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Despite significant advances in the deep clustering research, there remain three critical limitations to most of the existing approaches. First, they often derive the clustering result by associating some distribution-based loss to specific network layers, neglecting the potential benefits of leveraging the contrastive sample-wise relationships. Second, they frequently focus on representation learning at the full-image scale, overlooking the discriminative information latent in partial image regions. Third, although some prior studies perform the learning process at multiple levels, they mostly lack the ability to exploit the interaction between different learning levels. To overcome these limitations, this paper presents a novel deep image clustering approach via Partial Information discrimination and Cross-level Interaction (PICI). Specifically, we utilize a Transformer encoder as the backbone, coupled with two types of augmentations to formulate two parallel views. The augmented samples, integrated with masked patches, are processed through the Transformer encoder to produce the class tokens. Subsequently, three partial information learning modules are jointly enforced, namely, the partial information self-discrimination (PISD) module for masked image reconstruction, the partial information contrastive discrimination (PICD) module for the simultaneous instance- and cluster-level contrastive learning, and the cross-level interaction (CLI) module to ensure the consistency across different learning levels. Through this unified formulation, our PICI approach for the first time, to our knowledge, bridges the gap between the masked image modeling and the deep contrastive clustering, offering a novel pathway for enhanced representation learning and clustering. Experimental results across six image datasets demonstrate the superiority of our PICI approach over the state-of-the-art. In particular, our approach achieves an ACC of 0.772 (0.634) on the RSOD (UC-Merced) dataset, which shows an improvement of 29.7% (24.8%) over the best baseline. The source code is available at https://github.com/Regan-Zhang/PICI.
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The rectum is an important part of the alimentary canal responsible for ion and water reabsorption of insects. However, it has rarely been studied in the larvae of Panorpidae, the largest family in Mecoptera. Here, we investigated the ultrastructure of larval rectum of the scorpionfly Panorpa liui Hua, 1997 using light and transmission electron microscopy. The rectum comprises tracheal muscular layers, connective tissue, non-cellular basal lamina, junctional cells, rectal epithelium, cuticle with irregular outlines, and a central lumen. The rectal epithelium is infolded to form six longitudinal rectal folds, which are distinct from rectal pads or papillae. In each rectal fold, the apical and basal plasma membranes of epithelial cells are infolded and the lateral plasma membranes form septate and scalariform junctions. The well-developed rectal folds are postulated to be closely associated with reabsorption of ions and water in the larvae. The associations of rectal folds with larval behaviors are briefly discussed in Mecoptera.
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Larva , Microscopia Eletrônica de Transmissão , Reto , Animais , Larva/ultraestrutura , Larva/crescimento & desenvolvimento , Reto/ultraestrutura , Insetos/ultraestruturaRESUMO
OBJECTIVE: To assess the rate at which sutureless partial nephrectomy (SLPN) transitions to standard partial nephrectomy (SPN), focusing on preoperative factors that might prompt such conversions. PATIENTS AND METHODS: In this retrospective study, we analyzed the efficacy of SLPN performed on adults at our institution from 2016 to 2023. The subjects were patients diagnosed with localized solid renal tumors. The primary technique employed was resection with scissors and argon beam coagulation for hemostasis, with suturing techniques used only when necessary. Predictive factors necessitating conversion to SPN were identified, and the associations among multiple variables were explored using various statistical analysis methods, including logistic regression, to identify key preoperative predictive factors. RESULTS: Our institution performed 353 SLPN, with 21 cases (5.9%) necessitating conversion to SPN. The conversion rates for the Laparoscopic Partial Nephrectomy (LPN) subgroup and the Robotic-assist Partial Nephrectomy (RPN) subgroup were 7.9% (17/215) and 2.9% (4/138), respectively, nearing statistical significance (P = .066). Significant differences were observed between the conversion group and the no conversion group in terms of preoperative estimated Glomerular Filtration Rate (eGFR), age at surgery, tumor size, and exophytic/endophytic characteristics. Multivariate analysis identified age at surgery, preoperative eGFR, radiological tumor size, and tumor exophytic/endophytic nature as significant predictors for conversion to SPN. CONCLUSION: This investigation highlights the efficacy and feasibility of SLPN while identifying critical factors influencing the necessity for conversion to SPN. The identified predictors, including younger surgical age, superior preoperative eGFR, and specific tumor characteristics, provide valuable insights for refining surgical strategies.
