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Quality control in quantitative proteomics is a persistent challenge, particularly in identifying and managing outliers. Unsupervised learning models, which rely on data structure rather than predefined labels, offer potential solutions. However, without clear labels, their effectiveness might be compromised. Single models are susceptible to the randomness of parameters and initialization, which can result in a high rate of false positives. Ensemble models, on the other hand, have shown capabilities in effectively mitigating the impacts of such randomness and assisting in accurately detecting true outliers. Therefore, we introduced SEAOP, a Python toolbox that utilizes an ensemble mechanism by integrating multi-round data management and a statistics-based decision pipeline with multiple models. Specifically, SEAOP uses multi-round resampling to create diverse sub-data spaces and employs outlier detection methods to identify candidate outliers in each space. Candidates are then aggregated as confirmed outliers via a chi-square test, adhering to a 95% confidence level, to ensure the precision of the unsupervised approaches. Additionally, SEAOP introduces a visualization strategy, specifically designed to intuitively and effectively display the distribution of both outlier and non-outlier samples. Optimal hyperparameter models of SEAOP for outlier detection were identified by using a gradient-simulated standard dataset and Mann-Kendall trend test. The performance of the SEAOP toolbox was evaluated using three experimental datasets, confirming its reliability and accuracy in handling quantitative proteomics.
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Gerenciamento de Dados , Proteômica , Reprodutibilidade dos Testes , Controle de Qualidade , Interpretação Estatística de DadosRESUMO
With the rapid development of single-molecule sequencing (SMS) technologies, the output read length is continuously increasing. Mapping such reads onto a reference genome is one of the most fundamental tasks in sequence analysis. Mapping sensitivity is becoming a major concern since high sensitivity can detect more aligned regions on the reference and obtain more aligned bases, which are useful for downstream analysis. In this study, we present pathMap, a novel k-mer graph-based mapper that is specifically designed for mapping SMS reads with high sensitivity. By viewing the alignment chain as a path containing as many anchors as possible in the matched k-mer graph, pathMap treats chaining as a path selection problem in the directed graph. pathMap iteratively searches the longest path in the remaining nodes; more candidate chains with high quality can be effectively detected and aligned. Compared to other state-of-the-art mapping methods such as minimap2 and Winnowmap2, experiment results on simulated and real-life datasets demonstrate that pathMap obtains the number of mapped chains at least 11.50% more than its closest competitor and increases the mapping sensitivity by 17.28% and 13.84% of bases over the next-best mapper for Pacific Biosciences and Oxford Nanopore sequencing data, respectively. In addition, pathMap is more robust to sequence errors and more sensitive to species- and strain-specific identification of pathogens using MinION reads.
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Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento por Nanoporos , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genoma , Software , AlgoritmosRESUMO
Exosomes are increasingly being regarded as emerging and promising biomarkers for cancer screening, diagnosis, and therapy. The downstream molecular analyses of exosomes were greatly affected by the isolation efficiency from biosamples. Among the current exosome isolation strategies, affinity nanomaterials performed comparably better with selectivity and specificity. However, these techniques did not take the structure and size of exosomes into account, which may lead to a loss of isolation efficiency. In this article, a framework nucleic acid was employed to prepare a well-designed nanosized bead Fe3O4@pGMA@DNA TET@Ti4+ for enrichment of exosomes. The abundant phosphate groups in the framework nucleic acid provide binding sites to immobilize Ti4+, and its rigid three-dimensional skeleton makes them act as roadblocks to barricade exosomes and provide affinity interactions on a three-dimensional scale, resulting in the improvement of isolation efficiency. The model exosomes can be effectively isolated with 92% recovery in 5 min. From 100 µL of HeLa cell culture supernatant, 34 proteins out of the top 100 commonly identified exosomal proteins were identified from the isolated exosomes by the novel beads, which is obviously more than that by TiO2 (19 proteins), indicating higher isolation efficiency and exosome purity by Fe3O4@pGMA@DNA TET@Ti4+ beads. The nanobeads were finally applied for comparing exosomal proteomics analysis from real clinical serum samples. Twenty-five upregulated and 10 downregulated proteins were identified in the lung cancer patients group compared to the health donors group, indicating that the novel nanobeads have great potential in isolation of exosomes for exosomal proteomics analysis in cancer screening and diagnosis.
