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1.
Materials (Basel) ; 17(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473562

RESUMO

Antimonene has attracted much attention due to its excellent characteristics of high carrier mobility, thermoelectric properties and high stability. It has great application prospects in Q-switched lasers, laser protection and spintronics. At present, the epitaxy growth of antimonene mainly depends on molecular beam epitaxy. We have successfully prepared antimonene films on silicon, germanium/silicon substrates for the first time using electron beam evaporation coating and studied the effects of the deposition rate and substrate on the preparation of antimonene; film characterization was performed via confocal microprobe Raman spectroscopy, via X-ray diffraction and using a scanning electron microscope. Raman spectroscopy showed that different deposition rates can lead to the formation of different structures of antimonene, such as α phase and ß phase. At the same time, it was found that the growth of antimonene is also affected by different substrates and ion beams.

2.
Environ Sci Pollut Res Int ; 31(16): 23334-23362, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436845

RESUMO

Mono and polycyclic aromatic hydrocarbons are widely distributed and severely pollute the aqueous environment due to natural and human activities, particularly human activity. It is crucial to identify and address them in order to reduce the dangers and threats they pose to biological processes and ecosystems. In the fields of sensor detection and water treatment, electrochemistry plays a crucial role as a trustworthy and environmentally friendly technology. In order to accomplish trace detection while enhancing detection accuracy and precision, researchers have created and studied sensors using a range of materials based on electrochemical processes, and their results have demonstrated good performance. One cannot overlook the challenges associated with treating aromatic pollutants, including mono and polycyclic. Much work has been done and good progress has been achieved in order to address these challenges. This study discusses the mono and polycyclic aromatic hydrocarbon sensor detection and electrochemical treatment technologies for contaminants in the aqueous environment. Additionally mentioned are the sources, distribution, risks, hazards, and problems in the removal of pollutants. The obstacles to be overcome and the future development plans of the field are then suggested by summarizing and assessing the research findings of the researchers.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Purificação da Água , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Ambientais/análise , Ecossistema , Previsões
3.
Sensors (Basel) ; 24(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38339588

RESUMO

In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on a smart cane. The intelligent guide system relies on 2D LiDAR, an RGB-D camera, IMU, GPS, Jetson nano B01, STM32, and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on the cartographer algorithm, thus achieving simultaneous localization and mapping (SLAM). At the same time, through the improved YOLOv5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving, and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved YOLOv5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the omnidirectional wheels at the bottom of the smart cane and provide the smart cane with a self-leading blind guide function, like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach their predetermined destination, and can quickly and effectively identify the obstacles on the way out. The mapping and positioning accuracy of the system's laser SLAM is 1 m ± 7 cm, and the laser SLAM speed of this system is 25~31 FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor environments. The improved YOLOv5 helps to identify 86 types of objects. The recognition rates for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26 FPS.

4.
J Biol Chem ; 300(1): 105538, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072046

RESUMO

Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.


Assuntos
Fator de Ligação a CCCTC , Cromatina , Proteínas de Ligação a DNA , Regulação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade , Chaperonas de Histonas , Animais , Camundongos , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Cromatina/genética , Replicação do DNA , Chaperonas de Histonas/genética , Proteínas de Ligação a DNA/genética , Proteínas de Grupo de Alta Mobilidade/genética , Células NIH 3T3 , Reparo do DNA
5.
Neurosci Res ; 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38154662

RESUMO

Numerous evidences showed that human umbilical cord blood (UCB) mononuclear cells were a promising approach for the therapy of ischemic stroke(IS). The effect of stage-specific embryonic antigen 3 (SSEA3)positive subpopulation in UCB was not investigated in IS. In this study, we isolated SSEA3 positive cells from healthy UCB mononuclear cells, which comprised about 7.01% of the total UCB-mononuclear cells. Flow cytometry analysis revealed that SSEA3(+)UCB cells were almost positive for CD44 and CD45, and negative for CD73, CD90 and CD105. The expression of Oct3/4 in SSEA3(+)UCB cells were higher than that in UCB. SSEA3(+)UCB cells sorted by magnetic cell sorting were intravenously injected into the middle cerebral arterial occlusion(MCAO) rat model. Neurological score showed that SSEA3(+)UCB transplantation group exhibited significant improvements in the functional outcome of MCAO rats than UCB transplantation group. Nissl staining and microtubule association protein-2(MAP2) immunofluorescence staining showed that the SSEA3(+)UCB transplantation group decreased neuronal loss. SSEA3(+)UCB transplantation group reduced neuronal apoptosis, inhibited caspase3 expression, and decreased tumor necrosis factor α(TNF-α). These results indicate that SSEA3 positive cells are a novel subpopulation of UCB cells, which exhibit great potential for the treatment of ischemic stroke.

