Conformational switching and flexibility in cobalamin-dependent methionine synthase studied by small-angle X-ray scattering and cryoelectron microscopy.

Cobalamin-dependent methionine synthase (MetH) catalyzes the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate (CH3-H4folate) using the unique chemistry of its cofactor. In doing so, MetH links the cycling of S-adenosylmethionine with the folate cycle in one-carbon metabolism. Extensive biochemical and structural studies on Escherichia coli MetH have shown that this flexible, multidomain enzyme adopts two major conformations to prevent a futile cycle of methionine production and consumption. However, as MetH is highly dynamic as well as both a photosensitive and oxygen-sensitive metalloenzyme, it poses special challenges for structural studies, and existing structures have necessarily come from a "divide and conquer" approach. In this study, we investigate E. coli MetH and a thermophilic homolog from Thermus filiformis using small-angle X-ray scattering (SAXS), single-particle cryoelectron microscopy (cryo-EM), and extensive analysis of the AlphaFold2 database to present a structural description of the full-length MetH in its entirety. Using SAXS, we describe a common resting-state conformation shared by both active and inactive oxidation states of MetH and the roles of CH3-H4folate and flavodoxin in initiating turnover and reactivation. By combining SAXS with a 3.6-Å cryo-EM structure of the T. filiformis MetH, we show that the resting-state conformation consists of a stable arrangement of the catalytic domains that is linked to a highly mobile reactivation domain. Finally, by combining AlphaFold2-guided sequence analysis and our experimental findings, we propose a general model for functional switching in MetH.

A protein network refinement method based on module discovery and biological information.

BACKGROUND: The identification of essential proteins can help in understanding the minimum requirements for cell survival and development to discover drug targets and prevent disease. Nowadays, node ranking methods are a common way to identify essential proteins, but the poor data quality of the underlying PIN has somewhat hindered the identification accuracy of essential proteins for these methods in the PIN. Therefore, researchers constructed refinement networks by considering certain biological properties of interacting protein pairs to improve the performance of node ranking methods in the PIN. Studies show that proteins in a complex are more likely to be essential than proteins not present in the complex. However, the modularity is usually ignored for the refinement methods of the PINs. METHODS: Based on this, we proposed a network refinement method based on module discovery and biological information. The idea is, first, to extract the maximal connected subgraph in the PIN, and to divide it into different modules by using Fast-unfolding algorithm; then, to detect critical modules according to the orthologous information, subcellular localization information and topology information within each module; finally, to construct a more refined network (CM-PIN) by using the identified critical modules. RESULTS: To evaluate the effectiveness of the proposed method, we used 12 typical node ranking methods (LAC, DC, DMNC, NC, TP, LID, CC, BC, PR, LR, PeC, WDC) to compare the overall performance of the CM-PIN with those on the S-PIN, D-PIN and RD-PIN. The experimental results showed that the CM-PIN was optimal in terms of the identification number of essential proteins, precision-recall curve, Jackknifing method and other criteria, and can help to identify essential proteins more accurately.

Anion-Driven C-F Bond Activation of Trifluoromethyl N-Aryl Hydrazones: Application to the Synthesis of 1,3,4-Oxadiazoles.

The CF3 group attached to N-aryl hydrazone could be activated upon treatment with a suitable base, thus serving as an excellent C1 unit for the assembly of a series of 1,3,4-oxadiazoles by reaction with hydrazides. The transformation is proposed to proceed via the intermediate formation of a gem-difluorinated azoalkene. Furthermore, this reaction features simple conditions and a broad substrate scope with respect to both trifluoromethyl N-aryl hydrazones and hydrazides.

Evaluation of Clinical Features and Stroke Etiology in Patients with Bilateral Middle Cerebellar Peduncle Infarction.

OBJECTIVE: The aim of this study was to characterize clinical features, etiologies, and mechanisms of strokes due to bilateral middle cerebellar peduncle infarction (BMCPI). METHODS: Cases diagnosed as BMCPI in our hospital were retrieved, and a literature review was performed. Data on clinical features and brain MRI were obtained. Extracranial and intracranial segments of the vertebrobasilar artery were assessed by using digital subtraction angiography, magnetic resonance angiography, or computed tomography angiography. RESULTS: Thirteen cases (11 men and 2 women) of BMCPI were identified. A high-intensity signal of diffusion-weighted imaging sequence involving the bilateral middle cerebellar peduncle was observed in all patients. Most patients experienced vertigo, dysarthria, ataxia, and hearing disorders. Eleven of these cases were classified as large artery atherosclerosis, one as traumatic vertebral artery (VA) dissection, and one as giant cell arteritis. CONCLUSION: BMCPI is a rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria, which may also be accompanied by a hearing deficit or clinical signs of brainstem damage. BMCPI may be associated with hypoperfusion secondary to occlusive disease of the bilateral VA or proximal basilar artery.

