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Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.
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Antioxidantes , Glucanos , Glucanos/química , Glucanos/farmacologia , Glucanos/isolamento & purificação , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Agaricales/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Peso Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/isolamento & purificação , Basidiomycota/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS2-based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.
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Biomarcadores , Técnicas Biossensoriais , Quimiocina CCL2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/urina , Nefropatias Diabéticas/diagnóstico , Técnicas Biossensoriais/métodos , Quimiocina CCL2/urina , Biomarcadores/urina , Limite de Detecção , Técnicas Eletroquímicas/métodosRESUMO
Background: Breast cancer is the most common malignancy in female patients. In recent years, more and more studies have focused on how to improve the appearance and the quality of life for patients. This study aimed to compare the oncologic safety, aesthetic results, and upper extremity function between single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) and conventional open mastectomy (C-OM) in early-stage breast cancer treatment. Methods: In our retrospective cohort, 285 patients with stage I and II breast cancer were categorized into the SIE-NSM group (n=71) and the C-OM group (n=214). We assessed local recurrence, distant metastasis, and upper extremity function across the two groups. The BREAST-Q scale was employed to analyze differences in aesthetic results, psychosocial well-being, and sexual health. The risk of local recurrence was evaluated using multivariable binary logistic regression, while a multivariable linear regression model gauged upper extremity function and aesthetic outcomes. Results: Local recurrence rates between the two groups were statistically similar (1/71, 1.4% for SIE-NSM vs. 2/214, 0.9% for C-OM, P=0.735), as confirmed by the multivariable binary logistic regression analysis. Neither group exhibited distant metastases. The SIE-NSM group demonstrated higher scores in satisfaction with breasts, chest wellness, psychosocial health, and sexual well-being (P<0.001). The SIE-NSM group also exhibited superior outcomes regarding chest wall/breast pain, shoulder mobility, and daily arm usage (P<0.001). No subcutaneous effusion was reported in the SIE-NSM group, whereas the C-OM group had a 10.7% incidence rate (P=0.004). Conclusions: SIE-NSM offers comparable oncologic safety to C-OM but provides enhanced satisfaction regarding breast appearance, physical comfort, psychosocial health, sexual health, and improved upper extremity functionality. Consequently, this innovative approach is a suitable surgical alternative for treating early-stage breast cancer.
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Introduction: This study was designed to explore the associations between impaired cognition in chronic kidney disease (CKD) patients and the dysfunction of the glymphatic system. Method: Data were obtained from 77 CKD patients and 50 age-matched healthy control individuals from the First Affiliated Hospital of Zhengzhou University. CKD patients were stratified into with and without impaired cognitive function. T2-weighted magnetic resonance imaging results were used to assess area ratios for the perivascular space and ventricles in participants, while the Montreal Cognitive Assessment and the Mini-Mental State Examination were employed to measure cognitive function. Correlations between the perivascular space or ventricle area ratios and cognitive impairment were assessed in CKD patients. Results: Significant increases in the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia were observed in CKD patients with cognitive impairment relative to those without such impairment, with a concomitant increase in analyzed ventricle area ratios. Enlarged perivascular spaces in the frontal cortex, basal ganglia and increased area ratios of lateral ventricles and 4th ventricle exhibited relatively high sensitivity and specificity as means of differing between the CKD patients with and without cognitive impairment. Conclusion: These results indicate that the burden of enlarged perivascular spaces in the frontal cortex and basal ganglia and increases in ventricle area ratio values may offer utility as biomarkers that can aid in detection of even mild cognitive decline in individuals with CKD. The dysfunction of the glymphatic system may play a key role in the pathogenesis of CKD-related cognitive impairment.
