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1.
Article in English | MEDLINE | ID: mdl-38709558

ABSTRACT

INTRODUCTION: Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD. METHODS: The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements.To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05. RESULTS: There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05. CONCLUSION: We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

2.
J Am Chem Soc ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709897

ABSTRACT

Multivalent battery chemistries have been explored in response to the increasing demand for high-energy rechargeable batteries utilizing sustainable resources. Solvation structures of working cations have been recognized as a key component in the design of electrolytes; however, most structure-property correlations of metal ions in organic electrolytes usually build upon favorable static solvation structures, often overlooking solvent exchange dynamics. We here report the ion solvation structures and solvent exchange rates of magnesium electrolytes in various solvents by using multimodal nuclear magnetic resonance (NMR) analysis and molecular dynamics/density functional theory (MD/DFT) calculations. These magnesium solvation structures and solvent exchange dynamics are correlated to the combined effects of several physicochemical properties of the solvents. Moreover, Mg2+ transport and interfacial charge transfer efficiency are found to be closely correlated to the solvent exchange rate in the binary electrolytes where the solvent exchange is tunable by the fraction of diluent solvents. Our primary findings are (1) most battery-related solvents undergo ultraslow solvent exchange coordinating to Mg2+ (with time scales ranging from 0.5 µs to 5 ms), (2) the cation transport mechanism is a mixture of vehicular and structural diffusion even at the ultraslow exchange limit (with faster solvent exchange leading to faster cation transport), and (3) an interfacial model wherein organic-rich regions facilitate desolvation and inorganic regions promote Mg2+ transport is consistent with our NMR, electrochemistry, and cryogenic X-ray photoelectron spectroscopy (cryo-XPS) results. This observed ultraslow solvent exchange and its importance for ion transport and interfacial properties necessitate the judicious selection of solvents and informed design of electrolyte blends for multivalent electrolytes.

3.
J Cancer Res Clin Oncol ; 150(5): 225, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695944

ABSTRACT

PURPOSE: Primary lung cancer is extremely rare in children and adolescents. The aim of this study is to clarify clinical features and outcomes of primary lung cancer in children and adolescents. METHODS: Young patients (aged ≤ 20 years) diagnosed as primary lung cancer between 2012 and 2023 were retrospective reviewed. According to radiological appearance of the nodules, they were divided into solid nodule (SN) group and ground glass opacity (GGO) group. RESULTS: A total of 74 patients were identified, with a median age at diagnosis of 18 years old (range: 11-20), including 7 patients in SN group and 67 patients in GGO group. In the GGO group, none of the nodules enlarged or changed during an average surveillance period of 10.8 months before surgery, except one. Wedge resection was the most common procedure (82.1%), followed by segmentectomy (16.4%) and lobectomy (1.5%). Histopathological analysis revealed that 64.2% of GGO nodules were adenocarcinoma in situ and minimally invasive adenocarcinomas, while the remaining 35.8% were invasive adenocarcinomas. Mutational analysis was performed in nine patients, with mutations identified in all cases. After a mean follow-up period of 1.73 ± 1.62 years, two patients in the SN group died due to multiple distant metastases, while all patients in the GGO group survived without recurrence. The overall survival (100%) of the GGO group was significantly higher than SN group (66.7%). CONCLUSIONS: Primary lung cancer in children and adolescents are rare and histopathological heterogeneous. Persistent GGO nodules may indicate early-stage lung adenocarcinoma in children and adolescents.


