as well as later intraplate crustal reworking. Crustal architecture and zircon Hf-O isotopes indicate that proto-North China first formed in a stagnant/squishy lid geodynamic regime characterised by plume-related magmatic underplating. Such cratonic growth and maturation were prerequisites for the emergence of plate tectonics. Finally, these data suggest that North China was part of the Sclavia supercraton and that the Archaean onset of subduction occurred asynchronously worldwide.

6.
Animals (Basel) ; 14(14)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39061520

RESUMO

The tiger pufferfish (Takifugu rubripes), also known as fugu, has recently suffered from severe C. irritans infections under aquaculture environment, yet the underlying immune mechanisms against the parasite remain poorly understood. In this study, we conducted a comprehensive transcriptome analysis of the gill tissue from infected and uninfected fish using PacBio long-read (one pooled sample each for seriously infected and healthy individuals, respectively) and Illumina short-read (three pools for mildly infected, seriously infected, and healthy individuals, respectively) RNA sequencing technologies. After aligning sequence data to fugu's reference genome, 47,307 and 34,413 known full-length transcripts were identified and profiled in healthy and infected fish, respectively. Similarly, we identified and profiled 1126 and 803 novel genes that were obtained from healthy and infected fish, respectively. Interestingly, we found a decrease in the number of alternative splicing (AS) events and long non-coding RNAs (lncRNAs) after infection with C. irritans, suggesting that they may be involved in the regulation of the immune response in fugu. There were 687 and 1535 differentially expressed genes (DEGs) in moderately and heavily infected fish, respectively, compared to uninfected fish. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that immune-related DEGs in the two comparison groups were mainly enriched in cytokine-cytokine receptor interactions, ECM-receptor interactions, T-cell receptor signaling pathways, Th1 and Th2 cell differentiation, and Th17 cell differentiation pathways. Further analysis revealed that a large number of immune-related genes were downregulated in infected fish relative to uninfected ones, such as CCR7, IL7R, TNFRSF21, CD4, COL2A1, FOXP3B, and ITGA8. Our study suggests that C. irritans is potentially a highly efficient parasite that may disrupt the defense mechanisms of fugu against it. In addition, in combination of short-read RNA sequencing and previous genome-wide association analyses, we identified five key genes (NDUFB6, PRELID1, SMOX, SLC25A4, and DENND1B) that might be closely associated with C. irritans resistance. This study not only provides valuable resources of novel genic transcripts for further research, but also provides new insights into the immune mechanisms underlying C. irritans infection response in farmed fugu.

7.
Environ Sci Technol ; 58(23): 10388-10397, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38828512

RESUMO

Selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3-SCR) is an efficient NOx reduction strategy, while the denitrification (deNOx) catalysts suffer from serious deactivation due to the coexistence of multiple poisoning substances, such as alkali metal (e.g., K), SO2, etc., in industrial flue gases. It is essential to understand the interaction among various poisons and their effects on the deNOx process. Herein, the ZSM-5 zeolite-confined MnSmOx mixed (MnSmOx@ZSM-5) catalyst exhibited better deNOx performance after the poisoning of K, SO2, and/or K&SO2 than the MnSmOx and MnSmOx/ZSM-5 catalysts, the deNOx activity of which at high temperature (H-T) increased significantly (>90% NOx conversion in the range of 220-480 °C). It has been demonstrated that K would occupy both redox and acidic sites, which severely reduced the reactivity of MnSmOx/ZSM-5 catalysts. The most important, K element is preferentially deposited at -OH on the surface of ZSM-5 carrier due to the electrostatic attraction (-O-K). As for the K&SO2 poisoning catalyst, SO2 preferred to be combined with the surface-deposited K (-O-K-SO2ads) according to XPS and density functional theory (DFT) results, the poisoned active sites by K would be released. The K migration behavior was induced by SO2 over K-poisoned MnSmOx@ZSM-5 catalysts, and the balance of surface redox and acidic site was regulated, like a synergistic promoter, which led to K-poisoning buffering and activity recovery. This work contributes to the understanding of the self-detoxification interaction between alkali metals (e.g., K) and SO2 on deNOx catalysts and provides a novel strategy for the adaptive use of one poisoning substance to counter another for practical NOx reduction.