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Soft rot is a severe postharvest disease of kiwifruit that causes enormous economic losses annually. In this study, we aimed to explore an effective pullulan-based active coating, incorporating food additives to reduce soft rot and extend the shelf life of cold-stored kiwifruit. The results showed that 1 g/L potassium metabisulfite could completely inhibit the mycelial growth of Diaporthe sp., Botryosphaeria dothidea, Phomopsis sp. and Alternaria sp., which were the primary pathogens of kiwifruit soft rot. Furthermore, the pullulan coating, combined with a 10 g/L potassium metabisulfite group, had a decay rate 46% lower than the control (CK) group and maintained fruit quality at the end of shelf life. The retention of physicochemical properties such as soluble solid content (SSC), firmness, weight loss and respiration rate also confirmed the efficacy of the treatment. In addition, at the end of shelf life, pullulan coating, combined with potassium metabisulfite, increased the accumulation of total phenolic content (37.59%) and flavonoid content (9.28%), maintained a high energy charge (51.36%), and enhanced superoxide dismutase (SOD) (6.27%), peroxidase (POD) (62.50%), catalase (CAT) (84.62%) and phenylalanine ammonia lyase (PAL) (24.61%) enzyme activities as well as initiating the upregulation of their gene expression levels. As a result, the disease resistance of fruit was improved, and the occurrence of soft rot was delayed. Overall, this study demonstrated that using the pullulan-based active coating incorporating potassium metabisulfite treatment effectively controlled soft rot and retarded the senescence of postharvest kiwifruit.
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OBJECTIVE: To compare the biomechanical performance of the hybrid lumbar fixation technique with the traditional and cortical bone trajectory techniques using the finite element method. METHODS: Four adult wet lumbar spine specimens were provided by the Department of Anatomy and Research of Xinjiang Medical University, and four L1-S1 lumbar spine with transforaminal lumbar interbody fusion (TLIF) models at L4-L5 segment and four different fixation techniques were established: bilateral traditional trajectory screw fixation (TT-TT), bilateral cortical bone trajectory screw fixation (CBT-CBT), hybrid CBT-TT (CBT screws at L4 and TT screws at L5) and TT-CBT (TT screws at L4 and CBT screws at L5). The range of motion (ROM) of the L4-L5 segment, von Mises stress of cage, internal fixation, and rod were compared in flexion, extension, left and right bending, and left and right rotation. RESULTS: Compared with the TT-TT group, the TT-CBT group exhibited lower ROM of L4-L5 segment, especially in left-sided bending; the CBT-TT group had the lowest ROM of L4-L5 segment in flexion and extension among the four fixation methods. Compared with the CBT-CBT group, the peak cage stress in the TT-CBT group was reduced by 9.9%, 18.1%, 21.5%, 23.3%, and 26.1% in flexion, left bending, right bending, left rotation, and right rotation conditions, respectively, but not statistically significant (P > 0.05). The peak stress of the internal fixation system in the TT-CBT group was significantly lower than the other three fixation methods in all five conditions except for extension, with a statistically significant difference between the CBT-TT and TT-CBT groups in the left rotation condition (P = 0.017). In addition, compared with the CBT-CBT group, the peak stress of the rod in the CBT-TT group decreased by 34.8%, 32.1%, 28.2%, 29.3%, and 43.0% under the six working conditions of flexion, extension, left bending, left rotation, and right rotation, respectively, but not statistically significant (P > 0.05). CONCLUSIONS: Compared with the TT-TT and CBT-CBT fixation methods in TLIF, the hybrid lumbar fixation CBT-TT and TT-CBT techniques increase the biomechanical stability of the internal fixation structure of the lumbar fusion segment to a certain extent and provide a corresponding theoretical basis for further development in the clinic.
