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Neuromorphic computing draws inspiration from the brain to provide computing technology and architecture with the potential to drive the next wave of computer engineering1-13. Such brain-inspired computing also provides a promising platform for the development of artificial general intelligence14,15. However, unlike conventional computing systems, which have a well established computer hierarchy built around the concept of Turing completeness and the von Neumann architecture16-18, there is currently no generalized system hierarchy or understanding of completeness for brain-inspired computing. This affects the compatibility between software and hardware, impairing the programming flexibility and development productivity of brain-inspired computing. Here we propose 'neuromorphic completeness', which relaxes the requirement for hardware completeness, and a corresponding system hierarchy, which consists of a Turing-complete software-abstraction model and a versatile abstract neuromorphic architecture. Using this hierarchy, various programs can be described as uniform representations and transformed into the equivalent executable on any neuromorphic complete hardware-that is, it ensures programming-language portability, hardware completeness and compilation feasibility. We implement toolchain software to support the execution of different types of program on various typical hardware platforms, demonstrating the advantage of our system hierarchy, including a new system-design dimension introduced by the neuromorphic completeness. We expect that our study will enable efficient and compatible progress in all aspects of brain-inspired computing systems, facilitating the development of various applications, including artificial general intelligence.
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BACKGROUND: Colon adenocarcinoma (COAD) is a prevalent malignant tumor globally, contributing significantly to cancer-related mortality. COAD guidelines label MSI (Microsatellite instability) and MSS (Microsatellite stability) subtypes as global classification criteria and treatment strategy selection criteria for COAD. Various combination therapies involving PD-L1 inhibitors and adjuvant therapy to enhance anti-tumor efficacy. METHODS: Datasets from single-cell RNA sequencing and bulk RNA sequencing in the TCGA and GEO databases were utilized to identify differentially expressed genes (DEGs). Furthermore, the correlation between ATP8B3 and PD-L1 was validated using siRNA, shRNA, and western blot analysis. Additionally, the association between ATP8B3 and immune checkpoint blockade (ICB) therapy was investigated through immune infiltration analysis and flow cytometry in both in vivo and in vitro assays. RESULTS: In the COAD patient group, ATP8B3 significantly contributed to the establishment of an immunosuppressive microenvironment. Inhibiting ATP8B3 led to a reduction in PD-L1 expression in colon cancer cell lines. Additionally, ATP8B3 expression levels could serve as a potential guide for PD-L1 treatment in MSI-H COAD patients, with higher ATP8B3 expression associated with increased sensitivity to PD-L1 therapy. However, due to the lack of immuno-killer cells in the microenvironment of MSS subtypes, elevated ATP8B3 expression couldn't increase the sensitivity of MSS COAD patients to PD-L1 inhibitors. CONCLUSION: Our research results support that Inhibiting ATP8B3 could enhance TIL (tumor-infiltrating lymphocyte) infiltration by reducing PD-L1 expression in MSI-H COAD, thereby serving as an effective strategy to improve PD-L1 blocker efficacy. The treatment strategy of combining ATP8B3 inhibitors and immunotherapy for MSI/MSS COAD patients will be the best choice.
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Adenocarcinoma , Antígeno B7-H1 , Biomarcadores Tumorais , Neoplasias do Colo , Inibidores de Checkpoint Imunológico , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Animais , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Proteínas de Transferência de Fosfolipídeos/antagonistas & inibidores , Instabilidade de MicrossatélitesRESUMO
To expand the reliability of interferometry technology, this paper proposes a random two-frame algorithm with high accuracy, high robustness, and immunity to tilt phase-shift. This method uses the equivalence of inter-frame phase-shift and intra-frame phase difference to mine light intensity pixels carrying new phase-shift from different images. Then, the linear random phase-shift plane is fitted by least squares, and the inverse tangent relationship is used to obtain a high-precision phase distribution. This technology uses the principle of light intensity equivalence to fit the linear phase-shift plane and does not require any iterative process. It can effectively suppress the influence of tilt phase-shift while ensuring computational efficiency. The paper verifies that the proposed algorithm has excellent performance in both tilted and non-tilted conditions through simulation and experimental comparison.