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Ethylene, a plant hormone that significantly influences both plant growth and response to stress, plays a well-established role in stress signaling. However, its impact on stomatal opening and closure during dehydration and rehydration remains relatively unexplored and is still debated. Exogenous ethylene has been proven to induce stomatal closure through a series of signaling pathways, including the accumulation of reactive oxygen species (ROS), subsequent synthesis of nitric oxide (NO) and hydrogen sulfide (H2S), and SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1) activation. Thus, it has been suggested that ethylene might function to induce stomatal closure synergistically with abscisic acid (ABA). Furthermore, it has also been shown that increased ethylene can inhibit ABA- and jasmonic acid (JA)-induced stomatal closure, thus hindering drought-induced closure during dehydration. Simultaneously, other stresses, such as chilling, ozone pollution and K+ deficiency, inhibit drought and ABA-induced stomatal closure through an ethylene synthesis dependent way. However, ethylene has been shown to take on an opposing role during rehydration, preventing stomatal opening in the absence of ABA through its own signaling pathway. These findings offer novel insights into the function of ethylene in stomatal regulation during dehydration and rehydration, gaining a better understanding of the mechanisms underlying ethylene-induced stomatal movement in seed plants.
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With the increasing complexity of the electromagnetic environment, there is a growing demand for the manipulation of electromagnetic waves, leading to the rapid development in configurable microwave absorbers. All-dielectric absorbers offer broadband and high-intensity absorption effects in microwave absorption and shielding. However, they face a significant challenge: their performance is not adjustable once the design is completed. In this study, we propose a solution to this problem by creating all-dielectric absorbers with flexibly configurable absorbing properties. We achieve this by designing a composite material of ionogels/nano-graphite sheets into compressible deformable absorbing units that can be molded into different shapes using 3D printing modes. The plasticity allows us to change the performance of the all-dielectric absorber, including the microwave absorption intensity, absorption peak, frequency bandwidths, and wide-angle absorption performance. With this approach, we can flexibly manipulate electromagnetic waves using all-dielectric absorbers through different plasticity models.
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BACKGROUND: Angiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound. METHODS: CCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone. RESULTS: Based on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation. CONCLUSION: Overall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment.
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Three-dimensional (3D) self-supported Ge anode is one of the promising candidates to replace the traditional graphite anode material for high-performance binder-free lithium-ion batteries (LIBs). The enlarged surface area and the shortened ions/electrons transporting distance of the 3D electrode would greatly facilitate the rapid transfer of abundant lithium ions during cycling, thus achieve enhanced energy and power density during cycling. Cycle stability of the 3D self-supported Ge electrode would be improved due to the obtained enough space could effectively accommodate the large volume expansion of the Ge anode. In this review, we first describe the electrochemical properties and Li ions storage mechanism of Ge anode. Moreover, the recent advances in the 3D self-supported Ge anode architectures design are majorly illustrated and discussed. Challenges and prospects of the 3D self-supported Ge electrode are finally provided, which shed light on ways to design more reliable 3D Ge-based electrodes in energy storage systems.
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BACKGROUND: A 19-year-old female patient presented at 2 years of age with dysarthria, incoherent speech, and unsteady ambulation. She is prone to leaning backward when walking and has involuntary movements of the whole body. Besides, she has poor numeracy skills. She has been diagnosed with Wilson's disease (WD) in China and Japan. OBJECTIVE: The objective of this study was to further clarify the diagnosis of this patient. METHODS: The patient and her parents were detected with whole-exome sequencing. RESULTS: Based on the genetic test results, genetic analyses, and clinical manifestations, a diagnosis of WD in this patient was ruled out. The patient was eventually diagnosed with neurodevelopmental disorder with involuntary movements. CONCLUSIONS: This study reinterprets the genetic test results of a young female patient and leads to reflections on the genetic diagnostic criteria for WD: the Leipzig score is suitable for the diagnosis of most WD patients, and the genetic testing section of the score is of great diagnostic value. However, in some special cases, the proband and their first-degree relatives should further complete cosegregation analysis to determine the origin of the lesion gene and to verify the reliability of the genetic test. In addition, this study suggests that further improving the scoring rules of the gene testing part of the Leipzig scoring system may be more helpful in achieving an accurate diagnosis of WD. © 2024 International Parkinson and Movement Disorder Society.