6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(5): 1040-1045, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37866966

RESUMO

Objective: To analyze the application effect of continuous lumbar cistern fluid drainage combined with decompressive craniectomy in the treatment of severe craniocerebral injury. Methods: A total of 87 patients with severe craniocerebral injury admitted to our hospital between March 2016 and March 2021 were retrospectively enrolled. They were divided into two groups according to the decompression methods applied, with 42 patients who received standard decompressive craniectomy assigned to the control group and 45 patients who received continuous lumbar cistern fluid drainage combined with standard decompressive craniectomy assigned to the observation group. The primary indicators that were monitored and compared between the two group included the amount of time for patient CT imaging to be clear of subarachnoid hemorrhage, the length-of-stay, the duration of post-operative intubation, the mannitol dose, scores for Glasgow Coma Scale (GCS), prognosis, the incidence of cerebral edema and cerebral infarction, and complications. The secondary indicators that were monitored and compared included intracranial pressure, cerebrospinal fluid antinucleosome protein SP100, and red blood cell count of the two groups before treatment and after continuous drainage for 7 days. Results: The amount of time for CT imaging to be clear of subarachnoid hemorrhage and the length-of-stay of the observation group were shorter than those of the control group, the mannitol dose of the observation group was lower than that of the control group, the incidence of cerebral edema and the incidence of complications of the observation group were lower than those of the control group, and the rate of patients with good prognosis in the observation group was higher than that in the control group ( P<0.05). There was no significant difference in the rate of poor prognosis or mortality between the two groups ( P>0.05). The duration of postoperative intubation of the observation group was (8.24±1.09) d, while that of the control group was (9.22±1.26) d, and the difference between the two groups was statistically significant ( t=3.887, P<0.05). There were 2 cases (4.44%) of cerebral infarction in the observation group, with the infarct volume being (8.36±1.87) cm 3, while there were 9 cases (21.43%) of cerebral infarction in the control group, with the infarct volume being (8.36±1.87) cm 3, and there were statistically significant differences in the incidence and volume of cerebral infarction between the two groups ( χ 2=5.674, t=9.609, P<0.05). After treatment, the intracranial pressure and red blood cell count decreased in both groups and the intracranial pressure, cerebrospinal fluid SP100, and red blood cell count of the observation group were significantly lower than those of the control group ( P<0.05). The cerebrospinal fluid SP100 of the observation group decreased after treatment in comparison with the level before treatment ( P<0.05), while the pre- and post-treatment levels of the control group did not demonstrate any significant difference. Conclusion: Continuous lumbar cistern fluid drainage in patients with severe craniocerebral injury effectively shortens the time required for the body to recover, significantly reduces the level of intracranial pressure, improves the levels of cerebral edema and cerebral infarction, and has a high degree of safety for prognosis and recovery.


Assuntos
Edema Encefálico , Traumatismos Craniocerebrais , Craniectomia Descompressiva , Hemorragia Subaracnóidea , Humanos , Craniectomia Descompressiva/métodos , Edema Encefálico/etiologia , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Traumatismos Craniocerebrais/tratamento farmacológico , Traumatismos Craniocerebrais/cirurgia , Drenagem/métodos , Manitol/uso terapêutico , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/cirurgia
7.
Front Genet ; 14: 1147761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37811148

RESUMO

As one of the main types of structural variation in the human genome, copy number variation (CNV) plays an important role in the occurrence and development of human cancers. Next-generation sequencing (NGS) technology can provide base-level resolution, which provides favorable conditions for the accurate detection of CNVs. However, it is still a very challenging task to accurately detect CNVs from cancer samples with different purity and low sequencing coverage. Local distance-based CNV detection (LDCNV), an innovative computational approach to predict CNVs using NGS data, is proposed in this work. LDCNV calculates the average distance between each read depth (RD) and its k nearest neighbors (KNNs) to define the distance of KNNs of each RD, and the average distance between the KNNs for each RD to define their internal distance. Based on the above definitions, a local distance score is constructed using the ratio between the distance of KNNs and the internal distance of KNNs for each RD. The local distance scores are used to fit a normal distribution to evaluate the significance level of each RDS, and then use the hypothesis test method to predict the CNVs. The performance of the proposed method is verified with simulated and real data and compared with several popular methods. The experimental results show that the proposed method is superior to various other techniques. Therefore, the proposed method can be helpful for cancer diagnosis and targeted drug development.

