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1.
Clin Respir J ; 18(5): e13757, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38715380

RESUMEN

OBJECTIVE: This research was aimed to comprehensively investigate the expression levels, diagnostic and prognostic implications, and the relationship with immune infiltration of G2 and S phase-expressed-1 (GTSE1) across 33 tumor types, including lung adenocarcinoma (LUAD), through gene expression profiling. METHODS: GTSE1 mRNA expression data together with clinical information were acquired from Xena database of The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene Expression Omnibus (GEO) database for this study. The Wilcoxon rank-sum test was used to detect differences in GTSE1 expression between groups. The ability of GTSE1 to accurately predict cancer status was evaluated by calculating the area under the curve (AUC) value for the receiver operating characteristic curve. Additionally, we investigated the predictive value of GTSE1 in individuals diagnosed with neoplasms using univariate Cox regression analysis as well as Kaplan-Meier curves. Furthermore, the correlation between GTSE1 expression and levels of immune infiltration was assessed by utilizing the Tumor Immune Estimate Resource (TIMER) database to calculate the Spearman rank correlation coefficient. Finally, the pan-cancer analysis findings were validated by examining the association between GTSE1 expression and prognosis among patients with LUAD. RESULTS: GTSE1 exhibited significantly increased expression levels in a wide range of tumor tissues in contrast with normal tissues (p < 0.05). The expression of GTSE1 in various tumors was associated with clinical features, overall survival, and disease-specific survival (p < 0.05). In immune infiltration analyses, a strong correlation of the level of immune infiltration with the expression of GTSE1 was observed. Furthermore, GTSE1 demonstrated good discriminative and diagnostic value for most tumors. Additional experiments confirmed the relationship between elevated GTSE1 expression and unfavorable prognosis in individuals diagnosed with LUAD. These findings indicated the crucial role of GTSE1 expression level in influencing the development and immune infiltration of different types of tumors. CONCLUSIONS: GTSE1 might be a potential biomarker for the prognosis of pan-cancer. Meanwhile, it represented a promising target for immunotherapy.


Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Neoplasias Pulmonares , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Pronóstico
2.
Front Pharmacol ; 15: 1355507, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720778

RESUMEN

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors. Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound. Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs' biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

3.
Front Pharmacol ; 15: 1245825, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720775

RESUMEN

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

4.
Neural Netw ; 176: 106350, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38723309

RESUMEN

In recent years, self-supervised learning has emerged as a powerful approach to learning visual representations without requiring extensive manual annotation. One popular technique involves using rotation transformations of images, which provide a clear visual signal for learning semantic representation. However, in this work, we revisit the pretext task of predicting image rotation in self-supervised learning and discover that it tends to marginalise the perception of features located near the centre of an image. To address this limitation, we propose a new self-supervised learning method, namely FullRot, which spotlights underrated regions by resizing the randomly selected and cropped regions of images. Moreover, FullRot increases the complexity of the rotation pretext task by applying the degree-free rotation to the region cropped into a circle. To encourage models to learn from different general parts of an image, we introduce a new data mixture technique called WRMix, which merges two random intra-image patches. By combining these innovative crop and rotation methods with the data mixture scheme, our approach, FullRot + WRMix, surpasses the state-of-the-art self-supervision methods in classification, segmentation, and object detection tasks on ten benchmark datasets with an improvement of up to +13.98% accuracy on STL-10, +8.56% accuracy on CIFAR-10, +10.20% accuracy on Sports-100, +15.86% accuracy on Mammals-45, +15.15% accuracy on PAD-UFES-20, +32.44% mIoU on VOC 2012, +7.62% mIoU on ISIC 2018, +9.70% mIoU on FloodArea, +25.16% AP50 on VOC 2007, and +58.69% AP50 on UTDAC 2020. The code is available at https://github.com/anthonyweidai/FullRot_WRMix.