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Neoplasias Renais , Laparoscopia , Nefrectomia , Humanos , Nefrectomia/métodos , Laparoscopia/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Idoso , Técnicas de Sutura , Conversão para Cirurgia Aberta/estatística & dados numéricos , Adulto , Procedimentos Cirúrgicos RobóticosRESUMO
Microbial degradation is an important solution for antibiotic pollution in livestock and poultry farming wastes. This study reports the isolation and identification of the novel bacterial strain Serratia entomophila TC-1, which can degrade 87.8 % of 200 mg/L tetracycline (TC) at 35 °C, pH 6.0, and an inoculation amount of 1 % (v/v). Based on the intermediate products, a possible biological transformation pathway was proposed, including dehydration, oxidation ring opening, decarbonylation, and deamination. Using Escherichia coli and Bacillus subtilis as biological indicators, TC degraded metabolites have shown low toxicity. Whole-genome sequencing showed that the TC-1 strain contained tet (d) and tet (34), which resist TC through multiple mechanisms. In addition, upon TC exposure, TC-1 participated in catalytic and energy supply activities by regulating gene expression, thereby playing a role in TC detoxification. We found that TC-1 showed less interference with changes in the bacterial community in swine wastewater. Thus, TC-1 provided new insights into the mechanisms responsible for TC biodegradation and can be used for TC pollution treatment.
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Biodegradação Ambiental , Serratia , Tetraciclina , Serratia/metabolismo , Serratia/genética , Tetraciclina/metabolismo , Antibacterianos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Águas Residuárias/microbiologia , Animais , Eliminação de Resíduos Líquidos/métodosRESUMO
BACKGROUND: Erectile dysfunction (ED) seriously affects men's normal life, and obstructive sleep apnoea (OSA) has been diagnosed as a causative factor. Currently, exosomes secreted by adipose mesenchymal stem cells (ADSC) have been used in the non-clinical experimental treatment of ED disease with prominent efficacy due to the advantages of high stability and no immune exclusion. METHODS: In this study, chronic intermittent hypoxia (CIH) exposure was used to induce ED-corresponding phenotypes in Sprague Dawley (SD) rats as well as in cavernous smooth muscle cells (CCSMCs). ED symptoms were treated using exosomes secreted by ADSCs overexpressing circPIP5K1C (EXO-circ) injected into the rat corpus cavernosum. RESULTS: EXO-circ has the effect of ameliorating ED induced by CIH exposure in rats, the mechanism of which is to promote the expression of the downstream target gene SMURF1 after adsorption of miR-153-3p through the sponge so that SMURF1 and PFKFB3 occur protein-protein binding and ubiquitination degradation of PFKFB3 appears to inhibit the occurrence of spongiotic smooth muscle cells glycolysis, and to restore the function of the smooth muscle. CONCLUSIONS: These findings show that EXO-circ have a promising therapeutic potential in OSA-induced ED.
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Disfunção Erétil , Exossomos , Células-Tronco Mesenquimais , Miócitos de Músculo Liso , Ratos Sprague-Dawley , Ubiquitina-Proteína Ligases , Animais , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Exossomos/genética , Masculino , Ratos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Disfunção Erétil/genética , Disfunção Erétil/terapia , Disfunção Erétil/metabolismo , Disfunção Erétil/patologia , Miócitos de Músculo Liso/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/citologia , Humanos , Modelos Animais de DoençasRESUMO
BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.
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Bloqueio de Ramo , Terapia de Ressincronização Cardíaca , Humanos , Terapia de Ressincronização Cardíaca/métodos , Eletrocardiografia , Sistema de Condução Cardíaco , Ventrículos do Coração , Resultado do TratamentoRESUMO
The abdominal appendages of larval insects have a complex evolutionary history of gain and loss, but the regulatory mechanisms underlying the abdominal appendage development remain largely unclear. Here, we investigated the embryogenesis of abdominal prolegs in the scorpionfly Panorpa liui Hua (Mecoptera: Panorpidae) using in situ hybridization and parental RNA interference. The results show that RNAi-mediated knockdown of Ultrabithorax (Ubx) led to a homeotic transformation of the first abdominal segment (A1) into the third thoracic segment (T3) and changed the distributions of the downstream target Distal-less (Dll) expression but did not affect the expression levels of Dll. Knockdown of abdominal-A (abd-A) resulted in malformed segments, abnormal prolegs and disrupted Dll expression. The results demonstrate that the gene Ubx maintains an ancestral role of modulating A1 appendage fate without preventing Dll initiation, and a secondary adaptation of abd-A evolves the ability to specify abdominal segments and proleg identity. We conclude that changes in abdominal Hox gene expression and their target genes regulate abdominal appendage morphology during the evolutionary course of holometabolous larvae.