8.
Nat Commun ; 14(1): 5918, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37739935

RESUMO

The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and -resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.


Assuntos
Antifúngicos , Sepse , Humanos , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida glabrata/genética , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Hemocultura , Genótipo
9.
Artigo em Inglês | MEDLINE | ID: mdl-37600671

RESUMO

Objective: To investigate the diagnostic value of the combined detection of α-hydroxybutyrate dehydrogenase (α-HBDH), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) in early-stage breast cancer (ESBC). Methods: This was a retrospective analysis of 169 patients with ESBC, 138 patients with benign breast disease (BBD) and 200 normal healthy controls (NHCs). The levels of serum α-HBDH, CEA and CA125 in the two groups were detected. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyse the diagnostic value of the above indicators alone and in combination for ESBC. Results: The levels of α-HBDH, CEA and CA125 in the ESBC group were significantly higher than those in the BBD and NHC groups ([118.18 ± 11.19 vs 91.24 ± 9.17 vs 89.38 ± 9.01, F = 6.189, p = 0.004], [2.39 ± 1.12 vs 1.48 ± 0.76 vs 1.58 ± 0.58, F = 5.362, p = 0.017] and [14.44 ± 6.78 vs 11.19 ± 3.17 vs 7.18 ± 4.71, F = 8.912, p = 0.001], respectively). In the ESBC group, the positive rate of combined detection was higher than that of single detection (96.12% vs 72.64% vs 53.67% vs 42.41%, X2 = 27.174, p < 0.05). ROC curve analysis showed that serum α-HBDH, CEA, CA125 alone and combined detection in the diagnosis of ESBC. The sensitivity was 48.1%, 63.6%, 44.2% and 54.5%, the specificity was 75.4%, 75.4%, 86.0% and 91.2% and the AUC was 0.654, 0.715, 0.636 and 0.772, respectively. The diagnostic value of combined detection was the highest. Conclusion: The levels of serum α-HBDH, CEA and CA125 in ESBC are high, and the combined detection of the three has a high diagnostic value for ESBC.

10.
Sci Rep ; 13(1): 13810, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612422

RESUMO

Metabolic reprogramming is a hallmark of cancers, but pan-cancer level roles of lipid metabolism in cancer development are remains poorly understood. We investigated the possible roles of lipid metabolic genes (LMGs) in 14 cancer types. The results indicate that: (1) there is strong evidence for increased lipid metabolism in THCA and KICH. (2) Although the overall levels of lipid metabolic processes are down-regulated in some cancer types, fatty acid synthase activity and fatty acid elongation are moderately up-regulated in more than half of the cancer types. Cholesterol synthesis is up-regulated in five cancers including KICH, BLCA, COAD, BRCA, UCEC, and THCA. (3) The catabolism of cholesterols, triglycerides and fatty acids is repressed in most cancers, but a specific form of lipid degradation, lipophagy, is activated in THCA and KICH. (4) Lipid storage is enhanced in in kidney cancers and thyroid cancer. (5) Similarly to primary tumors, metastatic tumors tend to up-regulate biosynthetic processes of diverse lipids, but down-regulate lipid catabolic processes, except lipophagy. (6) The frequently mutated lipid metabolic genes are not key LMGs. (7) We established a LMG-based model for predicting cancer prognosis. Our results are helpful in expanding our understanding of the role of lipid metabolism in cancer.


Assuntos
Neoplasias Renais , Segunda Neoplasia Primária , Neoplasias da Glândula Tireoide , Humanos , Metabolismo dos Lipídeos , Ácidos Graxos
11.
Micromachines (Basel) ; 14(8)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37630135

RESUMO

In this work, a serpentine mixing unit model based on topology optimization is proposed to enhance the reverse flow in both horizontal and vertical directions. The increase in reverse flow in both directions can enhance the chaotic advection phenomenon, leading to a rapid increase in the mixing index. The proposed mixing unit model is applied in a T-shaped micromixer to create a new micromixer design, named TOD. Numerical simulations of TOD are performed using Comsol Multiphysics software to analyze the characteristics of the liquid flow, mixing surface, and pressure drop. The simulation results confirm that TOD has an outstanding mixing performance. By widening the surface area of contact and enhancing the chaotic advection phenomenon, TOD shows an excellent mixing performance at both a high and low Reynolds number, making it a promising micromixer design. For Re > 5, the mixing indexes of TOD are all beyond 90%.

