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How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clinical predictor of bone relapse and an enhancer of PI3K-Akt pathway activation by CXCL12 and IGF1. Carcinoma clones selected in this manner are primed for metastasis in the CXCL12-rich microenvironment of the bone marrow. The evidence suggests that stromal signals resembling those of a distant organ select for cancer cells that are primed for metastasis in that organ, thus illuminating the evolution of metastatic traits in a primary tumor and its distant metastases.
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Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Metástase Neoplásica , Transdução de Sinais , Animais , Medula Óssea/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimiocina CXCL12/metabolismo , Fibroblastos/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Transplante de Neoplasias , Transcrição Gênica , Transplante Heterólogo , Quinases da Família src/genética , Quinases da Família src/metabolismoRESUMO
Safeguarding Earth's tree diversity is a conservation priority due to the importance of trees for biodiversity and ecosystem functions and services such as carbon sequestration. Here, we improve the foundation for effective conservation of global tree diversity by analyzing a recently developed database of tree species covering 46,752 species. We quantify range protection and anthropogenic pressures for each species and develop conservation priorities across taxonomic, phylogenetic, and functional diversity dimensions. We also assess the effectiveness of several influential proposed conservation prioritization frameworks to protect the top 17% and top 50% of tree priority areas. We find that an average of 50.2% of a tree species' range occurs in 110-km grid cells without any protected areas (PAs), with 6,377 small-range tree species fully unprotected, and that 83% of tree species experience nonnegligible human pressure across their range on average. Protecting high-priority areas for the top 17% and 50% priority thresholds would increase the average protected proportion of each tree species' range to 65.5% and 82.6%, respectively, leaving many fewer species (2,151 and 2,010) completely unprotected. The priority areas identified for trees match well to the Global 200 Ecoregions framework, revealing that priority areas for trees would in large part also optimize protection for terrestrial biodiversity overall. Based on range estimates for >46,000 tree species, our findings show that a large proportion of tree species receive limited protection by current PAs and are under substantial human pressure. Improved protection of biodiversity overall would also strongly benefit global tree diversity.
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Efeitos Antropogênicos , Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , Árvores , Conservação dos Recursos Naturais/métodos , Humanos , Filogenia , Árvores/classificaçãoRESUMO
Grime's competitive, stress-tolerant, ruderal (CSR) theory predicts a shift in plant communities from ruderal to stress-tolerant strategies during secondary succession. However, this fundamental tenet lacks empirical validation using long-term continuous successional data. Utilizing a 60-year longitudinal data of old-field succession, we investigated the community-level dynamics of plant strategies over time. Our findings reveal that while plant communities generally transitioned from ruderal to stress-tolerant strategies during succession, initial abandonment conditions crucially shaped early successional strategies, leading to varied strategy trajectories across different fields. Furthermore, we found a notable divergence in the CSR strategies of alien and native species over succession. Initially, alien and native species exhibited similar ruderal strategies, but in later stages, alien species exhibited higher ruderal and lower stress tolerance compared to native species. Overall, our findings underscore the applicability of Grime's predictions regarding temporal shifts in CSR strategies depending on both initial community conditions and species origin.
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Espécies Introduzidas , Plantas , Fenômenos Fisiológicos Vegetais , Estresse Fisiológico , Ecossistema , Modelos Biológicos , Desenvolvimento VegetalRESUMO
Non-radiative bound states in the continuum (BICs) allow the construction of resonances with high-quality (Q) factors and have emerged as an attractive platform for manipulating light-matter interactions on the nanoscale. However, current studies on symmetry-protected BICs (SP-BICs) suffer from a fundamental trade-off between the Q factor and asymmetric parameters, presenting a significant hurdle for practical applications. Here, utilizing the eigenfield perturbations, we successfully break the conventional inverse quadratic law of the SP-BICs and realize the robust high-Q resonances against the asymmetric parameters. We find the introductions of the central notch can efficiently boost the resonance of the electric quadrupole, which results in the enhancement of multiple-mode interference, and thus improving Q factors, while the constant effective refractive index guarantees the resonance with a stable wavelength. Our findings provide a promising strategy for modulating the light-matter interaction and may pave the way for applications in future high-performance optoelectronic devices.
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BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.
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Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Exenteração Pélvica , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/etiologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/etiologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/etiologiaRESUMO
Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1ß (IL-1ß). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH.
