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1.
Opt Express ; 32(7): 11934-11951, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571030

RESUMO

Optical coherence tomography (OCT) can resolve biological three-dimensional tissue structures, but it is inevitably plagued by speckle noise that degrades image quality and obscures biological structure. Recently unsupervised deep learning methods are becoming more popular in OCT despeckling but they still have to use unpaired noisy-clean images or paired noisy-noisy images. To address the above problem, we propose what we believe to be a novel unsupervised deep learning method for OCT despeckling, termed Double-free Net, which eliminates the need for ground truth data and repeated scanning by sub-sampling noisy images and synthesizing noisier images. In comparison to existing unsupervised methods, Double-free Net obtains superior denoising performance when trained on datasets comprising retinal and human tissue images without clean images. The efficacy of Double-free Net in denoising holds significant promise for diagnostic applications in retinal pathologies and enhances the accuracy of retinal layer segmentation. Results demonstrate that Double-free Net outperforms state-of-the-art methods and exhibits strong convenience and adaptability across different OCT images.


Assuntos
Algoritmos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Cintilografia , Processamento de Imagem Assistida por Computador/métodos
2.
Small Methods ; : e2301793, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501843

RESUMO

Ultraviolet light (UV) has caused tremendous damage to perovskite solar cells (PSCs), degrading the perovskite and shortening their lifetime. Defects act as non-radiative recombination sites, accelerate the degradation process, reduce the efficiency of the device and weaken the stability of solar cell. In this work, to realize efficient and stable p-i-n wide bandgap solar cells under UV, a synergetic strategy utilizing UV light-absorbing passivator, (Trifluoroacetyl) benzotriazole (TFABI), enhance UV photostability and regulate the defect passivation is proposed. By using TFABI, the degradation of the perovskite absorption layer under UV light is suppressed, spectral response is enhanced and the Pb vacancy defects are passivated. As a result, the target device achieves an efficiency of 21.54%, exhibiting excellent long-term stability under 365 nm UV irradiation. After 60 h of irradiation, it retains 85% of its initial value (60 mW cm-2 , RH 25-30%, 25 °C).

3.
Front Neurosci ; 18: 1359631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516314

RESUMO

Background: Alzheimer's disease (AD) is a common, refractory, progressive neurodegenerative disorder in which cognitive and memory deficits are highly correlated with abnormalities in hippocampal brain regions. There is still a lack of hippocampus-related markers for AD diagnosis and prevention. Methods: Differently expressed genes were identified in the gene expression profile GSE293789 in the hippocampal brain region. Enrichment analyses GO, KEGG, and GSEA were used to identify biological pathways involved in the DEGs and AD-related group. WGCNA was used to identify the gene modules that are highly associated with AD in the samples. The intersecting genes of the genes in DEGs and modules were extracted and the top ten ranked hub genes were identified. Finally GES48350 was used as a validation cohort to predict the diagnostic efficacy of hub genes. Results: From GSE293789, 225 DEGs were identified, which were mainly associated with calcium response, glutamatergic synapses, and calcium-dependent phospholipid-binding response. WGCNA analysis yielded dark green and bright yellow modular genes as the most relevant to AD. From these two modules, 176 genes were extracted, which were taken to be intersected with DEGs, yielding 51 intersecting genes. Then 10 hub genes were identified in them: HSPA1B, HSPB1, HSPA1A, DNAJB1, HSPB8, ANXA2, ANXA1, SOX9, YAP1, and AHNAK. Validation of these genes was found to have excellent diagnostic performance. Conclusion: Ten AD-related hub genes in the hippocampus were identified, contributing to further understanding of AD development in the hippocampus and development of targets for therapeutic prevention.

