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High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.
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Genoma de Planta , Seleção Genética , Adaptação Fisiológica/genética , AltitudeRESUMO
Archaeal ribosomes have many domain-specific features; however, our understanding of these structures is limited. We present 10 cryo-electron microscopy (cryo-EM) structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac) at 2.7-5.7 Å resolution. We observed unstable conformations of H68 and h44 of ribosomal RNA (rRNA) in the subunit structures, which may interfere with subunit association. These subunit structures provided models for 12 rRNA expansion segments and 3 novel r-proteins. Furthermore, the 50S-aRF1 complex structure showed the unique domain orientation of aRF1, possibly explaining P-site transfer RNA (tRNA) release after translation termination. Sac 70S complexes were captured in seven distinct steps of the tRNA translocation reaction, confirming conserved structural features during archaeal ribosome translocation. In aEF2-engaged 70S ribosome complexes, 3D classification of cryo-EM data based on 30S head domain identified two new translocation intermediates with 30S head domain tilted 5-6° enabling its disengagement from the translocated tRNA and its release post-translocation. Additionally, we observed conformational changes to aEF2 during ribosome binding and switching from three different states. Our structural and biochemical data provide new insights into archaeal translation and ribosome translocation.
Archaeal ribosomes display variations in their ribosomal proteins and ribosomal RNA (rRNA) expansion segments (ESs). Protein translation in archaea combines features in both bacterial and eukaryotic translation. In this study, we present 10 cryo-electron microscopy structures of the archaeal ribosome from crenarchaeota Sulfolobus acidocaldarius (Sac). The 50S and 30S subunit structures present 3 novel ribosomal proteins and 12 rRNA ESs. The 70S Sac ribosome structures were captured in seven distinct functional states, including pre-, intermediate- and post-translocation states. Specifically, we identified two novel translocation intermediates, in which the 30S subunit head domain tilts outward to release the translocated P-site transfer RNA. The structures of archaeal ribosomes provide insights into the archaeal translation and ribosome translocation.
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Ribossomos , Sulfolobus acidocaldarius , Microscopia Crioeletrônica , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , RNA Ribossômico/metabolismo , RNA de Transferência/metabolismo , Sulfolobus acidocaldarius/citologia , Sulfolobus acidocaldarius/metabolismoRESUMO
BACKGROUND: Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family's largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria's taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. RESULTS: This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK-rps16, trnC-petN, petN-psbM, accD-psaI, petA-psbJ, rpl32-trnL, ccsA-ndhD, rps15-ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. CONCLUSIONS: The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.
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Genoma de Cloroplastos , Filogenia , Scutellaria , Scutellaria/genéticaRESUMO
The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor immune cells impede the infiltration and killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) and lysyl oxidase inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. The conjugated organic ligand and well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 and H2O2 to ·O2- and ·OH. This surge of reactive oxygen species (ROS) leads to impaired mitochondrial function and insufficient ATP supply, impacting the function of copper-transporting ATPase-1 and causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms and glutathione peroxidase 4 depletion also induce lipid peroxidation and trigger ferroptosis. Simultaneously, the ROS-triggered release of LOX-IN-3 reshapes the ECM by inhibiting lysyl oxidase activity and further enhances the infiltration of cytotoxic T lymphocytes (CD8+ T cells). CHO-triggered cholesterol depletion not only increases ·OH generation but also downregulates the expression of ICs such as PD-1 and TIM-3, restoring the antitumor activity of tumor-infiltrating CD8+ T cells. Therefore, Cu-DBCO/CL exhibits efficient properties in activating a potent antitumor immune response by cascade-enhanced CD8+ T cell viability. More importantly, ECM remodeling and cholesterol depletion could suppress the metastasis and proliferation of the tumor cells. In short, this immune nanoremodeler can greatly enhance the infiltration and antitumor activity of T cells by enhancing tumor immunogenicity, remodeling ECM, and downregulating ICs, thus achieving effective inhibition of tumor growth and metastasis.