5.
Asian J Surg ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38724372

RESUMEN

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

6.
ACS Infect Dis ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725130

RESUMEN

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

7.
Plant Physiol Biochem ; 211: 108695, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38744088

RESUMEN

The presence of sugar in plant tissue can lead to an increase in the osmotic pressure within cells, a decrease in the freezing point of plants, and protection against ice crystal damage to the tissue. Trehalose is closely related to sucrose, which comprises the largest proportion of sugar and has become a hot topic of research in recent years. Our previous studies have confirmed that a key trehalose synthesis gene, TaTPS11, from the cold-resistant winter wheat DM1, could enhance the cold resistance of plants by increasing sugar content. However, the underlying mechanism behind this phenomenon remains unclear. In this study, we cloned TaTPS11-6D, edited TaTPS11-6D using CRISPR/Cas9 technology and transformed 'Fielder' to obtain T2 generation plants. We screened out OE3-3 and OE8-7 lines with significantly higher cold resistance than that of 'Fielder' and Cri 4-3 edited lines with significantly lower cold resistance than that of 'Fielder'. Low temperature storage limiting factors were measured for OE3-3, OE8-7 and Cri 4-3 treated at different temperatures.The results showed that TaTPS11-6D significantly increased the content of sugar in plants and the transfer of sugar from source to storage organs under cold conditions. The TaTPS11-6D significantly increased the levels of salicylic, jasmonic, and abscisic acids while also significantly decreasing the level of gibberellic acid. Our research improves the model of low temperature storage capacity limiting factor.

8.
Molecules ; 29(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731417

RESUMEN

In recent years, renewable and sustainable triboelectric nanogenerators have attracted attention due to their high energy conversion rate, and enhancing their functionality further contributes to their applicability across various fields. A pH-sensitive triboelectric nanogenerator (pH-TENG) has been prepared by electrostatic spinning technology, with anthocyanin as the pH indicator and environmentally friendly polyvinyl alcohol (PVA) as the substrate. Among many friction-negative materials, the pH-TENG exhibits the best combination with fluorinated ethylene propylene (FEP) and yields an open-circuit voltage of 62 V, a short-circuit current of 370 nA, and a transferred charge of 21.8 nC. At a frequency of 3 Hz, it can charge a 4.7 µF capacitor to 2 V within 45 s, effectively powering a thermometer. Furthermore, the presence of anthocyanin does not affect the pH-TENG's power generation performance and enables the monitoring of a wide range of environmental pH changes, with an ΔE change of 28.8 ± 7.6. Therefore, pH-TENG prepared with environmentally friendly materials can bring new available materials to the biological and medical fields.

9.
Foods ; 13(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731658

RESUMEN

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

10.
Plants (Basel) ; 13(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732475

RESUMEN

JASMONATE-ZIM DOMAIN (JAZ) repressor proteins work as co-receptors in the jasmonic acid (JA) signalling pathway and are essential for plant development and environmental adaptation. Despite wheat being one of the main staple food crops, until recently, comprehensive analysis of its JAZ gene family has been limited due to the lack of complete and high-quality reference genomes. Here, using the latest reference genome, we identified 17 JAZ genes in the wheat D-genome donor Aegilops tauschii. Then, 54 TaJAZs were identified in common wheat. A systematic examination of the gene structures, conserved protein domains, and phylogenetic relationships of this gene family was performed. Five new JAZ genes were identified as being derived from tandem duplication after wheat divergence from other species. We integrated RNA-seq data and yield QTL information and found that tandemly duplicated TaJAZ genes were prone to association with spike-related traits. Moreover, 12 TaJAZ genes were located within breeding selection sweeps, including 9 tandemly duplicated ones. Haplotype variation analysis of selected JAZ genes showed significant association of TaJAZ7A and TaJAZ13A with thousand-grain weight. Our work provides a clearer picture of wheat JAZ gene evolution and puts forward the possibility of using these genes for wheat yield improvement.

11.
BMC Surg ; 24(1): 148, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734630

RESUMEN

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.


