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Fine audiovocal control is a hallmark of human speech production and depends on precisely coordinated muscle activity guided by sensory feedback. Little is known about shared audiovocal mechanisms between humans and other mammals. We hypothesized that real-time audiovocal control in bat echolocation uses the same computational principles as human speech. To test the prediction of this hypothesis, we applied state feedback control (SFC) theory to the analysis of call frequency adjustments in the echolocating bat, Hipposideros armiger. This model organism exhibits well-developed audiovocal control to sense its surroundings via echolocation. Our experimental paradigm was analogous to one implemented in human subjects. We measured the bats' vocal responses to spectrally altered echolocation calls. Individual bats exhibited highly distinct patterns of vocal compensation to these altered calls. Our findings mirror typical observations of speech control in humans listening to spectrally altered speech. Using mathematical modeling, we determined that the same computational principles of SFC apply to bat echolocation and human speech, confirming the prediction of our hypothesis.
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Quirópteros , Ecolocação , Retroalimentação Sensorial , Vocalização Animal , Animais , Percepção Auditiva/fisiologia , Quirópteros/fisiologia , Ecolocação/fisiologia , Retroalimentação Sensorial/fisiologia , Feminino , Humanos , Modelos Biológicos , Fala/fisiologia , Vocalização Animal/fisiologiaRESUMO
BACKGROUND: Jilin white goose is an excellent local breed in China, with a high annual egg production and laying eggs mainly from February to July each year. The testis, as the only organ that can produce sperm, can affect the sexual maturity and fecundity of male animals. Its growth and development are affected and regulated by a variety of factors. Proteomics is generally applied to identify and quantify proteins in cells and tissues in order to understand the physiological or pathological changes that occur in tissues or cells under specific conditions. Currently, the female poultry reproductive system has been extensively studied, while few related studies focusing on the regulatory mechanism of the reproductive system of male poultry have been conducted. RESULTS: A total of 1753 differentially expressed proteins (DEPs) were generated in which there were 594, 391 and 768 different proteins showing differential expression in three stages, Initial of Laying Cycle (ILC), Peak of Laying Cycle (PLC) and End of Laying Cycle (ELC). Furthermore, bioinformatics was used to analyze the DEPs. Gene ontology (GO) enrichment, Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were adopted. All DEPs were found to be implicated in multiple biological processes and pathways associated with testicular development, such as renin secretion, Lysosomes, SNARE interactions in vesicle trafficking, the p53 signaling pathway and pathways related to metabolism. Additionally, the reliability of transcriptome results was verified by real-time quantitative PCR by selecting the transcript abundance of 6 selected DEPs at the three stages of the laying cycle. CONCLUSIONS: The funding in this study will provide critical insight into the complex molecular mechanisms and breeding practices underlying the developmental characteristics of testicles in Jilin white goose.
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Gansos , Testículo , Animais , Masculino , Feminino , Gansos/genética , Reprodutibilidade dos Testes , Sêmen , Transcriptoma , Perfilação da Expressão GênicaRESUMO
Legumain is overexpressed in diverse tumors, serving as a significant tumor biomarker. Our study aimed to develop a new positron emission tomography (PET) probe [68Ga]Ga-NOTA-SF-AANM for imaging the expression level of legumain in vivo. The radio-labeling of [68Ga]Ga-NOTA-SF-AANM was accomplished within 15 min. The probe has good stability in vitro. NOTA-SF-AANM exhibited rapid response to recombinant human legumain enzyme, enabling intramolecular condensation cyclization. Cellular uptake and lysosomal co-localization experiments demonstrated that the probe was able to differentiate specifically between MDA-MB-468 and PC-3 cancer cells with varying degrees of legumain expression. PET imaging displayed a significant and persistent signal (3.59 ± 0.30 %ID/mL at 60 min) in MDA-MB-468 tumors, while PC-3 tumors exhibited lower radioactivity (1.08 ± 0.35 %ID/mL at 60 min), further validating the specific targeting of [68Ga]Ga-NOTA-SF-AANM towards legumain. [68Ga]Ga-NOTA-SF-AANM is a promising tool for precise diagnosis of legumain-related diseases due to its advantages in radio-labeling and accurate monitoring of legumain expression levels.