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Linfócitos T CD8-Positivos , Neoplasias , Humanos , Proteína-Lisina 6-Oxidase , Cobre , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Colesterol , Linhagem Celular Tumoral , Imunoterapia , Microambiente TumoralRESUMO
Obtaining a robust phylogeny proves challenging due to the intricate evolutionary history of species, where processes such as hybridization and incomplete lineage sorting can introduce conflicting signals, thereby complicating phylogenetic inference. In this study, we conducted comprehensive sampling of Elsholtzieae, with a particular focus on its largest genus, Elsholtzia. We utilized 503 nuclear loci and complete plastome sequences obtained from 99 whole-genome sequencing datasets to elucidate the interspecific relationships within the Elsholtzieae. Additionally, we explored various sources of conflicts between gene trees and species trees. Fully supported backbone phylogenies were recovered, and the monophyly of Elsholtzia and Keiskea was not supported. Significant gene tree heterogeneity was observed at numerous nodes, particularly regarding the placement of Vuhuangia and the E. densa clade. Further investigations into potential causes of this discordance revealed that incomplete lineage sorting (ILS), coupled with hybridization events, has given rise to substantial gene tree discordance. Several species, represented by multiple samples, exhibited a closer association with geographical distribution rather than following a strictly monophyletic pattern in plastid trees, suggesting chloroplast capture within Elsholtzieae and providing evidence of hybridization. In conclusion, this study provides phylogenomic insights to untangle taxonomic problems in the tribe Elsholtzieae, especially the genus Elsholtzia.
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Hibridização Genética , Lamiaceae , Filogenia , Lamiaceae/genética , Lamiaceae/classificação , Genoma de PlantaRESUMO
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Exosomes (Exo) derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) have been demonstrated to be an effective therapy for DKD, but the underlying mechanisms of this action remain poorly defined. We investigated the association of DKD with inflammasome activation and the pathophysiological relevance of Exo-mediated inflammation relief as well as damage repair in this progression. We co-cultured podocytes and HUC-MSCs derived Exo (MSCs-Exo) under high glucose (HG) and injected MSCs-Exo into diabetic mice, then we detected the NLRP3 inflammasome both in vitro and in vivo. We found that HG reduced the viability of podocytes, activated the NLRP3 signaling pathway and increased inflammation in podocytes and diabetic mice. MSCs-Exo attenuated the inflammation, including the expression of IL-6, IL-1ß, IL-18, TNF-α; depressed the activation of NLRP3 signaling pathway in podocytes under HG and diabetic mice, ameliorated kidney injury. Furthermore, miR-22-3p, which is relatively highly expressed miRNAs in exosomes of MSCs, may be the key point in this progress, by suppressing the expression of its known target, NLRP3. Knocking down miR-22-3p from MSCs-Exo abolished their anti-inflammation activity and beneficial function both in vitro and in vivo. Collectively, our results have demonstrated that exosomes transferring miR-22-3p protected the podocytes and diabetic mice from inflammation by mediating NLRP3 inflammasome, indicating that MSC-derived exosomes may be a promising therapeutic cell-free strategy for DKD.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Camundongos , Humanos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/terapia , Exossomos/metabolismo , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
Phormia regina (Meigen, 1826) (Diptera: Calliphoridae) can colonize carcasses quickly, and its immature stages are reliable entomological evidence for the estimation of the minimum postmortem interval (PMImin). There are discrepancies in the developmental data from previous studies on P. regina, and the related PMImin indicators need to be refined. We investigated the accuracy of forensic entomological evidence using development durations, growth accumulated degree hours, and larval body length variations of P. regina at seven constant temperatures ranging from 16 to 34 °C. We also established development models such as the isomorphen diagram, thermal summation model, isomegalen diagram, and body length simulation equation to assist with PMImin estimation. The developmental duration of P. regina from egg to adult at 16, 19, 22, 25, 28, 31, and 34 °C was 840.8 ± 42.8 h, 580.1 ± 10.1 h, 390.4 ± 8.7 h, 316.8 ± 9.4 h, 291.4 ± 21.2 h, 238.4 ± 2.8 h, and 222.5 ± 5.2 h, respectively. The lower threshold temperature TL was 9.97 ± 0.50 °C, while the thermal constant K was 5052.7 ± 229 degree days. The lower developmental thresholds, intrinsic optimum temperature, and upper lethal developmental threshold obtained by the Optim SSI models were 13.15, 21.20, and 36.86 °C, respectively. This study aims to provide developmental models for P. regina aimed at common case-site temperatures in the northern provinces of China, which can be used for accurate PMImin estimation.
