Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.390
Filtrar
1.
Nat Commun ; 15(1): 4692, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824127

RESUMO

Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

2.
J Cell Mol Med ; 28(11): e18443, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837873

RESUMO

The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5se/J and Prkralear-3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.


Assuntos
Movimento Celular , Condrócitos , Microtia Congênita , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac1 de Ligação ao GTP , Animais , Feminino , Humanos , Masculino , Camundongos , Condrócitos/metabolismo , Condrócitos/citologia , Microtia Congênita/metabolismo , Microtia Congênita/genética , Microtia Congênita/patologia , Modelos Animais de Doenças , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/genética
3.
BMJ Glob Health ; 9(6)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857946

RESUMO

The use of traditional medicine is a global phenomenon, and the WHO advocated its appropriate integration into modern healthcare systems. However, there is a hot debate about the legitimacy of traditional medicine among the general public. Here, we investigated the debate in the Chinese digital context by analysing 1954 responses related to 100 questions about traditional Chinese medicine (TCM) treatment against COVID-19 on the Zhihu platform. Attitude function theory was applied to understand the reasons underlying public attitudes.Results showed that Zhihu users generally held a supportive attitude toward TCM. Their attitudes mainly came from their own experience and traditional media. The general users were more negative while medical professionals were more positive toward TCM. Ego defence (eg, derogating evidence sources) was used the most to support attitudes, followed by value expression (eg, believing in science). Supporters showed fewer expressions of faith (eg, the use of TCM is a kind of faith), politics (eg, supporting TCM is about politics) and science value (eg, TCM is a field of science), fewer ego defence, more patriotism and cultural confidence expressions (eg, TCM is a cultural pride) and more knowledge explanation (eg, TCM accelerates the metabolism of phlegm) than expected. Opposers showed fewer utilitarian and knowledge functions, fewer expressions of patriotism and more expressions of faith, politics and economics, but more ego defence functions than expected. Opposing posts were more likely to attract engagement than supporting and neutral posts. Posts that mentioned attitude functions generally attracted more engagement.Our findings indicate that TCM debate in modern China is not only relevant to medical science and health, but also rooted deeply in cultural ideology, politics and economics. The findings can provide global insights into the development of proactive policies and action plans that will help the integration of traditional medicine into modern healthcare systems.


Assuntos
COVID-19 , Medicina Tradicional Chinesa , SARS-CoV-2 , Humanos , China , Rede Social , Opinião Pública , Tratamento Farmacológico da COVID-19 , Masculino , Adulto , Feminino
4.
Front Bioeng Biotechnol ; 12: 1366408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840667

RESUMO

Purpose: This study aims to investigate the differences in binocular corneal parameters and their interrelation with binocular biometric parameters asymmetry in patients with simple myopic anisometropia, thereby elucidating the influence of myopia process on various corneal parameters. Methods: In this cross-sectional study, 65 patients with anisometropia in monocular myopia were included. They were divided into low anisometropia group: 3.00D<Δ spherical equivalent (SE)≤-1.00D (Δ represents the difference between the two eyes, i.e., myopic data minus emmetropic data) and high anisometropia group: ΔSE ≤ -3.00D. Corneal and ocular biometric parameters were measured using Pentacam, Corvis ST, and IOL Master 700. Statistical analyses focused on the binocular corneal parameters asymmetry, using the contralateral emmetropia as a control. Results: The mean age of participants was 18.5 ± 1.3 years, with the average SE for myopia and emmetropia being -2.93 ± 1.09D and -0.16 ± 0.41D, respectively. The central corneal thickness (CCT), flat keratometry (Kf), keratometry astigmatism (Ka), total corneal aberration (6 mm) (TOA), surface variance index (ISV), vertical asymmetry index (IVA), stress-strain index (SSI), and first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) showed significant differences between anisometropic fellow eyes (p < 0.05). There were significant differences in ΔIVA, Δ the difference between the mean refractive power of the inferior and superior corneas (I-S), Δ deviation value of Belin/Ambrósio enhanced ectasia display (BAD-D), Δ deformation amplitude ratio max (2 mm) (DAR)and Δ tomographic biomechanical index (TBI) (p < 0.05) in two groups. Asymmetry of corneal parameters was correlated with asymmetry of ocular biometric parameters. Anisometropia (ΔSE) was positively correlated with ΔIVA (r = 0.255, p = 0.040), ΔBAD-D (r = 0.360, p = 0.006), and ΔSSI (r = 0.276, p = 0.039) and negatively correlated with ΔDAR (r = -0.329, p = 0.013) in multiple regression analysis. Δ mean keratometry (Km), Δ anterior chamber depth (ACD), and Δ biomechanically corrected intraocular pressure (bIOP) were also associated with binocular corneal differences. Conclusion: Compared to contralateral emmetropia, myopic eyes have thinner corneas and smaller corneal astigmatism. Myopic corneas exhibit relatively more regular surface morphology but are more susceptible to deformation and possess marginally inferior biomechanical properties. In addition, there is a certain correlation between anisometropia and corneal parameter asymmetry, which would be instrumental in predicting the development of myopia.