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Cisteína Endopeptidases , Radioisótopos de Gálio , Neoplasias , Humanos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Lisossomos , Linhagem Celular TumoralRESUMO
As quantum circuits become more integrated and complex, additional error sources that were previously insignificant start to emerge. Consequently, the fidelity of quantum gates benchmarked under pristine conditions falls short of predicting their performance in realistic circuits. To overcome this problem, we must improve their robustness against pertinent error models besides isolated fidelity. Here, we report the experimental realization of robust quantum gates in superconducting quantum circuits based on a geometric framework for diagnosing and correcting various gate errors. Using quantum process tomography and randomized benchmarking, we demonstrate robust single-qubit gates against quasistatic noise and spatially correlated noise in a broad range of strengths, which are common sources of coherent errors in large-scale quantum circuits. We also apply our method to nonstatic noises and to realize robust two-qubit gates. Our Letter provides a versatile toolbox for achieving noise-resilient complex quantum circuits.
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Anyons, exotic quasiparticles in two-dimensional space exhibiting nontrivial exchange statistics, play a crucial role in universal topological quantum computing. One notable proposal to manifest the fractional statistics of anyons is the toric code model; however, scaling up its size through quantum simulation poses a serious challenge because of its highly entangled ground state. In this Letter, we demonstrate that a modular superconducting quantum processor enables hardware-pragmatic implementation of the toric code model. Through in-parallel control across separate modules, we generate a 10-qubit toric code ground state in four steps and realize six distinct braiding paths to benchmark the performance of anyonic statistics. The path independence of the anyonic braiding statistics is verified by correlation measurements in an efficient and scalable fashion. Our modular approach, serving as a hardware embodiment of the toric code model, offers a promising avenue toward scalable simulation of topological phases, paving the way for quantum simulation in a distributed fashion.
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PURPOSE: Due to tumor heterogeneity, immunohistochemistry (IHC) showed poor accuracy in detecting the expression of programmed cell death ligand-1 (PD-L1) in patients. Positron emission tomography (PET) imaging is considered as a non-invasive technique to detect PD-L1 expression at the molecular level visually, real-timely and quantitatively. This study aimed to develop novel peptide-based radiotracers [68Ga]/[18F]AlF-NOTA-IMB for accurately detecting the PD-L1 expression and guiding the cancer immunotherapy. METHODS: NOTA-IMB was prepared by connecting 2,2'-(7-(2-((2,5-dioxopyrrolidin-1-yl)oxy)- 2-oxoethyl)-1,4,7-triazonane-1,4-diyl) diacetic acid (NOTA-NHS) with PD-L1-targeted peptide IMB, and further radiolabeled with 68Ga or 18F-AlF. In vitro binding assay was conducted to confirm the ability of [68Ga]/[18F]AlF-NOTA-IMB to detect the expression of PD-L1. In vivo PET imaging of [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB in different tumor-bearing mice was performed, and dynamic changes of PD-L1 expression level induced by immunotherapy were monitored. Radioautography, western blotting, immunofluorescence staining and biodistribution analysis were carried out to further evaluate the specificity of radiotracers and efficacy of PD-L1 antibody immunotherapy. RESULTS: [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were both successfully prepared with high radiochemical yield (> 95% and > 60%, n = 5) and radiochemical purity (> 95% and > 98%, n = 5). Both tracers showed high affinity