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BACKGROUND: The effectiveness of flipped classroom (FC) on puncture skills in medical education is still uncertain. This study aimed to assess the role of the FC model in puncture skills and investigate the acceptance and approval of FC among medical students and instructors. METHODS: A mixed research approach of quasi-experimental research design and descriptive qualitative research was conducted in September 2022 for one month, using an FC teaching method that combined instructional videos and group learning. The study participants were 71 fifth-year medical students from two classes at a Chinese medical school and four instructors. The medical students were randomly divided into two groups: the traditional classroom (TC) group (Group A) and the FC group (Group B). For teaching, Group B used FC, and Group A used PowerPoint-based TC. The effectiveness of the two teaching models was assessed with Objective Structured Clinical Examination (OSCE), and questionnaires were distributed to the medical students and instructors after the assessment. Two independent sample t-tests were used to analyse the differences in demographic data and the OSCE scores of the two groups of medical students. RESULTS: Group B scored higher in puncture skills than Group A, especially regarding abdominal puncture (p = 0.03), thoracentesis (p < 0.001), bone marrow puncture (p < 0.001) and average performance of puncture skills (p < 0.001). For lumbar puncture, no difference in skill scores was observed between groups A and B (p > 0.409). The medical students thought that the FC improved their self-learning ability and helped them acquire knowledge. Regarding the OSCE of their skills, most medical students thought that it was more innovative and objective than traditional examinations and that it was better for assessing their overall abilities. Both the FC and OSCE were supported by the medical students. The instructors were also satisfied with the students' performance in the FC and supported the teaching model, agreeing to continue using it. CONCLUSIONS: This study shows that FC teaching that combines instructional videos and group learning is a reliable and well-received teaching method for puncture skills, which supplements and expands existing teaching methods in the medical field.
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Aprendizagem , Estudantes de Medicina , Humanos , Exame Físico , Punções , Inquéritos e Questionários , Ensino , Aprendizagem Baseada em Problemas/métodos , CurrículoRESUMO
Neurodegenerative diseases associated with aging are often accompanied by cognitive decline and gut microbiota disorder. But the impact of gut microbiota on these cognitive disturbances remains incompletely understood. Short chain fatty acids (SCFAs) are major metabolites produced by gut microbiota during the digestion of dietary fiber, serving as an energy source for gut epithelial cells and/or circulating to other organs, such as the liver and brain, through the bloodstream. SCFAs have been shown to cross the blood-brain barrier and played crucial roles in brain metabolism, with potential implications in mediating Alzheimer's disease (AD) and Parkinson's disease (PD). However, the underlying mechanisms that SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, the dietary sources which determine these SCFAs production was not thoroughly evaluated yet. This comprehensive review explores the production of SCFAs by gut microbiota, their transportation through the gut-brain axis, and the potential mechanisms by which they influence age-related neurodegenerative disorders. Also, the review discusses the importance of dietary fiber sources and the challenges associated with harnessing dietary-derived SCFAs as promoters of neurological health in elderly individuals. Overall, this study suggests that gut microbiota-derived SCFAs and/or dietary fibers hold promise as potential targets and strategies for addressing age-related neurodegenerative disorders.
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PURPOSE: The Asia-Pacific Colorectal Screening (APCS) score and its derivatives have been used to predict advanced colorectal neoplasia (ACN). However, it remains unknown whether they apply to the current Chinese population in general clinical practice. Therefore, we aimed to update the APCS score system by applying data from two independent asymptomatic populations to predict the risk of ACN in China. METHODS: We developed an adjusted APCS (A-APCS) score by using the data of asymptomatic Chinese patients undergoing colonoscopies from January 2014 to December 2018. Furthermore, we validated this system in another cohort of 812 patients who underwent screening colonoscopy between January and December 2021. The discriminative calibration ability of the A-APCS and APCS scores was comparatively evaluated. RESULTS: Univariate and multivariate logistic regression were applied to assess the risk factors for ACN, and an adjusted scoring system of 0 to 6.5 points was schemed according to the results. Utilizing the developed score, 20.2%, 41.2%, and 38.6% of patients in the validation cohort were classified as average, moderate, and high risk, respectively. The corresponding ACN incidence rates were 1.2%, 6.0%, and 11.1%, respectively. In addition, the A-APCS score (c-statistics: 0.68 for the derivation and 0.80 for the validation cohort) showed better discriminative power than using predictors of APCS alone. CONCLUSIONS: The A-APCS score may be simple and useful in clinical applications for predicting ACN risk in China.