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Parafusos Pediculares , Fusão Vertebral , Adulto , Humanos , Análise de Elementos Finitos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Amplitude de Movimento Articular , Fixação Interna de Fraturas , Osso Cortical/diagnóstico por imagem , Osso Cortical/cirurgia , Fenômenos BiomecânicosRESUMO
Background: Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, with a high prevalence and poor prognosis. Early intervention is crucial to improve the outcomes of DN. CXCL8 is related to podocyte damage in incipient DN; however, the role and expression level of CXCL8 have never been elucidated, especially in those with undiminished creatinine clearance. Methods: Consecutive inpatients with type 2 diabetes were included in this study. Patients were assigned into four groups based on the Mogensen stage, reflecting pathological features through clinical manifestations: non-DN group, hyperfiltration group, microalbuminuria group and overt DN group. Clinical and laboratory data were retrospectively collected and analyzed. Urinary CXCL8 (uCXCL8) was measured using an enzyme-linked immunosorbent assay (ELISA) method and adjusted for urinary creatinine (Cr) from the same urine sample. Results: In total, 88 eligible consecutive inpatients with type 2 diabetes were included in this study. uCXCL8 was differentially expressed in different stages of incipient DN; it decreased in the hyperfiltration phase of incipient DN (1.40±1.01 pg/µmol Cr) and was highly expressed in patients in the microalbuminuria stage (5.01±4.01 pg/µmol Cr). uCXCL8 was positively correlated with age, diabetes course, cystatin C and urinary albuminuria-to-creatinine ratio, but negatively correlated with estimated glomerular filtration rate (P<0.05). uCXCL8 was a risk factor for classic DN after adjusting for age, diabetes course and cystatin C (OR=1.17, 95% CI 0.98-1.4, P=0.045). Conclusion: CXCL8 played an important role in the progression of incipient DN. The unique expression profile of uCXCL8 may provide a reference for understanding the prognosis and mechanisms of incipient DN progression. uCXCL8 was an independent risk factor for the development of classic DN.
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Diseases caused by bacterial infection have resulted in serious harm to human health. It is crucial to develop a multifunctional antibiotic-independent antibacterial platform for combating drug-resistant bacteria. Herein, titanium diboride (TiB2) nanosheets integrated with quaternized chitosan (QCS) and indocyanine green (ICG) were successfully prepared as a synergetic photothermal/photodynamic antibacterial nanoplatform (TiB2-QCS-ICG). The TiB2-QCS-ICG nanocomposites exhibit effective photothermal conversion efficiency (24.92%) and excellent singlet oxygen (1O2) production capacity simultaneously under 808 nm near-infrared irradiation. QCS improved TiB2 stability and dispersion, while also enhancing adhesion to bacteria and further accelerating the destruction of bacteria by heat and 1O2. In vitro experiments indicated that TiB2-QCS-ICG had excellent antibacterial properties with an inhibition rate of 99.99% against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), respectively. More importantly, in vivo studies revealed that the nanoplatform can effectively inhibit bacterial infection and accelerate wound healing. The effective wound healing rate in the TiB2-QCS-ICG treatment group was 99.6% which was much higher than control groups. Taken together, the as-developed TiB2-QCS-ICG nanocomposite provides more possibilities to develop metal borides for antibacterial infection applications.
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Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Escherichia coli , Verde de Indocianina/farmacologia , Compostos de Boro/farmacologia , Nanocompostos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Obstructive sleep apnea (OSA) is highly prevalent but easily undiagnosed and is an independent risk factor for cognitive impairment. However, it remains unclear how OSA is linked to cognitive impairment. In the present study, we found the correlation between morphological changes of perivascular spaces (PVSs) and cognitive impairment in OSA patients. Moreover, we developed a novel set of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate the fluid dynamics of glymphatic drainage system. We found that the inflow and outflow parameters of the glymphatic drainage system in patients with OSA were obviously changed, indicating impairment of glymphatic drainage due to excessive perfusion accompanied with deficient drainage in OSA patients. Moreover, parameters of the outflow were associated with the degree of cognitive impairment, as well as the hypoxia level. In addition, continuous positive airway pressure (CPAP) enhances performance of the glymphatic drainage system after 1 month treatment in OSA patients. We proposed that ventilation improvement might be a new strategy to ameliorate the impaired drainage of glymphatic drainage system due to OSA-induced chronic intermittent hypoxia, and consequently improved the cognitive decline.