to human and murine PD-L1 with the dissociation constant (Kd) of 1.00 ± 0.16/1.09 ± 0.21 nM (A375-hPD-L1, n = 3) and 1.56 ± 0.58/1.21 ± 0.39 nM (MC38, n = 3), respectively. In vitro cell uptake assay revealed that both tracers can specifically bind to PD-L1 positive cancer cells A375-hPD-L1 and MC38 (5.45 ± 0.33/3.65 ± 0.15%AD and 5.87 ± 0.27/2.78 ± 0.08%AD at 120 min, n = 3). In vivo PET imaging and biodistribution analysis showed that the tracer [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB had high accumulation in A375-hPD-L1 and MC38 tumors, but low uptake in A375 tumor. Treatment of Atezolizumab induced dynamic changes of PD-L1 expression in MC38 tumor-bearing mice, and the tumor uptake of [68Ga]NOTA-IMB decreased from 3.30 ± 0.29%ID/mL to 1.58 ± 0.29%ID/mL (n = 3, P = 0.026) after five treatments. Similarly, the tumor uptake of [18F]AlF-NOTA-IMB decreased from 3.27 ± 0.63%ID/mL to 0.89 ± 0.18%ID/mL (n = 3, P = 0.0004) after five treatments. However, no significant difference was observed in the tumor uptake before and after PBS treatment. Biodistribution, radioautography, western blotting and immunofluorescence staining analysis further demonstrated that the expression level of PD-L1 in tumor-bearing mice treated with Atezolizumab significantly reduced about 3 times and correlated well with the PET imaging results. CONCLUSION: [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB were successfully prepared for PET imaging the PD-L1 expression noninvasively and quantitatively. Dynamic changes of PD-L1 expression caused by immunotherapy can be sensitively detected by both tracers. Hence, the peptide-based radiotracers [68Ga]NOTA-IMB and [18F]AlF-NOTA-IMB can be applied for accurately detecting the PD-L1 expression in different tumors and monitoring the efficacy of immunotherapy.
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Antígeno B7-H1 , Neoplasias , Humanos , Camundongos , Animais , Antígeno B7-H1/metabolismo , Distribuição Tecidual , Radioisótopos de Gálio/química , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Peptídeos/metabolismo , Imunoterapia , Neoplasias/diagnóstico por imagem , Neoplasias/terapiaRESUMO
Immune checkpoint inhibitors (ICIs) therapy based on programmed cell death ligand 1 (PD-L1) has shown significant development in treating several carcinomas, but not all patients respond to this therapy due to the heterogeneity of PD-L1 expression. The sensitive and accurate quantitative analysis of in vivo PD-L1 expression is critical for treatment decisions and monitoring therapy. In the present study, an aptamer-based dual-modality positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging probe was developed, and its specificity and sensitivity to PD-L1 were assessed in vitro and in vivo. The probe precursor NOTA-Cy5-R1 was prepared by using automated solid-phase oligonucleotide synthesis. PET/NIRF dual-modality probe [68Ga]Ga-NOTA-Cy5-R1 was successfully synthesized and radiolabeled. The binding specificity of [68Ga]Ga-NOTA-Cy5-R1 to PD-L1 was evaluated by flow cytometry, fluorescence imaging, and cellular uptake in A375-hPD-L1 and A375 cells, and it showed good fluorescence properties and stability in vitro. In vivo PET/NIRF imaging studies illustrated that [68Ga]Ga-NOTA-Cy5-R1 can sensitively and specifically bind to PD-L1 positive tumors. Meanwhile, the rapid clearance of probes from nontarget tissues achieved a high signal-to-noise ratio. In addition, changes of PD-L1 expression in NCI-H1299 xenografts treated with cisplatin (CDDP) were sensitivity monitored by [68Ga]Ga-NOTA-Cy5-R1 PET imaging, and ex vivo autoradiography and western blot analyses correlated well with the change of PD-L1 expression in vivo. Overall, [68Ga]Ga-NOTA-Cy5-R1 showed notable potency as a dual-modality PET/NIRF imaging probe for visualizing tumors and monitoring the dynamic changes of PD-L1 expression, which can help to direct and promote the clinical practice of ICIs therapy.