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Neoplasias Colorretais , População do Leste Asiático , Humanos , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , População do Leste Asiático/estatística & dados numéricos , Doenças Assintomáticas/epidemiologia , Medição de Risco , Indicadores Básicos de SaúdeRESUMO
Colorimetric analysis for mercury detection has great application potential in the prevention of health damage caused by mercury in the environment. Sensitivity, selectivity, and portability are core competencies of sensors, and concentrating these properties in a single sensor for efficient mercury detection remains a great challenge. Herein, a hollow structure CuS@CuSe@PVP (CCP) was prepared in which the enzyme-like activities could be activated by Hg2+ due to the antagonism between Hg and Se, inspiring the establishment of a colorimetric method for Hg2+ detection. As for Hg2+ detection performance, the linear range (LR) and limit of detection (LOD) were 1-900 and 0.81 nM in the POD-like activity system, respectively. Also, 5-550 nM of LR and 2.34 nM of LOD were achieved in the OD-like activity system. Further, a smartphone-mediated portable RGB nanosensor was fabricated, with a LOD down to 6.65 nM in the POD-like system and 7.97 nM in the OD-like system. Moreover, the excellent self-calibration and satisfactory recovery of 94.77%-106.16% were shown in the application of real water samples analysis. This study represented advanced progress toward emerging applications of nanozymes with multiple enzyme-like activities in heavy metal detection and will accelerate the development of efficient and portable heavy metal sensors.
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Colorimetria , Mercúrio , Calibragem , Limite de DetecçãoRESUMO
We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.
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Anticorpos Monoclonais Humanizados , Medicamentos Biossimilares , Carcinoma Hepatocelular , Hipertensão , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Estudos Prospectivos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Phosphorus (P) deficiency is one of the major limitations for soybean production. Moreover, it has been well reported P and other mineral elements function interdependently or antagonistically to control nutrients homeostasis in plants. Thus, it is urgently needed to understand the genetic mechanism of the accumulation of mineral elements in response to low-P stress. In this study, to identify single nucleotide polymorphisms (SNPs) and candidate genes controlling the accumulation of mineral elements suffering low-P stress in seedling stage of soybean plants, we measured concentrations of mineral elements, including P, Zn, Fe, Mn, Mg and Ca, in shoots of 211 soybean accessions under normal phosphorus (+P) and low phosphorus (-P) conditions in two hydroponic experiments. And genome-wide association study (GWAS) using high density NJAU 355K SoySNP array and concentrations of five of these mineral elements except P was performed. A total of 36 SNPs distributed on 13 chromosomes were identified to be significantly associated with low-P tolerance, and nine SNPs on chromosome 10 formed a SNP cluster. Meanwhile, the candidate gene GmFeB1 was found to serve as a negative regulator element involved in soybean P metabolism and the haplotype1 (Hap1) of GmFeB1 showed significantly higher shoot Fe concentration under -P condition than that of Hap2. In summary, we uncover 36 SNPs significantly associated with shoot mineral elements concentrations under different P conditions and a soybean low-P related gene GmFeB1, which will provide additional genetic information for soybean low-P tolerance and new gene resources for P-efficient soybean varieties breeding.
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Estudo de Associação Genômica Ampla , Glycine max , Minerais , Fósforo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Glycine max/genéticaRESUMO
BACKGROUND: The causal association between educational attainment (EA) and stroke remains unclear. Hence, a novel multivariable Mendelian randomization (MVMR) approach was applied to solve this issue. METHODS: The single nucleotide polymorphisms (SNPs) from a recent genome-wide association study (GWAS) on years of schooling served as instruments. Univariable mendelian randomization (MR) and MVMR analyses were performed to detect the relationship between genetically predicted EA and the stroke risk. In the MVMR, cigarette consumption, alcohol consumption, body mass index (BMI), intelligence, and hypertension were adjusted. The summary statistics for stroke from the MEGASTROKE consortium included 446,696 participants (40,585 cases of stroke and 34,217 cases of ischemic stroke), most of whom were of European descent. RESULTS: In the univariable MR, genetically predicated EA could decrease the risks of total stroke (OR = 0.66, 95% CI 0.61-0.72, P = 2.70 × 10-23), ischemic stroke (OR = 0.67, 95% CI 0.61-0.73, P = 2.58 × 10-18), large artery atherosclerosis (OR = 0.51, 95% CI 0.40-0.64, P = 1.80 × 10-8), small vessel stroke (OR = 0.60, 95% CI 0.49-0.73, P = 5.59 × 10-7), and cardioembolic stroke (OR = 0.81, 95% CI 0.68-0.96, P = 1.46 × 10-2) using the inverse-variance weighted (IVW) estimator. Higher EA might be negatively correlated with the odds of total stroke (OR = 0.62, 95% CI 0.50-0.77, P = 1.44 × 10-5), ischemic stroke (OR = 0.63, 95% CI 0.50-0.80, P = 1.41 × 10-4), and cardioembolic stroke (OR = 0.59, 95% CI 0.39-0.90, P = 0.01), but was not significant in large artery atherosclerosis (OR = 0.65, 95% CI 0.37-1.15, P = 0.14) and small vessel stroke (OR = 0.68, 95% CI 0.41-1.13, P = 0.14) after controlling other exposures. CONCLUSIONS: We found that genetically predicated higher EA decreased the risks of total stroke, ischemic stroke, and cardioembolic stroke, independent of smoking, alcohol consumption, BMI, intelligence, and hypertension.