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Disfunção Cognitiva , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/terapia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Hipóxia/complicações , Fatores de RiscoRESUMO
PURPOSE: To determine whether the stress-induced hyperglycemia ratio (SHR) is independently associated with in-hospital mortality in critically ill patients in nonresuscitation ICUs. METHODS: In this retrospective cohort study, clinical- and laboratory-related data from patients first admitted to nonresuscitation ICUs were extracted from an open-access database of >50,000 ICU admissions. Patients were assigned to one of two groups according to an SHR threshold of 1.1. The primary end point of this study was the in-hospital mortality rate. The associations between SHR and length of stay in the ICU and hospital, duration of mechanical ventilation use, and vasopressor use were secondary end points. Logistic regression models were established in the analysis of in-hospital mortality risk, and areas under the receiver operating characteristic curve (AUC) were analyzed to investigate the association between the primary end point and SHR used alone or together with the Simplified Acute Physiology Scale (SAPS) II score. The Youden index, specificity, and sensitivity of SHR and SAPS-II were also assessed. FINDINGS: In this study, 1859 patients were included, 187 of whom (10.06%) died during hospitalization. The group with an SHR of ≥1.1 had a greater in-hospital mortality rate (13.7% vs 7.4%; P < 0.001), longer length of stay both in the ICU and in the hospital, a longer duration of mechanical ventilation use, and a greater rate of vasopressor use. On adjustment for multivariate risk, a 0.1-point increment in SHR was significantly associated with in-hospital mortality (OR = 1.08; 95% CI, 1.00-1.16; P = 0.036). The AUC of the association between risk and the SAPS-II score was significantly greater than that with SHR (0.797 [95% CI, 0.576-0.664] vs 0.620 [95% CI, 0.764-0.830]; P < 0.001). The AUC with SAPS-II + SHR was significantly greater than that with SAPS-II used alone (0.802 [95% CI, 0.770-0.835] vs 0.797 [95% CI, 0.764-0.830]; P = 0.023). The Youden index, specificity, and sensitivity of SAPS-II + SHR were 0.473, 0.703, and 0.770, respectively. IMPLICATIONS: Stress-induced hyperglycemia, as evaluated using the SHR, was associated with increased in-hospital mortality and worse clinical outcomes in these critically ill patients in nonresuscitation ICUs. SHR was an independent risk factor for in-hospital mortality, and when used together with the SAPS-II, added to the capacity to predict mortality in these patients in nonresuscitation ICUs. Prospective data are needed to validate the capacity of SHR in predicting in-hospital mortality in patients in the nonresuscitation ICU.
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Estado Terminal , Unidades de Terapia Intensiva , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Estudos Prospectivos , Fatores de Risco , Curva ROC , PrognósticoRESUMO
Ensemble learning systems (ELS) have been widely utilized for human activity recognition (HAR) with multiple homogeneous or heterogeneous sensors. However, traditional ensemble approaches for HAR cannot always work well due to insufficient accuracy and diversity of base classifiers, the absence of ensemble pruning, as well as the inefficiency of the fusion strategy. To overcome these problems, this paper proposes a novel selective ensemble approach with group decision-making (GDM) for decision-level fusion in HAR. As a result, the fusion process in the ELS is transformed into an abstract process that includes individual experts (base classifiers) making decisions with the GDM fusion strategy. Firstly, a set of diverse local base classifiers are constructed through the corresponding mechanism of the base classifier and the sensor. Secondly, the pruning methods and the number of selected base classifiers for the fusion phase are determined by considering the diversity among base classifiers and the accuracy of candidate classifiers. Two ensemble pruning methods are utilized: mixed diversity measure and complementarity measure. Thirdly, component decision information from the selected base classifiers is combined by using the GDM fusion strategy and the recognition results of the HAR approach can be obtained. Experimental results on two public activity recognition datasets (The OPPORTUNITY dataset; Daily and Sports Activity Dataset (DSAD)) suggest that the proposed GDM-based approach outperforms the well-known fusion techniques and other state-of-the-art approaches in the literature.
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Algoritmos , Atividades Humanas , Humanos , Tomada de DecisõesRESUMO
Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit numerous virus infections by impeding viral entry into target cells. However, increasing evidence suggests diverse functions of IFITMs in virus infection, especially with the coronavirus. We analyzed the effect of chicken interferon-induced transmembrane proteins (chIFITMs) on coronavirus infectious bronchitis virus (IBV) infection in vitro. We demonstrated that the antiviral effects of IFITMs are dependent on cell and virus types. The overexpression of chIFITM1 dramatically promoted the replication of IBV Beaudette strain in the chicken hepatocellular carcinoma cell line, LMH. Mechanistically, chIFITMs share roughly the same subcellular localization in different host cells, and overexpressed of chIFITM1 have no effect of viral attachment and entry. Further studies revealed that mutations of amino acids at key positions (60KSRD63, 68KDFV71) in the intracellular loop domain (CIL) caused loss of the promoted function. Interaction with downstream proteins in co-response to viral infection could be the primary reason behind variable functions of chIFITM1 in different cells. In all, our study explored the functions of chIFITMs in viral infection from a new perspective.