Assuntos
Zeolitas , Zeolitas/química , Catálise , Oxirredução , Óxidos de Nitrogênio/química , Óxidos/química , Amônia/química , Desnitrificação , Metais/química
8.
Environ Res ; 258: 119284, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823618

RESUMO

High concentrations of PM2.5 with enriched levels of metallic constituents could significantly affect the health and comfort of metro employees. To avoid overestimating the exposure risks, we investigated the bioaccessibility of toxic metals (TMs) bound in PM2.5 from the Nanchang metro using Gamble's solution method, and qualitatively analyzed the impact of valence state and various sources on the bioaccessibility of TMs bound to PM2.5. The results showed that the bioaccessibility of the studied TMs ranged from 2.1% to 88.1%, with As, Ba, Co and Pb being the most bioaccessible and V, Fe and Cr being the less bioaccessible. The bioaccessibility of TMs in our subway PM2.5 samples varied based on their valence and species, showing higher valence states associated with increased bioaccessibility. Vehicle traffic, secondary aerosols and wheel/rail sources were found to be significantly and positively associated with the bioaccessibility of several TMs, implying a severe potential risk from these three sources. Although both non-carcinogenic and carcinogenic risks associated with total TMs were found to be high, only As and Cr(VI) posed a considerable carcinogenic risk to metro workers based on the bioaccessible fractions and were therefore priority pollutants. In addition, potential carcinogenic risk was found to be more severe in platform than that in ticket counter. The results indicate that considerable efforts are required to control and manage PM2.5 and the associated TMs in the Nanchang subway, particularly from traffic, wheel/rail and secondary sources, to protect the health of metro staff and the public.


Assuntos
Exposição Ocupacional , Material Particulado , Material Particulado/análise , Medição de Risco , Humanos , Exposição Ocupacional/análise , China , Ferrovias , Poluentes Atmosféricos/análise , Metais/análise , Monitoramento Ambiental/métodos
9.
Plant Commun ; : 100939, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725245

RESUMO

Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in the plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE, CarE10, that is specifically expressed in salivary glands and is secreted into the rice phloem as a saliva component. Leafhopper CarE10 directly binds to rice jasmonate resistant 1 (JAR1) and promotes its degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 clearly impairs JAR1 enzyme activity for conversion of JA to JA-Ile in an in vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes the co-secretion of virions and CarE10 via virus-induced vesicles into the saliva-storing salivary cavities of the leafhopper vector and ultimately into the rice phloem to establish initial infection. Furthermore, a virus-mediated increase in CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes reduced levels of JAR1 and thus suppresses JA-Ile synthesis, promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insight into how the insect salivary protein CarE10 suppresses host JA-Ile synthesis to promote initial virus transmission in the rice phloem.

10.
Mitochondrial DNA B Resour ; 9(3): 309-313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450410

RESUMO

Ammodendron bifolium, a rare deciduous shrub, is the only species of Ammodendron (Fabaceae) in China, which distributes in Huocheng county, Xinjiang. This study employed high-throughput sequencing technology to assemble the complete chloroplast genome sequence of A. bifolium. The entire length of chloroplast genome is 154,426 bp. It comprises 128 genes, which include 85 protein-coding genes, 35 tRNA genes, and 8 rRNA genes. The A. bifolium chloroplast genome has a GC content of 36.41%. Phylogenetic analysis strongly supported that A. bifolium is sister to the members of the Sophora genus. This study will provide the genetic information data for further phylogenetic studies of Ammodendron.