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Aterosclerose , AVC Embólico , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genéticaRESUMO
The novel fourth-generation fluoroquinolones (FQs) were developed to improve the antimicrobial activity and their utilization has rapidly increased in recent years. However, knowledge of the ecotoxicity and microalgae-mediated biodegradation of these novel FQs is limited. In this research, the toxic effects of moxifloxacin (MOX) and gatifloxacin (GAT) on Chlamydomonas reinhardtii as well as their biodegradation and metabolic fate were investigated. The results showed that the toxicity of MOX to C. reinhardtii was higher than that of GAT, and increased with culture time. Chlorophyll fluorescence and pigment content analyses suggested that the decrease in photosynthetic efficiency was primarily caused by the inhibition of electron transport after QA in PSII complex. These FQs induced oxidative damage in cells, and the antioxidation mechanisms of C. reinhardtii were analyzed. The maximum MOX removal of 77.67% by C. reinhardtii was achieved at 1 mg/L MOX, whereas the maximum GAT removal of 34.04% was attained at 20 mg/L GAT. The different hydrophilicity and lipophilicity of these FQs resulted in distinct findings in biodegradation experiments. Identification of the transformation products suggested that the likely biodegradation pathways of FQs by C. reinhardtii were hydroxylation, demethylation, and ring cleavage.
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Chlamydomonas reinhardtii , Biodegradação Ambiental , Fluoroquinolonas/metabolismo , Fluoroquinolonas/toxicidade , Gatifloxacina/farmacologia , Moxifloxacina/metabolismo , Moxifloxacina/farmacologia , FotossínteseRESUMO
Tumor-associated macrophages (TAMs), one of the most common cell components in the tumor microenvironment, have been reported as key contributors to cancer-related inflammation and enhanced metastatic progression of tumors. To explore the underlying mechanism of TAM-induced tumor progression, TAMs were isolated from colorectal cancer patients, and the functional interaction with colorectal cancer cells was analyzed. Our study found that coculture of TAMs contributed to a glycolytic state in colorectal cancer, which promoted the stem-like phenotypes and invasion of tumor cells. TAMs produced the cytokine transforming growth factor-ß to support hypoxia-inducible factor 1α (HIF1α) expression, thereby upregulating Tribbles pseudokinase 3 (TRIB3) in tumor cells. Elevated expression of TRIB3 resulted in activation of the ß-catenin/Wnt signaling pathway, which eventually enhanced the stem-like phenotypes and cell invasion in colorectal cancer. Our findings provided evidence that TAMs promoted colorectal cancer progression in a HIF1α/TRIB3-dependent manner, and blockade of HIF1α signals efficiently improved the outcome of chemotherapy, describing an innovative approach for colorectal cancer treatment.