Subject(s)
Lung Neoplasms , Humans , Adolescent , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lung Neoplasms/diagnostic imaging , Male , Child , Female , Retrospective Studies , Young Adult
4.
Front Plant Sci ; 15: 1368697, 2024.
Article in English | MEDLINE | ID: mdl-38716342

ABSTRACT

Maize leaf diseases significantly impact yield and quality. However, recognizing these diseases from images taken in natural environments is challenging due to complex backgrounds and high similarity of disease spots between classes.This study proposes a lightweight multi-level attention fusion network (LFMNet) which can identify maize leaf diseases with high similarity in natural environment. The main components of LFMNet are PMFFM and MAttion blocks, with three key improvements relative to existing essential blocks. First, it improves the adaptability to the change of maize leaf disease scale through the dense connection of partial convolution with different expansion rates and reduces the parameters at the same time. The second improvement is that it replaces a adaptable pooling kernel according to the size of the input feature map on the original PPA, and the convolution layer to reshape to enhance the feature extraction of maize leaves under complex background. The third improvement is that it replaces different pooling kernels to obtain features of different scales based on GMDC and generate feature weighting matrix to enhance important regional features. Experimental results show that the accuracy of the LFMNet model on the test dataset reaches 94.12%, which is better than the existing heavyweight networks, such as ResNet50 and Inception v3, and lightweight networks such as DenseNet 121,MobileNet(V3-large) and ShuffleNet V2. The number of parameters is only 0.88m, which is better than the current mainstream lightweight network. It is also effective to identify the disease types with similar disease spots in leaves.

5.
Cerebellum ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558026

ABSTRACT

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

6.
Int J Biol Macromol ; 268(Pt 1): 131746, 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38653425

ABSTRACT

Biodegradable poly(L-lactic acid) (PLLA) has seldom used for dairy packaging due to medium permeability and brittleness. Novel PLLA copolymers, poly (L-lactic acid-co-butylene itaconate-co-glycolic acid) (PLBIGA), were developed by integrating glycolic acid (GA) and poly(butylene itaconate) (PBI) into PLLA's structure using low molecular weight PLLA as a key initiator. Then, packaging materials with better barrier and mechanical properties were obtained by blended PLBIGA with PLLA. Both PLLA/PLBIGA films and polyethylene nylon composite film (PE/NY) were used for stirred yogurt packaging and storage at 4 °C for 25 days. Results revealed that yogurt packed by PLLA/PLBIGA films maintained stabler water-holding capacity, color, and viscosity over the storage period. Moreover, the integrity of the gel structure and the total viable count of lactic acid bacteria in yogurt packaged in PLLA/40-PLBIGA8 were also found to be superior to those in PE/NY packages, highlighting its eco-friendly advantages in dairy packaging.

7.
Transl Lung Cancer Res ; 13(3): 573-586, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38601448

ABSTRACT

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

8.
Pharm Res ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649535

ABSTRACT

PURPOSE: A comparative assessment was performed to evaluate the potential of particle sizing by an ensemble based conventional dynamic light scattering (DLS) technique and an emerging technology based on tunable resistive pulse sensing (TRPS) using particle by particle approach by evaluating three different types of vaccine formulations representing three case studies and showing the limitation of each technique, instrument variability, sensitivity, and the resolution in mixed population. METHODS: Three types of in-house vaccine formulations- a protein antigen, an outer membrane vesicle and viral particles were simultaneously evaluated by TRPS based Exoid and two DLS instruments-Zetatrac and Zetasizer for particle size distribution, aggregates, and resolution of polydisperse species. RESULTS: The data from first case study show the risk of possible size overestimation and size averaging in polydisperse samples in DLS measurements which can be addressed by the TRPS analysis. It also shows how TRPS may be utilized only to large size antigens due to its limited size range. The second case study highlights the difference in the sensitivities of two DLS instruments working on the same principle. The third case study show that how TRPS can better resolve the large aggregate species compare to DLS in polydisperse samples. CONCLUSION: This analysis shows that TRPS can be used as an orthogonal technique in addition to conventional DLS based methods for more precise and in-depth characterization. Both techniques are efficient in size characterization and produce comparable results, however the choice will depend on the type of formulation and size range to be evaluated.