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Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Radioisótopos de Gálio/química , Tomografia por Emissão de Pósitrons/métodos , Anticorpos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
Because of the pathological indication and the physiological functions, bile acids (BAs) have occupied the research hotspot in recent decades. Although extensive efforts have been paid onto BAs sub-metabolome characterization, as the subfamily, BA glucuronides (gluA-BAs) profile is seldom concerned. Here, we made efforts to develop a LC-MS/MS program enabling quantitative gluA-BAs sub-metabolome characterization and to explore the differential species in serum between intrahepatic cholestasis of pregnancy (ICP) patients and healthy subjects. To gain as many authentic gluA-BAs as possible, liver microsomes from humans, rats, and mice were deployed to conjugate glucuronyl group to authentic BAs through in vitro incubation. Eighty gluA-BAs were captured and subsequently served as authentic compounds to correlate MS/MS spectral behaviors to structural features using squared energy-resolved MS program. Optimal collision energy (OCE) of [M-H]->[M-H-176.1]- was jointly administrated by [M-H]- mass and glucuronidation site, and identical exciting energies corresponding to 50% survival rate of 1st-generation fragment ion (EE50) were observed merely when the aglycone of a gluA-BA was consistent with the suspected structure. Through integrating high-resolution m/z, OCE, and EE50 information to identify gluA-BAs in a BAs pool, 97 ones were found and identified, and further, quantitative program was built for all annotated gluA-BAs by assigning OCEs to [M-H]->[M-H-176.1]- ion transitions. Quantitative gluA-BAs sub-metabolome of ICP was different from that of the healthy group. More GCDCA-3-G, GDCA-3-G, TCDCA-7-G, TDCA-3-G, and T-ß-MCA-3-G were distributed in the ICP group. Above all, this study not only offered a promising analytical tool for in-depth gluA-BAs sub-metabolome characterization, but also clarified gluA-BAs allowing the differentiation of ICP and healthy subjects.
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With the rapid development of Carbon Capture, Utilization and Storage (CCUS) technology, it is necessary to explore the feasibility of coal slime as a porous carbon material for CO2 capture. In this paper, scanning electron microscopy (SEM) was used to observe the morphological characteristics of coal slime samples with different metamorphic degrees, and the pore structure of coal slime was explored by low temperature N2 adsorption and low-pressure CO2 adsorption experiments. The pore distribution characteristics were analyzed, and the adsorption law of different metamorphic degrees were summarized through CO2 isothermal adsorption experiments. The results showed that: The specific surface area (SSA) and pore volume (PV) of the mesopores of the coal slime exhibited a U-shaped distribution with coal rank, and are much smaller than that of its micropores. Micropores less than 2 nm are the main adsorption space of coal slime, its PV accounted for 59%, 60%, 71%, and SSA accounted for 92%, 93%, 95%, obviously, which are dominant at all stages. The linear correlation fitting coefficients R2 between the limiting adsorbed amount a of CO2 and the micropores PV and the SSA were up to 0.830 and 0.887, respectively. The coal slime has good adsorption performance for CO2. Based on the Langmuir model to fit the limit adsorption amount, a-value can reach 41.774 cm3 g-1, 32.072 cm3 g-1, 38.457 cm3 g-1 at 303 K with the increase of Rmax. Studying the impact of coal slime on CO2 adsorption performance provides a theoretical basis for the subsequent preparation of energy storage materials and is of great significance for the safe, efficient and economic capture and sequestration of CO2, to alleviate the serious situation of the environment and realizing the dual-carbon goal.