11.
Microb Biotechnol ; 17(2): e14402, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38393322

RESUMO

Apoptosis-like programmed cell death is associated with fungal development, ageing, pathogenicity and stress responses. Here, to explore the potential of Botrytis cinerea type II inhibitor of apoptosis (IAP) BcBIR1 in elevating the biocontrol efficacy of Coniothyrium minitans, the BcBIR1 gene was heterologously expressed in C. minitans. Results indicated that the strains expressing BcBIR1 had higher rates of conidiation, mycelial growth and biomass growth than the wild-type strain. Moreover, BcBIR1 was found to inhibit apoptosis, indicating its role as an IAP in C. minitans. Under various abiotic stresses, the growth rates of BcBIR1-expressing strains were significantly higher than that of the wild-type strain. Moreover, the conidial survival rate of the BcBIR1-expressing strains treated with ultraviolet irradiation was enhanced. In antifungal activity assay, the culture filtrates of BcBIR1-expressing strains displayed a stronger inhibitory effect on B. cinerea and Sclerotinia sclerotiorum than the wild-type strain. The study also found that BcBIR1 expression increased the mycoparasitism against the sclerotia, but not the hyphae of S. sclerotiorum. Taken together, these results suggest that BcBIR1 enhances vegetative growth, conidiation, anti-apoptosis activity, abiotic stress resistance, antifungal activity and mycoparasitism in C. minitans. As an IAP, BcBIR1 may improve the control capacity of C. minitans against S. sclerotiorum.


Assuntos
Antifúngicos , Ascomicetos , Botrytis , Botrytis/genética , Apoptose
12.
Ecol Lett ; 27(1): e14339, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037734

RESUMO

Increased atmospheric nitrogen (N) deposition affects biodiversity in terrestrial ecosystems. However, we do not know whether the effects of N on above-ground plant ß-diversity are coupled with changes occurring in the soil seed bank. We conducted a long-term N-addition experiment in a typical steppe and found that above-ground ß-diversity increased and then decreased with increasing N addition, whereas below-ground ß-diversity decreased linearly. This suggests decoupled dynamics of plant communities and their soil seed bank under N enrichment. Species substitution determined above- and below-ground ß-diversity change via an increasing role of deterministic processes with N addition. These effects were mostly driven by differential responses of the above-ground vegetation and the soil seed bank ß-diversities to N-induced changes in environmental heterogeneity, increased soil inorganic N concentrations and soil acidification. Our findings highlight the importance of considering above- and below-ground processes simultaneously for effectively conserving grassland ecosystems under N enrichment.


Assuntos
Ecossistema , Pradaria , Nitrogênio , Plantas , Solo
13.
Nat Plants ; 9(8): 1221-1235, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37550371

RESUMO

The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.


Assuntos
Domesticação , Oryza , Filogenia , Oryza/genética , China , Alelos
14.
Proc Natl Acad Sci U S A ; 120(29): e2305705120, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37428922

RESUMO

The assimilation of antibiotic resistance genes (ARGs) by pathogenic bacteria poses a severe threat to public health. Here, we reported a dual-reaction-site-modified CoSA/Ti3C2Tx (single cobalt atoms immobilized on Ti3C2Tx MXene) for effectively deactivating extracellular ARGs via peroxymonosulfate (PMS) activation. The enhanced removal of ARGs was attributed to the synergistic effect of adsorption (Ti sites) and degradation (Co-O3 sites). The Ti sites on CoSA/Ti3C2Tx nanosheets bound with PO43- on the phosphate skeletons of ARGs via Ti-O-P coordination interactions, achieving excellent adsorption capacity (10.21 × 1010 copies mg-1) for tetA, and the Co-O3 sites activated PMS into surface-bond hydroxyl radicals (•OHsurface), which can quickly attack the backbones and bases of the adsorbed ARGs, resulting in the efficient in situ degradation of ARGs into inactive small molecular organics and NO3. This dual-reaction-site Fenton-like system exhibited ultrahigh extracellular ARG degradation rate (k > 0.9 min-1) and showed the potential for practical wastewater treatment in a membrane filtration process, which provided insights for extracellular ARG removal via catalysts design.