9.
Int J Ophthalmol ; 17(4): 610-615, 2024.
Article in English | MEDLINE | ID: mdl-38638262

ABSTRACT

AIM: To propose an algorithm for automatic detection of diabetic retinopathy (DR) lesions based on ultra-widefield scanning laser ophthalmoscopy (SLO). METHODS: The algorithm utilized the FasterRCNN (Faster Regions with CNN features)+ResNet50 (Residua Network 50)+FPN (Feature Pyramid Networks) method for detecting hemorrhagic spots, cotton wool spots, exudates, and microaneurysms in DR ultra-widefield SLO. Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate. Feature fusion was carried out by the feature pyramid network FPN, which significantly improved lesion detection rates in SLO fundus images. RESULTS: By analyzing 1076 ultra-widefield SLO images provided by our hospital, with a resolution of 2600×2048 dpi, the accuracy rates for hemorrhagic spots, cotton wool spots, exudates, and microaneurysms were found to be 87.23%, 83.57%, 86.75%, and 54.94%, respectively. CONCLUSION: The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO, providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.

10.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1517-1525, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621935

ABSTRACT

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.


Subject(s)
Cornus , Deer , Animals , Polymorphism, Restriction Fragment Length , Cornus/genetics , Polymerase Chain Reaction/methods , Deer/genetics , DNA Primers
11.
ACS Appl Mater Interfaces ; 16(15): 19529-19536, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38564290

ABSTRACT

Flexible and stretchable transparent heaters (THs) have been widely used in various applications, including deicing and defogging of flexible screens as well as thermotherapy pads. Ionic THs based on ionogels have emerged as a promising alternative to conventional electronic THs due to their unique advantages in terms of transparency-conductance conflict, uniform heating, and interfacial adhesion. However, the commonly used hydrophilic ionogels inevitably introduce a moisture-sensitive issue. In this work, we present a stretchable and transparent hydrophobic ionogel-based heater that utilizes ionic current-induced Joule heating under high-frequency alternating current. This ionogel-based TH exhibits exceptional multifunctional properties with low hysteresis, a fracture strain of 840%, transmittance of 93%, conductivity of 0.062 S m-1, temperature resistance up to 165 °C, voltage resistance up to 120 V, heating rate of 0.1 °C s-1, steady-state temperature at 115 °C, and uniform heating even when bent or stretched (up to 200%). Furthermore, it maintains its heating performance when it is directly exposed to water. This hydrophobic ionogel-based TH expands the range of materials available for ionic THs and paves the way for their practical applications.

12.
J Thorac Dis ; 16(3): 2019-2031, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38617777

ABSTRACT

Background: Robot-assisted esophagectomy (RAE), video-assisted minimally invasive esophagectomy (VAMIE), and open esophagectomy (OE) all have significant roles in the management of esophageal cancer (EC). Few studies have compared efficacy and safety between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Therefore, this study aimed to explore the short-term outcomes between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Methods: Ninety-eight patients were consecutively enrolled who underwent esophagectomy. A retrospective study was performed including 98 consecutive patients treated from January 2021 to August 2022 who received neoadjuvant treatment (including immunochemotherapy and chemoradiotherapy) followed by RAE, VAMIE or OE. Evaluated endpoints in the present study consisted of pathological outcomes, intraoperative and postoperative outcomes, as well as postoperative complications. Results: No significant differences were seen in the operating time, blood loss, length of intensive care unit (ICU) stay, R0 resection, and number of dissected lymph nodes between the three RAE, VAMIE, or OE groups. The achievement rate of right recurrent laryngeal nerve (RLN) lymph node removal (P=0.01) and the total cost (P<0.001) were higher in RAE. The postoperative hospital stay of OE was longer than the other two groups (P<0.05). There were no significant differences in postoperative complications. Conclusions: Compared to VAMIE, no clear benefit exists for RAE in the treatment of resectable EC after neoadjuvant therapy. OE resulted in a longer hospital stay. Although the rate of successful right RLN node removal was higher with RAE, the clinical relevance for this is yet unclear.