Dnmt3a is required for the tumor stemness of B16 melanoma cells.

The relationship of carcinogenesis and DNA methyltransferases has attracted extensive attention in tumor research. We reported previously that inhibition of de novo DNA methyltransferase 3a (Dnmt3a) in murine B16 melanoma cells significantly suppressed tumor growth and metastasis in xenografted mouse model. Here, we further demonstrated that knockdown of Dnmt3a enhanced the proliferation in anchor-independent conditions of B16 cells, but severely disrupted its multipotent differentiation capacity in vitro. Furthermore, transforming growth factor ß1, a key trigger in stem cell differentiation and tumor cell epithelial-mesenchymal transition (EMT), mainly induced apoptosis, but not EMT in Dnmt3a-deficient B16 cells. These data suggested that Dnmt3a is required for maintaining the tumor stemness of B16 cells and it assists B16 cells to escape from death during cell differentiation. Thus it is hypothesized that not only extraordinary self-renewal ability, but also the capacity of multipotent differentiation is necessary for the melanoma tumorigenesis. Inhibition of multipotent differentiation of tumor cells may shed light on the tumor treatment.

The pretreatment of chronic restraint stress exerts little impact on the progression of heart failure in mice.

Stress is a potent risk factor for depression. Chronic stress can exacerbate and induce symptoms of depression. Clinical studies suggested that depressive patients are more likely to develop coronary artery diseases. However, the causal relationship between depression and heart failure progression remains unclear. In this study, we aimed to explore the relevance between stress and heart failure (HF) in a mouse model subjected to chronic restraint stress and left anterior descending coronary artery (LAD) ligation. Mice were restrained for 3 h daily for 21 days and the processes were repeated once 3 months later. After the repeated chronic restraint stress, mice showed dramatically increased immobility time in the forced swim test, indicating a state of despair. Restrained and control mice were further subjected to LAD ligation surgery. Echocardiography was conducted 1 week, 2 weeks, and 1 month afterward. LAD-operated mice showed a significant decrease in the values of left ventricular ejection fraction (LVEF), and there was no difference in the LVEF values between the restrained and control mice. Relevant gene expression, neurotransmitter system, glial activation, and morphology of the heart-brain axis were comprehensively evaluated. We found no overall differences between the restrained and control mice with HF. Our results revealed that the repeated chronic restraint stress may have little effects on the progression of heart failure.

Association between the MMP-9-1562 C>T polymorphism and the risk of stroke: a meta-analysis.

Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (-1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C-1562T variant on stroke risk under the T allele versus C allele [OR T vs. C 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR TT+TC vs. CC 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR TT vs. TC+CC 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR TT vs. CC 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR TC vs. CC 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9-1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene-gene and gene-environment interactions, and provide a more convincing explanation for this association.

Visiting the studies of resilience in language learning: From concepts to themes.

Resilience, as a positive personal trait, has been a topic of hot debate in the field of general education with the booming perspective of positive psychology. The exploration of learner resilience is conducive to understanding how learners grapple with setbacks, positively adapt, and function well in the presence of challenging situations. To date, some attention is paid to the structure of learner resilience, its relationships with other psychological variables, and its impacts on academic achievement. However, research on the overall profile of resilience in the field of foreign language (FL) or second language (L2) from a holistic and systematic perspective is still lacking. Against this backdrop, the current study reviewed and synthesized research evidence on resilience in the FL/L2 learning context. Specifically, 27 high-quality empirical studies published between 2017 and 2023 were selected, and then they were analyzed in terms of substantive characteristics of the literature and research participants, models of resilience, methodological features, and research foci. The results revealed a steady increase in language learner resilience research and displayed the detailed distribution of reviewed articles in publication year and sources as well as participants' educational backgrounds. Moreover, the conceptualization of resilience displayed complex and diverse features, the quantitative approach took a dominant position in the reviewed literature, and resilience models from psychology were widely utilized in language learner resilience research directly or indirectly. Finally, the implications of these findings were discussed for the further development of language learner resilience research.

