RESUMO
Conventional microalgal-bacterial consortia have limited capacity to treat low-C/N wastewater due to carbon limitation and single nitrogen (N) removal mode. In this work, indigenous synergetic microalgal-bacterial consortia with high N removal performance and bidirectional interaction were successful in treating rare earth tailing wastewaters with low-C/N. Ammonia removal reached 0.89 mg N L-1 h-1, 1.84-fold more efficient than a common microalgal-bacterial system. Metagenomics-based metabolic reconstruction revealed bidirectional microalgal-bacterial interactions. The presence of microalgae increased the abundance of bacterial N-related genes by 1.5- to 57-fold. Similarly, the presence of bacteria increased the abundance of microalgal N assimilation by 2.5- to 15.8-fold. Furthermore, nine bacterial species were isolated, and the bidirectional promotion of N removal by the microalgal-bacterial system was verified. The mechanism of microalgal N assimilation enhanced by indole-3-acetic acid was revealed. In addition, the bidirectional mode of the system ensured the scavenging of toxic byproducts from nitrate metabolism to maintain the stability of the system. Collectively, the bidirectional enhancement system of synergetic microalgae-bacteria was established as an effective N removal strategy to broaden the stable application of this system for the effective treatment of low C/N ratio wastewater.
Assuntos
Microalgas , Águas Residuárias , Microalgas/metabolismo , Desnitrificação , Nitrogênio/metabolismo , Bactérias/metabolismo , BiomassaRESUMO
Microalgal technology holds great promise for both low C/N wastewater treatment and resource recovery simultaneously. Nevertheless, the advancement of microalgal technology is hindered by its reduced nitrogen removal efficiency in low C/N ratio wastewater. In this work, microalgae and waste oyster shells were combined to achieve a total inorganic nitrogen removal efficiency of 93.85% at a rate of 2.05 mg L-1 h-1 in low C/N wastewater. Notably, over four cycles of oyster shell reuse, the reactor achieved an average 85% ammonia nitrogen removal extent, with a wastewater treatment cost of only $0.092/ton. Moreover, microbial community analysis during the reuse of oyster shells revealed the critical importance of timely replacement in inhibiting the growth of non-functional bacteria (Poterioochromonas_malhamensi). The work demonstrated that the oyster shell - microalgae system provides a time- and cost-saving, environmental approach for the resourceful treatment of harsh low C/N wastewater.
Assuntos
Exoesqueleto , Carbono , Microalgas , Nitrogênio , Ostreidae , Eliminação de Resíduos Líquidos , Águas Residuárias , Animais , Nitrogênio/análise , Nitrogênio/metabolismo , Microalgas/crescimento & desenvolvimento , Águas Residuárias/química , Exoesqueleto/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análiseRESUMO
Fish represent a large part of the taxonomic diversity of vertebrates and are of high commercial value. However, the factors influencing the gut microbiota composition of freshwater fish over large spatial scales remain unclear. Therefore, this study explored gut microbiome diversity in 24 fish species from the Yellow River, which spans over 1500 km across China. The results showed that geographical distance, host phylogeny and diet significantly influenced gut microbial community diversity, whereas sex, body length and body weight had minimal influence. Geographical distance was the primary factor shaping gut microbiota, and dissimilarity in microbial community structure increased with an increase in geographical distance, which was mainly driven by dispersal limitation. The microbial communities were more homogeneous at higher host taxonomic resolutions due to the dominant role of homogeneous selection in community convergence. Phylosymbiosis was observed across all host species, with a stronger pattern in Cypriniformes, which harbour host-specific microbial taxa. Host diet explained little variation in gut microbiome diversity, although it was significant for all diversity metrics tested. These findings collectively suggest that the geographical and host-based patterns of fish gut microbiota tend to be shaped by different ecological forces across the Yellow River. The present work provides a robust assessment of multiple factors driving fish gut microbial community assembly and offers insight into the mechanisms underlying shifts in fish gut microbiota in rivers across large spatial scales.
Assuntos
Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/genética , Rios , Peixes , Evolução Biológica , Filogenia , Dieta , RNA Ribossômico 16S/genéticaRESUMO
Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.