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Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Animais , Vírus da Bronquite Infecciosa/genética , Galinhas , Infecções por Coronavirus/veterinária , Antivirais/farmacologia , Interferons/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Replicação ViralRESUMO
Objective: To study the protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats and explore the regulatory mechanism of toll-like receptors 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in this process. Methods: Sixty male SD rats were randomly divided into control group (C), model group (M), low-dose Lycium ruthenicum Murr. juice group (LLM), medium-dose Lycium ruthenicum Murr. juice group (MLM) and high-dose Lycium ruthenicum Murr. juice group (HLM), 12 rats in each group. The group M, LLM, MLM and HLM were treated with 20 ml/kg (8 g/(kg·d)) ethanol (400 g/L) intragastrically and the gavage was divided into two sessions, group C was treated with an equal volume of distilled water at the same time point. Four hours before the first alcohol gavage session, rats in each dose group of Lycium ruthenicum Murr. juice were administered with 2.4, 4.8, 9.6 ml/(kg·d) Lycium ruthenicum Murr. juice respectively, and the other groups were given equal volume of distilled water at the corresponding time points. Four weeks later, the rats were sacrificed 24 hours after the end of the last experiment, blood and liver were collected. The liver index was calculated. The morphology of the liver was observed by HE staining. The expressions of hepatic TLR4, p38 MAPK and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were detected by immunohistochemistry. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The levels of hepatic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-10 (IL-10) and interleukin-18 (IL-18) were detected by enzyme linked immunosorbent assay. Results: Compared with group C, the alcoholic liver injury model was established successfully in Group M. Compared with group M, related indicators in each dose group of Lycium ruthenicum Murr. juice were improved, the improvement of hepatic morphology in group HLM was the most significant, the liver index, the levels of serum ALT, AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-1ß, IL-18 were decreased (Pï¼ 0.05 or Pï¼0.01), while the level of hepatic IL-10 was increased (Pï¼0.01). Comparison among the dose groups of Lycium ruthenicum Murr. juice, the levels of liver index, serum AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-18 in HLM were lower than those in LLM (Pï¼0.05 or Pï¼0.01); the level of hepatic IL-10 in HLM was higher than that in LLM and MLM (Pï¼0.05 or Pï¼0.01); the other indicators in each dose group had no statistical difference (Pï¼0.05). Conclusion: Lycium ruthenicum Murr. juice can improve the inflammatory stress by regulating TLR4/p38 MAPK signaling pathway, relieve alcoholic liver injury in rats, and the effect of high-dose group is better than the others.
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Sucos de Frutas e Vegetais , Hepatopatias Alcoólicas , Lycium , Animais , Interleucina-10 , Interleucina-18 , Fígado/metabolismo , Hepatopatias Alcoólicas/terapia , Lycium/química , Masculino , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of diabetes and hyperglycemia on in-hospital mortality in critically ill patients older than 75 years. METHODS: This was a single-center retrospective cohort study of patients older than 75 years in the first intensive care unit stay. The patients were divided into the following 4 groups: time-weighted average glucose (TWAG) <140 mg/dL without diabetes (group 1), TWAG ≥140 mg/dL without diabetes (group 2), TWAG <180 mg/dL with diabetes (group 3), and TWAG ≥180 mg/dL with diabetes (group 4). Clinical and laboratory data were analyzed. RESULTS: A total of 6760 patients over 75 years of age were included, including 2089 patients previously diagnosed with diabetes. The patients in group 2 had the highest in-hospital mortality (27.4%). In the fully adjusted regression model, the risk of in-hospital mortality increased by 76% (odds ratio = 1.76, 95% CI: 1.49-2.08) in group 2 as compared with group 1. Those from groups 3 and 4 exhibited risks equivalent to the risks of those in group 1; similar results were observed in the subgroup analysis. A J-shaped curve relationship and threshold effect were observed in patients without diabetes. For those with diabetes, a flatter curve pattern with a small slope was observed. CONCLUSION: Stress hyperglycemia was more detrimental to short-term prognosis than diabetes status in these patients. Looser glucose control may be suitable for patients older than 75 years with diabetes but unnecessary for those without diabetes. Patients with diabetes may be more resistant to the detrimental effects of glucose variations.