5.
Heliyon ; 10(11): e31677, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841453

RESUMO

Background: Metagenomic next-generation sequencing (mNGS) of plasma DNA has become an attractive diagnostic method for infectious diseases; however, the rate of false-positive results is high. This study aims to evaluate the diagnostic accuracy of mNGS in plasma versus blood cell samples for immunocompromised children with febrile diseases. Methods: The results of conventional microbiological test (CMT) and mNGS using plasma and blood cells in 106 patients with 128 episodes of febrile diseases from the Department of Hematology/Oncology were analyzed and described. Results: The positivity rates for CMT and mNGS of plasma and blood cells were 35.9 %, 84.4 % and 46.9 %, respectively (P < 0.001). Notably, mNGS identified multiple pathogens in a single specimen in 68.5 % of plasma samples and 38.3 % of blood cell samples (P < 0.001). Furthermore, plasma and blood cell mNGS identified causative pathogens in 58 and 46 cases, accounting for 53.7 % and 76.7 % of the mNGS-positive cases for each sample type, respectively (P = 0.002). By integrating results from both plasma and blood cell samples, causative pathogens were identified in 77 cases (60.2 %), enhancing sensitivity to 87.5 % but reducing specificity to 15.0 %, compared to plasma (65.9 % sensitivity and 20.0 % specificity) and blood cell samples (52.3 % sensitivity and 80.0 % specificity). Conclusions: mNGS of plasma is sensitive but has a high false-positive rate, while mNGS of blood cells has low sensitivity but higher specificity.

6.
Ecotoxicol Environ Saf ; 280: 116557, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38850695

RESUMO

Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.

7.
Carbohydr Polym ; 339: 122214, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823900

RESUMO

The polysaccharide, RGP2, was isolated from Russula griseocarnosa and its immunostimulatory effects were confirmed in cyclophosphamide (CTX)-induced immunosuppressed mice. Following purification via chromatography, structural analysis revealed that RGP2 had a molecular weight of 11.82 kDa and consisted of glucose (Glc), galactose (Gal), mannose, glucuronic acid and glucosamine. Bond structure analysis and nuclear magnetic resonance characterization confirmed that the main chain of RGP2 was formed by →6)-ß-D-Glcp-(1→, →3)-ß-D-Glcp-(1→ and →6)-α-D-Galp-(1→, which was substituted at O-3 of →6)-ß-D-Glcp-(1→ by ß-D-Glcp-(1→. RGP2 was found to ameliorate pathological damage in the spleen and enhance immune cell activity in immunosuppressed mice. Based on combined multiomics analysis, RGP2 altered the abundance of immune-related microbiota (such as Lactobacillus, Faecalibacterium, and Bacteroides) in the gut and metabolites (uridine, leucine, and tryptophan) in the serum. Compared with immunosuppressed mice, RGP2 also restored the function of antigen-presenting cells, promoted the polarization of macrophages into the M1 phenotype, positively affected the differentiation of helper T cells, and inhibited regulatory T cell differentiation through the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, ultimately exerting an immune boosting function. Overall, our findings highlight therapeutic strategies to alleviate CTX-induced immunosuppression in a clinical setting.