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Dípteros , Ciências Forenses , Humanos , Adulto , Animais , Temperatura , Larva , AutopsiaRESUMO
MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.
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Complexo do Signalossomo COP9 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B , Transdução de Sinais , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Complexo do Signalossomo COP9/metabolismo , Complexo do Signalossomo COP9/genética , NF-kappa B/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Ubiquitinação , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genética , Progressão da Doença , Camundongos Endogâmicos BALB C , Feminino , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Dissolved organic matter (DOM), the most reactive fraction of forest soil organic matter, is increasingly impacted by wildfires worldwide. However, few studies have quantified the temporal changes in soil DOM quantity and quality after fire. Here, soil samples were collected after the Qipan Mountain Fire (3-36 months) from pairs of burned and unburned sites. DOM contents and characteristics were analyzed using carbon quantification and various spectroscopic and spectrometric techniques. Compared with the unburned sites, burned sites showed higher contents of bulk DOM and most DOM components 3 months after the fire but lower contents of them 6-36 months after the fire. During the sharp drop of DOM from 3 to 6 months after the fire, carboxyl-rich alicyclic molecule-like and highly unsaturated compounds had greater losses than condensed aromatics. Notably, the burned sites had consistently higher abundances of oxygen-poor dissolved black nitrogen and fluorescent DOM 3-36 months after the fire, particularly the abundance of pyrogenic C2 (excitation/emission maxima of <250/â¼400 nm) that increased by 150% before gradually declining. This study advances the understanding of temporal variations in the effects of fire on different soil DOM components, which is crucial for future postfire environmental management.
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Incêndios , Solo , Solo/química , China , Incêndios Florestais , FlorestasRESUMO
A comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bonds (H-bonds) on the obscure reaction of a hydroxyl radical (HOË) and guanine (G) by selecting the building block of parallel triplex DNA, C(H+)GC, as the model. By mapping the energy profiles for addition and hydrogen abstraction reactions, the favorable pathway is predicted. The results reveal that in the C(H+)GC context, barrierless hydrogen abstraction from N2 of G leading to a neutral radical G(N2-H)Ë appears to become significant, but electrophilic attack by HOË on C8 of G resulting in 8-oxoG is the most thermodynamically favorable course. This shows a strong structural dependence due to the context constrained by the H-bond, which is dramatically different from the situation in unencumbered G. More interestingly, it proves that the stability order of resulting adduct radicals is not altered by H-bonding, but the activity for possible sites of the hydroxylation reaction changes. The significant influence of the H-bond on elementary reactions involved in the reaction is emphasized in the C(H+)GC context but is not restricted to the H-abstraction reaction. It is greatly anticipated that the present study could provide thoughtful insights into the vague hydroxyl radical-induced oxidation chemistry.
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Silicon photonics devices benefit greatly from a partially etched platform and inverse design. Herein, we propose a bi-layer polarization splitter and rotator with a topology pattern and demonstrate it on a silicon-on-insulator platform. Our device exhibits a significantly reduced physical footprint of only 2µm×6µm, compared to traditional directional couplers and tapered waveguides. The device accomplishes the functions of polarization conversion and separation in such a compact design without redundant tapered or bending waveguides. The tested minimum insertion loss with the fabrication batch reaches 0.57 and 0.67 dB for TE and TM modes, respectively. The TE mode demonstrates a wider bandwidth and lower ILs than the TM modes, averaging around 1 dB from 1530 to 1565 nm. The M modes exhibit approximately 2 dB ILs at the same wavelength range, decreasing to about 1 dB between 1565 and 1580 nm. Improved designs and fabrication conditions strongly suggest the potential for further performance enhancement in the device. This successful initiative validates the exceptional performance resulting from the integration of the partially etched platform and inverse design, providing valuable insights for future photonic integrated device designs.