5.
Sci Transl Med ; 16(739): eadg5553, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507470

RESUMO

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/tratamento farmacológico , Ferro/metabolismo , Glioma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Células-Tronco Neoplásicas/patologia , Enxofre/metabolismo , Enxofre/uso terapêutico , Fumaratos , Linhagem Celular Tumoral , PTEN Fosfo-Hidrolase/metabolismo
6.
J Am Chem Soc ; 146(11): 7605-7615, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38467427

RESUMO

Cu-SSZ-13 has been commercialized for selective catalytic reduction with ammonia (NH3-SCR) to remove NOx from diesel exhaust. As its synthesis usually requires toxic and costly organic templates, the discovery of alternative Cu-based zeolite catalysts with organotemplate-free synthesis and comparable or even superior NH3-SCR activity to that of Cu-SSZ-13 is of great academic and industrial significance. Herein, we demonstrated that Cu-T with an intergrowth structure of offretite (OFF) and erionite (ERI) synthesized by an organotemplate-free method showed better catalytic performance than Cu-ERI and Cu-OFF as well as Cu-SSZ-13. Structure characterizations and density functional theory calculations indicated that the intergrowth structure promoted more isolated Cu2+ located at the 6MR of the intergrowth interface, resulting in a better hydrothermal stability of Cu-T than Cu-ERI and Cu-OFF. Strikingly, the low-temperature activity of Cu-T significantly increased after hydrothermal aging, while that of Cu-ERI and Cu-OFF substantially decreased. Based on in situ diffuse reflectance infrared Fourier transform spectra analysis and density functional theory calculations, the reason can be attributed to the fact that NH4NO3 formed on the CuxOy species within ERI polymorph of Cu-T underwent a fast SCR reaction pathway with the assistance of Brønsted acid sites at the intergrowth interfaces under standard SCR reaction conditions. Significantly, Cu-T exhibited a wider temperature window at a catalytic activity of over 90% than Cu-SSZ-13 (175-550 vs 175-500 °C for fresh and 225-500 vs 250-400 °C for hydrothermal treatment). This work provides a new direction for the design of high-performance NH3-SCR catalysts in terms of the interplay of the intergrowth structure of zeolites.

7.
J Nanobiotechnology ; 22(1): 126, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38519957

RESUMO

The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.


Assuntos
Infecções Bacterianas , Óxido de Zinco , Animais , Camundongos , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Óxido de Zinco/farmacologia , Anti-Inflamatórios , Antibacterianos/farmacologia
8.
iScience ; 27(3): 109277, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455971

RESUMO

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM-derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall survival and immune activation, particularly in T cell-mediated responses. Altogether, our analysis suggests that TRM abundance is associated with melanoma TIME activation and patient survival, and the TRM-based machine learning model can potentially predict prognosis in melanoma patients.

9.
Quant Imaging Med Surg ; 14(3): 2225-2239, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545061

RESUMO

Background: An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. Methods: In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. Results: The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). Conclusions: The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

10.
Mol Pharm ; 21(4): 1691-1704, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430187

RESUMO

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.


Assuntos
Omalizumab , Proteínas , Temperatura , Liofilização , Estabilidade de Medicamentos
11.
BJPsych Open ; 10(2): e41, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297498

RESUMO

BACKGROUND: COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. AIMS: To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. METHOD: A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. RESULTS: The average participant SIS score was 42.66 ± 14.61 (range: 24-96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker-Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061-1.115; area under the curve: 0.84, 95% CI 0.788-0.892). CONCLUSIONS: The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

12.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167082, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367899

RESUMO

Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35-40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.


Assuntos
NF-kappa B , Choque Hemorrágico , Animais , Ratos , Íleo/metabolismo , NF-kappa B/metabolismo , Choque Hemorrágico/complicações , Transdução de Sinais
13.
Sci Bull (Beijing) ; 69(8): 1091-1099, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38395650