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Transcytosis-based tubular reabsorption of endogenous proteins is a well-known energy-saving pathway that prevents nutrient loss. However, utilization of this well-known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2-targeted Gly-Sar peptide as a ligand, renal-clearable luminescent gold nanoparticles (P-AuNPs) were developed as protein mimics to investigate the transcytosis-based tubular reabsorption of exogenous substances. By regulating the influential factors (H+ content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly-Sar-mediated transcytosis, the specific and efficient interaction between P-AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P-AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high-contrast tumor imaging.
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Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Ouro/química , Nanopartículas Metálicas/química , Transcitose , Rim/metabolismo , Neoplasias/metabolismoRESUMO
Dispersion of single atoms (SAs) in the host is important for optimizing catalytic activity. Herein, we propose a novel strategy to tune oxygen vacancies in CeO2-X directionally anchoring the single atom platinum (PtSA), which is uniformly dispersed on the rGO. The catalyst's performance for the hydrogen evolution reaction (HER) can be enhanced by controlling different densities of CeO2-X in rGO. The PtSA performs best optimally densified and loaded on homogeneous and moderately densified CeO2-X/rGO (PtSA-M-CeO2-X/rGO). It exhibited higher activity in HER with an overpotential of 25â mV at 0.5â M H2SO4 and 33â mV at 1 KOH than that of almost reported electrocatalysts. Furthermore, it exhibited stability for 90â hours at -100â mA cm-2 in 1 KOH and -150â mA cm-2 in 0.5â M H2SO4 conditions, respectively. Through comprehensive experiments and theoretical calculations, the suitable dispersion density of PtSA on the defects of CeO2-X with more active sites gives the potential for practical applications. This research paves the way for developing single-atom catalysts with exceptional catalytic activity and stability, holding promise in advanced green energy conversion through defects engineering.
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For the electrooxidation of propylene into 1,2-propylene glycol (PG), the process involves two key steps of the generation of *OH and the transfer of *OH to the CâC bond in propylene. The strong *OH binding energy (EB(*OH)) favors the dissociation of H2O into *OH, whereas the transfer of *OH to propylene will be impeded. The scaling relationship of the EB(*OH) plays a key role in affecting the catalytic performance toward propylene electrooxidation. Herein, we adopt an immobilized Ag pyrazole molecular catalyst (denoted as AgPz) as the electrocatalyst. The pyrrolic N-H in AgPz could undergo deprotonation to form pyrrolic N (denoted as AgPz-Hvac), which can be protonated reversibly. During propylene electrooxidation, the strong EB(*OH) on AgPz favors the dissociation of H2O into *OH. Subsequently, the AgPz transforms into AgPz-Hvac that possesses weak EB(*OH), benefiting to the further combination of *OH and propylene. The dynamically reversible interconversion between AgPz and AgPz-Hvac accompanied by changeable EB(*OH) breaks the scaling relationship, thus greatly lowering the reaction barrier. At 2.0 V versus Ag/AgCl electrode, AgPz achieves a remarkable yield rate of 288.9 mmolPG gcat-1 h-1, which is more than one order of magnitude higher than the highest value ever reported.
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Gate-based quantum computation has been extensively investigated using quantum circuits based on qubits. In many cases, such qubits are actually made out of multilevel systems but with only two states being used for computational purpose. While such a strategy has the advantage of being in line with the common binary logic, it in some sense wastes the ready-for-use resources in the large Hilbert space of these intrinsic multidimensional systems. Quantum computation beyond qubits (e.g., using qutrits or qudits) has thus been discussed and argued to be more efficient than its qubit counterpart in certain scenarios. However, one of the essential elements for qutrit-based quantum computation, two-qutrit quantum gate, remains a major challenge. In this Letter, we propose and demonstrate a highly efficient and scalable two-qutrit quantum gate in superconducting quantum circuits. Using a tunable coupler to control the cross-Kerr coupling between two qutrits, our scheme realizes a two-qutrit conditional phase gate with fidelity 89.3% by combining simple pulses applied to the coupler with single-qutrit operations. We further use such a two-qutrit gate to prepare an EPR state of two qutrits with a fidelity of 95.5%. Our scheme takes advantage of a tunable qutrit-qutrit coupling with a large on:off ratio. It therefore offers both high efficiency and low crosstalk between qutrits, thus being friendly for scaling up. Our Letter constitutes an important step toward scalable qutrit-based quantum computation.