Assuntos
Basidiomycota , Diferenciação Celular , Glucanos , Animais , Camundongos , Basidiomycota/química , Glucanos/química , Glucanos/farmacologia , Glucanos/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Masculino , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Ciclofosfamida/farmacologia , Camundongos Endogâmicos BALB C , Microbioma Gastrointestinal/efeitos dos fármacos
8.
J Colloid Interface Sci ; 672: 142-151, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38833734

RESUMO

The remarkable optical properties of carbon dots, particularly their tunable room-temperature phosphorescence, have garnered significant interest. However, challenges such as aggregation propensity and complex phosphorescence control via energy level manipulation during synthesis persist. Addressing these issues, we present a facile gel platform for tunable afterglow materials. This involves chemically cross-linking biomass-derived silicon-doped carbon dots with carboxymethylcellulose and incorporating non-precious metal salts (BaCl2, CaCl2, MgCl2, ZnCl2, ZnBr2, ZnSO4) to enhance phosphorescence. Metal salts boost intersystem crossing via spin-orbit coupling, elevating triplet state transitions and activating phosphorescence. Chemical bonding and salt-induced coordination/electrostatic interactions establish confinement effects, suppressing non-radiative transitions. Diverse salt-gel interactions yield gels with tunable phosphorescence lifetimes (9.48 ms to 32.13-492.39 ms), corresponding to afterglow durations ranging from 3.20 to 11.86 s. With its broad tunability and high recognition, this gel material exhibits promising potential for dynamic multilevel anti-counterfeiting applications.

9.
Clin Nutr ESPEN ; 63: 2-12, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38879879

RESUMO

BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

10.
Nat Commun ; 15(1): 5080, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871724

RESUMO

The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

11.
Biol Res Nurs ; : 10998004241261273, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881252

RESUMO

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00522340.

12.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38892361

RESUMO

Sophora alopecuroides has important uses in medicine, wind breaking, and sand fixation. The CHY-zinc-finger and RING-finger (CHYR) proteins are crucial for plant growth, development, and environmental adaptation; however, genetic data regarding the CHYR family remain scarce. We aimed to investigate the CHYR gene family in S. alopecuroides and its response to abiotic stress, and identified 18 new SaCHYR genes from S. alopecuroides whole-genome data, categorized into 3 subclasses through a phylogenetic analysis. Gene structure, protein domains, and conserved motifs analyses revealed an exon-intron structure and conserved domain similarities. A chromosome localization analysis showed distribution across 12 chromosomes. A promoter analysis revealed abiotic stress-, light-, and hormone-responsive elements. An RNA-sequencing expression pattern analysis revealed positive responses of SaCHYR genes to salt, alkali, and drought stress. SaCHYR4 overexpression considerably enhanced alkali and drought tolerance in Arabidopsis thaliana. These findings shed light on SaCHYR's function and the resistance mechanisms of S. alopecuroides, presenting new genetic resources for crop resistance breeding.


Assuntos
Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas , Sophora , Estresse Fisiológico , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sophora/genética , Arabidopsis/genética , Genoma de Planta , Secas , Cromossomos de Plantas/genética
13.
Nat Microbiol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886584

RESUMO

Cyst nematodes are the most damaging species of plant-parasitic nematodes. They antagonize the colonization of beneficial microbial symbionts that are important for nutrient acquisition of plants. The molecular mechanism of the antagonism, however, remains elusive. Here, through biochemical combined with structural analysis, we reveal that Heterodera glycines, the most notorious soybean cyst nematode, suppresses symbiosis by secreting an enzyme named HgCht2 to hydrolyse the key symbiotic signalling molecules, lipochitooligosaccharides (LCOs). We solved the three-dimensional structures of apo HgCht2, as well as its chitooligosaccharide-bound and LCO-bound forms. These structures elucidated the substrate binding and hydrolysing mechanism of the enzyme. We designed an HgCht2 inhibitor, 1516b, which successfully suppresses the antagonism of cyst nematodes towards nitrogen-fixing rhizobia and phosphorus-absorbing arbuscular mycorrhizal symbioses. As HgCht2 is phylogenetically conserved across all cyst nematodes, our study revealed a molecular mechanism by which parasitic cyst nematodes antagonize the establishment of microbial symbiosis and provided a small-molecule solution.