13.
Small ; : e2301074, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38659180

ABSTRACT

The coating of filter media with silver is typically achieved by chemical deposition and aerosol processes. Whilst useful, such approaches struggle to provide uniform coating and are prone to blockage. To address these issues, an in situ method for coating glass fibers is presented via the dopamine-mediated electroless metallization method, yielding filters with low air resistance and excellent antibacterial performance. It is found that the filtration efficiency of the filters is between 94 and 97% and much higher than that of silver-coated filters produced using conventional dipping methods (85%). Additionally, measured pressure drops ranged between 100 and 150 Pa, which are lower than those associated with dipped filters (171.1 Pa). Survival rates of Escherichia coli and Bacillus subtilis bacteria exposed to the filters decreased to 0 and 15.7%±1.49, respectively after 2 h, with no bacteria surviving after 6 h. In contrast, survival rates of E. coli and B. subtilis bacteria on the uncoated filters are 92.5% and 89.5% after 6 h. Taken together, these results confirm that the in situ deposition of silver onto fiber surfaces effectively reduces pore clogging, yielding low air resistance filters that can be applied for microbial filtration and inhibition in a range of environments.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 395-401, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660842

ABSTRACT

OBJECTIVE: To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+ acute myeloid leukemia (AML) cell line and its potential regulatory mechanism. METHODS: By knocking out miR-155 gene in FLT3-ITD+ AML cell line MV411 through CRISPR/Cas9 gene-editing technology, monoclonal cells were screened. The genotype of these monoclonal cells was validated by PCR and Sanger sequencing. The expression of mature miRNA was measured by RT-qPCR. The treatment response of doxorubicin, quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity. Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout, gene set enrichment analysis to analyze change of signaling pathway, and Western blot to verify expressions of key molecules in signaling pathway. RESULTS: Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing. RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones. MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+ AML drugs increased significantly after miR-155 knockout compared with wild-type clones. RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout. Western blot showed that the expressions of key molecules p-mTOR, Wnt5α and ß-catenin in signaling pathway were down-regulated. CONCLUSION: Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.


Subject(s)
Leukemia, Myeloid, Acute , MicroRNAs , Phenylurea Compounds , Staurosporine/analogs & derivatives , fms-Like Tyrosine Kinase 3 , MicroRNAs/genetics , Humans , Leukemia, Myeloid, Acute/genetics , fms-Like Tyrosine Kinase 3/genetics , Cell Line, Tumor , Signal Transduction , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Benzothiazoles/pharmacology , Staurosporine/pharmacology , TOR Serine-Threonine Kinases/metabolism , Wnt Signaling Pathway
15.
Biochemistry ; 63(8): 1038-1050, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38577885

ABSTRACT

The ethylene-forming enzyme (EFE) is an Fe(II), 2-oxoglutarate (2OG), and l-arginine (l-Arg)-dependent oxygenase that either forms ethylene and three CO2/bicarbonate from 2OG or couples the decarboxylation of 2OG to C5 hydroxylation of l-Arg. l-Arg binds with C5 toward the metal center, causing 2OG to change from monodentate to chelate metal interaction and OD1 to OD2 switch of D191 metal coordination. We applied anaerobic UV-visible spectroscopy, X-ray crystallography, and computational approaches to three EFE systems with high-resolution structures. The ineffective l-Arg analogue l-canavanine binds to the EFE with O5 pointing away from the metal center while promoting chelate formation by 2OG but fails to switch the D191 metal coordination from OD1 to OD2. Substituting alanine for R171 that interacts with 2OG and l-Arg inactivates the protein, prevents metal chelation by 2OG, and weakens l-Arg binding. The R171A EFE had electron density at the 2OG binding site that was identified by mass spectrometry as benzoic acid. The substitution by alanine of Y306 in the EFE, a residue 12 Å away from the catalytic metal center, generates an interior cavity that leads to multiple local and distal structural changes that reduce l-Arg binding and significantly reduce the enzyme activity. Flexibility analyses revealed correlated and anticorrelated motions in each system, with important distinctions from the wild-type enzyme. In combination, the results are congruent with the currently proposed enzyme mechanism, reinforce the importance of metal coordination by OD2 of D191, and highlight the importance of the second coordination sphere and longer range interactions in promoting EFE activity.