Assuntos
Diploide , Tetraploidia , Humanos , Filogenia , Evolução Biológica , PoliploidiaRESUMO
To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
Assuntos
Encefalite , Infecções por Vírus Epstein-Barr , Masculino , Humanos , Feminino , Autoimunidade , Estudos Retrospectivos , Herpesvirus Humano 4 , Autoanticorpos , Imunoglobulina GRESUMO
BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.
Assuntos
Analgesia Epidural , Nalbufina , Retenção Urinária , Gravidez , Recém-Nascido , Feminino , Humanos , Ropivacaina , Estudos Retrospectivos , Dor , FentanilaRESUMO
OBJECTIVE: To investigative the performance of intratumoral and peritumoral radiomics based on contrast-enhanced spectral mammography (CESM) to preoperatively predict the effect of the neoadjuvant chemotherapy (NAC) of breast cancers. MATERIALS AND METHODS: A total of 118 patients with breast cancer who underwent preoperative CESM and NAC from July 2017 to June 2020 were retrospectively analyzed, and the patients were grouped into training (n = 81) and test sets (n = 37) according to the CESM examination time. NAC effect for each patient was assessed by pathology. Intratumoral and peritumoral radiomics features were extracted from CESM images, and feature selection was performed through the Mann-Whitney U test and least absolute shrinkage and selection operator regression (LASSO). Five radiomics signatures based on intratumoral regions, 5-mm peritumoral regions, 10-mm peritumoral regions, intratumoral regions + 5-mm peritumoral regions, and intratumoral regions + 10-mm peritumoral regions were calculated through a linear combination of selected features weighted by their respective coefficients. The prediction performance of radiomics signatures was assessed by the area under the receiver operator characteristic (ROC) curve, the precision-recall (P-R) curve, the calibration curve, and decision curve analysis (DCA). RESULTS: Ten radiomics features were selected to establish the radiomics signature of intratumoral regions + 5-mm peritumoral regions, which yielded a maximum AUC of 0.85 (95% CI, 0.72-0.98) in the test set. The calibration curves, P-R curves, and DCA showed favorable predictive performance of the five radiomics signatures. CONCLUSION: The intratumoral and peritumoral radiomics based on CESM exhibited potential for predicting the NAC effect in breast cancer, which could guide treatment decisions. KEY POINTS: ⢠The intratumoral and peritumoral CESM-based radiomics signatures show good performance in predicting the NAC effect in breast cancer.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamografia/métodos , Estudos RetrospectivosRESUMO
No sunlight can reach the hadal trench, but some fishes dwelling there still have apparent eye morphology. However, whether they are capable of sensing light remains unknown. In this study, the eyes of the dominant hadal endemic snailfish Pseudoliparis swirei from the Mariana Trench were analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A total of 2088 proteins were identified in the eye proteome, most of which had at least one hit against public databases and could be mapped to 316 metabolic pathways. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways directly contributing to visual phototransduction were significantly enriched from the top 10% dominant proteins, implying abundant metabolic activities in the eye and it is still a functional visual organ. One rhodopsin was identified in the eye proteome, sequence analysis indicated that it might have an absorption maximum at â¼480 nm and be sensitive to dim blue light. In addition, proteins that might contribute to extreme environment adaptation, such as heat shock proteins and chaperonin-containing T-complex protein 1, were also highly expressed in the eye. Overall, these results provide insights into the molecular mechanism underlying the vision of hadal snailfish and provide a useful database for further research.