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Proteínas de Drosophila , Genes Homeobox , Animais , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Desenvolvimento Embrionário , Insetos/genética , Larva , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Drosophila/genéticaRESUMO
The treatment of cooking oil wastewater is an urgent issue need to be solved. We aimed to screen for efficient oil-degrading bacteria and develop a new microbial agent for degrading waste cooking oil in oily wastewater. Three extremely effective oil-degrading bacteria, known as YZQ-1, YZQ-3, and YZQ-4, were found by the enrichment and acclimation of samples from various sources and separation using oil degradation plates. The 16S rRNA sequencing analysis and phylogenetic tree construction showed that the three strains were Bacillus tropicus, Pseudomonas multiresinivorans, and Raoultella terrigena. Under optimal degradation conditions, the maximal degradation rates were 67.30 ± 3.69%, 89.65 ± 1.08%, and 79.60 ± 5.30%, respectively, for YZQ-1, YZQ-3, and YZQ-4. Lipase activity was highest for YZQ-3, reaching 94.82 ± 12.89 U/L. The best bacterial alliance was obtained by adding equal numbers of microbial cells from the three strains. Moreover, when this bacterial alliance was applied to oily wastewater, the degradation rate of waste cooking oil was 61.13 ± 7.30% (3.67% ± 2.13% in the control group), and COD removal was 62.4% ± 5.65% (55.60% ± 0.71% in the control group) in 72 h. Microbial community analysis results showed YZQ-1 and YZQ-3 were adaptable to wastewater and could coexist with local bacteria, whereas YZQ-4 could not survive in wastewater. Therefore, the combination of YZQ-1 and YZQ-3 can efficiently degrade oil and shows great potential for oily wastewater treatment.
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Óleos , Águas Residuárias , RNA Ribossômico 16S/metabolismo , Filogenia , Bactérias/metabolismo , Biodegradação AmbientalRESUMO
A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.
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Medicina Tradicional Chinesa , Deficiência da Energia Yin , Humanos , Deficiência da Energia Yin/diagnóstico , Deficiência da Energia Yang/diagnóstico , Estudos Transversais , SíndromeRESUMO
Myeloid-derived suppressor cells (MDSCs), major components maintaining the immune suppressive microenvironment in lung cancer, are relevant to the invasion, metastasis, and poor prognosis of lung cancer, through the regulation of epithelial-mesenchymal transition, remodeling of the immune microenvironment, and regulation of angiogenesis. MDSCs regulate T-cell immune functions by maintaining a strong immunosuppressive microenvironment and promoting tumor invasion. This raises the question of whether reversing the immunosuppressive effect of MDSCs on T cells can improve lung cancer treatment. To understand this further, this review explores the interactions and specific mechanisms of different MDSCs subsets, including regulatory T cells, T helper cells, CD8 + T cells, natural killer T cells, and exhausted T cells, as part of the lung cancer immune microenvironment. Second, it focuses on the guiding significance confirmed via clinical liquid biopsy and tissue biopsy that different MDSC subsets improve the prognosis of lung cancer. Finally, we conclude that targeting MDSCs through action targets or signaling pathways can help regulate T-cell immune functions and suppress T-cell exhaustion. In addition, immune checkpoint inhibitors targeting MDSCs may serve as a new approach for enhancing the efficiency of immunotherapy and targeted therapy for lung cancer in the future, providing better comprehensive options for lung cancer treatment.
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Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.