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Diabetes Mellitus , Hiperglicemia , Humanos , Estado Terminal , Mortalidade Hospitalar , Estudos Retrospectivos , Glucose , Glicemia/análise , Diabetes Mellitus/epidemiologia , Unidades de Terapia IntensivaRESUMO
OBJECTIVES: The aim of this study was to characterise the whole genome sequence of a multidrug-resistant (MDR) Proteus mirabilis strain ChSC1905 isolated from a swine farm in China. METHODS: The genome was sequenced by Illumina NovaSeq and Oxford Nanopore platforms, and it was assembled via Canu v.1.5. The acquired antimicrobial resistance genes (ARGs) were identified by ResFinder. A conjugation experiment was carried out to determine the mobilisation of integrative and conjugative element. RESULTS: Strain ChSC1905 exhibited a MDR phenotype. The genome of strain ChSC1905 was 4 038 038 bp in length with a GC content of 39.1%, which contained 3645 coding sequences and 110 RNA genes. A total of 23 acquired ARGs were identified, among which 21 ARGs including the clinically important resistance genes blaCTX-M-65, cfr, fosA3, and aac(6')-Ib-cr were located on a SXT/R391 integrative and conjugative element (ICE). BLAST analysis showed that this new SXT/R391-family ICE (ICEPmiChnChSC1905 of 143 689 bp) was involved in sequence inversion mediated by ISVsa3 and genetic rearrangement mediated by IS26, and it could be transferred to E. coli EC600. CONCLUSION: In this study, we report the genome sequence of MDR P. mirabilis strain ChSC1905 that harboured a novel SXT/R391-family ICE (ICEPmiChnChSC1905) involved in genetic rearrangement in China, which promotes the diversity of ICE and should receive more attention.
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Conjugação Genética , Proteus mirabilis , Animais , Antibacterianos , Elementos de DNA Transponíveis , Escherichia coli/genética , Proteus mirabilis/genética , SuínosRESUMO
Chronic wounds resulting from bacterial infection are a global healthcare challenge as they usually impair the healing process and induce various complications. In this work, a chitosan (CS) membrane loaded with copper boron-imidazolate framework (Cu-BIF) was successfully prepared by self-assembly method for bacterial-infected wound-healing dressing. The as-prepared Cu-BIF/CS membrane possessed desirable biocompatibility. The antibacterial activity of Cu-BIF/CS membrane was evaluated by the spread plate and disc diffusion method, which was also verified by the fluorescence-based viability and morphological changes of bacteria. Moreover, Cu-BIF/CS membrane could increase wound closure rate and accelerate skin regeneration via combination therapy with chitosan, Cu2+ and hydroxyl radicals during infected wound healing process. These results exhibit that Cu-BIF/CS membrane has great potential as wound dressings in the field of clinical treatment of bacterial-infected wounds.
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Quitosana , Infecção dos Ferimentos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Bandagens/microbiologia , Boro , Quitosana/farmacologia , Cobre/farmacologia , Humanos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
The spread of bacterial resistance is a rising serious threat to global public health, and has created an urgent need for the development of a new generation of antibacterial nano-agents to take the place of antibiotics. In this work, a multifunctional nanoplatform based on boron nanosheet (B NS)-coated quaternized chitosan (QCS) and the nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6) (B-QCS-BNN6) was prepared via a liquid-phase exfoliation and electrostatic adsorption method. The 2D B NSs could convert near-infrared (NIR) light into heat energy as well as assemble positively charged QCS and BNN6 to trap negatively charged bacteria, and the positive charge made it easily captured by bacteria, increasing the opportunities for NO diffusion to the bacterial surface. The B-QCS-BNN6 nanoplatform not only exhibited photothermal therapy (PTT) efficacy but could also control NO release precisely after stimulation with an 808 nm laser for the rapid and effective treatment of typical Gram-negative and Gram-positive bacteria. The enhanced PTT/NO antibacterial function achieved >99.9% inactivation of bacteria within 5 min. Furthermore, this synergetic antibacterial strategy could also be conveniently employed for highly efficient disinfection of a methicillin-resistant Staphylococcus aureus (MRSA) infected wound and promotion of the reconstruction of damaged tissues for in vivo MRSA-infected wound therapy.