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Heat shock protein 90α (HSP90α) has been regarded as an important indicator for judging tumor metastasis and prognosis due to its significant upregulation in various tumors. Therefore, the accurate quantification of HSP90α is of great significance for clinical diagnosis and therapy of cancers. However, the lack of HSP90α certified reference material (CRM) leads to the accuracy and consistency of quantification methods not being effectively evaluated. Besides, quantitative results without traceability make comparisons between different studies difficult. In this study, an HSP90α solution CRM was developed from the recombinant protein raw material. The recombinant protein is a dimer, and the purity of the CRM candidate reached 96.71%. Both amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) and unique peptide analysis-isotope dilution mass spectrometry (UPA-IDMS) were performed to measure the content of HSP90α in the solution CRM candidate, and the certified value was assessed to be 66.2 ± 8.8 µg/g. Good homogeneity of the CRM was identified, and the stability examination suggested that the CRM was stable for at least 4 months at - 80 °C and for 7 days at 4 °C. With traceability to SI unit (kg), this CRM has potential to help establish a metrological traceability chain for quantification of HSP90α, which will make the quantification results standardized and comparable regardless of the quantitative methods.
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Isótopos , Neoplasias , Padrões de Referência , Espectrometria de Massas/métodos , Calibragem , Proteínas Recombinantes/análise , Neoplasias/diagnósticoRESUMO
Metrology is the science of measurement and its applications, whereas biometrology is the science of biological measurement and its applications. Biometrology aims to achieve accuracy and consistency of biological measurements by focusing on the development of metrological traceability, biological reference measurement procedures, and reference materials. Irreproducibility of biological and multi-omics research results from different laboratories, platforms, and analysis methods is hampering the translation of research into clinical uses and can often be attributed to the lack of biologists' attention to the general principles of metrology. In this paper, the progresses of biometrology including metrology on nucleic acid, protein, and cell measurements and its impacts on the improvement of reliability and comparability in biological research are reviewed. Challenges in obtaining more reliable biological and multi-omics measurements due to the lack of primary reference measurement procedures and new standards for biological reference materials faced by biometrology are discussed. In the future, in addition to establishing reliable reference measurement procedures, developing reference materials from single or multiple parameters to multi-omics scale should be emphasized. Thinking in way of biometrology is warranted for facilitating the translation of high-throughput omics research into clinical practices.
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Proteômica , Humanos , Reprodutibilidade dos Testes , Proteômica/métodos , Padrões de Referência , Animais , Genômica/métodos , MultiômicaRESUMO
BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).
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Anestésicos Inalatórios , Anestésicos Intravenosos , Procedimentos Cirúrgicos Cardíacos , Desflurano , Complicações Pós-Operatórias , Propofol , Humanos , Propofol/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Anestésicos Intravenosos/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Idoso , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Adulto , Sevoflurano/efeitos adversos , Anestesia Intravenosa/métodos , China/epidemiologia , Tempo de Internação/estatística & dados numéricos , Anestesia por Inalação/métodos , Anestesia por Inalação/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the external validation and scalability of four predictive models regarding new vertebral fractures following percutaneous vertebroplasty. METHODS: Utilizing retrospective data acquired from two centers, compute the area under the curve (AUC), calibration curve, and Kaplan-Meier plot to assess the model's discrimination and calibration. RESULTS: In the external validation of Zhong et al.'s 2015 predictive model for the probability of new fractures post-vertebroplasty, the AUC for re-fracture at 1, 2, and 3 years postoperatively was 0.570, 0.617, and 0.664, respectively. The AUC for Zhong et al.'s 2016 predictive model for the probability of new fractures in neighboring vertebrae was 0.738. Kaplan-Meier plot results for both models indicated a significantly lower incidence of re-fracture in low-risk patients compared to high-risk patients. Li et al.'s 2021 model had an AUC of 0.518, and its calibration curve suggested an overestimation of the probability of new fractures. Li et al.'s 2022 model had an AUC of 0.556, and its calibration curve suggested an underestimation of the probability of new fractures. CONCLUSION: The external validation of four models demonstrated that the predictive model proposed by Zhong et al. in 2016 exhibited superior external generalization capabilities.
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Soy protein gel can be developed into a variety of products, ranging from traditional food (e.g., tofu) to newly developed food (e.g., soy yogurt and meat analog). So far, efforts are still needed to be made on modifying the gel properties of soy protein for improving its sensory properties as animal protein-based food substitutes. Furthermore, there is always a need to regulate its gel properties for designing novel and tailored products of soy protein gels due to the fast-growing plant protein-based product market. This review gave an emphasis on the latest modification strategies and applications of gel properties of soy protein. The modifying methods of soy protein gel properties were reviewed from an aspect of composition or processing. Compositional modification included changing protein composition and gelling conditions and using additives, whereas processing strategies can be achieved through physical, chemical, and enzymatic treatments. Several compositional modification and processing strategies have been both proven to alter the gel properties of soy protein effectively. So far, soy protein gel has been applied in the field of food and biomedicine. In the future, more mechanistic studies on the modification methods are still needed to facilitate the full application of soy protein gel.