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BACKGROUND: The US confronted a "triple-demic" of influenza, respiratory syncytial virus (RSV), and COVID-19 in the winter of 2022, leading to increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze these epidemics and their spatial-temporal co-occurrence, identifying hotspots and informing public health strategies. METHODS: We employed retrospective and prospective space-time scan statistics to assess the situations of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and from October 2022 to February 2023, respectively. This enabled monitoring of spatiotemporal variations for each epidemic individually and collectively. RESULTS: Compared to winter 2021, COVID-19 cases decreased while influenza and RSV infections significantly increased in winter 2022. We found a high-risk cluster of influenza and COVID-19 (not all three) in winter 2021. In late November 2022, a large high-risk cluster of triple-demic emerged in the central US. The number of states at high risk for multiple epidemics increased from 15 in October 2022 to 21 in January 2023. CONCLUSIONS: Our study offers a novel spatiotemporal approach that combines both univariate and multivariate surveillance, as well as retrospective and prospective analyses. This approach offers a more comprehensive and timely understanding of how the co-occurrence of COVID-19, influenza, and RSV impacts various regions within the United States. Our findings assist in tailor-made strategies to mitigate the effects of these respiratory infections.
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COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Estados Unidos/epidemiologia , Influenza Humana/epidemiologia , Estudos Retrospectivos , COVID-19/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Surtos de DoençasRESUMO
BACKGROUND: Hungarian white goose has excellent down production performance and was introduced to China in 2010. The growth and development of feather follicles has an important impact on down production. Goose feather follicles can be divided into primary and secondary feather follicles, both of which originate in the embryonic stage. Msx2 (Msh Homeobox 2) plays a regulatory role in tissues and organs such as eyes, teeth, bones and skin. However, its regulatory mechanism on goose feather follicles development remains unclear. RESULTS: Msx2 gene first increased, then decreased and increased at the end (E13, E18, E23, E28) during embryonic feather follicle development, and the expression level was the highest at E18. The pEGFP-N1-Msx2 overexpression vector and si-Msx2 siRNA vector were constructed to transfect goose embryo dermal fibroblasts. The results showed that the cell viability of ov-Msx2 group was significantly increased, and the gene expression levels of FGF5 and TGF-ß1 genes were significantly down-regulated (P < 0.05), the expressions of PCNA, Bcl2, CDK1, FOXN1 and KGF genes were significantly up-regulated (P < 0.05). After transfection of siRNA vector, the cell viability of the si-Msx2 group was significantly decreased (P < 0.01) compared with the si-NC group. TGF-ß1 expression was significantly up-regulated (P < 0.05), FGF5 expression was extremely significantly up-regulated (P < 0.01), while PCNA, Bcl2, CDK1, FOXN1 and KGF gene expression was significantly down-regulated (P < 0.05). High-throughput sequencing technology was used to mine the exon SNPs of Msx2. A total of 11 SNP loci were screened, four of the SNPs located in exon 1 were missense mutations. The feather follicle diameter of the GC genotype at the G78C site is significantly larger than that of the other two genotypes. CONCLUSIONS: Msx2 maybe inhibit the apoptosis of goose dermal fibroblasts and promotes their proliferation. G78C can be used as a potential molecular marker for downy Variety.