Assuntos
Proteômica , Espectrometria de Massas em Tandem , Aclimatação , Animais , Cromatografia Líquida , PeixesRESUMO
BACKGROUND: Most cancer cells are more glycolytic even under aerobic conditions compared with their normal counterparts. Recent evidence of tumor cell metabolism, however, shows that some tumors also increase mitochondrial oxidative phosphorylation (ox-phos) at some disease states during progression and/or development of drug resistance. Our data show that anti-androgen enzalutamide (ENZA) resistant prostate cancer (PCa) cells use more mitochondrial metabolism leading to higher ox-phos as compared to the ENZA-sensitive cells and can become vulnerable to mitochondrial metabolism targeted therapies. METHODS: Seahorse assay, mass spectrometry and high resolution fluorescence confocal microscopy coupled with image analysis has been used to compare mitochondrial metabolism in ENZA-treated and -untreated anti-androgen-sensitive LNCaP and -resistant C4-2, CWR22ν1, and PCa2b cells. Ex vivo fluorescence microscopy and image analysis has been standardized to monitor mitochondrial electron transport (ETS) activity that likely increases ox-phos in circulating tumor cells (CTCs) isolated fom patients undergoing AR-targeted therapies. RESULTS: Our data show that PCa cells that are resistant to anti-androgen ENZA switch from glycolysis to ox-phos leading to an increased ETS activity. ENZA pretreated cells are more vulnerable to ETS component complex I inhibitor IACS-010759 (IACS) and mitochondrial glutaminase inhibitor CB-839 that reduces glutamate supply to tricarboxylic acid cycle. CTCs isolated from 6 of 20 patient blood samples showed relatively higher ETS activity than the rest of the patients. All six patients have developed ENZA resistance within less than 6 months of the sample collection. CONCLUSION: The enhanced growth inhibitory effects of mitochondrial metabolic inhibitors IACS and CB-839 in ENZA pretreated PCa cells provides a rationale for designing a drug combination trial. Patients can be selected for such trials by monitoring the mitochondrial ETS activities in their CTCs to maximize success.
Assuntos
Antagonistas de Androgênios/farmacologia , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Glicólise/fisiologia , Mitocôndrias/metabolismo , Nitrilas/farmacologia , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Benzenoacetamidas/farmacologia , Benzenoacetamidas/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Glicólise/efeitos dos fármacos , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêuticoRESUMO
To investigate the factors associated with the duration of severe acute respiratory syndrome coronavirus 2 RNA shedding in patients with coronavirus disease 2019 (COVID-19). A retrospective cohort of COVID-19 patients admitted to a designated hospital in Beijing was analyzed to study the factors affecting the duration of viral shedding. The median duration of viral shedding was 11 days (IQR, 8-14.3 days) as measured from illness onset. Univariate regression analysis showed that disease severity, corticosteroid therapy, fever (temperature>38.5°C), and time from onset to hospitalization were associated with prolonged duration of viral shedding (P < .05). Multivariate regression analysis showed that fever (temperature>38.5°C) (OR, 5.1, 95%CI: 1.5-18.1), corticosteroid therapy (OR, 6.3, 95%CI: 1.5-27.8), and time from onset to hospitalization (OR, 1.8, 95%CI: 1.19-2.7) were associated with increased odds of prolonged duration of viral shedding. Corticosteroid treatment, fever (temperature>38.5°C), and longer time from onset to hospitalization were associated with prolonged viral shedding in COVID-19 patients.
Assuntos
COVID-19/virologia , SARS-CoV-2/fisiologia , Eliminação de Partículas Virais/fisiologia , Corticosteroides/uso terapêutico , Adulto , COVID-19/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/isolamento & purificação , Fatores de Risco , Fatores de Tempo , Tratamento Farmacológico da COVID-19RESUMO
Almost all prey live in habitats with predators with different hunting modes; however, most studies on predation have investigated the effects of only one predator at a time. In this study, we aimed to investigate whether qingbo (Spinibarbus sinensis), a common cyprinid fish, responds differently to active hunting and ambush predators and how qingbo responds when both types of predators coexist. Juvenile qingbo were subjected to catfish (Clarias fuscus, active hunter) exposure, snakehead fish (Channa argus, ambush hunter) exposure, or mixed predator exposure (catfish and snakehead coexistence) for a duration of 60 days. Then, their growth, behaviors, swimming performance, and metabolism were measured. Qingbo subjected to active hunting predator exposure exhibited decreased activity and predator inspection and improved fast-start escape performance compared to those in the control group. However, none of the parameters of the fish subjected to ambush predator exposure changed significantly. Fish subjected to mixed predator exposure exhibited improved fast-start escape performance but increased maintenance energy expenditure, whereas no changes were observed in any of the behavioral variables. Qingbo showed a stronger anti-predator response to active hunting predators than to ambush predators, suggesting that the fish exhibit a stronger anti-predator response to a current direct threat than to a potential threat (a predator exists nearby but seldom presents in attack behavior). Additionally, the response of prey fish to multiple predators was quite complex, and the coexistence and interaction of multiple predator species with different hunting modes may lead to serious stress responses and confound the prey's behavioral responses to each predator.