Asunto(s)
Laparoscopía , Hepatopatías , Complicaciones Posoperatorias , Impresión Tridimensional , Humanos , Femenino , Masculino , Persona de Mediana Edad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Hepatopatías/cirugía , Anciano , Enfermedades de las Vías Biliares/prevención & control , Enfermedades de las Vías Biliares/cirugía , Enfermedades de las Vías Biliares/etiología , Hepatectomía/métodos , Hepatectomía/efectos adversos , Adulto , Estudios Retrospectivos , Estudios de Cohortes
12.
Transl Lung Cancer Res ; 13(4): 763-784, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38736486

RESUMEN

Background: Albeit considered with superior survival, around 30% of the early-stage non-squamous non-small cell lung cancer (Ns-NSCLC) patients relapse within 5 years, suggesting unique biology. However, the biological characteristics of early-stage Ns-NSCLC, especially in the Chinese population, are still unclear. Methods: Multi-omics interrogation of early-stage Ns-NSCLC (stage I-III), paired blood samples and normal lung tissues (n=76) by whole-exome sequencing (WES), RNA sequencing, and T-cell receptor (TCR) sequencing were conducted. Results: An average of 128 exonic mutations were identified, and the most frequently mutant gene was EGFR (55%), followed by TP53 (37%) and TTN (26%). Mutations in MUC17, ABCA2, PDE4DIP, and MYO18B predicted significantly unfavorable disease-free survival (DFS). Moreover, cytobands amplifications in 8q24.3, 14q13.1, 14q11.2, and deletion in 3p21.1 were highlighted in recurrent cases. Higher incidence of human leukocyte antigen loss of heterozygosity (HLA-LOH), higher tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were identified in ever-smokers than never-smokers. HLA-LOH also correlated with higher TMB, TNB, intratumoral heterogeneity (ITH), and whole chromosomal instability (wCIN) scores. Interestingly, higher ITH was an independent predictor of better DFS in early-stage Ns-NSCLC. Up-regulation of immune-related genes, including CRABP2, ULBP2, IL31RA, and IL1A, independently portended a dismal prognosis. Enhanced TCR diversity of peripheral blood mononuclear cells (PBMCs) predicted better prognosis, indicative of a noninvasive method for relapse surveillance. Eventually, seven machine-learning (ML) algorithms were employed to evaluate the predictive accuracy of clinical, genomic, transcriptomic, and TCR repertoire data on DFS, showing that clinical and RNA features combination in the random forest (RF) algorithm, with area under the curve (AUC) of 97.5% and 83.3% in the training and testing cohort, respectively, significantly outperformed other methods. Conclusions: This study comprehensively profiled the genomic, transcriptomic, and TCR repertoire spectrums of Chinese early-stage Ns-NSCLC, shedding light on biological underpinnings and candidate biomarkers for prognosis development.

13.
Front Hum Neurosci ; 18: 1371648, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736529

RESUMEN

Human postural control system is inherently complex with nonlinear interaction among multiple subsystems. Accordingly, such postural control system has the flexibility in adaptation to complex environments. Previous studies applied complexity-based methods to analyze center of pressure (COP) to explore nonlinear dynamics of postural sway under changing environments, but direct evidence from central nervous system or muscular system is limited in the existing literature. Therefore, we assessed the fractal dimension of COP, surface electromyographic (sEMG) and electroencephalogram (EEG) signals under visual-vestibular habituation balance practice. We combined a rotating platform and a virtual reality headset to present visual-vestibular congruent or incongruent conditions. We asked participants to undergo repeated exposure to either congruent (n = 14) or incongruent condition (n = 13) five times while maintaining balance. We found repeated practice under both congruent and incongruent conditions increased the complexity of high-frequency (0.5-20 Hz) component of COP data and the complexity of sEMG data from tibialis anterior muscle. In contrast, repeated practice under conflicts decreased the complexity of low-frequency (<0.5 Hz) component of COP data and the complexity of EEG data of parietal and occipital lobes, while repeated practice under congruent environment decreased the complexity of EEG data of parietal and temporal lobes. These results suggested nonlinear dynamics of cortical activity differed after balance practice under congruent and incongruent environments. Also, we found a positive correlation (1) between the complexity of high-frequency component of COP and the complexity of sEMG signals from calf muscles, and (2) between the complexity of low-frequency component of COP and the complexity of EEG signals. These results suggested the low- or high-component of COP might be related to central or muscular adjustment of postural control, respectively.

