Transforming growth factor-beta 1 enhances discharge activity of cortical neurons.

JOURNAL/nrgr/04.03/01300535-202502000-00031/figure1/v/2024-05-28T214302Z/r/image-tiff Transforming growth factor-beta 1 (TGF-ß1) has been extensively studied for its pleiotropic effects on central nervous system diseases. The neuroprotective or neurotoxic effects of TGF-ß1 in specific brain areas may depend on the pathological process and cell types involved. Voltage-gated sodium channels (VGSCs) are essential ion channels for the generation of action potentials in neurons, and are involved in various neuroexcitation-related diseases. However, the effects of TGF-ß1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear. In this study, we investigated the effects of TGF-ß1 on VGSC function and firing properties in primary cortical neurons from mice. We found that TGF-ß1 increased VGSC current density in a dose- and time-dependent manner, which was attributable to the upregulation of Nav1.3 expression. Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase (PD98059), p38 mitogen-activated protein kinase (SB203580), and Jun NH2-terminal kinase 1/2 inhibitor (SP600125). Interestingly, TGF-ß1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons. These findings suggest that TGF-ß1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway, which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions. Thus, this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

Improving Microstructural Estimation in Time-Dependent Diffusion MRI With a Bayesian Method.

BACKGROUND: Accurately fitting diffusion-time-dependent diffusion MRI (td-dMRI) models poses challenges due to complex and nonlinear formulas, signal noise, and limited clinical data acquisition. PURPOSE: Introduce a Bayesian methodology to refine microstructural fitting within the IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) model and optimize the prior distribution within the Bayesian framework. STUDY TYPE: Retrospective. POPULATION: Involving 69 pediatric patients (median age 6 years, interquartile range [IQR] 3-9 years, 61% male) with 41 low-grade and 28 high-grade gliomas, of which 76.8% were identified within the brainstem or cerebellum. FIELD STRENGTH/SEQUENCE: 3 T, oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE). ASSESSMENT: The Bayesian method's performance in fitting cell diameter ( d $$ d $$ ), intracellular volume fraction ( f in $$ {f}_{in} $$ ), and extracellular diffusion coefficient ( D ex $$ {D}_{ex} $$ ) was compared against the NLLS method, considering simulated and experimental data. The tumor region-of-interest (ROI) were manually delineated on the b0 images. The diagnostic performance in distinguishing high- and low-grade gliomas was assessed, and fitting accuracy was validated against H&E-stained pathology. STATISTICAL TESTS: T-test, receiver operating curve (ROC), area under the curve (AUC) and DeLong's test were conducted. Significance considered at P < 0.05. RESULTS: Bayesian methodology manifested increased accuracy with robust estimates in simulation (RMSE decreased by 29.6%, 40.9%, 13.6%, and STD decreased by 29.2%, 43.5%, and 24.0%, respectively for d $$ d $$ , f in $$ {f}_{in} $$ , and D ex $$ {D}_{ex} $$ compared to NLLS), indicating fewer outliers and reduced error. Diagnostic performance for tumor grade was similar in both methods, however, Bayesian method generated smoother microstructural maps (outliers ratio decreased by 45.3% ± 19.4%) and a marginal enhancement in correlation with H&E staining result (r = 0.721 for f in $$ {f}_{in} $$ compared to r = 0.698 using NLLS, P = 0.5764). DATA CONCLUSION: The proposed Bayesian method substantially enhances the accuracy and robustness of IMPULSED model estimation, suggesting its potential clinical utility in characterizing cellular microstructure. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Surface defect detection method for discarded mechanical parts under heavy rust coverage.

With a significant number of mechanical products approaching the retirement phase, the batch recycling of discarded mechanical parts necessitates a preliminary assessment of their surface condition. However, the presence of surface rust poses a challenge to defect identification. Therefore, this paper proposes a method for detecting heavily rusted surface defects based on an improved YOLOv8n network. In the Backbone, the C2f-DBB module of re-parameterized deep feature extraction was introduced, and the attention module was designed to improve the accuracy of information extraction. In the Neck part, a Bi-Afpn multiscale feature fusion strategy is designed to facilitate information exchange between features at different scales. Finally, Focal-CIoU is employed as the bounding box loss function to enhance the network's localization performance and accuracy for defects. Experimentally, it is proved that the improved network in this paper improves the Recall, Precision, and mAP0.5 by 1.2%, 2.1%, and 1.9%, respectively, on the original basis, which is better than other network models.