Assuntos
Antibacterianos , Genes Bacterianos , Antibacterianos/farmacologia , Cobalto , Titânio/farmacologia , Adsorção , Águas Residuárias , Resistência Microbiana a Medicamentos/genética
15.
Clin Exp Pharmacol Physiol ; 50(9): 719-727, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37311598

RESUMO

Chronic intermittent hypoxia (CIH) mimicking obstructive sleep apnea elicits divergent outcomes in the cardiovascular systems. The effect of renal denervation (RDN) on the heart during CIH remains unclear. We aimed to explore the effect of RDN on cardiac remodelling in rats exposed to CIH and to discuss the underlying mechanisms. Adult Sprague Dawley rats were divided into four groups: control, control+RDN, CIH (CIH exposure for 6 weeks, nadir of 5%-7% to peak of 21% O2, 20 cycles/h, 8 h/day) and CIH+ RDN group. Echocardiography, cardiac fibrosis, left ventricle (LV) expressions of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inflammatory factors were tested at the end of the study. Cardiac structural remodelling and dysfunction were induced by CIH and attenuated by RDN. Myocardial fibrosis was more severe in the CIH group than in the control group and improved in the CIH + RDN group. Sympathetic activity reflected by tyrosine hydroxylase (TH) expression and noradrenaline were significantly elevated after CIH but blunted by RDN. CIH downregulated LV protein expressions of Nrf2 and HO-1, which was activated by RDN. The downstream of Nrf2/HO-1, such as NQO1 and SOD expression, elevated following RDN. RDN also decreased the mRNA expression of IL-1ß and IL-6. Notably, control+RDN did not affect cardiac remodelling and Nrf2/HO-1 compared with the control. Taken together, we found that RDN exerted cardio-protective effects in a rat model of CIH involving Nrf2/HO-1 pathway and inflammation.


Assuntos
Cardiomiopatias , Remodelação Ventricular , Ratos , Animais , Ratos Sprague-Dawley , Fator 2 Relacionado a NF-E2 , Hipóxia , Denervação
16.
Environ Sci Pollut Res Int ; 30(36): 85466-85481, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37386225

RESUMO

Green technological innovation has gained in importance in regional policy making towards gaining competitive advantage and sustainable development. This paper used the data envelopment analysis method to calculate regional green innovation efficiency in China, and empirically tested the effect of fiscal decentralization through Tobit model. The regression results show that the local governments with higher fiscal autonomy would prefer to strengthen environmental protection; thus, the regional green innovation efficiency was improved. After the guidance of relevant national development strategies, these effects became more apparent. Our research provided theoretical support and practical guidance for promoting regional led green innovation, improving environmental quality, achieving carbon neutrality, and promoting the high-quality and sustainable development.


Assuntos
Conservação dos Recursos Naturais , Governo Local , Desenvolvimento Sustentável , China , Eficiência , Política , Desenvolvimento Econômico , Política Ambiental
17.
Sleep Breath ; 27(5): 1769-1777, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36719525

RESUMO

OBJECTIVE: To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury. METHODS: Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O2 concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively. RESULTS: Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-ß1 and tumor necrosis factor-alpha in the aorta. CONCLUSION: SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.


Assuntos
Microbioma Gastrointestinal , Ratos , Animais , Ratos Sprague-Dawley , Hipóxia/patologia , Valsartana/farmacologia
18.
Mol Cancer Ther ; 22(2): 215-226, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228090

RESUMO

CRISPR Cas9-based screening is a powerful approach for identifying and characterizing novel drug targets. Here, we elucidate the synthetic lethal mechanism of deubiquitinating enzyme USP1 in cancers with underlying DNA damage vulnerabilities, specifically BRCA1/2 mutant tumors and a subset of BRCA1/2 wild-type (WT) tumors. In sensitive cells, pharmacologic inhibition of USP1 leads to decreased DNA synthesis concomitant with S-phase-specific DNA damage. Genome-wide CRISPR-Cas9 screens identify RAD18 and UBE2K, which promote PCNA mono- and polyubiquitination respectively, as mediators of USP1 dependency. The accumulation of mono- and polyubiquitinated PCNA following USP1 inhibition is associated with reduced PCNA protein levels. Ectopic expression of WT or ubiquitin-dead K164R PCNA reverses USP1 inhibitor sensitivity. Our results show, for the first time, that USP1 dependency hinges on the aberrant processing of mono- and polyubiquitinated PCNA. Moreover, this mechanism of USP1 dependency extends beyond BRCA1/2 mutant tumors to selected BRCA1/2 WT cancer cell lines enriched in ovarian and lung lineages. We further show PARP and USP1 inhibition are strongly synergistic in BRCA1/2 mutant tumors. We postulate USP1 dependency unveils a previously uncharacterized vulnerability linked to posttranslational modifications of PCNA. Taken together, USP1 inhibition may represent a novel therapeutic strategy for BRCA1/2 mutant tumors and a subset of BRCA1/2 WT tumors.