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AIM: Acute kidney injury is a severe disease that is closely associated with substantial morbidity and mortality. The most common cause of AKI is renal ischemia-reperfusion injury. Mesenchymal stem cells (MSCs) have previously been shown to have renoprotective effects. However, extracellular vesicles secreted by MSCs are thought to be the key for the therapeutic effects of MSCs. This study investigated whether small EVs derived from ACE2-modified human umbilical cord MSCs could alleviate RIRI and explored their underlying molecular mechanisms METHODS: A lentivirus carrying an ACE2 overexpression vector was constructed and used to infect MSCs. The small EVs were isolated from MSC-conditioned medium by ultracentrifugation. HK-2 cells were cocultured with MSC-ACE2-EVs and subjected to hypoxia/reoxygenation injury. MSCs-ACE2-EVs were injected into RIRI mice. Biochemical and morphological characteristics were assessed, and the levels of inflammatory-related factors, oxidative stress products, and apoptosis in HK-2 cells and kidney tissues were assessed RESULTS: In vitro, MSC-ACE2-EVs had stronger anti-inflammatory, antioxidative stress, and antiapoptotic effects in HK-2 cells subjected to H/R than MSC-NC-EVs. In vivo, MSC-ACE2-EVs could target the injured kidney, reduce blood creatinine and urea nitrogen levels, and protect the kidney from I/R, and this effect may have been related to the activation of the Nrf2/HO-1 signalling pathway CONCLUSION: Taken together, our results demonstrated the anti-inflammatory, antioxidative stress, and antiapoptotic effects of MSC-ACE2-EVs, which protected against I/R injury in vitro and vivo. MSC-ACE2-EVs may be therapeutic agents for RIRI.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Humanos , Camundongos , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Rim/metabolismo , Vesículas Extracelulares/fisiologia , Anti-Inflamatórios/metabolismo , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: Sarcopenia and cognitive impairment have been linked in prior research, and both are linked to an increased risk of mortality in the general population. Muscle mass is a key factor in the diagnosis of sarcopenia. The relationship between low muscle mass and cognitive function in the aged population, and their combined impact on the risk of death in older adults, is currently unknown. This study aimed to explore the correlation between low muscle mass and cognitive function in the older population, and the relationship between the two and mortality in older people. METHODS: Data were from the National Health and Nutrition Examination Survey 1999-2002. A total of 2540 older adults aged 60 and older with body composition measures were included. Specifically, 17-21 years of follow-up were conducted on every participant. Low muscle mass was defined using the Foundation for the National Institute of Health and the Asian Working Group for Sarcopenia definitions: appendicular lean mass (ALM) (< 19.75 kg for males; <15.02 kg for females); or ALM divided by body mass index (BMI) (ALM: BMI, < 0.789 for males; <0.512 for females); or appendicular skeletal muscle mass index (ASMI) (< 7.0 kg/m2 for males; <5.4 kg/m2 for females). Cognitive functioning was assessed by the Digit Symbol Substitution Test (DSST). The follow-up period was calculated from the NHANES interview date to the date of death or censoring (December 31, 2019). RESULTS: We identified 2540 subjects. The mean age was 70.43 years (43.3% male). Age-related declines in DSST scores were observed. People with low muscle mass showed lower DSST scores than people with normal muscle mass across all age groups, especially in the group with low muscle mass characterized by ALM: BMI (60-69 years: p < 0.001; 70-79 years: p < 0.001; 80 + years: p = 0.009). Low muscle mass was significantly associated with lower DSST scores after adjusting for covariates (ALM: 43.56 ± 18.36 vs. 47.56 ± 17.44, p < 0.001; ALM: BMI: 39.88 ± 17.51 vs. 47.70 ± 17.51, p < 0.001; ASMI: 41.07 ± 17.89 vs. 47.42 ± 17.55, p < 0.001). At a mean long-term follow-up of 157.8 months, those with low muscle mass were associated with higher all-cause mortality (ALM: OR 1.460, 95% CI 1.456-1.463; ALM: BMI: OR 1.452, 95% CI 1.448-1.457); ASMI: OR 3.075, 95% CI 3.063-3.088). In the ALM: BMI and ASMI-defined low muscle mass groups, participants with low muscle mass and lower DSST scores were more likely to incur all-cause mortality ( ALM: BMI: OR 0.972, 95% CI 0.972-0.972; ASMI: OR 0.957, 95% CI 0.956-0.957). CONCLUSIONS: Low muscle mass and cognitive function impairment are significantly correlated in the older population. Additionally, low muscle mass and low DSST score, alone or in combination, could be risk factors for mortality in older adults.