14.
J Thorac Dis ; 16(4): 2539-2549, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38738241

RESUMEN

Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI. Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China. All 80 participants underwent simultaneous blood culture, blood mNGS, and blood tNGS after admission when febrile, and the results were compared. Results: Among the 80 participants, 11 were clinically diagnosed with noninfectious fever, and 69 were diagnosed with BSI. Blood tNGS had a higher sensitivity for the diagnosis of BSI than blood culture (91.3% vs. 23.2%, P<0.001) and blood mNGS (91.3% vs. 69.6%, P=0.001). There was no significant difference in specificity between blood mNGS and tNGS (81.8% vs. 100.0%, P=0.13). Blood tNGS demonstrated a faster turnaround time than blood culture and blood mNGS. In 22 (31.9%) patients with BSI, targeted adjustment of the anti-infectious therapy according to the blood tNGS results resulted in clinical improvement. Conclusions: Blood tNGS may be a promising tool for detecting potential pathogens in patients with BSI. The application of blood tNGS for BSI could guide anti-infectious treatment strategies and might improve clinical outcomes.

15.
J Colloid Interface Sci ; 669: 529-536, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38729001

RESUMEN

Solid polymer electrolytes (SPEs) are effective solutions for the development of high-performance and flexible lithium metal batteries (LMBs). However, the key problems of SPEs including low ionic conductivity and inability to repair damage have hindered their industrialization process. In this work, a three-dimensional (3D) cross-linked network gel polymer electrolyte (CNGPE) is designed. The addition of deep eutectic solvent (DES) improves the ionic conductivity of CNGPE. The hydrogen bonds and dynamic disulfide bonds in the 3D cross-linked network endow CNGPE rapid self-healing ability at ambient temperature. In addition, the addition of lithium difluoro(oxalato)borate (LiDFOB) and lithium nitrate (LiNO3) helps to form a stable solid electrolyte interface (SEI). Due to the ingenious design, the Li/CNGPE/Li symmetrical cell exhibits excellent interface stability and no short circuit occurs for more than 800 h. The assembled LiFePO4/CNGPE/Li cell exhibits a discharge specific capacity of 126 mAh g-1 after 960 cycles at 0.5C. This work has shown that the self-healing gel polymer electrolyte containing DES provides an effective and feasible method for the development of high-performance LMBs.

16.
Sci Adv ; 10(19): eadn6206, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728408

RESUMEN

Light carrying orbital angular momentum (OAM) holds unique properties and boosts myriad applications in diverse fields. However, the generation of an ultrafast wave packet carrying numerous vortices with various transverse OAM modes, i.e., vortex string, remains challenging, and the corresponding detection method is lacking. Here, we demonstrate that a vortex string with 28 spatiotemporal optical vortices (STOVs) with customizable topological charge (TC) arrangements can be generated in one wave packet. The diffraction rules of STOV strings are revealed theoretically and experimentally. Following these rules, the TC values and positions of all STOVs in a vortex string can be simultaneously recognized from the diffraction pattern. Such STOV strings facilitate STOV-based optical communication. As a proof-of-principle demonstration, the transmission of an image is realized with 16-STOV strings. This work provides guidance for revealing the underlying properties of the transverse OAM light and opens up opportunities for applications of the structured light in optical communication, quantum information processing, etc.

17.
Small ; : e2401457, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733086

RESUMEN

The separator is an important component in batteries, with the primary function of separating the positive and negative electrodes and allowing the free passage of ions. Porous organic framework materials have a stable connection structure, large specific surface area, and ordered pores, which are natural places to store electrolytes. And these materials with specific functions can be designed according to the needs of researchers. The performance of porous organic framework-based separators used in rechargeable lithium metal batteries is much better than that of polyethylene/propylene separators. In this paper, the three most classic organic framework materials (MOF, COF, and HOF) are analyzed and summarized. The applications of MOF, COF, and HOF separators in lithium-sulfur batteries, lithium metal anode, and solid electrolytes are reviewed. Meanwhile, the research progress of these three materials in different fields is discussed based on time. Finally, in the conclusion, the problems encountered by MOF, COF, and HOF in different fields as well as their future research priorities are presented. This review will provide theoretical guidance for the design of porous framework materials with specific functions and further stimulate researchers to conduct research on porous framework materials.