12.
Updates Surg ; 75(7): 2033-2038, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37395931

RESUMO

OBJECTIVES: To evaluate whether venous tumor thrombus (VTT) consistency is a risk factor for the patient's prognosis with renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 190 RCC patients with VTT, who were treated at Department of Urology, Chinese PLA General Hospital, were retrospectively analyzed in this study. The baseline clinical characteristics, postoperative outcomes, and pathological findings were analyzed. Tumor thrombus was classified as solid and friable based on their respective characteristics. Survival curves were estimated using the Kaplan-Meier survival curve analysis, and univariable and multivariable cox proportional hazard regression models were used. RESULTS: Among the total 190 patients included in this study, 145 (76.3%) patients had solid VTT, and 45 (23.7%) patients had friable VTT in their renal veins and inferior vena cava (IVC). There were no significant differences in the age, gender, BMI, symptoms, complex diseases, tumor side, tumor size, TNM stage, Mayo stage, tumor grade, sarcomatous differentiation, pelvic invasion, and sinus fat invasion of patients. Solid VTT consistency was more likely to have a capsule as compared to those with friable VTT (P = 0.007). Kaplan-Meier survival curve analysis demonstrated no statistically significant differences in the overall survival (OS) (P = 0.973) and progression-free survival (PFS) (P = 0.667) of patients. Moreover, VTT consistency was not associated with OS (P = 0.706) of PFS (P = 0.504) in multivariate cox regression analysis. CONCLUSIONS: RCC VTT consistency was not a prognostic risk factor for predicting the OS and PFS of patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Trombose , Humanos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Prognóstico , Estudos Retrospectivos , Veia Cava Inferior , Nefrectomia
13.
IEEE J Biomed Health Inform ; 27(9): 4433-4443, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37310831

RESUMO

Automated classification of lymph node metastasis (LNM) plays an important role in the diagnosis and prognosis. However, it is very challenging to achieve satisfactory performance in LNM classification, because both the morphology and spatial distribution of tumor regions should be taken into account. To address this problem, this article proposes a two-stage dMIL-Transformer framework, which integrates both the morphological and spatial information of the tumor regions based on the theory of multiple instance learning (MIL). In the first stage, a double Max-Min MIL (dMIL) strategy is devised to select the suspected top-K positive instances from each input histopathology image, which contains tens of thousands of patches (primarily negative). The dMIL strategy enables a better decision boundary for selecting the critical instances compared with other methods. In the second stage, a Transformer-based MIL aggregator is designed to integrate all the morphological and spatial information of the selected instances from the first stage. The self-attention mechanism is further employed to characterize the correlation between different instances and learn the bag-level representation for predicting the LNM category. The proposed dMIL-Transformer can effectively deal with the thorny classification in LNM with great visualization and interpretability. We conduct various experiments over three LNM datasets, and achieve 1.79%-7.50% performance improvement compared with other state-of-the-art methods.


Assuntos
Metástase Linfática , Aprendizado de Máquina , Humanos
15.
Exp Brain Res ; 241(6): 1585-1598, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37142782

RESUMO

Cerebral infarction is one of the most prevalent cerebrovascular disorders. Microglia and infiltrating macrophages play a key role in regulating the inflammatory response after ischemic stroke. Regulation of microglia/macrophages polarization contributes to the recovery of neurological function in cerebral infarction. In recent decades, human umbilical cord blood mononuclear cells (hUCBMNCs) have been considered a potential therapeutic alternative. However, the mechanism of action is yet unclear. Our study aimed to explore whether hUCBMNCs treatment for cerebral infarction is via regulation of microglia/macrophages polarization. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and were treated by intravenous routine with or without hUCBMNCs at 24 h following MCAO. We evaluated the therapeutic effects of hUCBMNCs on cerebral infarction by measuring animal behavior and infarct volume, and further explored the possible mechanisms of hUCBMNCs for cerebral infarction by measuring inflammatory factors and microglia/macrophages markers using Elisa and immunofluorescence staining, respectively. We found that administration with hUCBMNCs improved behavioral functions and reduced infarct volume. Rats treated with hUCBMNCs showed a significant reduction in the level of IL-6, and TNF-α and increased the level of IL-4 and IL-10 compared to those treated without hUCBMNCs. Furthermore, hUCBMNCs inhibited M1 polarization and promoted M2 polarization of microglia/macrophages after MCAO. We conclude that hUCBMNCs could ameliorate cerebral brain injury by promoting microglia/macrophages M2 polarization in MCAO Rats. This experiment provides evidence that hUCBMNCs represent a promising therapeutic option for ischemic stroke.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Ratos , Humanos , Masculino , Animais , Infarto da Artéria Cerebral Média/tratamento farmacológico , Microglia , Sangue Fetal , Ratos Sprague-Dawley , Isquemia Encefálica/tratamento farmacológico , Macrófagos
16.
Sci Total Environ ; 892: 164508, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37247731