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Cognição , Inquéritos Nutricionais , Sarcopenia , Humanos , Masculino , Feminino , Sarcopenia/epidemiologia , Sarcopenia/mortalidade , Idoso , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Cognição/fisiologia , Idoso de 80 Anos ou mais , Músculo Esquelético/patologia , Mortalidade/tendências , Disfunção Cognitiva/epidemiologia , Composição Corporal/fisiologia , Índice de Massa Corporal , SeguimentosRESUMO
Methanotrophs of the genus Methylocystis are frequently found in rice paddies. Although more than ten facultative methanotrophs have been reported since 2005, none of these strains was isolated from paddy soil. Here, a facultative methane-oxidizing bacterium, Methylocystis iwaonis SD4, was isolated and characterized from rhizosphere samples of rice plants in Nanjing, China. This strain grew well on methane or methanol but was able to grow slowly using acetate or ethanol. Moreover, strain SD4 showed sustained growth at low concentrations of methane (100 and 500 ppmv). M. iwaonis SD4 could utilize diverse nitrogen sources, including nitrate, urea, ammonium as well as dinitrogen. Strain SD4 possessed genes encoding both the particulate methane monooxygenase and the soluble methane monooxygenase. Simple and rapid genetic manipulation methods were established for this strain, enabling vector transformation and unmarked genetic manipulation. Fast growth rate and efficient genetic tools make M. iwaonis SD4 an ideal model to study facultative methanotrophs, and the ability to grow on low concentration of methane implies its potential in methane removal.
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Metano , Methylocystaceae , Oryza , Rizosfera , Microbiologia do Solo , Oryza/microbiologia , Methylocystaceae/genética , Methylocystaceae/metabolismo , Methylocystaceae/isolamento & purificação , Metano/metabolismo , Oxigenases/genética , Oxigenases/metabolismo , China , Metanol/metabolismoRESUMO
Rapid and accurate identification of tumor metabolic markers is important for early tumor diagnosis and individualized treatment. Here, a stable monodisperse sub-nanometer platinum (Pt) material was developed as a highly efficient nanozyme with a specific activity of peroxidase as high as 20.86 U mg-1 through the growth of in situ domain-limited Pt quantum dots via the polymer polyvinylpyrrolidone. Further, the synthesis of large quantities of Pt-loaded SiO2 (Pt-SiO2 ) was determined by silylation reaction and used for naked eye colorimetric testing of human alpha-fetoprotein (AFP). In particular, the immunization incubation process occurred in preprepared microplates. A nanozyme-based immunomodel was constructed in the presence of the target AFP, and a chromogenic reaction occurred with exogenous hydrogen peroxide and the chromogenic substrate tetramethylbenzidine. On optimization of experimental conditions, the dynamic working response range for AFP was found to be 0.05-20 ng mL-1 , with a limit of detection of 38.7 pg mL-1 . This work provides a new strategy to design efficient nanozyme-based enzyme-linked immunochromatographic platforms to meet the practical use of replacing natural enzymes.
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Imunoadsorventes , Neoplasias , Humanos , Platina/química , alfa-Fetoproteínas , Dióxido de Silício/química , Peroxidase , Ensaio de Imunoadsorção Enzimática , Peróxido de Hidrogênio/química , Colorimetria/métodosRESUMO
BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study. METHODS: We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo. RESULTS: In vitro, HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1ß, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it's downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo, MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue. CONCLUSION: MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.
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Apoptose , Nefropatias Diabéticas , Exossomos , Células-Tronco Mesenquimais , Proteína Adaptadora de Sinalização NOD2 , Podócitos , Transdução de Sinais , Animais , Exossomos/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/terapia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteína Adaptadora de Sinalização NOD2/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Masculino , Camundongos Endogâmicos C57BL , Glucose/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Técnicas de Cocultura , Transplante de Células-Tronco Mesenquimais/métodos , Espécies Reativas de Oxigênio/metabolismo , Rim/patologia , Rim/metabolismo , Diabetes Mellitus Experimental/complicaçõesRESUMO
Gold nanoclusters (Au NCs) are potential emitters for electroluminescent light-emitting diodes (EL-LEDs) but restricted by the limited photoluminescence quantum yield (PLQY) and poor device compatibility. Herein, triple ligand engineered Au NCs enable the fabrication of Au NC-based LEDs with improved EL efficiency. Rigidified triple ligand shells greatly reduce the nonradiative transition and thus increase the PLQY of Au NCs from 2.1 to 73.4%. Most importantly, this strategy significantly improves the compatibility between Au NCs and charge transport materials in EL-LED fabrication. As a result, the EL-LEDs reach a maximum brightness of 1104 cd/m2 and an external quantum efficiency of 5.1%, which is the highest recorded for any reported Au NC-based EL-LEDs.