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Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Ratos , Canais de Potássio Ativados por Cálcio de Condutância Alta , Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase , Isquemia Encefálica/tratamento farmacológicoRESUMO
Adult hangingflies are very sensitive to humidity, thereby frequently being used as ecological indicators to assess the degradation of the environment, especially forest ecosystems. Studies on the sense organs associated with hygro- and thermo-sensitivity, however, have been scant. Here, the ultramorphology and distribution of the flagellar sensilla were investigated in the adult hangingflies Bittacus planus Cheng, 1949 and Bittacus sinicus Issiki, 1931 using scanning electron microscopy. Four types of sensilla are identified in B. planus, including sensilla campaniformia, sensilla chaetica (SC1, SC2), sensilla basiconica (SB1, SB2), and sensilla coeloconica. In B. sinicus, sensilla chaetica III are present additionally from 7th to 14th flagellomeres. Abundant sensilla coeloconica are present on the flagella of Bittacus. Sensilla basiconica I are situated at the joints of flagellomeres. Sensilla campaniformia are densely distributed on the basal half of the first flagellomere, but scarcely on other flagellomeres. Sensilla chaetica II are present on the distal three flagellomeres. The size, abundance, and distribution of flagellar sensilla differ considerably between B. planus and B. sinicus. We infer that the abundance of sensilla coeloconica is likely associated with the hygro- and thermo-sensitivity in Bittacidae. Studies of flagellar sensilla can provide valuable information for subsequent electrophysiological, behavioral, biogeographical, and phylogenetic analyses of Bittacidae.
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Ecossistema , Holometábolos , Animais , Filogenia , Sensilas , FlagelosRESUMO
Waste classification management is effective in addressing the increasing waste output and continuous deterioration of environmental conditions. The waste classification behaviour of resident is an important basis for managers to collect and allocate resources. Traditional analysis methods, such as questionnaire, have limitations considering the complexity of individual behaviour. An intelligent waste classification system (IWCS) was applied and studied in a community for 1 year. Time-based data analysis framework was constructed to describe the residents' waste sorting behaviour and evaluate the IWCS. The results showed that residents preferred to use face recognition than other modes of identification. The ratio of waste delivery frequency was 18.34% in the morning and 81.66% in the evening, respectively. The optimal time windows of disposing wastes were from 6:55 to 9:05 in the morning and from 18:05 to 20:55 in the evening which can avoid crowding. The percentage of accuracy of waste disposal increased gradually in a year. The amount of waste disposal was largest on every Sunday. The average accuracy was more than 94% based on monthly data, but the number of participating residents decreased gradually. Therefore, the study demonstrates that IWCS is a potential platform for increasing the accuracy and efficiency of waste disposal and can promote regulations implementation.
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Reciclagem , Eliminação de Resíduos , Resíduos Sólidos , Gerenciamento de Resíduos , Resíduos de Alimentos , Resíduos Sólidos/classificação , Gerenciamento de Resíduos/métodos , ChinaRESUMO
Removing erythromycin from the environment is a major challenge. In this study, a dual microbial consortium (Delftia acidovorans ERY-6A and Chryseobacterium indologenes ERY-6B) capable of degrading erythromycin was isolated, and the erythromycin biodegradation products were studied. Coconut shell activated carbon was modified and its adsorption characteristics and erythromycin removal efficiency of the immobilized cells were studied. It was indicated that alkali-modified and water-modified coconut shell activated carbon and the dual bacterial system had excellent erythromycin removal ability. The dual bacterial system follows a new biodegradation pathway to degrade erythromycin. The immobilized cells removed 95% of erythromycin at a concentration of 100 mg L-1 within 24 h through pore adsorption, surface complexation, hydrogen bonding, and biodegradation. This study provides a new erythromycin removal agent and for the first time describes the genomic information of erythromycin-degrading bacteria, providing new clues regarding bacterial cooperation and efficient erythromycin removal.
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Carvão Vegetal , Eritromicina , Eritromicina/química , Bactérias/genética , Biodegradação Ambiental , AdsorçãoRESUMO
Two new species of Terrobittacus Tan & Hua, 2009 are described and illustrated from Sichuan and Guangxi provinces of China, increasing the species number of Terrobittacus to eight. Terrobittacusemeishanicussp. nov. is differentiated from its congeners by wings with distinct markings and a female subgenital plate with a V-shaped carina. Terrobittacuslaoshanicussp. nov. can be recognized by the black terga VI-IX. A key to species of Terrobittacus is updated. The species distribution and the relationship between adult morphology and mating behavior were briefly discussed.