RESUMO

Controlling the atomic arrangement of elemental atoms in intermetallic catalysts to govern their surface and subsurface properties is a crucial but challenging endeavor in electrocatalytic reactions. In hydrogen evolution reaction (HER), adjusting the d-band center of the conventional noble-metallic Pt by introducing Fe enables the optimization of catalytic performance. However, a notable gap exists in research on the effective transition from disordered Fe/Pt alloys to highly ordered intermetallic compounds (IMCs) such as FePt3 in the alkaline HER, hampering their broader application. In this study, a series of catalysts FePt3-xH (x = 5, 6, 7, 8 and 9) supported on carbon nanotubes (CNTs) were synthesized via a simple impregnation method, along with a range of heat treatment processes, including annealing in a reductive atmosphere, to regulate the order degree of the arrangement of Fe/Pt atoms within the FePt3 catalyst. By using advanced microscopy and spectroscopy techniques, we systematically explored the impact of the order degree of FePt3 in the HER. The as-prepared FePt3-8H exhibited notable HER catalytic activity with low overpotentials (η = 37 mV in 1.0 mol L-1 KOH) at j = 10 mA cm-2. The surface of the L12 FePt3-8H catalyst was demonstrated to be Pt-rich. The Pt on the surface was not easily oxidized due to the unique Fe/Pt coordination, resulting in significant enhancement of HER performance.

14.
Environ Pollut ; 346: 123610, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38382728

RESUMO

As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.


Assuntos
Dietilexilftalato , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácidos Ftálicos , Humanos , Animais , Camundongos , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Receptor 4 Toll-Like/metabolismo , Chaperonina 60/farmacologia , Piroptose , Dietilexilftalato/toxicidade , Baço/metabolismo , Camundongos Endogâmicos ICR
15.
Curr Med Chem ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38310397

RESUMO

BACKGROUND: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The clinical efficacy and safety of an administered tofacitinib, either monotherapy or in combination with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate (MTX), have been evaluated. The high plasma concentration with delayed medicine clearance may affect the liver and/or kidney functions. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC- MS/MS) method for the quantitative analysis of methotrexate, tofacitinib, and metabolite M9 in plasma of Sprague Dawley (SD) rats was developed, and its effectiveness was validated as well. METHODS: Methotrexate, tofacitinib, M9 and fedratinib (internal standard, IS) were separated by gradient elution. The chromatography was performed on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 µm) column with the mobile phases of acetonitrile and 0.1% formic acid aqueous solution with different proportions at the flow rate of 0.30 mL/min. In the positive ionization mode, the analyzes were detected using a Xevo TQ-S triple quadrupole tandem mass spectrometer, with the following mass transition pairs: m/z 313.12 → 148.97 for tofacitinib, m/z 329.10 → 165.00 for M9 and m/z 455.12 → 308.05 for methotrexate. RESULTS: The obtained results manifested good calibration linearity over the ranges of tofacitinib at 0.1-100 ng/mL, M9 at 0.05-100 ng/mL, and methotrexate at 0.05-100 ng/mL. The lower limit of quantifications (LLOQs) of methotrexate, tofacitinib and M9 were 0.05 ng/mL, 0.1 ng/mL and 0.05 ng/mL, respectively. Intra-day and inter-day accuracy values were confirmed with a range of -6.3% to 12.7%, while intra-day and inter-- day precision values were ≤14.4%. Additionally, recoveries were greater than 86.5% for each compound without significant matrix effects. CONCLUSION: The currently established analytical method exhibited great potential for the evaluation of plasma concentrations of methotrexate, tofacitinib and M9 simultaneously, greatly reducing the detection time, which would serve as a supplementary role in formulating dose decisions to achieve personalized treatment, identify drugs that cause adverse reactions and finally, to assess drug-drug interactions on clinical studies.

16.
Front Microbiol ; 15: 1359340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414769

RESUMO

Background: The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably ß-lactams, constitutes a formidable challenge for healthcare and global public health management. Methods: This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features. Results: The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments. Conclusion: In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