GABA transporter mGat4 is involved in multiple neural functions in mice.

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of GABA transporters (GATs). mGAT4 (encoded by Slc6a11) is another GAT besides GAT1 (encoded by Slc6a1) that functions in GABA reuptake in CNS. Research on the function of mGAT4 is still in its infancy. We developed an mGat4 knockout mouse model (mGat4-/- mice) and performed a series of behavioral analyses for the first time to study the effect of mGat4 on biological processes in CNS. Our results indicated that homozygous mGat4-/- mice had less depression, anxiety-like behavior and more social activities than their wild-type littermate controls. However, they had weight loss and showed motor incoordination and imbalance. Meanwhile, mGat4-/- mice showed increased pain threshold and hypoalgesia behavior in nociceptive stimulus and learning and memory impairments. The expression of multiple components of the GABAergic system including GAD67, GABAA and KCC2 was altered. There is little or no compensatory change in mGat1. In a word, mGat4 may play a key role in normal motor coordination, sensation, emotion, learning and memory and could be the potential target of neurological disorders.

Antitumour mechanisms of traditional Chinese medicine elicited by regulating tumour-associated macrophages in solid tumour microenvironments.

Tumour-associated macrophages (TAMs), particularly M2-TAMs, constitute the largest proportion of immune cells in the solid tumour microenvironment, playing a crucial role in tumour progression and correlating with poor prognosis. TAMs promote the proliferation, invasion, and metastasis of tumour cells by remodelling the extracellular matrix, inhibiting immunity, promoting immune escape and tumour angiogenesis, and affecting cell metabolism. Traditional Chinese medicine (TCM) has been used clinically in China for millennia. Chinese herbs exhibit potent antitumour effects with minimal to no toxicity, substantially contributing to prolonging the lives of patients with cancer and improving their quality of life. TCM has unique advantages in improving the solid tumour microenvironment, particularly in regulating TAMs to further inhibit tumour angiogenesis, reduce drug resistance, reverse immunosuppression, and enhance antitumour immunity. This review highlights the TAM-associated mechanisms within the solid tumour microenvironment, outlines the recent advancements in TCM targeting TAMs for antitumour effects, emphasises the superiority of combining TCM with standard treatments or new nano-drug delivery systems, and evaluates the safety and efficacy of TCM combined with conventional treatments via clinical trials to provide insights and strategies for future research and clinical treatment.

Conformational switching and flexibility in cobalamin-dependent methionine synthase studied by small-angle X-ray scattering and cryo-electron microscopy.

Cobalamin-dependent methionine synthase (MetH) catalyzes the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate (CH 3 -H 4 folate) using the unique chemistry of its cofactor. In doing so, MetH links the cycling of S -adenosylmethionine with the folate cycle in one-carbon metabolism. Extensive biochemical and structural studies on Escherichia coli MetH have shown that this flexible, multi-domain enzyme adopts two major conformations to prevent a futile cycle of methionine production and consumption. However, as MetH is highly dynamic as well as both a photosensitive and oxygen-sensitive metalloenzyme, it poses special challenges for structural studies, and existing structures have necessarily come from a "divide and conquer" approach. In this study, we investigate E. coli MetH and a thermophilic homolog from Thermus filiformis using small-angle X-ray scattering (SAXS), single-particle cryo-electron microscopy (cryo-EM), and extensive analysis of the AlphaFold2 database to present the first structural description of MetH in its entirety. Using SAXS, we describe a common resting-state conformation shared by both active and inactive oxidation states of MetH and the roles of CH 3 -H 4 folate and flavodoxin in initiating turnover and reactivation. By combining SAXS with a 3.6-Å cryo-EM structure of the T. filiformis MetH, we show that the resting-state conformation consists of a stable arrangement of the catalytic domains that is linked to a highly mobile reactivation domain. Finally, by combining AlphaFold2-guided sequence analysis and our experimental findings, we propose a general model for functional switching in MetH.

Effects of stumping on fine root architecture, growth, and physiology of Hippophae rhamnoides.