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Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Fator de Crescimento Transformador beta/fisiologia , Macrófagos Associados a Tumor/fisiologia , Animais , Proliferação de Células , Técnicas de Cocultura , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica , Células-Tronco Neoplásicas , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismo , Regulação para Cima , Via de Sinalização Wnt/fisiologiaRESUMO
Gene transcription is a complex biological process that involves a set of factors, enzymes and nucleotides. Ssu72 plays a crucial role in every step of gene transcription. RNA polymerase II (RNAPII) occupies an important position in the synthesis of mRNAs. The largest subunit of RNAPII, Rpb1, harbors its C-terminal domain (CTD), which participates in the initiation, elongation and termination of transcription. The CTD consists of heptad repeats of the consensus motif Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 and is highly conserved among different species. The CTD is flexible in structure and undergoes conformational changes in response to serine phosphorylation and proline isomerization, which are regulated by specific kinases/phosphatases and isomerases, respectively. Ssu72 is a CTD phosphatase with catalytic activity against phosphorylated Ser5 and Ser7. The isomerization of Pro6 affects the binding of Ssu72 to its substrate. Ssu72 can also indirectly change the phosphorylation status of Ser2. In addition, Ssu72 is a member of the 3'-end cleavage and polyadenylation factor (CPF) complex. Together with other CPF components, Ssu72 regulates the 3'-end processing of premature mRNA. Recent studies have revealed other roles of Ssu72, including its roles in balancing phosphate homeostasis and controlling chromosome behaviors, which should be further explored. In conclusion, the protein Ssu72 is an enzyme worthy of attention, not confined to its role in gene transcription.
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Fosfoproteínas Fosfatases/genética , RNA Polimerase II/genética , Transcrição Gênica , Sequência de Aminoácidos/genética , Animais , Humanos , Fosforilação , Saccharomyces cerevisiae/genética , Serina/genética , Fatores de Poliadenilação e Clivagem de mRNA/genéticaRESUMO
BACKGROUND: Eucalyptus bacterial wilt caused by Ralstonia solanacearum is an important eucalyptus disease. Endophytic fungi, an important source of natural active substances, provide a new breakthrough for the control of plant diseases. RESULTS: In the present study, 80 endophytic fungal isolates were obtained from the healthy branches and fruits of Eucalyptus exserta. Fifteen distinct isolates (MK120854-MK120868) were selected for further taxonomic identification through morphological trait assessments and internal transcribed spacer (ITS) region-rRNA gene sequence analysis. Thirteen genera, namely, Phyllosticta, Penicillium, Eutypella, Purpureocillium, Talaromyces, Lophiostoma, Cladosporium, Pestalotiopsis, Chaetomium, Fusarium, Gongronella, Scedosporium and Pseudallescheria, were identified on the basis of their morphological characteristics. Members of the genus Phyllosticta were the primary isolates, with a colonization frequency (CF) of 27.5 %. Most of the fungal isolates displayed antibacterial activity. The crude extracts obtained from Lophiostoma sp. Eef-7, Pestalotiopsis sp. Eef-9 and Chaetomium sp. Eef-10 exhibited strong inhibition on the test bacteria, and Lophiostoma sp. Eef-7 was further cultured on a large scale. Three known compounds, scorpinone (1), 5-deoxybostrycoidin (2) and 4-methyl-5,6-dihydro-2 H-pyran-2-one (3), were isolated from the endophytic fungus Lophiostoma sp. Eef-7 associated with E. exserta. The structures of these compounds were elucidated by analysis of 1D and 2D NMR and HR-ESI-MS spectra and a comparison of their spectral data with published values. Compounds 1 and 2 showed weak antimicrobial activity against Ralstonia solanacearum. CONCLUSIONS: Endophytic fungi from Eucalyptus exserta may represent alternative sources of antimicrobial agents. Lophiostoma sp. Eef-7 can produce 2-azaanthraquinone derivatives and shows weak antibacterial activity against Ralstonia solanacearum.