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Gansos , Fator de Crescimento Transformador beta1 , Animais , Fator de Crescimento Transformador beta1/metabolismo , Gansos/genética , Plumas , Desenvolvimento Embrionário/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Chaetominine (CHA), an alkaloid with a biological activity obtained from Aspergillus fumigatus CY018, has strong anticancer activity against the human leukemia cells. However, its physiological and biochemical research is limited by CHA yield in the liquid-state fermentation, which is a problem that urgently needs effective biological solution. In this work, Ca2+ and Al3+ were found to have a strong promoting effect on CHA production after multiple metal ions screening. Then, the addition condition of Ca2+ and Al3+ was, respectively, optimized CHA production and dry cell weight. The intermediate metabolites were increased with coaddition of Ca2+ and Al3+ . The activities of key enzymes of DAHPs, AroAs, and TrpCs in the CHA biosynthesis pathway were improved by 3.58-, 3.60-, and 3.34-fold, respectively. Meanwhile, the transcription level of laeA, dahp, cs, and trpC was upregulated by 3.22-, 12.65-, 5.58-, and 6.99-fold, respectively, by coaddition of Ca2+ and Al3+ . Additionally, the fermentation strategy was successfully scaled up to a 5-L bioreactor, in which CHA production could attain 75.6 mg/L at 336 h. This work demonstrated that Ca2+ and Al3+ coaddition was an effective strategy for increasing CHA production, and the information obtained might be useful in the fermentation of filamentous fungi with the addition of metal ions.
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Aspergillus fumigatus , Reatores Biológicos , Humanos , Fermentação , Aspergillus fumigatus/metabolismo , Alcaloides Indólicos/metabolismo , Alcaloides Indólicos/farmacologiaRESUMO
BACKGROUND: Approximately 1 in 5 patients feel unsatisfied after total knee arthroplasty (TKA). Prognostic tools may aid in the patient selection process and reduce the proportion of patients who experience unsatisfactory surgery. This study uses the prognostic tool SMART Choice (Patient Prognostic Tool for Total Knee Arthroplasty) to predict patient improvement after TKA. The tool aims to be used by the patient without clinician input and does not require clinical data such as X-ray findings or blood results. The objective of this study is to evaluate the SMART Choice tool on patient decision making, particularly willingness for surgery. We hypothesise that the use of the SMART Choice tool will influence willingness to undergo surgery, especially when used earlier in the patient TKA journey. METHODS: This is a multicentred, pragmatic, randomised controlled trial conducted in Melbourne, Australia. Participants will be recruited from the St. Vincent's Hospital, Melbourne (SVHM) Orthopaedic Clinic, and the client base of HCF, Australia (private health insurance company). Patients over 45 years of age who have been diagnosed with knee osteoarthritis and considering TKA are eligible for participation. Participants will be randomised to either use the SMART Choice tool or treatment as usual. The SMART Choice tool provides users with a prediction for improvement or deterioration / no change after surgery based on utility score change calculated from the Veterans-RAND 12 (VR-12) survey. The primary outcome of the study is patient willingness for TKA surgery. The secondary outcomes include evaluating the optimal timing for tool use and using decision quality questionnaires to understand the patient experience when using the tool. Participants will be followed up for 6 months from the time of recruitment. DISCUSSION: The SMART Choice tool has the potential to improve patient decision making for TKA. Although many prognostic tools have been developed for other areas of surgery, most are confined within academic bodies of work. This study will be one of the first to evaluate the impact of a prognostic tool on patient decision making using a prospective clinical trial, an important step in transitioning the tool for use in clinical practice. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12622000072718 . Prospectively registered - 21 January 2022.