Background: Fine roots are vital to a plant's ability to absorb water and nutrients. Stumping is a practice that may encourage fine root growth and the rapid recovery of decaying Hippophae rhamnoides plants. However, the effect of stumping on the fine roots and physiological indices is still unknown. The differential indices between stumped forests and non-stumped forests must also be defined. Methods: We recorded the changes in the fine roots of structure H. rhamnoides one year after stumping. Using single factor analysis of variance and general linear models we comprehensively analyzed the number of root tips and the plant's growth and physiological indices in response to stumping. Partial least squares discriminant analysis (PLS-DA) was used to compare fine root growth and physiological indices with and without stumping in order to identify the differential indices. Results: The proportion of root tips in the vertical layers at 30-40 cm and 40-50 cm and in the horizontal layers at 60-80 cm and 80-100 cm, increased after stumping by 1.85%, 2.60%, 1.96% and 4.32%, respectively. In the 0-50 cm soil layer, the fine root dry weight rose by 27.6% compared with the control, which was not significant. However, other indices were significantly different from the control. The proportions in the growth indices in the 30-40 cm and 40-50 cm layers increased after stumping. Stumping had a significant, negative effect on proline and malondialdehyde content, which dropped by 40.95% and 55.32%, respectively, indicating that the harms caused by these two chemicals was alleviated. Stumping had a significant positive effect on root activity and soluble sugar contents, which increased by 68.58% and 36.87%, respectively, and improved the growing ability of fine roots. PLS-DA revealed that malondialdehyde, soluble sugars, root density, and the number of root tips ranked from having the least to greatest effect on the classification of stumping and no-stumping. Conclusions: The process of stumping may promote fine roots growth in H. rhamnoides, and is favorable for their longitudinal development. The fine root growing indices of H. rhamnoides responded positively to this process. Stumping promotes root activity and the creation of soluble sugar to maintain the growth and development of fine roots. It also inhibits the negative effects of proline and malondialdehyde on fine roots. Our study showed that the differential physiological indices were more important for classification than the differential growing indices.

A Construction Method of Dynamic Protein Interaction Networks by Using Relevant Features of Gene Expression Data.

Essential proteins play an important role in various life activities and are considered to be a vital part of the organism. Gene expression data are an important dataset to construct dynamic protein-protein interaction networks (DPIN). The existing methods for the construction of DPINs generally utilize all features (or the features in a cycle) of the gene expression data. However, the features observed from successive time points tend to be highly correlated, and thus there are some redundant and irrelevant features in the gene expression data, which will influence the quality of the constructed network and the predictive performance of essential proteins. To address this problem, we propose a construction method of DPINs by using selected relevant features rather than continuous and periodic features. We adopt an improved unsupervised feature selection method based on Laplacian algorithm to remove irrelevant and redundant features from gene expression data, then integrate the chosen relevant features into the static protein-protein interaction network (SPIN) to construct a more concise and effective DPIN (FS-DPIN). To evaluate the effectiveness of the FS-DPIN, we apply 15 network-based centrality methods on the FS-DPIN and compare the results with those on the SPIN and the existing DPINs. Then the predictive performance of the 15 centrality methods is validated in terms of sensitivity, specificity, positive predictive value, negative predictive value, F-measure, accuracy, Jackknife and AUPRC. The experimental results show that the FS-DPIN is superior to the existing DPINs in the identification accuracy of essential proteins.

Soil Water Deficit Reduced Root Hydraulic Conductivity of Common Reed (Phragmites australis).

Alterations in root hydraulics in response to varying moisture conditions remain a subject of debate. In our investigation, we subjected common reeds (Phragmites australis) to a 45-day treatment with four distinct soil moisture levels. The findings unveiled that, in response to drought stress, the total root length, surface area, volume, and average diameter exhibited varying degrees of reduction. Anatomically, drought caused a reduction in root diameter (RD), cortex thickness (CT), vessel diameter (VD), and root cross-sectional area (RCA). A decrease in soil moisture significantly reduced both whole- and single-root hydraulic conductivity (Lpwr, Lpsr). The total length, surface area, volume, and average diameter of the reed root system were significantly correlated with Lpwr, while RD, CT, and RCA were significantly correlated with Lpsr. A decrease in soil moisture content significantly influenced root morphological and anatomical characteristics, which, in turn, altered Lpr, and the transcriptome results suggest that this may be associated with the variation in the expression of abscisic acid (ABA) and aquaporins (AQPs) genes. Our initial findings address a gap in our understanding of reed hydraulics, offering fresh theoretical insights into how herbaceous plants respond to external stressors.

Introduction to diffuse scattering and data collection.