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Fígado Gorduroso Alcoólico , MicroRNAs , Animais , Camundongos , Células de Kupffer , Piroptose , Hepatócitos , MetiltransferasesRESUMO
We aimed to explore the association between the serum 25-hydroxyvitamin D concentration and all-cause and cancer-specific mortality in 2,463 adult patients with cancer from the National Health and Nutrition Examination Survey 2007-2018. We linked mortality data from the survey to the National Death Index records up to December 31, 2019. During a median follow-up period of 70 months, 567 patients died, of whom 194 died due to cancer. Multivariate adjustment was performed for demographic characteristics, lifestyle, dietary factors, 25-hydroxyvitamin D testing period, and cancer site. Higher serum 25-hydroxyvitamin D concentrations up to 75 nmol/L significantly reduced the risk of all-cause and cancer-specific mortality. When 25-hydroxyvitamin D quartiles were compared, the multivariable-adjusted hazard ratios were 0.59 (95% confidence interval: 0.42, 0.84) for all-cause mortality (P for trend <0.001) and 0.48 (95% confidence interval: 0.29, 0.79) for cancer-specific mortality (P for trend = 0.037) in quartile 3 (79.3-99.2 nmol/L). A threshold of 75 nmol/L for serum 25-hydroxyvitamin D may represent an intervention target to reduce mortalities in patients with cancer, and maintaining 25(OH)D concentrations within range (79.3-99.2 nmol/L) is beneficial for reducing all-cause and cancer-specific mortality.
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Doenças Cardiovasculares , Neoplasias , Deficiência de Vitamina D , Adulto , Humanos , Inquéritos Nutricionais , Vitamina D , Vitaminas , Calcifediol , Fatores de RiscoRESUMO
PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.
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Carbapenêmicos , Transplante de Pulmão , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Transplantados , Pulmão , Programas de Rastreamento , Transplante de Pulmão/efeitos adversosRESUMO
An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.
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Three new strains of dissimilatory perchlorate-reducing bacteria (DPRB), QD19-16, QD1-5, and P3-1, were isolated from an active sludge. Phylogenetic trees based on 16S rRNA genes indicated that QD19-16, QD1-5, and P3-1 belonged to Brucella, Acidovorax, and Citrobacter, respectively, expanding the distribution of DPRB in the Proteobacteria. The three strains were gram-negative and facultative anaerobes with rod-shaped cells without flagella, which were 1.0-1.6 µm long and 0.5-0.6 µm wide. The three DPRB strains utilized similar broad spectrum of electron donors and acceptors and demonstrated a similar capability to reduce perchlorate within 6 days. The enzyme activity of perchlorate reductase in QD19-16 toward chlorate was higher than that toward perchlorate. The high sequence similarity of the perchlorate reductase operon and chlorite dismutase genes in the perchlorate reduction genomic islands (PRI) of the three strains implied that they were monophyletic origin from a common ancestral PRI. Two transposase genes (tnp1 and tnp2) were found in the PRIs of strain QD19-16 and QD1-5, but were absent in the strain P3-1 PRI. The presence of fragments of IR sequences in the P3-1 PRI suggested that P3-1 PRI had previously contained these two tnp genes. Therefore, it is plausible to suggest that a common ancestral PRI transferred across the strains Brucella sp. QD19-16, Acidovorax sp. QD1-5, and Citrobacter sp. P3-1 through horizontal gene transfer, facilitated by transposases. These results provided a direct evidence of horizontal gene transfer of PRI that could jump across phylogenetically unrelated bacteria through transposase. KEY POINTS: ⢠Three new DPRB strains can effectively remove high concentration of perchlorate. ⢠The PRIs of three DPRB strains are acquired from a single ancestral PRI. ⢠PRIs are incorporated into different bacteria genome through HGT by transposase.
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Ilhas Genômicas , Percloratos , Filogenia , Oxirredução , Transferência Genética Horizontal , RNA Ribossômico 16S/genética , Bactérias/genética , Oxirredutases/genética , Ecossistema , Transposases/genéticaRESUMO
Osteosarcoma, known for its rapid progression and high metastatic potential, poses significant challenges in adolescent oncology. This study delves into the roles of lipid metabolism and acetylation genes in the disease's pathogenesis. Utilizing gene set variation analysis, we examined 14 lipid metabolism-related pathways in osteosarcoma patients, identifying significant variances in three pathways between metastatic and primary cases. Additionally, differences in four acetylation genes between these groups were observed. A comprehensive analysis pinpointed 62 lipid metabolism-related genes, with 39 exhibiting significant correlations with acetylation genes, termed lipid metabolism acetylation (LMA) genes. Employing machine learning techniques like Lasso+RSF and GBM, we developed a predictive model for overall survival based on LMA genes. This model, with an average c-index of 0.771, focuses on three key genes: CYP2C8, PAFAH2, and ACOX3, whose prognostic value was confirmed through survival and receiver operating characteristic curve analyses. Quantitative RT-PCR results indicated higher expression levels of ACOX3 and PAFAH2 in OS cells (143B, HOS, MG63) than in osteoblasts (hFOB1.19), while CYP2C8 was lower in OS cells. Furthermore, drug sensitivity analysis through the pRRophetic algorithm suggested potential targeted therapies, revealing drugs with differential sensitivity based on LMA scores and varied treatment responses related to the expression of core genes. This study not only highlights the crucial role of lipid metabolism and acetylation in osteosarcoma but also offers a foundation for personalized treatment strategies, marking a notable advancement in combating this severe form of adolescent cancer.