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Alimentos de Soja , Proteínas de Soja , Animais , Proteínas de Soja/química , Géis/química , Proteínas de PlantasRESUMO
Lignan, a beneficial constituent of Flaxseed (Linum usitatissimum L.) showed great interest in researchers because of its multiple functional properties. Nonetheless, a challenge arises due to the glycosidic structure of lignans, which the gut epithelium cannot readily absorb. Therefore, we screened 18 strains of Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Pediococcus pentosaceus, Pediococcus acidilactici, and Enterococcus durans to remove glycosides from flaxseed lignan extract enzymatically. Among our findings, Lactiplantibacillus plantarum SCB0151 showed the highest activity of ß-glucosidase (8.91 ± 0.04 U/mL) and higher transformed efficiency of Secoisolariciresinol (SECO) (8.21 ± 0.13%). The conversion rate of Secoisolariciresinol diglucoside (SDG) and the generation rate of SECO was 58.30 ± 3.78% and 32.13 ± 2.78%, respectively, under the optimized conditions. According to the LC-HRMSMS analysis, SECO (68.55 ± 6.57 µM), Ferulic acid (FA) (32.12 ± 2.50 µM), and Coumaric acid (CA) (79.60 ± 6.21 µM) were identified in the biotransformation products (TP) of flaxseed lignan extract. Results revealed that the TP exhibited a more pronounced anti-inflammatory effect than the flaxseed lignan extract. SECO, FA, and CA demonstrated a more inhibitory effect on NO than that of SDG. The expression of iNOS and COX-2 was significantly suppressed by TP treatment in LPS-induced Raw264.7 cells. The secretion of IL-6, IL-2, and IL-1ß decreased by 87.09 ± 0.99%, 45.40 ± 0.87%, and 53.18 ± 0.83%, respectively, at 60 µg/mL of TP treatment. Given these data, the bioavailability of flaxseed lignan extract and its anti-inflammatory effect were significantly enhanced by Lactiplantibacillus plantarum SCB0151, which provided a novel approach to commercializing flaxseed lignan extract for functional food.
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Linho , Glucosídeos , Lignanas , Linho/química , Linho/metabolismo , Fermentação , Lignanas/farmacologia , Lignanas/química , Lignanas/metabolismo , Glicosídeos , Butileno Glicóis/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Inflamatórios/farmacologiaRESUMO
Autophagy, a conserved degradation and reuse process, plays a crucial role in plant cellular homeostasis during abiotic stress. Although numerous autophagy-related genes (ATGs) that regulate abiotic stress have been identified, few functional studies have shown how they confer tolerance to copper (Cu) stress. Here, we cloned a novel Vitis vinifera ATG6 gene (VvATG6) which was induced by 0.5 and 10 mM Cu stress based on transcriptomic data, and transgenic Arabidopsis thaliana, tobacco (Nicotiana tabacum), and grape calli were successfully obtained through Agrobacterium-mediated genetic transformation. The overexpression of VvATG6 enhanced the tolerance of transgenic lines to Cu. After Cu treatment, the lines that overexpressed VvATG6 grew better and increased their production of biomass compared with the wild-type. These changes were accompanied by higher activities of antioxidant enzymes and a lower accumulation of deleterious malondialdehyde and hydrogen peroxide in the transgenic plants. The activities of superoxide dismutase, peroxidase, and catalase were enhanced owing to the elevation of corresponding antioxidant gene expression in the VvATG6 overexpression plants under Cu stress, thereby promoting the clearance of reactive oxygen species (ROS). Simultaneously, there was a decrease in the levels of expression of RbohB and RbohC that are involved in ROS synthesis in transgenic plants under Cu stress. Thus, the accelerated removal of ROS and the inhibition of its synthesis led to a balanced ROS homeostasis environment, which alleviated the damage from Cu. This could benefit from the upregulation of other ATGs that are necessary for the production of autophagosomes under Cu stress. To our knowledge, this study is the first to demonstrate the protective role of VvATG6 in the Cu tolerance of plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01415-y.