A long-standing goal in X-ray crystallography has been to extract information about the collective motions of proteins from diffuse scattering: the weak, textured signal that is found in the background of diffraction images. In the past few years, the field of macromolecular diffuse scattering has seen dramatic progress, and many of the past challenges in measurement and interpretation are now considered tractable. However, the concept of diffuse scattering is still new to many researchers, and a general set of procedures needed to collect a high-quality dataset has never been described in detail. Here, we provide the first guidelines for performing diffuse scattering experiments, which can be performed at any macromolecular crystallography beamline that supports room-temperature studies with a direct detector. We begin with a brief introduction to the theory of diffuse scattering and then walk the reader through the decision-making processes involved in preparing for and conducting a successful diffuse scattering experiment. Finally, we define quality metrics and describe ways to assess data quality both at the beamline and at home. Data obtained in this way can be processed independently by crystallographic software and diffuse scattering software to produce both a crystal structure, which represents the average atomic coordinates, and a three-dimensional diffuse scattering map that can then be interpreted in terms of models for protein motions.

Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11.

BACKGROUND: Sustained liver fibrosis may lead to cirrhosis. Activated hepatic stellate cells (HSCs) are crucial for liver fibrosis development. Ferroptosis, a newly iron-dependent regulated cell death, has been demonstrated to be involved in HSC inactivation. PURPOSE: Ginsenoside Rh2 (GRh2), a natural bioactive product derived from ginseng, has been shown to promote HSC inactivation. However, the effect of GRh2 on HSC ferroptosis remains unclear. METHODS: We explored the effects of GRh2 on liver fibrosis in vivo and in vitro. RNA-sequence analysis was performed in HSCs after GRh2 treatment. The crosstalk between ferroptotic HSCs and macrophages was also explored. RESULTS: GRh2 alleviated liver fibrosis in vivo. In vitro, GRh2 reduced HSC proliferation and activation via ferroptosis, with increased intracellular iron, reactive oxygen species, malondialdehyde and glutathione depletion. The expression of SLC7A11, a negative regulator of ferroptosis, was obviously reduced by GRh2. Interestingly, interferon regulatory factor 1 (IRF1), a transcription factor, was predicted to bind the promoter region of SCL7A11. The interaction between IRF1 and SCL7A11 was further confirmed by the results of chromatin immunoprecipitation and luciferase reporter assays. Furthermore, loss of IRF1 led to an increase in SCL7A11, which contributed to the suppression of HSC ferroptosis and the enhancement of HSC activation in GRh2-treated HSCs. Further studies revealed that GRh2-induced HSC ferroptosis contributed to the inhibition of macrophage recruitment via regulation of inflammation-related genes. Moreover, GRh2 caused a reduction in liver inflammation in vivo. CONCLUSION: Collectively, GRh2 up-regulates IRF1 expression, resulting in the suppression of SLC7A11, which contributes to HSC ferroptosis and inactivation. GRh2 ameliorates liver fibrosis through enhancing HSC ferroptosis and inhibiting liver inflammation. GRh2 may be a promising drug for treating liver fibrosis.

Non-contact wearable synchronous measurement method of electrocardiogram and seismocardiogram signals.

Cardiovascular disease is one of the leading threats to human lives and its fatality rate still rises gradually year by year. Driven by the development of advanced information technologies, such as big data, cloud computing, and artificial intelligence, remote/distributed cardiac healthcare is presenting a promising future. The traditional dynamic cardiac health monitoring method based on electrocardiogram (ECG) signals only has obvious deficiencies in comfortableness, informativeness, and accuracy under motion state. Therefore, a non-contact, compact, wearable, synchronous ECG and seismocardiogram (SCG) measuring system, based on a pair of capacitance coupling electrodes with ultra-high input impedance, and a high-resolution accelerometer were developed in this work, which can collect the ECG and SCG signals at the same point simultaneously through the multi-layer cloth. Meanwhile, the driven right leg electrode for ECG measurement is replaced by the AgCl fabric sewn to the outside of the cloth for realizing the total gel-free ECG measurement. Besides, synchronous ECG and SCG signals at multiple points on the chest surface were measured, and the recommended measuring points were given by their amplitude characteristics and the timing sequence correspondence analysis. Finally, the empirical mode decomposition algorithm was used to adaptively filter the motion artifacts within the ECG and SCG signals for measuring performance enhancement under motion states. The results demonstrate that the proposed non-contact, wearable cardiac health monitoring system can effectively collect ECG and SCG synchronously under various measuring situations.