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Neoplasias Ósseas , Metabolismo dos Lipídeos , Osteossarcoma , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Humanos , Acetilação , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
In order to ensure the reliability and accuracy of long-term temperature measurement where the thermometers are discommodious or even impossible to access for conventional periodical calibration, a study on miniaturized in-situ self-calibrated (MISSC) thermometers based on Ga and Ga-Zn fixed points was conducted using temperature scale transfer technology. One MISSC thermometer consists of three parts: the first is the fixed-points hardware, including a container with two cells separately filled with Ga and Ga-Zn; the second is the temperature sensing hardware, made of a Type T thermocouple; the third is the mini-power heating hardware, made of a film resistance. The measurement and calibration (M&C) system comprises a temperature measurement and data processing subsystem and a mini-power heating control subsystem. Then, an in-situ self-calibration can be carried out by mini-power heating from a room temperature of about 20 °C, and then by comparison between the measured phase transition plateau results and the standard fixed-points, i.e., Ga fixed point (about 29.76 °C) and Ga-Zn fixed point (about 25.20 °C). A series of experiments were performed, and the results show that: (1) both the proposed hardware design and the self-calibration method are feasible, and (2) the Φ16 mm × 25 mm MISSC thermometer is found to be the most miniaturized one that can realize reliable self-calibration in this study.
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Passive convergence-permeable reactive barrier (PC-PRB) represents a green and sustainable technology for in-situ remediation of contaminated groundwater. A laboratory-scale PC-PRB tracer simulation system was established to quantify its contaminant plume capture performance using image analysis method. Results indicate that PC-PRB captures the plume 65% wider than C-PRB, which means that fewer PRB sizes and materials volume would be necessary to treat an equivalent contaminated plume. This improvement is due to a significant drawdown within the PC-PRB's passive well, known as the passive hydraulic decompression-convergent flow effect. We further evaluated the effects of water pipe length, hydraulic gradient, and media particle size on PC-PRB's plume capture performance. Results indicate that an increased water pipe length enhances the PC-PRB's plume capture capacity due to greater well drawdown. PC-PRB not only captures the plume but also acts as a hydraulic barrier. The retardation effect of PC-PRB on plume migration increases with water pipe length. Conversely, both hydraulic gradient and media particle size impact the plume capture capacity of PC-PRB by modifying groundwater flow velocity and pollutant dispersion. An increase in either hydraulic gradient or media particle size decreases the plume capture performance of PC-PRB. Therefore, PC-PRB technology may be more effective in contaminated sites characterized by low hydraulic gradients and permeability. Overall, PC-PRB demonstrates significant effectiveness in enhancing plume capture performance, which can notably reduce remediation costs and environmental footprint, broadening its application scope.
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BACKGROUND: This study highlights the need for precise and efficient methods to measure palatal mucosal thickness in the maxillary anterior teeth, particularly for soft tissue augmentation in the aesthetic zone. The research evaluates three digital imaging techniques, suggesting that Cone Beam Computed Tomography (CBCT) combined with intraoral scanners (IOS) is a promising approach for reliable clinical assessment. METHODS: Ten volunteers with healthy periodontium were selected, and three methods were employed: CBCT-based indirect gingival imaging, modified soft tissue CBCT (ST-CBCT), and CBCT combined with IOS. Measurements of palatal mucosal thickness were taken at multiple points along the palatal gingival margin. Statistical analysis included Bland-Altman plots for method agreement and intraclass Correlation Coefficient (ICC) analysis for reliability. All measurements were standardized, repeated for consistency, and accurate to 0.01 mm to ensure reliability. RESULTS: The Bland-Altman plots showed that less than 5% of the points for palatal mucosal thickness differences measured by the gingival indirect radiographic method, modified ST-CBCT, and CBCT combined with IOS were located outside the 95% limits of agreement (LoA). The mean value of the differences was within 0.2 mm, indicating good clinical agreement among the three methods. The inter- and intra-study ICC values for palatal mucosal thickness measurements of the maxillary anterior teeth using the three CBCT methods were greater than 0.75 (P < 0.001), demonstrating reproducibility. CONCLUSIONS: Based on the evaluation of three digital imaging techniques, this study indicates that the combination of CBCT with IOS is a feasible method for measuring palatal mucosal thickness in the maxillary anterior teeth and demonstrates good reproducibility.