Assuntos
Cyprinidae , Caça , Animais , Ecossistema , Locomoção , Comportamento PredatórioRESUMO
Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Interleucina-6/biossíntese , Interleucina-6/genética , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 µM, 1.87 µM, and 1.19 µM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 µM and 1.37 µM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 µM.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzofenantridinas/química , Fenantridinas/química , Fenantridinas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Fenantridinas/síntese química , Relação Estrutura-AtividadeRESUMO
Fish typically prefer to live in big shoals due to the associated ecological benefits. Shoaling is a behavior that depends on the ability to quantitatively discriminate. The fundamental mechanism involved in quantity discrimination determines whether fish can discriminate a shoal using numerical discrete cues (e.g., number of shoal members), non-numerical continuous traits (e.g., total body surface area) or both; however, the mechanism is currently a controversial topic. In the present study, we used a spontaneous choice experiment to test whether guppy (Poecilia reticulata), zebrafish (Danio rerio), Chinese crucian carp (Carassius auratus) and qingbo (Spinibarbus sinensis) rely on continuous (i.e., body surface area) or discrete (i.e., number of shoal members) information for shoal selection by altering the body surface area (cumulative body surface area ratio of 3:2 or 1:1) between two stimulus shoals with a different number of members (2 individuals vs 3 individuals). All four fish species preferred to shoal with the stimulus shoal with the larger cumulative surface area even if the shoal had fewer members; however, fish showed no shoal preference when the cumulative surface body areas of both stimulus shoals were equal. Furthermore, qingbo did not numerically discriminate between a shoal with 1 individual and a shoal with 3 individuals when the cumulative surface areas of both stimulus shoals were equal; however, qingbo showed a preference for the shoal with the larger cumulative surface area when the two stimulus shoals each had 3 individuals. In conclusion, the present study demonstrated that all four fish species relied only on non-numerical continuous quantity information for shoal selection, at least under a difficult task (i.e., 2 vs 3).
Assuntos
Comportamento de Escolha , Peixes/fisiologia , Comportamento Social , Animais , Comportamento Animal , Superfície Corporal , Sinais (Psicologia)RESUMO
Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic potentials of EZH2 by targeting both its catalytic and non-catalytic functions. To date, there have been no reported high-throughput screening (HTS) assays for inhibitors acting at the EZH2-EED interface. In this study, we developed a fluorescence polarization (FP)-based HTS system for the discovery of EZH2-EED interaction inhibitors. The tracer peptide sequences, positions of fluorescein labeling, and a variety of physicochemical conditions were optimized. The high Z' factors (>0.9) at a variety of DMSO concentrations suggested that this system is robust and suitable for HTS. The minimal sequence requirement for the EZH2-EED interaction was determined by using this system. A pilot screening of an in-house compound library containing 1600 FDA-approved drugs identified four compounds (apomorphine hydrochloride, oxyphenbutazone, nifedipine and ergonovine maleate) as potential EZH2-EED interaction inhibitors.
Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Complexo Repressor Polycomb 2/antagonistas & inibidores , Complexo Repressor Polycomb 2/metabolismo , Multimerização Proteica/efeitos dos fármacos , Apomorfina/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/síntese química , Ergonovina/farmacologia , Polarização de Fluorescência , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Nifedipino/farmacologia , Oxifenilbutazona/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , TemperaturaRESUMO
OBJECTIVE: To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. METHODS: Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. RESULTS: Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). CONCLUSION: Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.