The catalytic triad of rice NARROW LEAF1 involves H234.

NARROW LEAF1 (NAL1) exerts a multifaceted influence on leaf morphology and crop yield. Recent crystal study proposed that histidine 233 (H233) is part of the catalytic triad. Here we report that unlike suggested previously, H234 instead of H233 is a component of the catalytic triad alongside residues D291 and S385 in NAL1. Remarkably, residue 233 unexpectedly plays a pivotal role in regulating NAL1's proteolytic activity. These findings establish a strong foundation for utilizing NAL1 in breeding programs aimed at improving crop yield.

An analysis of neutrophil-to-lymphocyte ratios and monocyte-to-lymphocyte ratios with six-month prognosis after cerebral contusions.

Background and purpose: Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes. Methods: Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR. Results: A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively. Conclusion: NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.

Remarkable response to third-generation EGFR-TKI plus crizotinib in a patient with pulmonary adenocarcinoma harboring EGFR and ROS1 co-mutation: a case report.

Background: Driver oncogene mutations, such as c-ros oncogene 1 (ROS1) and epidermal growth factor receptor (EGFR) were previously believed to be mutually exclusive in non-small cell lung cancer (NSCLC). Only sporadic cases of ROS1 and EGFR co-mutations have been reported. Hence, appropriate treatment options for these patients are still controversial. Case presentation: A 48-year-old female patient presented at our hospital complaining of a persistent cough that had been ongoing for a month. A chest computed tomography showed a mass in the left lung along with hilar and mediastinal lymphadenopathy. Pathological analysis of bronchoscopic biopsy and lung mass puncture confirmed the presence of lung adenocarcinoma. The patient was diagnosed with stage IIIC left lung adenocarcinoma with a clinical stage of cT2N3M0. Next-generation sequencing analysis conducted at both puncture sites revealed an EFGR 19 deletion mutation combined with ROS1 rearrangement. The lung mass exhibited a higher mutation abundance. Treatment with a combination of third-generation EGFR tyrosine kinase inhibitors (TKIs) and crizotinib yielded satisfactory results. During the follow-up period, the mass significantly reduced and almost disappeared. Conclusion: The co-mutation of EGFR and ROS1 is a rare phenomenon. Nevertheless, the combination of EGFR-TKI and crizotinib treatment appears to hold promise in providing positive results for patients, with manageable side effects. This therapeutic approach has the potential to enhance patients' overall prognosis.

ID2 promotes tumor progression and metastasis in thyroid cancer.

BACKGROUND: Inhibitor of DNA Binding 2 (ID2) plays a crucial role in tumor cell proliferation, invasion, metastasis, and stemness. Aberrant ID2 expression is associated with poor prognosis in various cancers. However, the specific function of ID2 in thyroid cancer remain unclear. METHOD: The TCGA database were utilized to explore the clinical relevance of ID2 in cancer. GO, KEGG, and TIMER were employed to predict the potential roles of ID2 in cancer. Functional analysis, including CCK-8, colony formation, transwell, wound healing, and sphere formation experiments, were conducted to determine the biological functions of ID2 in human cancers. Western blot (WB), RT-qPCR, and immunohistochemical (IHC) analyses were used to investigate the relationship between ID2 and downstream targets. RESULTS: Our study revealed significant overexpression of ID2 in various malignant tumor cells. Knocking ID2 significantly inhibited cancer cell proliferation and invasion, while overexpressing ID2 enhanced these capabilities. Additionally, ID2 mediates resistance of cancer cells to protein kinase B (or Akt) inhibitions. Further WB and IHC experiments indicated that ID2 promotes the phosphorylation activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, thereby upregulating the expression of downstream proliferation, epithelial-mesenchymal transition (EMT), and stemness-related markers. CONCLUSION: We found that ID2 significantly promotes thyroid cancer cell proliferation, migration, EMT, and stemness through the PI3K/Akt pathway. Moreover, ID2 plays a crucial role in regulating cancer immune responses. It may serve as a potential biomarker for enhancing the efficacy of chemotherapy, targeted therapy, and immunotherapy against cancer.