14.
Opt Express ; 32(10): 17388-17399, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858923

RESUMO

Aiming at the problem of luminance uniformity for injection electroluminescent display panels, we present a new sample compensation method based on column-control according to successive scans theory. On the basis of our ideas, a small part of pixels of each column are selected as samples, and the column gating time calculated by sample average luminance value of corresponding column is written in hardware program. We adopt the 64 × 32 LEDs display panel as an example to expound the compensation method and obtain good result that the reduction in amplitude of luminance non-uniformity is 65.42% for the sample area, 58.67% for the non-sample area and 60.21% for the entire display panel.

15.
Talanta ; 277: 126379, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852343

RESUMO

Mercury (Hg) is a notorious toxic heavy metal, causing neurotoxicity and liver damage, posing grave threats to human health and environmental safety. There is an urgent imperative for developing novel Hg2+ detection methods. In this work, we developed a CRISPR-based method for Hg2+ detection named CRISPR-Hg. A CRISPR/Cas12a system was employed and could be activated by the PCR product, generating fluorescence signals based on the trans-cleavage activity. CRISPR-Hg exhibited remarkable selectivity and specificity, achieving a detection limit of 10 pM and minimal interference with background signals. This approach has been successfully applied to detect Hg2+ in real samples, including water, soil, and mushroom. Ulteriorly, a portable device was devised to streamline the readout of fluorescence signals by a smartphone within 30 min. We offer an affordable, highly selective and visually interpretable method for Hg2+ detection, with the potential for broad application in Hg2+ monitoring for food safety and public health.

16.
Vet Microbiol ; 295: 110153, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889618

RESUMO

Bovine leukemia virus (BLV) is a widespread virus that decreases milk production and quality in dairy cows. As crucial components of BLV, BLV-encoded microRNAs (BLV-miRNAs) affect BLV replication and may impact the synthesis of Lactoferrin (LTF), Lactoperoxidase (LPO), Alpha-lactalbumin (alpha-LA), and Beta-lactoglobulin (beta-LG). In this study, we investigated the targeting relationship between BLV-miRNAs and LTF, LPO, alpha-LA, and beta-LG in cow's milk. Additionally, we investigated the possible mechanisms by which BLV reduces milk quality. The results showed that cow's milk had significantly lower levels of LTF, LPO, and alpha-LA proteins in BLV-positive cows than in BLV-negative cows. BLV-△miRNAs (miRNA-deleted BLV) enhanced the reduction of LPO, alpha-LA, and beta-LG protein levels caused by BLV infection. Multiple BLV-miRNAs have binding sites with LTF and LPO mRNA; however, only BLV-miR-B1-5 P has a targeting relationship with LPO mRNA. The results revealed that BLV-miR-B1-5 P inhibits LPO protein expression by targeting LPO mRNA. However, BLV does not directly regulate the expression of LTF, alpha-LA, or beta-LG proteins through BLV-miRNAs.

17.
Vascular ; : 17085381241254428, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797865

RESUMO

BACKGROUND: Carotid body tumors extending to the skull base are hypervascular tumors which are difficult to access using a traditional lateral cervical approach. Preoperative embolization can reduce intraoperative blood loss. CASE PRESENTATION: We report two patients with a carotid body tumor extending to the skull base who underwent preoperative embolization of the external carotid artery using an Amplatzer vascular plug. Two days after embolization, surgical resection was performed. Embolization was successful in both patients and resection proceeded smoothly. Both were discharged on postoperative day 9 without complications. The tumor in each patient was classified as Shamblin group III. Computed tomography angiography of the neck six months after surgery showed patency of the ipsilateral internal carotid artery and no tumor recurrence. CONCLUSION: Preoperative embolization of the external carotid artery using the Amplatzer vascular plug is safe and feasible for patients with carotid body tumors extending to the skull base.

18.
PLoS Pathog ; 20(5): e1012187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718038

RESUMO

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Klebsiella pneumoniae , RNA Bacteriano , Pequeno RNA não Traduzido , beta-Lactamases , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Regulação Bacteriana da Expressão Gênica , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética
19.
Nat Commun ; 15(1): 4534, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806482

RESUMO

We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

20.
Front Nutr ; 11: 1380727, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812930

RESUMO

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (-0.39 mmol), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison<0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (-29.1 U/L and - 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both p < 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...