A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma.

Oral, gut, and tumor microbiota have been implicated as important regulators in the carcinogenesis and progression of gastrointestinal malignancies. However, few studies focused on the existence and association of resident microbes within different body regions. Herein, we aim to reveal the durability of the oral-gut-tumor microbiome and its diagnostic performance in hepatocellular carcinoma (HCC). Our study included two cohorts: a retrospective discovery cohort of 364 HBV-HCC patients and 160 controls with oral or fecal samples, a prospective validation cohort of 91 cases, and 124 controls for matching samples, as well as 48 HBV, and 39 HBV-cirrhosis patients for gut microbial patterns examined by 16S rRNA gene sequencing. With the random forest analysis, 10 oral and 9 gut genera that could distinguish HCC from controls in the retrospective cohort were validated among the prospective matching participants, with area under the curve (AUC) values of 0.7971 and 0.8084, respectively. When influential taxa were merged, the AUC of the consistent classifier increased to 0.9405. The performance continued to improve to 0.9811 when combined with serum levels of alpha-fetoprotein (AFP). Specifically, microbial biomarkers represented by Streptococcus displayed a constantly increasing trend during the disease transition. Furthermore, the presence of several dominant microbiota species was confirmed in hepatic tumor and non-tumor tissues with fluorescence in situ hybridization (FISH) and 5 R 16S rRNA gene sequencing. Overall, our findings based on the oral-gut-tumor microbiota provide a reliable approach for the early detection of HCC.

Non-Targeted Serum Lipidomics Analysis and Potential Biomarkers of Laryngeal Cancer Based on UHPLC-QTOF-MS.

Laryngeal cancer is a common head and neck malignant cancer type. However, effective biomarkers for diagnosis are lacking and pathogenesis is unclear. Lipidomics is a powerful tool for identifying biomarkers and explaining disease mechanisms. Hence, in this study, non-targeted lipidomics based on ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) were applied to screen the differential lipid metabolites in serum and allowed for exploration of the remodeled lipid metabolism of laryngeal cancer, laryngeal benign tumor patients, and healthy crowds. Multivariate analysis and univariate analysis were combined to screen for differential lipid metabolites among the three groups. The results showed that, across a total of 57 lipid metabolic markers that were screened, the regulation of the lipid metabolism network occurred mainly in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) metabolism. Of note, the concentration levels of sphingolipids 42:2 (SM 42:2) and sphingolipids 42:3 (SM 42:3) correlated with laryngeal cancer progression and were both significantly different among the three groups. Both of them could be considered as potential biomarkers for diagnosis and indicators for monitoring the progression of laryngeal cancer. From the perspective of lipidomics, this study not only revealed the regulatory changes in the lipid metabolism network, but also provided a new possibility for screening biomarkers in laryngeal cancer.

High-Voltage FDS of Thermally Aged XLPE Cable and Its Correlation with Physicochemical Properties.

This paper aims to investigate the influence of thermal aging on a crosslinked polyethylene (XLPE) cable, and the relationships between the macroscopical high-voltage dielectric and the microscopical physicochemical properties are also elucidated. To better simulate thermal aging under working condition, the medium-voltage-level cable is subjected to accelerated inner thermal aging for different aging times. Then, high-voltage frequency domain spectroscopy (FDS) (cable sample) and analyses of microscopic physical and chemical properties (sampling from the cable), including Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elongation at the break (EAB), are conducted at different cable aging stages. The dielectric test results show that after a certain aging time, the high-voltage FDS curves of the cable have layered characteristics, and this phenomenon is more obvious as the aging degree increases. Moreover, the slope and the integral of the high-voltage FDS curves rise with aging time. The mechanism is deduced by the physicochemical results that thermo-oxidative aging results in increasing polar groups and dislocation defects in the crystal region, which leads to the above phenomenon. On the one hand, the appearance of polar groups increases the density of the dipole. On the other hand, the destruction of the crystal region increases the probability and amplitude of dipole reversal. In addition, the breaking of molecular bonds and the increase in the amorphous phase also reduce the rigidity of the XLPE molecular main chain. The above factors lead to obvious delamination and larger dielectric parameters of the thermally aged cable. Finally, according to the experimental results, an on-site diagnosis method of cable insulation thermal aging based on high-voltage FDS is discussed.