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Antibacterianos/química , Endófitos/química , Eucalyptus/microbiologia , Fungos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Endófitos/classificação , Endófitos/genética , Endófitos/metabolismo , Frutas/microbiologia , Fungos/classificação , Fungos/genética , Fungos/metabolismo , Caules de Planta/microbiologia , Ralstonia solanacearum/efeitos dos fármacos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: Overexpression of ABC transporters is a big challenge on cancer therapy which will lead cancer cells resistance to a series of anticancer drugs. Gedatolisib is a dual PI3K and mTOR inhibitor which is under clinical evaluation for multiple types of malignancies, including colorectal cancer. The growth inhibitory effects of gedatolisib on colorectal cancer cells have been specifically studied. However, the role of ABC transporters on gedatolisib resistance remained unclear. In present study, we illustrated the role of ABC transporters on gedatolisib resistance in colorectal cancer cells. METHODS: Cell viability investigations of gedatolisib on colorectal cancer cells were determined by MTT assays. The verapamil and Ko143 reversal studies were determined by MTT assays as well. ABCB1 and/or ABCG2 siRNA interference assays were conducted to verify the role of ABCB1- and ABCG2-overexpression on gedatolisib resistance. The accumulation assays of gedatolisib were conducted using tritium-labeled paclitaxel and mitoxantrone. The effects of gedatolisib on ATPase activity of ABCB1 or ABCG2 were conducted using PREDEASY ATPase Kits. The expression level of ABCB1 and ABCG2 after gedatolisib treatment were conducted by Western blotting and immunofluorescence assays. The well-docked position of gedatolisib with crystal structure of ABCB1 and ABCG2 were simulated by Autodock vina software. One-way ANOVA was used for the statistics analysis. RESULTS: Gedatolisib competitively increased the accumulation of tritium-labeled substrate-drugs in both ABCB1- and ABCG2-overexpression colorectal cancer cells. Moreover, gedatolisib significantly increased the protein expression level of ABCB1 and ABCG2 in colorectal cancer cells. In addition, gedatolisib remarkably simulated the ATPase activity of both ABCB1 and ABCG2, suggesting that gedatolisib is a substrate drug of both ABCB1 and ABCG2 transporters. Furthermore, a gedatolisib-resistance colorectal cancer cell line, SW620/GEDA, was selected by increasingly treatment with gedatolisib to SW620 cells. The SW620/GEDA cell line was proved to resistant to gedatolisib and a series of chemotherapeutic drugs, except cisplatin. The ABCB1 and ABCG2 were observed overexpression in SW620/GEDA cell line. CONCLUSIONS: These findings suggest that overexpression of ABCB1 and ABCG2 may restrict the efficacy of gedatolisib in colorectal cancer cells, while co-administration with ABC transporter inhibitors may improve the potency of gedatolisib.
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Microplastics and nonylphenol (NP) are considered as emerging pollutant and have attracted wide attention, while their combined toxicity on aquatic organisms is barely researched. Therefore, the combined toxicity influence of NP with three types of microplastics containing polyethylene (PE1000, 13 µm and PE, 150 µm), polyamide (PA1000, 13 µm and PA, 150 µm) polystyrene (PS, 150 µm) on microalgae Chlorella pyrenoidosa was analyzed. Both growth inhibition, chlorophyll fluorescence, superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were determined. We found that single microplastics and NP both inhibited algal growth, thereby causing oxidative stress. The order of inhibition effect in single microplastics experiment was PE1000 > PA1000 > PE ≈ PS > PA. The combined toxicity experiment results indicated that the presence of microplastics had positive effect in terms of alleviating NP toxicity to C. pyrenoidosa, and the microplastics adsorption capacity to NP was the dominant contributing factor for this effect. According to the independent action model, the combined toxicity was antagonistic. Because the negative effect of smaller size microplastics on algal growth was aggravated with prolonged exposure time, the optimum effect of microplastics alleviated NP toxicity was PA1000 at 48 h, while this effect was substituted by PA at 96 h during combined toxicity. Thus, the toxicity of smaller size microplastics has a nonnegligible influence on combined toxicity. This study confirms that microplastics significantly affected the toxicity of organic pollutants on microalgae. Further research on the combined toxicity of smaller size microplastics with pollutants in chronic toxicity is needed.
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Chlorella/efeitos dos fármacos , Microplásticos/toxicidade , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Adsorção , Catalase/metabolismo , Chlorella/enzimologia , Chlorella/metabolismo , Interações Medicamentosas , Malondialdeído/metabolismo , Microalgas/efeitos dos fármacos , Microalgas/enzimologia , Microalgas/metabolismo , Microplásticos/química , Estresse Oxidativo , Poliestirenos/toxicidade , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/químicaRESUMO
Metamaterials, artificially engineered structures with extraordinary physical properties, offer multifaceted capabilities in interdisciplinary fields. To address the looming threat of stealthy monitoring, the detection and identification of metamaterials is the next research frontier but have not yet been explored. Here, we show that the crypto-oriented convolutional neural network (CNN) makes possible the secure intelligent detection of metamaterials in mixtures. Terahertz signals were encrypted by homomorphic encryption and the ciphertext was submitted to the CNN directly for results, which can only be decrypted by the data owner. The experimentally measured terahertz signals were augmented and further divided into training sets and test sets using 5-fold cross-validation. Experimental results illustrated that the model achieved an accuracy of 100% on the test sets, which highly outperformed humans and the traditional machine learning. The CNN took 9.6 s to inference on 92 encrypted test signals with homomorphic encryption backend. The proposed method with accuracy and security provides private preserving paradigm for artificial intelligence-based material identification.