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Objective To evaluate the performance of myPKFiT,a tool guiding the dosing of antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM),in maintaining the coagulation factor â § (Fâ §) level above a target threshold at the steady state and estimating the pharmacokinetics (PK) parameters in hemophilia A patients in China. Methods The data of 9 patients with severe hemophilia A in a trial (CTR20140434) assessing the safety and efficacy of rAHF-PFM in the Chinese patients with hemophilia A were analyzed.The myPKFiT was used to predict the adequate dose to maintain a patient's Fâ § level above target threshold at the steady state.Furthermore,the performance of myPKFiT in estimating the pharmacokinetics parameters of individuals was evaluated. Results Twelve combinations of two dosing intervals and six sparse sampling schedules were investigated,and 57%-88% of the patients remained the Fâ § level above the target threshold of 1 U/dl (1%) for at least 80% of the dosing interval.The clearance and time to Fâ § level of 1% obtained from sparse sampling by myPKFiT were similar to those obtained from extensive sampling. Conclusions The myPKFiT can provide adequate dose estimates to maintain the Fâ § level above the target threshold at the steady state in Chinese patients with severe hemophilia A.Moreover,it demonstrates good performance for estimating key pharmacokinetics parameters,including clearance and time to Fâ § level of 1%.
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Fator VIII , Hemofilia A , Humanos , China , População do Leste Asiático , Fator VIII/farmacocinética , Hemofilia A/tratamento farmacológicoRESUMO
Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML. Results: We developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype. Conclusions: Our study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML.
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The Bittacidae are unique in holometabolous insects in that their larvae bear a dorsal ocellus on the frons. The fine structure of the dorsal ocellus, however, has not been investigated to date. Here, the ultrastructure of the larval dorsal ocellus was studied in the hangingfly Bittacus planus Cheng, 1949 using light, scanning, and transmission electron microscopy. The dorsal ocellus of the larvae comprises a cornea, corneagenous cells, and retinula cells. The cornea is a laminated structure. A layer of corneagenous cells is located below the cornea. Numerous retinula cells are arranged tightly beneath the corneagenous cells. The retinula cells modify their adjacent membranes into numerous linear microvilli, which form an analogue of the rhabdom among adjacent retinula cells. The results show that the dorsal ocellus of larval Bittacidae is a highly vestigial organ and appears to be degenerating during the postembryonic development. The presence of the vestigial dorsal ocellus is likely to represent an ancestral plesiomorphy of holometabolous insects, providing new evidence for exploring the evolutionary origin of holometabolous larvae.
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Holometábolos , Insetos , Animais , Larva/ultraestrutura , Insetos/ultraestrutura , Microscopia Eletrônica de Transmissão , Evolução Biológica , Córnea/ultraestruturaRESUMO
OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Terapia CombinadaRESUMO
Background: We explored the characteristics of single-cell differentiation data in glioblastoma and established prognostic markers based on CRYAB to predict the prognosis of glioblastoma patients. Aberrant expression of CRYAB is associated with invasive behavior in various tumors, including glioblastoma. However, the specific role and mechanisms of CRYAB in glioblastoma are still unclear. Methods: We assessed RNA-seq and microarray data from TCGA and GEO databases, combined with scRNA-seq data on glioma patients from GEO. Utilizing the Seurat R package, we identified distinct survival-related gene clusters in the scRNA-seq data. Prognostic pivotal genes were discovered through single-factor Cox analysis, and a prognostic model was established using LASSO and stepwise regression algorithms. Moreover, we investigated the predictive potential of these genes in the immune microenvironment and their applicability in immunotherapy. Finally, in vitro experiments confirmed the functional significance of the high-risk gene CRYAB. Results: By analyzing the ScRNA-seq data, we identified 28 cell clusters representing seven cell types. After dimensionality reduction and clustering analysis, we obtained four subpopulations within the oligodendrocyte lineage based on their differentiation trajectory. Using CRYAB as a marker gene for the terminal-stage subpopulation, we found that its expression was associated with poor prognosis. In vitro experiments demonstrated that knocking out CRYAB in U87 and LN229 cells reduced cell viability, proliferation, and invasiveness. Conclusion: The risk model based on CRYAB holds promise in accurately predicting glioblastoma. A comprehensive study of the specific mechanisms of CRYAB in glioblastoma would contribute to understanding its response to immunotherapy. Targeting the CRYAB gene may be beneficial for glioblastoma patients.