Assuntos
Precondicionamento Isquêmico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Estresse Oxidativo , Substâncias Protetoras , Xenônio , Animais , Infarto do Miocárdio , Miocárdio/patologia , CoelhosRESUMO
PURPOSE: To assess T1 mapping performance in distinguishing between benign and malignant breast lesions and to explore its correlation with histopathologic features in breast cancer. METHODS: This study prospectively enrolled 103 participants with a total of 108 lesions, including 25 benign and 83 malignant lesions. T1 mapping, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) were performed. Two radiologists independently outlined the ROIs and analyzed T1 and apparent diffusion coefficient (ADC) values for each lesion, assessing interobserver reliability with the intraclass correlation coefficient (ICC). T1 and ADC values were compared between benign and malignant lesions, across different histopathological characteristics (histological grades, estrogen, progesterone and HER2 receptors expression, Ki67, N status). Receiver operating characteristic (ROC) analysis and Pearson correlation coefficient (ρ) were performed. RESULTS: T1 values showed statistically significant differences between benign and malignant groups (P < 0.001), with higher values in the malignant (1817.08 ms ± 126.64) compared to the benign group (1429.31 ms ± 167.66). In addition, T1 values significantly increased in the ER (-) group (P = 0.001). No significant differences were found in T1 values among HER2, Ki67, N status, and histological grades groups. Furthermore, T1 values exhibited a significant correlation (ρ) with ER (P < 0.01) and PR (P = 0.03). The AUC for T1 value in distinguishing benign from malignant lesions was 0.69 (95 % CI: 0.55 - 0.82, P = 0.005), and for evaluating ER status, it was 0.75 (95 % CI: 0.62 - 0.87, P = 0.002). CONCLUSIONS: T1 mapping holds the potential as an imaging biomarker to assist in the discrimination of benign and malignant breast lesions and assessing the ER expression status in breast cancer.
Assuntos
Neoplasias da Mama , Meios de Contraste , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Reprodutibilidade dos Testes , Idoso , Diagnóstico Diferencial , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Sensibilidade e EspecificidadeRESUMO
Alkaline lakes are extreme environments inhabited by diverse microbial extremophiles. However, large-scale distribution patterns, environmental adaptations, community assembly, and evolutionary dynamics of microbial communities remain largely underexplored. This study investigated the characteristics of microbial communities on rare and abundant taxa in alkaline lake sediments in west and northwest China. We observed that abundant taxa varied significantly with geographical distance, while rare taxa remained unaffected by regional differences. The assembly process of abundant taxa was influenced by dispersal limitation, whilst rare taxa were predominantly driven by heterogeneous selection. Network analysis indicated that rare taxa as core species for community interactions and community stability. Rare taxa exhibited higher speciation and transition rate than abundant taxa, serving as a genetic reservoir and potential candidates to become abundance taxa, highlighting their crucial role in maintaining microbial diversity. These insights underscore the significant influence of rare taxa on ecosystem biodiversity and stability in alkaline lakes.
Assuntos
Bactérias , Biodiversidade , Sedimentos Geológicos , Lagos , Lagos/microbiologia , Sedimentos Geológicos/microbiologia , China , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Filogenia , RNA Ribossômico 16S/genética , Microbiota , Archaea/classificação , Archaea/genética , Archaea/isolamento & purificação , Concentração de Íons de Hidrogênio , Ecossistema , Álcalis/análiseRESUMO
Five new compounds, including two sesquiterpenoid glycosides (1 and 2), two monoterpenoid glycosides (3 and 4), and a quinovose ester (5), together with four known compounds (6-9) were isolated from branches and leaves of Pittosporum pulchrum Gagnep. Their structures were established by 1D and 2D NMR, HR-ESI-MS, IR and UV spectral analyses. This is the first time to investigate the chemical constituents of P. pulchrum. Subsequently, the anti-inflammatory and antioxidant activities of different solvent fractions of ethanol extract and isolated compounds were evaluated. Dichloromethane and ethyl acetate fractions dramatically inhibited the production of NO in a concentration-dependent manner in LPS-induced RAW264.7 cells. Ethyl acetate and n-butanol fractions showed excellent DPPH radical scavenging activities with IC50 values of 24.31 µg/mL and 27.81 µg/mL, respectively. Compounds 7 and 8 might be potential natural antioxidants with IC50 values of 16.13 µM and 24.81 µM, respectively.
Assuntos
Anti-Inflamatórios , Antioxidantes , Compostos Fitoquímicos , Folhas de Planta , Folhas de Planta/química , Camundongos , Células RAW 264.7 , Animais , Estrutura Molecular , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/química , Óxido Nítrico/metabolismo , Caules de Planta/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/química , China , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologiaRESUMO
Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.