17.
Int J Biometeorol ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363363

RESUMO

Intensive urban development has resulted in the degradation of the urban thermal environment in most regions. There is a growing consensus on the need to enhance urban thermal comfort through well-designed forms, especially in open spaces like urban canyons. To address this, our study focuses on Xi'an's commercial pedestrian streets, employing K-means clustering analysis to create 32 representative models based on actual scenes, capturing their textural characteristics. Simultaneously, 11 geometric indicators (2D/3D) were chosen to quantify the canyon's geometric form. We assessed the spatial and temporal distribution differences in the thermal environment across these models using Envi-met simulation. Finally, Spearman correlation analysis was employed to examine the correlation and significance of the two sets of indicators, culminating in formulating an ideal model. The findings reveal that (1) wind conditions are predominantly influenced by the canyon's geometric form, followed by solar radiation and temperature, with the lowest relative humidity change amplitude among the assessed thermal parameters. (2) Among the 11 geometric form indicators, 3D indicators correlate more significantly with thermal environment parameters than 2D indicators. Specifically, street orientation significantly impacts the thermal environment, Build-To-Line Rat holds greater significance than interface density, and both building shape coefficient and block surface ratio are significantly correlated with air temperature and wind speed, with a weaker correlation to solar radiation. (3) In the Xi'an region, courtyards oriented north-south demonstrate a more favorable trend in the thermal environment.

18.
Sci Rep ; 14(1): 3500, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347041

RESUMO

Long non-coding RNAs (lncRNAs) involved in metabolism are recognized as significant factors in breast cancer (BC) progression. We constructed a novel prognostic signature for BC using metabolism-related lncRNAs and investigated their underlying mechanisms. The training and validation cohorts were established from BC patients acquired from two public sources: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The prognostic signature of metabolism-related lncRNAs was constructed using the least absolute shrinkage and selection operator (LASSO) cox regression analysis. We developed and validated a new prognostic risk model for BC using the signature of metabolism-related lncRNAs (SIRLNT, SIAH2-AS1, MIR205HG, USP30-AS1, MIR200CHG, TFAP2A-AS1, AP005131.2, AL031316.1, C6orf99). The risk score obtained from this signature was proven to be an independent prognostic factor for BC patients, resulting in a poor overall survival (OS) for individuals in the high-risk group. The area under the curve (AUC) for OS at three and five years were 0.67 and 0.65 in the TCGA cohort, and 0.697 and 0.68 in the GEO validation cohort, respectively. The prognostic signature demonstrated a robust association with the immunological state of BC patients. Conventional chemotherapeutics, such as docetaxel and paclitaxel, showed greater efficacy in BC patients classified as high-risk. A nomogram with a c-index of 0.764 was developed to forecast the survival time of BC patients, considering their risk score and age. The silencing of C6orf99 markedly decreased the proliferation, migration, and invasion capacities in MCF-7 cells. Our study identified a signature of metabolism-related lncRNAs that predicts outcomes in BC patients and could assist in tailoring personalized prevention and treatment plans.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , RNA Longo não Codificante/genética , Prognóstico , Nomogramas , Docetaxel
19.
IEEE Trans Med Imaging ; PP2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324426

RESUMO

Optical coherence tomography (OCT) can perform non-invasive high-resolution three-dimensional (3D) imaging and has been widely used in biomedical fields, while it is inevitably affected by coherence speckle noise which degrades OCT imaging performance and restricts its applications. Here we present a novel speckle-free OCT imaging strategy, named toward-ground-truth OCT (tGT-OCT), that utilizes unsupervised 3D deep-learning processing and leverages OCT 3D imaging features to achieve speckle-free OCT imaging. Specifically, our proposed tGT-OCT utilizes an unsupervised 3D-convolution deep-learning network trained using random 3D volumetric data to distinguish and separate speckle from real structures in 3D imaging volumetric space; moreover, tGT-OCT effectively further reduces speckle noise and reveals structures that would otherwise be obscured by speckle noise while preserving spatial resolution. Results derived from different samples demonstrated the high-quality speckle-free 3D imaging performance of tGT-OCT and its advancement beyond the previous state-of-the-art. The code is available online: https://github.com/Voluntino/tGT-OCT.

20.
Front Immunol ; 15: 1295693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312840

RESUMO

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Antígenos B7 , Proliferação de Células , Bases de Dados Factuais , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
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