Ultra-Bend-Resistant 4-Core Simplex Cable Used for Short-Reach Dense Spatial Division Multiplexing Optical Transmission.

We optimized and fabricated an ultra-bend-resistant 4-core simplex cable (SXC) employing 4-core multicore fiber (MCF) suitable for short-reach dense spatial division multiplexing (DSDM) optical transmission in the O-band. The characteristics of transmission loss, macro-bending and cross-talk (XT) between adjacent cores after cabling were firstly clarified. By introducing the trapezoid index and optimizing the cabling process, the maximum values of added XT of 1.17 dB/km due to 10 loops with a bending radius of 6 mm imposed over the 4-core SXC and a macro-bending loss of 0.37 dB/10 turns were, respectively, achieved.P Then, the optical transmission with low bit error rate (BER) was presented using a 100GBASE-LR4 transceiver over the 1.2 km long 4-core SXC. The excellent bending resistance of the 4-core SXC may pave the way for a reduction in space pressure and increase in access density on short-reach optical interconnect (OI) based on DSDM.

Functionalized magnetic metal organic framework nanocomposites for high throughput automation extraction and sensitive detection of antipsychotic drugs in serum samples.

Due to the complexity of biological sample matrix, the automated and high-throughput pretreatment technology is urgently needed for monitoring the antipsychotic drugs for mental patients. In this study, functionalized magnetic zirconium-based organic framework nanocomposites (Fe3O4@SiO2@Zr-MOFs) were successfully designed and synthesized by the layer-by-layer growth. Among them, Fe3O4@SiO2@UiO-67-COOH showed the best adsorption performance, and at the same time it exhibited excellent water dispersibility, high thermal stability, chemical stability and high hydrophobicity. Results of adsorption kinetics, isotherm and FT-IR showed that the adsorption process was dominated by chemical adsorption (hydrogen bond, electrostatic interaction, π-π interaction) and monolayer adsorption. Moreover, the smaller pore size improved the protein exclusion rate which reached 98.9-99.8%. Based on the above result, the synthesized magnetic nanoparticles were introduced to 96-well automatic extractor, antipsychotic drugs in 96 serum samples were automatically extracted within 9 min, which most greatly saved the time and labor costs and avoided artificial errors. By further integrating with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), antipsychotic drugs can be detected in the range of 0.2-3.0 ng mL-1 with a quantitative limit of 0.06-0.9 ng mL-1. The recoveries of antipsychotic drugs and their metabolites in serum ranged from 95.7% to 112.3% within 1.4-6.5% of RSD. These features indicate that the proposed method is promising for high throughput and sensitively monitoring of drugs and other hazardous substances.

A Proteomic Analysis of Human Follicular Fluid: Proteomic Profile Associated with Embryo Quality.

Embryo selection is a key point of in vitro fertilization (IVF). The most commonly used method for embryo selection is morphological assessment. However, it is sometimes inaccurate. Follicular fluid (FF) contains a complex mixture of proteins that are essential for follicle development and oocyte maturation. Analyzing human FF proteomic profiles and identifying predictive biomarkers might be helpful for evaluating embryo quality. A total of 22 human FF samples were collected from 19 infertile women who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment between October 2021 and November 2021. FFs were grouped into two categories on the basis of the day 3 embryo quality, grade I or II in the hqFF group and grade III in the nhqFF group. FF was analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The key differentially expressed proteins (DEPs) were validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). Differentially expressed proteins were further analyzed using DAVID software. A total of 558 proteins were identified, of which 50 proteins were differentially expressed in the hqFF versus nhqFF group, including 32 upregulated proteins (> 1.20-fold, P < 0.05) and 18 downregulated proteins (< 0.67-fold, P < 0.05). Bioinformatics analyses showed that the upregulated DEPs were enriched in components of the coagulation and complement systems and negative regulation of peptidase activity, while the downregulated DEPs were enriched in molecular function of extracellular matrix structural and constituent collagen binding. Our results suggested that a number of protein biomarkers in FF were associated with embryo quality. It may help develop an effective and noninvasive method for embryo selection.