18.
Nat Med ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740994

RESUMEN

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

19.
Am J Case Rep ; 25: e942921, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38715342

RESUMEN

BACKGROUND Rapid diagnosis is critical for effective treatment of severe pneumonia during the COVID-19 pandemic. Chlamydia psittaci, an atypical community-acquired pathogen, typically exhibits nonspecific clinical signs and requires stringent conditions for microbiological culture, complicating its identification. Metagenomic next-generation sequencing (mNGS), which involves shotgun sequencing of DNA or RNA from clinical samples, is a key technology in clinical settings. Although mNGS technology identifies nucleic acids, it should not be directly equated with the presence of pathogenic microorganisms. Nonetheless, it shows promise as a principal method for detecting atypical pathogens in severe infectious diseases in the future. CASE REPORT We present a case of severe community-acquired Chlamydia psittaci pneumonia, highlighting the ongoing mutations and frequent spread of COVID-19. The patient's severe pulmonary infection rapidly advanced, resulting in multiple organ failure, necessitating extracorporeal membrane oxygenation (ECMO) support. Despite initial inconclusive routine laboratory tests, diagnosis of Chlamydia psittaci pneumonia was confirmed through mNGS. Antibiotic treatment and multi-organ functional support were administered, leading to the patient's successful recovery and hospital discharge. CONCLUSIONS Diagnosing severe pneumonia caused by atypical pathogens amid the COVID-19 pandemic presents significant challenges. Initiating ECMO support without effective infection control poses considerable risks, such as increasing risk of catheter-related infections and antimicrobial treatment failure. In the case presented, mNGS proved instrumental in screening for atypical pathogens in critical infectious diseases. Application of multi-organ function support in reversible conditions affords clinicians time for pathogen identification and treatment, offering novel approaches for diagnosing and treating severe pneumonia induced by unconventional pathogens during epidemic outbreaks.


Asunto(s)
COVID-19 , Chlamydophila psittaci , Humanos , COVID-19/diagnóstico , Chlamydophila psittaci/aislamiento & purificación , Psitacosis/diagnóstico , Masculino , Antibacterianos/uso terapéutico , SARS-CoV-2 , Persona de Mediana Edad , Secuenciación de Nucleótidos de Alto Rendimiento
20.
Environ Pollut ; 352: 124119, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38718964

RESUMEN

Phosphorus (P) is an essential nutrient for algal growth in nearshore ecosystems. In recent years, there has been a shift in nutrient dynamics in nearshore areas, leading to an exacerbation of P limitation, although the underlying mechanisms remain unclear. This study analyzed the P species and budget in the Bohai Sea (BS) from 2011 to 2020, aiming to explore the intrinsic mechanisms of P limitation in the BS. The results show that the main external source of P in the BS was river transport (89%), and the primary fate of P was burial (96%) into the sediment. Due to excessive nitrogen (N) input and biological processes in the BS, the P budget in the BS is unbalanced, resulting in an increase in the N/P ratio, particularly in nearshore areas. Nearshore areas typically have lower concentrations of dissolved inorganic P (DIP) in the water and higher concentrations of reactive P (Reac-P) in the sediments. This pattern is particularly evident in Bohai Bay and the northwest nearshore region, where harmful algal blooms occur frequently. To cope with enhanced P limitation, the biologically driven P regeneration and cycling processes within the BS are accelerated. From 2011 to 2020, the concentration of DIP in the BS during autumn increased, while the content of Reac-P in sediments slightly decreased. Historical data indicate that P depletion in the BS is intensifying and expanding, primarily due to N enrichment and algal production. N enrichment alters the structure and composition of primary production, potentially exacerbating P depletion in the BS. Excessive N may have significant impacts on the P pool, potentially influencing the stability of future coastal ecosystems.

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