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Tomografia Computadorizada de Feixe Cônico , Maxila , Humanos , Tomografia Computadorizada de Feixe Cônico/métodos , Maxila/diagnóstico por imagem , Maxila/anatomia & histologia , Feminino , Adulto , Masculino , Mucosa Bucal/diagnóstico por imagem , Mucosa Bucal/anatomia & histologia , Reprodutibilidade dos Testes , Gengiva/diagnóstico por imagem , Gengiva/anatomia & histologia , Incisivo/diagnóstico por imagem , Incisivo/anatomia & histologia , Palato/diagnóstico por imagem , Palato/anatomia & histologia , Adulto Jovem , Processamento de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.
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Diferenciação Celular , Lipopolissacarídeos , NF-kappa B , Osteogênese , Ligamento Periodontal , Transdução de Sinais , Células-Tronco , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Osteogênese/efeitos dos fármacos , NF-kappa B/metabolismo , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Células Cultivadas , Proliferação de Células/efeitos dos fármacos , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Western BlottingRESUMO
The practical application of solid-state polymer lithium-metal batteries (LMBs) is plagued by the inferior ionic conductivity of the applied polymer electrolytes (PEs), which is caused by the coupling of ion transport with the motion of polymer segments. Here, solvated molecules based on ionic liquid and lithium salt with strong Li+-solvent interaction are inserted into an elaborately engineered perfluoropolymer electrolyte via ionic dipole interaction, extensively facilitating Li+ transport and improving mechanical properties. The intensified formation of solvation structures of contact ion pairs and ionic aggregates, as well as the strong electron-withdrawal properties of the F atoms in perfluoropolymers, give the PE high electrochemical stability and excellent interfacial stability. As a result, Li||Li symmetric cells demonstrate a lifetime of 2500â h and an exceptionally high critical current density above 2.3â mA cm-2, Li||LiFePO4 batteries exhibit consistent cycling for 550â cycles at 10â C, and Li||uncoated LiNi0.8Co0.1Mn0.1O2 cells achieve 1000â cycles at 0.5â C with an average Coulombic efficiency of 98.45 %, one of the best results reported to date based on PEs. Our discovery sheds fresh light on the targeted synergistic regulation of the electro-chemo-mechanical properties of PEs to extend the cycle life of LMBs.
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Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.
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To achieve high-performance solid-state lithium-metal batteries (SSLMBs), solid electrolytes with high ionic conductivity, high oxidative stability, and high mechanical strength are necessary. However, balancing these characteristics remains dramatically challenging and is still not well addressed. Herein, a simple yet effective design strategy is presented for the development of high-performance polymer electrolytes (PEs) by exploring the synergistic effect between dynamic H-bonded networks and conductive zwitterionic nanochannels. Multiple weak intermolecular interactions along with ample nanochannels lead to high oxidative stability (over 5 V), improved mechanical properties (strain of 1320%), and fast ion transport (ionic conductivity of 10-4 S cm-1 ) of PEs. The amphoteric ionic functional units also effectively regulate the lithium ion distribution and confine the anion transport to achieve uniform lithium ion deposition. As a result, the assembled SSLMBs exhibit excellent capacity retention and long-term cycle stability (average Coulombic efficiency: 99.5%, >1000 cycles with LiFePO4 cathode; initial capacity: 202 mAh g-1 , average Coulombic efficiency: 96%, >230 cycles with LiNi0.8 Co0.1 Mn0.1 O2 cathode). It is exciting to note that the corresponding flexible cells can be cycled stably and can withstand severe deformation. The resulting polyzwitterion-mediated PE therefore offers great promise for the next-generation safe and high-energy-density flexible energy storage devices.
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Karyological characteristics are among the traits underpinning the invasion success of vascular plants. Using 11 049 species, we tested the effects of genome size and ploidy levels on plant naturalization (species forming self-sustaining populations where they are not native) and invasion (naturalized species spreading rapidly and having environmental impact). The probability that a species naturalized anywhere in the world decreased with increasing monoploid genome size (DNA content of a single chromosome set). Naturalized or invasive species with intermediate monoploid genomes were reported from many regions, but those with either small or large genomes occurred in fewer regions. By contrast, large holoploid genome sizes (DNA content of the unreplicated gametic nucleus) constrained naturalization but favoured invasion. We suggest that a small genome is an advantage during naturalization, being linked to traits favouring adaptation to local conditions, but for invasive spread, traits associated with a large holoploid genome, where the impact of polyploidy may act, facilitate long-distance dispersal and competition with other species.
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Ecossistema , Traqueófitas , Tamanho do Genoma , Cidadania , Ploidias , Espécies Introduzidas , DNARESUMO
BACKGROUND: Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections. METHODS: The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines. RESULTS: Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits. CONCLUSIONS: The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.