A Point-Cloud Segmentation Network Based on SqueezeNet and Time Series for Plants.

The phenotyping of plant growth enriches our understanding of intricate genetic characteristics, paving the way for advancements in modern breeding and precision agriculture. Within the domain of phenotyping, segmenting 3D point clouds of plant organs is the basis of extracting plant phenotypic parameters. In this study, we introduce a novel method for point-cloud downsampling that adeptly mitigates the challenges posed by sample imbalances. In subsequent developments, we architect a deep learning framework founded on the principles of SqueezeNet for the segmentation of plant point clouds. In addition, we also use the time series as input variables, which effectively improves the segmentation accuracy of the network. Based on semantic segmentation, the MeanShift algorithm is employed to execute instance segmentation on the point-cloud data of crops. In semantic segmentation, the average Precision, Recall, F1-score, and IoU of maize reached 99.35%, 99.26%, 99.30%, and 98.61%, and the average Precision, Recall, F1-score, and IoU of tomato reached 97.98%, 97.92%, 97.95%, and 95.98%. In instance segmentation, the accuracy of maize and tomato reached 98.45% and 96.12%. This research holds the potential to advance the fields of plant phenotypic extraction, ideotype selection, and precision agriculture.

Two fiber-bundle-type FI/FO devices of low insertion loss and cross talk applied for connecting 13-core 5-mode fiber.

Two fiber-bundle-typed fan-in/fan-out (FI/FO) devices, "wavy hexagon-shaped silhouette" type (W-FI/FO) and "tortoise-shaped silhouette" type (T-FI/FO), have been proposed and manufactured based on tapering glass tubes for docking with a self-made 13-core 5-mode fiber. The W-FI/FO device consists of 19 5-mode fibers and has an extended layout based on the 13-core 5-mode fiber structure. It could dock multiple fibers with 19 or 13 cores of the same size standards. When connecting it with 13-core 5-mode, the average losses (ILs) of its five modes are 1.07 dB, 2.95 dB, 3.42 dB, 3.65 dB, and 4.38 dB. The cross talks of the five linearly polarized (LP) modes are -69.1 dB, -64.7 dB, -44.2 dB, -43.9 dB, and -39.1 dB. The T-FI/FO device has a similar core arrangement to the 13-core 5-mode fiber and its average ILs of the five LP modes are 0.23 dB, 1.31 dB, 2.09 dB, 2.66 dB, and 3.03 dB. The cross talks of its five LP modes between adjacent cores are -72.8 dB, -67.8 dB, -43.6 dB, -40.0 dB, and -35.3 dB. The IL and cross talk of the LP01 mode are of satisfactory values, which are 0.23 dB and -72.8 dB, respectively. These two proposed FI/FO devices are expected to be used for high-speed optical interconnection and fiber communication.

Transmissive fluorescent temperature sensor based on Er3+/Yb3+/Mo6+ tri-doped tellurite fiber for real-time thermal monitoring of motors using the FIR technique.

In this paper, we fabricate a transmissive fluorescent temperature sensor (TFTS) that based on Er3+/Yb3+/Mo6+ tri-doped tellurite fiber, which has the advantages of compactness and simplicity, corrosion resistance, high stability and anti-electromagnetic interference. The doping of Mo6+ ions will enhance the up-conversion (UC) fluorescence emission efficiency of Er3+ ions, thus improving the signal-to-noise ratio of TFTS. Using the fluorescence intensity ratio (FIR) technique, the real-time thermal monitoring performance of TFTS is evaluated experimentally. Apart from good stability, its maximum relative sensitivity is 0.01068 K-1 at 274 K in the measured temperature range. In addition, it is successfully used to monitor the temperature variation of the stator core and stator winding of the motor in actual operation. The results show that the maximum error between the FIR-demodulated temperature and the reference temperature is less than 1.2 K, which fully confirms the effectiveness of the TFTS for temperature monitoring. Finally, the FIR-based TFTS in this work is expected to provide a new solution for accurate and real-time thermal monitoring of motors and the like.