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Quitosana , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Boro , Escherichia coli , Óxido Nítrico , Doadores de Óxido Nítrico , CicatrizaçãoRESUMO
The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into four groups as follows, normal control group, normal aerobic exercise group, high-fat diet group (HFD), and high-fat diet plus aerobic exercise (8 weeks, 6 days/week, 18 m/min for 50 min, 6% slope) group (HAE). After 8 weeks, the mice in the HAE group showed significant improvement in hepatic steatosis. Body weight as well as blood TC, LDL-C, and liver TG levels were significantly lower in the HAE group than in the HFD group. Compared with the HFD group, the expression of SRA was markedly suppressed and the expression of ATGL was significantly increased in the HAE group. Additionally, the JNK/P38 signaling was inhibited, the pro-inflammatory factors were down-regulated, and the anti-inflammatory factor was increased. In addition to this, the same results were shown in experiments with overexpression of SRA. The results of this study provided new support for aerobic exercise to improve hepatic lipid metabolism via lncRNA.
Assuntos
Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Animais , Exercício Físico , Inflamação/genética , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/terapia , RNA Longo não Codificante/genéticaRESUMO
The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped Bi2S3@Cu(II) boron imidazolate framework (Bi2S3:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, Bi2S3:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that Bi2S3:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by Bi2S3:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated Bi2S3@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.
Assuntos
Antineoplásicos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Escherichia coli , Imagem Multimodal , Espécies Reativas de Oxigênio , Oxigênio Singlete , Nanomedicina Teranóstica/métodosRESUMO
The heterometallic Pb-iodoargentate hybrid [Pb(18-crown-6)(PbAg2I6)]n (1; 18-crown-6 = 1,4,7,10,13,16-hexaoxacyclooctadecane) was prepared via self-assembly of the tetrahedal AgI4 and octahedral PbI6 primary units using crown ether 18-crown-6 as an organic ligand in DMF solvent. The hybrid heterocomposite cocatalyst based on 1 and graphitic carbon nitride (g-C3N4) was prepared by a facile solvothermal method. In 1, the dimeric units Ag2I6 and Pb2I10 are joined via face sharing, leading to a ternary heterometallic 1-D [PbAg2I62-]n chain containing novel Ag2Pb2I4 cubes. The 1-D chains are joined by the discoid [Pb(18-crown-6)]2+ complex cations, forming the 2-D [Pb(18-crown-6)(PbAg2I6)]n hybrid with the skeleton of [Pb2Ag2I6]n. Compound 1 shows photocatalytic activity in the degradation of MB at room temperature under visible-light irradiation. The photoelectric response measurement showed that the photocurrent of 1 increased from 1.41 to 2.43 µA/cm-2 when g-C3N4 was loaded, indicating that the introduction of a certain amount of g-C3N4 on the surface of 1 improves the separation and migration rate of photoinduced electrons and holes. The 1/g-C3N4 composite showed much higher photocatalytic efficiency in comparison to pristine 1 and g-C3N4 for MB degradation, which suggests the synergistic effect between 1 and g-C3N4 toward visible-light-driven photocatalytic performance. Meanwhile, the 1/g-C3N4 composite exhibited good reusability and stability in the photocatalytic reaction. Free radical quenching experiments showed that the â¢O2- radical is the main reactive substance over catalyst 1, while h+, â¢OH, and â¢O2- species have synergistic effects over the 1/g-C3N4 composite catalyst in the process of photodegradation.