Assuntos
Neoplasias , Mutações Sintéticas Letais , Humanos , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ubiquitina/genética , Ubiquitinação , Dano ao DNA , Neoplasias/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
19.
Glob Chang Biol ; 29(4): 1144-1159, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36349544

RESUMO

Specific leaf area (SLA) is one of the most important plant functional traits. It integrates multiple functions and reflects strategies of plants to obtain resources. How plants employ different strategies (e.g., through SLA) to respond to dynamic environmental conditions remains poorly understood. This study aimed to explore the spatial variation in SLA and its divergent adaptation through the lens of biogeographic patterns, evolutionary history, and short-term responses. SLA data for 5424 plant species from 76 natural communities in China were systematically measured and integrated with meta-analysis of field experiments (i.e., global warming, drought, and nitrogen addition). The mean value of SLA across all species was 21.8 m2  kg-1 , ranging from 0.9 to 110.2 m2  kg-1 . SLA differed among different ecosystems, temperature zones, vegetation types, and functional groups. Phylogeny had a weak effect on SLA, but plant species evolved toward higher SLA. Furthermore, SLA responded nonlinearly to environmental change. Unexpectedly, radiation was one of the main factors determining the spatial variation in SLA on a large scale. Conversely, short-term manipulative experiments showed that SLA increased with increased resource availability and tended to stabilize with treatment duration. However, different species exhibited varying response patterns. Overall, variation in long-term adaptation of SLA to environmental gradients and its short-term response to resource pulses jointly improve plant adaptability to a changing environment. Overall SLA-environment relationships should be emphasized as a multidimensional strategy for elucidating environmental change in future research.


Assuntos
Ecossistema , Plantas , Aclimatação , Temperatura , Folhas de Planta/fisiologia
20.
J Clin Hypertens (Greenwich) ; 24(12): 1598-1605, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36411588

RESUMO

We investigated the alteration of gut microbiota and the associated metabolic risks in hypertensive patients with obstructive sleep apnea (OSA) comorbidity. Fecal and blood samples were collected from 52 hypertensive patients, who were divided into three groups: A (controls, apnea-hypopnea index[AHI] < 5, n = 15), B (mild OSA, 5 < AHI < 20, n = 17), and C (moderate-to-severe OSA, AHI > 20, n = 20). The composition of the gut microbiota was studied through 16s RNA sequencing of variable regions 3-4. Analysis of the results revealed that group C had a significant higher concentration of total cholesterol, low-density lipoprotein, and IL-1ß compared with group A. The Shannon index showed that bacterial biodiversity was lower in OSA patients. At the phylum level, the ratio of Firmicutes to Bacteroidetes (F/B) was significantly higher in group C than in groups A and B. At the genus level, the relative abundance of short-chain fatty acids (SCFA)-producing bacteria (e.g., Bacteroides and Prevotella) was lower while the number of inflammation-related bacteria (e.g., Lactobacillus) was increased in patients with OSA. We found that the IL-1ß level was negatively correlated with Bacteroidetes. The area under the receiver operating characteristic curve was .672 for F/B ratio in determining hypertensive patients with OSA. In patients with hypertension, OSA was associated with worse gut dysbiosis, as evidenced by decreased levels of short-chain fatty acids-producing bacteria and increased number of inflammation-related bacteria. The differences in gut microbiota discriminate hypertensive patients with OSA from those without and may result in an enhanced inflammatory response and increase the risk of metabolic diseases.


Assuntos
Hipertensão , Apneia Obstrutiva do Sono , Humanos , Hipertensão/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Ácidos Graxos Voláteis
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