Subject(s)
Canavanine , Ferrous Compounds , Lyases , Ferrous Compounds/metabolism , Binding Sites , Alanine , Ketoglutaric Acids/metabolism
16.
J Exp Med ; 221(5)2024 May 06.
Article in English | MEDLINE | ID: mdl-38597926

ABSTRACT

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.


Subject(s)
Cognitive Dysfunction , Neoplasms , Humans , Neoplasms/therapy , Mental Fatigue , Disease Progression
17.
Neuro Endocrinol Lett ; 45(2)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38583192

ABSTRACT

BACKGROUND: Obesity has long been regarded as a risk factor for abnormal liver function, although the quantitative relationship between them is not clear. This study aimed to investigate the relationship between body mass index (BMI) and gamma-glutamyl transpeptidase (GGT) in different gender populations. METHODS: The cross-sectional study included 221,934 people aged over 18 years and under 90 years who underwent physical examinations at Yijishan Hospital in Wuhu City from 2011 to 2016. t-test and Chi-square test were used to compare the differences in demographic characteristics and biochemical indexes between men and women. Linear regression model and smooth curve method were used to investigate the relationship between BMI and GGT. RESULTS: The smooth curve shows a checkmark association between GGT and BMI. After adjusting for confounders, the cut-off BMI for the whole population was 19.5 kg/m2. When BMI was less than 19.5 kg/m2, GGT levels decreased with increasing BMI, and when BMI was greater than 19.5 kg/m2, GGT levels increased with increasing BMI. After gender stratification, there was a checkmark association between male and female GGT levels and BMI, but the trend of male GGT levels changing with BMI was more obvious than that of females. CONCLUSIONS: Our investigation demonstrated that the GGT level in obese Chinese people is significantly higher than that in non-obese people living in Wuhu City. BMI level can be considered as an early warning index for diseases related to liver function injury in the clinic, although the influence of gender difference should be specifically considered.

18.
Adv Mater ; : e2311129, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557985

ABSTRACT

Air pollution threats to human health have increased awareness of the role of filter units in air cleaning applications. As an ideal energy-saving strategy for air filters, the slip effect on nanofiber surfaces can potentially overcome the trade-off between filtration efficiency and pressure drop. However, the potential of the slip effect in nanofibrous structures is significantly limited by the tight nanofiber stacks. In this study, trichome-like biomimetic (TLB) air filters with 3D-templated silicone nanofilaments (average diameter: ≈74 nm) are prepared based on an in situ chemical vapor deposition (CVD) method inspired by plant purification. Theoretical modeling and experimental results indicate that TLB air filters make significant use of the slip effect to overcome the efficiency-resistance tradeoff. The selectable filter class (up to U15, ≈99.9995%) allows TLB air filters to meet various requirements, and their integral filtration performance surpasses that of most commodity air filters, including melt-blown cloth, ePTFE membranes, electrospun mats, and glass fiber paper. The proposed strategy directly transforms commercial filter media and filters into TLB air filters using a bottom-up, one-step approach. As a proof-of-concept, reusable N95 respirators and air purifiers equipped with TLB air filters are fabricated, overcoming the limitations of existing filter designs and fabrication methods.

19.
J Investig Med ; : 10815589241248073, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594222

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the clinical features, pathological characteristics and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies-associated glomerulonephritis (AAGN) with renal arteritis. METHODS: The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups were evaluated. RESULT: In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine (Scr), IL-6 (interleukin-6), urinary neutrophil gelatinase-associated lipocalin (NGAL), negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2=4.278, P=0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. CONCLUSION: Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

20.
Lung Cancer ; 191: 107558, 2024 May.
Article in English | MEDLINE | ID: mdl-38569278

ABSTRACT

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.


Subject(s)
Mediastinal Neoplasms , Humans , Male , Female , Mediastinal Neoplasms/epidemiology , Mediastinal Neoplasms/pathology , Mediastinal Neoplasms/diagnosis , Mediastinal Neoplasms/diagnostic imaging , Adult , Middle Aged , Retrospective Studies , Adolescent , Young Adult , Aged , Child , Spatio-Temporal Analysis , Child, Preschool , Tomography, X-Ray Computed , Incidence
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