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Bioleaching, a technologically and economically feasible technology, is considered as the high efficiency method to improve dewaterability in sewage sludge. The objective of this study was to investigate the effect of different sludge concentrations on bioleaching dewaterability and understand the mechanism of the effect of bioleaching on sludge dewaterability. Variation in pH, oxidation-reduction potential (ORP), capillary suction time (CST), specific resistance to filtration (SRF) and different fractions of extracellular polymeric substances (EPS) including slime EPS (S-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) were determined. Different sludge concentrations (5, 10, 15, 20 and 30 g·L-1) were selected to investigate during bioleaching. Results indicated that sludge buffering capacity significantly inhibited bioleaching efficiency as sludge concentrations increased. Optimum enhancements in sludge dewaterability were observed during the 10 g·L-1 sludge concentration treatment, and reached a maximum when the pH was 2.11. The variation of different fractions of EPS revealed that the ratio of S-EPS/TB-EPS significantly affected sludge dewaterability. Principal component analysis and Pearson's correlation analysis both provided evidence that the higher TB-EPS followed by a very large reduction was positively correlated with sludge dewaterability. However, the increase of protein and DNA in S-EPS content was negatively correlated with sludge dewaterability.
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Esgotos , Água , Matriz Extracelular de Substâncias Poliméricas , Filtração , ProteínasRESUMO
OBJECTIVE: To explore the feasibility, safety and effectiveness of percutaneous cryoablation combined with systemic chemotherapy in the treatment of liver metastases from esophageal carcinoma (ECLM). MATERIALS AND METHODS: We retrospectively collected data of 16 patients who received CT-guided percutaneous cryoablation concurrent systemic chemotherapy for liver metastases after primary esophageal carcinoma resection. Functional Assessment of Cancer Therapy-General (FACT-G) was used for the assessment of quality of life (QOL), and overall survival (OS), progression-free survival (PFS) and complications were also evaluated. RESULTS: The technical success rate was 96%, and no major complications related to cryoablation procedure were detected. Median OS and PFS after cryoablation were 14.5 months (range, 4-51 months) and 7.5 months (range, 1-31 months), respectively. The 1-year, 2-year, and 3-year survival rates were 56.3%, 31.3%, and 18.8%, respectively. The PFS rate at 6-month, 1-year, and 2-year after procedure were 68.8%, 31.3% and 18.8%, respectively. Furthermore, the QOL of patients was improved after cryoablation therapy compared with preoperative scores (Pâ¯<â¯0.05). CONCLUSIONS: Percutaneous cryoablation combined with systemic chemotherapy is a safe, feasible and effective method to treat liver metastases from esophageal carcinoma. And to a certain extent, this approach is very efficacious in improving the QOL of patients with ECLM.
Assuntos
Criocirurgia/métodos , Neoplasias Esofágicas/patologia , Neoplasias Hepáticas , Intervalo Livre de Progressão , Adulto , Idoso , Criocirurgia/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The present research examined the feasibility of cultivating Chlorella pyrenoidosa in pickle industry wastewater for simultaneous nutrient removal and lipid production. The characteristics of microalgae growth, nutrient removal, lipid accumulation and composition of C. pyrenoidosa cultivated in pickle wastewater with different dilution ratios were investigated. The results showed the maximum algae biomass concentration of 1.57 ± 0.12 g L-1 was achieved in non-diluted pickle wastewater with the highest biomass productivity of 170.65 mg L-1 day-1. Maximum nutrient removal efficiency was observed in 20.0% pickle wastewater with removal rates of chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN) and NH4-N at 84.67%, 92.46%, 85.82% and 93.42%, respectively. The lipid content of C. pyrenoidosa growing in pickle wastewater ranged from 29.73% to 31.78%, with a highest lipid productivity of 57.23 mg L-1 day-1. The relative content of triolefinic acids (C16:3 and C18:3) decreased while the monoenoic acids (C16:1 and C18:1) increased synchronously with the pickle wastewater concentration. Unsaturated fatty acid methyl esters were the main components, ranging from 73.04% to 77.6%. The biodiesel properties satisfied the major specifications in US and European biodiesel standards. The results indicated that C. pyrenoidosa is a promising species for nutrient removal together with lipid production in pickle industry wastewater.