Curling Leaf 1, Encoding a MYB-Domain Protein, Regulates Leaf Morphology and Affects Plant Yield in Rice.

The leaf is the main site of photosynthesis and is an important component in shaping the ideal rice plant architecture. Research on leaf morphology and development will lay the foundation for high-yield rice breeding. In this study, we isolated and identified a novel curling leaf mutant, designated curling leaf 1 (cl1). The cl1 mutant exhibited an inward curling phenotype because of the defective development of sclerenchymatous cells on the abaxial side. Meanwhile, the cl1 mutant showed significant reductions in grain yield and thousand-grain weight due to abnormal leaf development. Through map-based cloning, we identified the CL1 gene, which encodes a MYB transcription factor that is highly expressed in leaves. Subcellular localization studies confirmed its typical nuclear localization. Transcriptome analysis revealed a significant differential expression of the genes involved in photosynthesis, leaf morphology, yield formation, and hormone metabolism in the cl1 mutant. Yeast two-hybrid assays demonstrated that CL1 interacts with alpha-tubulin protein SRS5 and AP2/ERF protein MFS. These findings provide theoretical foundations for further elucidating the mechanisms of CL1 in regulating leaf morphology and offer genetic resources for practical applications in high-yield rice breeding.

linc00511 Knockdown Inhibits Lung Cancer Progression by Regulating miR-16-5p/MMP11.

Lung cancer (LC) is a malignant tumor that extremely impairs people. According to numerous studies, long non-coding RNA (lncRNA) was inextricably involved in the advancement of LC. The work aspired to identify linc00511 expression in LC and to dig for the underlying mechanisms linc00511 regulated LC progression. Experimental outcomes revealed that linc00511 was obviously upregulated in LC, and linc00511 knockdown significantly impaired the malignant phenotype of LC cells in vitro. For an in-depth study on the contribution of linc00511 to LC advancement, it was disclosed that miR-16-5p had binding sites to the sequence of linc00511, which also inversely affected linc00511 expression in LC. Further experimental data demonstrated that miR-16-5p directly and negatively targeted matrix metallopeptidase 11 (MMP11). Also, rescue experiments displayed that miR-16-5p inhibition or MMP11 overexpressing offset the suppressive impacts of linc00511 silencing on LC progression. To sum up, our findings indicated that linc00511 performed a crucial role in facilitating LC progression, and mechanistic studies demonstrated that linc00511 aggravated LC progression via targeting the miR-16-5p/MMP11 axis.

Structure-function analysis of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases.

N 6-threonylcarbamoyladenosine (t6A) is a post-transcriptional modification found uniquely at position 37 of tRNAs that decipher ANN-codons in the three domains of life. tRNA t6A plays a pivotal role in promoting translational fidelity and maintaining protein homeostasis. The biosynthesis of tRNA t6A requires members from two evolutionarily conserved protein families TsaC/Sua5 and TsaD/Kae1/Qri7, and a varying number of auxiliary proteins. Furthermore, tRNA t6A is modified into a cyclic hydantoin form of t6A (ct6A) by TcdA in bacteria. In this work, we have identified a TsaD-TsaC-SUA5-TcdA modular protein (TsaN) from Pandoraviruses and determined a 3.2 Å resolution cryo-EM structure of P. salinus TsaN. The four domains of TsaN share strong structural similarities with TsaD/Kae1/Qri7 proteins, TsaC/Sua5 proteins, and Escherichia coli TcdA. TsaN catalyzes the formation of threonylcarbamoyladenylate (TC-AMP) using L-threonine, HCO3- and ATP, but does not participate further in tRNA t6A biosynthesis. We report for the first time that TsaN catalyzes a tRNA-independent threonylcarbamoyl modification of adenosine phosphates, leading to t6ADP and t6ATP. Moreover, TsaN is also active in catalyzing tRNA-independent conversion of t6A nucleoside to ct6A. Our results imply that TsaN from Pandoraviruses might be a prototype of the tRNA t6A- and ct6A-modifying enzymes in some cellular organisms.