RESUMO

The feedback between nitrous oxide (N2O) emissions, straw management and future climate scenarios is not well understood, especially in wheat ecosystems. In this study, the changes in N2O emissions, soil properties, enzymes, and functional genes involved in N cycling were measured with straw return (incorporation and mulching) and straw removal, under elevated [CO2] (+200 µmol mol-1 above ambient [CO2]), elevated temperature (+2 °C above ambient temperature), and their combination. The net global warming potential (NGWP) and greenhouse gas intensity (GHGI) were evaluated in combination with greenhouse gas emissions, yield, and soil organic carbon (C) sequestration. Compared with the ambient condition, elevated [CO2] and elevated temperature suppressed N2O emission by 41 %-46 %. Straw return significantly increased N2O emission by 31 %-109 % through increasing soil C and N substrates and denitrifying genes abundance, compared with straw removal. In addition, the impact of straw return on N2O emission was greater than that of elevated [CO2] or temperature. Straw return generally reduced NGWP by 166.2-3353.3 kg CO2-eq ha-1 and GHGI by 0.4-1.1 kg CO2-eq kg-1 through increasing soil organic C sequestration by 0.1-1.1 t C ha-1 and grain yield by 280.8 kg ha-1-1595.4 kg ha-1. Straw return would stimulate N2O emissions from this wheat cropping system under future warmer, elevated [CO2] climates, but simultaneously increase grain yield and soil organic C sequestration to a greater extent. Overall, straw return is beneficial to climate change mitigation; in particular, straw incorporation would be more effective than straw mulching.


Assuntos
Gases de Efeito Estufa , Solo , Solo/química , Agricultura , Dióxido de Carbono/análise , Triticum , Carbono , Ecossistema , Temperatura , Óxido Nitroso/análise , Grão Comestível/química , China , Fertilizantes/análise
17.
Res Sq ; 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37066226

RESUMO

The longstanding paradigm is that most bloodstream infections (BSIs) are caused by a single organism. We performed whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrated that BCs contained mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibited phenotypes that were potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identified mixed fluconazole-susceptible and â€"resistant populations. Diversity in drug susceptibility was likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants were fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a new population-based paradigm of C. glabrata genotypic and phenotypic diversity during BSIs.

18.
Cancer Immunol Res ; 11(6): 830-846, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-36996321

RESUMO

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV-positive (EBV+) NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell-based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV+ NPC tissues and found that EBV infection-induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection-induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti-PD-L1 treatment restored NK cell-mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. On the basis of our findings, we conclude that EBV infection can inhibit NK cell-mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell-based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Animais , Camundongos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Herpesvirus Humano 4/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Fatores de Transcrição/metabolismo , Células Matadoras Naturais/metabolismo
19.
Neurosurgery ; 93(1): 24-32, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36794961

RESUMO

BACKGROUND: The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins. OBJECTIVE: To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH. METHODS: We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis. RESULTS: A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79). CONCLUSION: Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Teorema de Bayes , Metanálise em Rede , Vasoespasmo Intracraniano/etiologia
20.
Genes (Basel) ; 14(2)2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36833414

RESUMO

The broodiness traits of domestic geese are a bottleneck that prevents the rapid development of the goose industry. To reduce the broodiness of the Zhedong goose and thus improve it, this study hybridized it with the Zi goose, which has almost no broody behavior. Genome resequencing was performed for the purebred Zhedong goose, as well as the F2 and F3 hybrids. The results showed that the F1 hybrids displayed significant heterosis in growth traits, and their body weight was significantly greater than those of the other groups. The F2 hybrids showed significant heterosis in egg-laying traits, and the number of eggs laid was significantly greater than those of the other groups. A total of 7,979,421 single-nucleotide polymorphisms (SNPs) were obtained, and three SNPs were screened. Molecular docking results showed that SNP11 located in the gene NUDT9 altered the structure and affinity of the binding pocket. The results suggested that SNP11 is an SNP related to goose broodiness. In the future, we will use the cage breeding method to sample the same half-sib families to accurately identify SNP markers of growth and reproductive traits.


Assuntos
Gansos , Polimorfismo de Nucleotídeo Único , Animais , Gansos/genética , Simulação de Acoplamento Molecular , Reprodução , Oviposição
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