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The evolution of two-dimensional conjugated metal-organic frameworks (2D c-MOFs) provides a significant prospect for researching the next generation of green and advanced energy storage systems (ESSs). Especially, conjugation and topology engineering serve as an irreplaceable character in adjusting the electrochemical properties of ESSs. Herein, we proposed a novel strategy using conjugation and topology engineering to demonstrate the application of 2D c-MOFs in robust potassium-ion batteries (PIBs) for the first time. By comparing 2D c-MOFs with the rhombus/kagome structure as well as three/four-arm core, the rhombus structure (sql-Cu-TBA-MOF) cathode for PIBs can display the impressive electrochemical performance, including a high specific discharge capacity of 178.4â mAh g-1 (at 0.2â A g-1) and a well long-term cycle stability of more than 9,000 (at 10.0â A g-1). Moreover, full PIBs (FPIBs) are constructed by pairing sql-Cu-TBA-MOF cathode with dipotassium terephthalate (KTP) anode, which delivers a high reversible discharge specific capacity of 146.6â mAh g-1 (at 0.1â A g-1) and great practical application prospect. These findings provide reasonable implications for the design of 2D c-MOFs from the perspective of conjugation and topology engineering for advanced energy storage systems.
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Immunotherapy is currently the most promising treatment strategy for long-term tumor regression. However, current cancer immunotherapy shows low response rates due to insufficient immunogenicity of tumor cells. Herein, we report a strategy to keep tumor cells highly immunogenic by triggering cascade immunogenic tumor ferroptosis. We developed a six-enzyme co-expressed nanoplatform: lipoxygenase (LOX) and phospholipase A2 (PLA2)-co-loaded FeCo/Fe-Co dual-metal atom nanozyme (FeCo/Fe-Co DAzyme/PL), which can not only induce initial immunogenic tumor ferroptosis through its own multi-enzyme mimetic activities but also up-regulate arachidonic acid (AA) expression to synergize with CD8+ T cell-derived IFN-γ to induce ACSL4-mediated immunogenic tumor ferroptosis. During this process, FeCo/Fe-Co DAzyme/PL can induce lipid peroxidation (LPO) by efficiently generating reactive oxygen species (ROS) and depleting GSH and GPX4 at tumor sites. Additionally, free AA released from PLA2 catalysis is converted into arachidonyl-CoA under the activation of ACSL4 stimulated by IFN-γ, which is further incorporated into phospholipids on membranes and peroxidized with the participation of LOX. Consequently, FeCo/Fe-Co DAzyme/PL can promote irreversible cascade immunogenic ferroptosis through multiple ROS storms, GSH/GPX4 depletion, LOX catalysis, and IFN-γ-mediated ACSL4 activation, constructing an effective pathway to overcome the drawbacks of current immunotherapy.
Assuntos
Ferroptose , Neoplasias , Humanos , Interferon gama , Ácido Araquidônico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fosfolipases A2 , Neoplasias/metabolismo , Linhagem Celular TumoralRESUMO
We experimentally demonstrate a hybrid mode division multiplexer (MDM) based on asymmetric directional couplers (ADCs) without transition tapers in between. The proposed MDM can couple five fundamental modes from access waveguides into the bus waveguide as the hybrid modes (TE0, TE1, TE2, TM0, and TM1). To eliminate the transition tapers between cascaded ADCs as well as to enable arbitrary add-drop to the bus waveguide, we maintain the bus waveguide width to be the same, while a partially etched subwavelength grating is introduced to reduce the effective refractive index of the bus waveguide. The experimental results demonstrate a working bandwidth of up to 140â nm.