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BACKGROUND: In the overall surgical population, inadvertent perioperative hypothermia has been associated with an increased incidence of surgical site infection (SSI). However, recent clinical trials did not validate this notion. This study aimed to investigate the potential correlation between inadvertent perioperative hypothermia and SSIs following liver resection. METHODS: This retrospective cohort study included all consecutive patients who underwent liver resection between January 2019 and December 2021 at the First Affiliated Hospital, Zhejiang University School of Medicine. Perioperative temperature managements were implemented for all patients included in the analysis. Estimated propensity score matching (PSM) was performed to reduce the baseline imbalances between the normothermia and hypothermia groups. Before and after PSM, univariate analyses were performed to evaluate the correlation between hypothermia and SSI. Multivariate regression analysis was performed to determine whether hypothermia was an independent risk factor for postoperative transfusion and major complications. Subgroup analyses were performed for diabetes mellitus, age > 65 years, and major liver resection. RESULTS: Among 4000 patients, 2206 had hypothermia (55.2%), of which 150 developed SSI (6.8%). PSM yielded 1434 individuals in each group. After PSM, the hypothermia and normothermia groups demonstrated similar incidence rates of SSI (6.3% vs. 7.0%, P = 0.453), postoperative transfusion (13.3% vs. 13.7%, P = 0.743), and major complications (9.0% vs. 10.1%, P = 0.309). Univariate regression analysis revealed no significant effects of hypothermia on the incidence of SSI in the group with the highest hypothermia exposure [odds ratio (OR) = 1.25, 95% confidence interval (CI): 0.84-1.87, P = 0.266], the group with moderate exposure (OR = 1.00, 95% CI: 0.65-1.53, P = 0.999), or the group with the lowest exposure (OR = 1.11, 95% CI: 0.73-1.65, P = 0.628). The subgroup analysis revealed similar results. Regarding liver function, patients in the hypothermia group demonstrated lower γ-glutamyl transpeptidase (37 vs. 43 U/L, P = 0.001) and alkaline phosphatase (69 vs. 72 U/L, P = 0.016). However, patients in the hypothermia group exhibited prolonged activated partial thromboplastin time (29.2 vs. 28.6 s, P < 0.01). CONCLUSIONS: In our study of patients undergoing liver resection, we found no significant association between mild perioperative hypothermia and SSI. It might be due to the perioperative temperature managements, especially active warming measures, which limited the impact of perioperative hypothermia on the occurrence of SSI.
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This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 â, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.
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Asma , Medicamentos de Ervas Chinesas , Interleucina-4 , Ratos , Masculino , Animais , Camundongos , Interleucina-4/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Asma/tratamento farmacológico , Asma/genética , Pulmão , Líquido da Lavagem Broncoalveolar , RNA Mensageiro/metabolismo , Colágeno/metabolismo , Mucinas/metabolismo , Mucinas/farmacologia , Mucinas/uso terapêutico , Ovalbumina , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in children. A retrospective study was conducted to explore the uropathogen and its antibiotic resistance in children with UTI. Data of urine culture and antimicrobial susceptibility test was collected. Consequently, 840 children were included. The overall culture-positive UTI was 458 (54.52 %) with Escherichia coli 166 (36.24 %), followed by Enterococcus faecalis 59 (12.88 %), Enterococcus faecium 70 (15.28 %) and others. They were highly resistant to the most commonly used antibiotics. In 694 children with complicated UTI, there were 8 children with fungal infection. Multiple drug resistance (MDR) was recorded in 315 (80.98 %). The overall proportion of Extended Spectrum ß-Lactamase (ESßL) production was 25 (6.43 %). In 146 children with simple UTI, MDR were also detected in 47 (77.05 %). There were 6 (9.84 %) positive for ESßL production. Our study found that complicated UTI was relatively common. Escherichia coli was the most prevalent isolate, followed by Enterococcus faecium and Enterococcus faecalis. These organisms were highly resistant to the most commonly used antibiotics. Relatively high prevalence of MDR and low ESßL-producing organisms were observed.
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Plants regularly encounter various environmental stresses such as salt, drought, cold, heat, heavy metals and pathogens, leading to changes in their proteome. Of these, a post-translational modification, SUMOylation is particularly significant for its extensive involvement in regulating various plant molecular processes to counteract these external stressors. Small ubiquitin-like modifiers (SUMO) protein modification significantly contributes to various plant functions, encompassing growth, development and response to environmental stresses. The SUMO system has a limited number of ligases even in fully sequenced plant genomes but SUMO E3 ligases are pivotal in recognising substrates during the process of SUMOylation. E3 ligases play pivotal roles in numerous biological and developmental processes in plants, including DNA repair, photomorphogenesis, phytohormone signalling and responses to abiotic and biotic stress. A considerable number of targets for E3 ligases are proteins implicated in reactions to abiotic and biotic stressors. This review sheds light on how plants respond to environmental stresses by focusing on recent findings on the role of SUMO E3 ligases, contributing to a better understanding of how plants react at a molecular level to such stressors.