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Artroplastia do Joelho , Sistemas de Apoio a Decisões Clínicas , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/cirurgia , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: Impacts of molecular pathways have been discussed recently on restenosis after percutaneous coronary intervention (PCI). Hence, this study aimed to explore the impact of calcineurin-like phosphoesterase domain containing 1 (CPPED1) and specificity protein 1 (SP1) on restenosis after PCI. METHODS: A carotid balloon injury rat model was established, followed by western blot analysis of SP1 and CPPED1 expression in carotid artery (CA) tissues. After SP1 and CPPED1 were overexpressed, the neointimal hyperplasia and luminal stenosis were assessed. In addition, EPC underwent hypoxia/reoxygenation (H/R) treatment to construct an endothelial injury cell model. Then, cell proliferation, apoptosis, intracellular reactive oxygen species (ROS), and Ca2+ concentration were detected with cell counting kit-8 (CCK-8), flow cytometry, Chloromethyl-2'7'-dichlorofluorescein diacetate (CM-H2DCFDA) penetrant, and Fluo-4 AM staining, respectively. The binding relationship between SP1 and CPPED1 was verified by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS: SP1 and CPPED1 were lowly expressed in the model rats with carotid balloon injury. Mechanistically, SP1 bound to the promoter region of CPPED1 to activate CPPED1 expression. Overexpressing SP1 or CPPED1 lowered neointimal formation and restenosis rate, thus promoting the recovery of carotid balloon injury in rats. Meanwhile, SP1 and CPPED1 upregulation reduced ROS levels, Ca2+ concentration, and apoptosis of EPCs, accompanied by accelerated EPC viability. CONCLUSIONS: SP1 or CPPED1 overexpression reduced neointimal formation and restenosis rate in carotid balloon injury.
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Reestenose Coronária , Intervenção Coronária Percutânea , Ratos , Animais , Constrição Patológica , Espécies Reativas de Oxigênio , Proliferação de Células , Hiperplasia , Neointima , Reestenose Coronária/prevenção & controleRESUMO
In recent years, combined sewer overflow (CSO) has been identified as a significant contributor to the deterioration of the urban water environment. It is thought that remolding it to a separate sewer system is a thorough and effective method of controlling the CSO in the appropriate area. However, according to current research, the separate stormwater sewer systems will also have overflow pollution due to functional defects, damaged or inappropriately connected with sewage, which has serious consequences for the separate system's operational efficiencies and the urban water environment. The event mean concentration, first flush effect, source apportionment, and correlation analysis of variables in overflow pollution generated in three residential catchments in Nanning, China, were investigated in this study. The results showed that the event mean concentration values in drainage outlets inappropriately connected with sewage were 2-4 times higher than those in stormwater outlets, especially for NH3-N, TN, and TP. Meanwhile, more than 80% of overflow events at outlets inappropriately connected with sewage had a weak first flush or even a weak dilution effect, with peak pollutant concentrations occurring 40-60 min after the overflow began. Besides, the discharge pollution load was primarily derived from the inside of the sewer. When the rainfall was heavy, the contribution rate of sewer sediment erosion exceeded 60%, which was much higher than the contribution rate of rainfall runoff and sewage. The variability in event mean COD and TSS concentrations was primarily attributed to the antecedent dry period and rainfall intensity. The COD concentration increased from 140.7 to 277.1 mg/L with the increase of antecedent dry period from 3 to 10 days. This study could help guide the implementation of targeted measures to treat overflow pollution in urban residential catchments, as well as the development of strategies to mitigate the effects on receiving water bodies.
Assuntos
Esgotos , Movimentos da Água , Monitoramento Ambiental , Poluição Ambiental , ChuvaRESUMO
High-quality two-qubit gate operations are crucial for scalable quantum information processing. Often, the gate fidelity is compromised when the system becomes more integrated. Therefore, a low-error-rate, easy-to-scale two-qubit gate scheme is highly desirable. Here, we experimentally demonstrate a new two-qubit gate scheme that exploits fixed-frequency qubits and a tunable coupler in a superconducting quantum circuit. The scheme requires less control lines, reduces cross talk effect, and simplifies calibration procedures, yet produces a controlled-Z gate in 30 ns with a high fidelity of 99.5%, derived from the interleaved randomized benchmarking method. Error analysis shows that gate errors are mostly coherence limited. Our demonstration paves the way for large-scale implementation of high-fidelity quantum operations.