Main Subclasses Research Articles

Isolation of Small Extracellular Vesicles (sEVs) from the Apoplastic Wash Fluid of Nicotiana benthamiana Leaves.

Extracellular vesicles (EVs) are small membranous vesicles secreted by cells into their surrounding extracellular environment. Similar to mammalian EVs, plant EVs have emerged as essential mediators of intercellular communication in plants that facilitate the transfer of biological material between cells. They also play essential roles in diverse physiological processes including stress responses, developmental regulation, and defense mechanisms against pathogens. In addition, plant EVs have demonstrated promising health benefits as well as potential therapeutic effects in mammalian health. Despite the plethora of potential applications using plant EVs, their isolation and characterization remains challenging. In contrast to mammalian EVs, which benefit from more standardized isolation protocols, methods for isolating plant EVs can vary depending on the starting material used, resulting in diverse levels of purity and composition. Additionally, the field suffers from the lack of plant EV markers. Nevertheless, three main EV subclasses have been described from leaf apoplasts: tetraspanin 8 positive (TET8), penetration-1-positive (PEN1), and EXPO vesicles derived from exocyst-positive organelles (EXPO). Here, we present an optimized protocol for the isolation and enrichment of small EVs (sEVs; <200 nm) from the apoplastic fluid from Nicotiana benthamiana leaves by ultracentrifugation. We analyze the preparation through transmitted electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. We believe this method will establish a basic protocol for the isolation of EVs from N. benthamiana leaves, and we discuss technical considerations to be evaluated by each researcher working towards improving their plant sEV preparations. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Isolation and enrichment of small extracellular vesicles (sEVs) from the apoplastic fluid of Nicotiana benthamiana leaves.

Some Coefficient Problems for Subclasses of Holomorphic Functions in Complex Order Associating Sălăgeăn q-Differential Operator

A function with complex values and at every point of the specific domain contains a derivative is commonly known as analytic functions which is also referred as holomorphic functions. We begin by interpreting \(A\) as the class for all holomorphic functions \(L(\xi)\) with a Taylor series expansion written in the form: \[L(\xi) = \xi + \sum_{i=2}^{\infty} x_i \xi^i\] where \(x_i \in \mathbb{C}\) and \(\xi \in D\). \(D\) is the open unit disk where \(D = \{\xi : \xi \in \mathbb{C}, |\xi| &lt; 1 \}\). Furthermore, we suggest the subclass of \(A\) that is univalent in \(D\) represented as \(S\). It is commonly known that the main subclasses of class \(S\) are the class of starlike functions and the class of convex functions. To develop and analyze the Fekete-Szegö problems, the theory of geometric function contributes significantly to this. Moreover, the frequent use of \(q\)-calculus as a general direction of research among mathematicians has caught our attention. In this research, we attained the initial coefficients, \(x_2\) and \(x_3\), and the upper bound for the functional \(|x_3 - \nu x_2^2|\) of functions \(L\) in the two new subclasses that are introduced by involving the Sălăgeăn \(q\)-differential operator, \(M_q^\eta L(\xi)\) and the definition of subordination.

UPLC-ESI-MS/MS strategy to analyze fatty acids composition and lipid profiles of Pacific saury (Cololabis saira)

The Pacific saury (Cololabis saira) is a highly nutritious deep-sea fish, rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs). This study comprehensively investigated fatty acids composition and lipid profiles of different parts of Pacific saury based on an untargeted lipidomic strategy. Results suggested that the crude fat content of meat, head and viscera were 5.81%, 10.90%, and 19.46%, respectively. The contents of PUFAs were 41.08%, 34.96% and 33.14%, respectively. Among them, the n-3 PUFAs in the head (34.58%) were significantly higher than meat (29.40%) and viscera (27.95%). Moreover, 5752 lipid molecules were identified, where glycerophospholipids (GP) were the most numerous lipid type (45.58%), with phosphatidylcholine (PC) being main differential subclass. PC (20:3_22:6) was the most abundant molecule in the head (14.59%) and meat (19.60%). Head_vs_viscera group had higher characteristic PC abundance. This study will provide a theoretical basis for the physiological activity and lipid high-value utilization of Pacific saury.

Comparison of lipid profiles of male and female silkworm (Bombyx mori) pupae through high-resolution mass spectrometry-based lipidomics and chemometrics

Silkworm (Bombyx mori) pupae lipid profiles were analyzed using high-resolution mass spectrometry-based lipidomics. A total of 241 lipid molecular species were annotated with high confidence in male and female silkworm pupae. Triacylglycerol (TG), phosphoethanolamine (PE) and phosphocholine (PC) were the main lipid subclasses of silkworm pupae, accounting for 63, 41 and 38 lipid molecular species, respectively. No unique lipid molecular species were identified, but there were differences in the abundance of lipid molecular species between male and female silkworm pupae. Therefore, the differences in the lipid abundance of male and female silkworm pupae were analyzed by chemometrics. As a result, 8 lipid molecular species were screened for differential lipids. Hierarchical clustering analysis (HCA) showed that male and female silkworm pupae samples formed two distinct branches, indicating that these differential lipids could potentially be used as biomarkers to distinguish between male and female silkworm pupae.

Supersulphides suppress type-I and type-II interferon responses by blocking JAK/STAT signalling in macrophages.

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumour cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumour effects. The main subclasses of IFNs include type-I (e.g. IFN-α and IFN-β) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulphide donors, which have polysulphide structures in which three or more sulphur atoms are linked within the molecules, IFN-β-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulphides and the mechanism of this suppression are unknown. This study demonstrated that supersulphide donor N-acetyl-L-cysteine tetrasulphide (NAC-S2) can inhibit IFN signalling in macrophages stimulated not only with IFN-α/β but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributing to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, the hydrogen sulphide (H2S) donor NaHS failed to inhibit IFN signalling. Similar to NAC-S2, the carbohydrate-based supersulphide donor thioglucose tetrasulphide (TGS4) was capable of strongly inhibiting tumour necrosis factor-α production, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of the molecular mechanisms by which supersulphide donors exhibit their inhibitory actions towards JAK/STAT signalling is a necessary basis for the development of supersulphide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signalling.

HGG-16. PEDIATRIC-TYPE DIFFUSE HIGH-GRADE GLIOMA OF METHYLATION-BASED RTK2A AND RTK2B SUBCLASSES PRESENT DISTINCT RADIOLOGICAL AND HISTOMOLECULAR FEATURES

Abstract BACKGROUND Diffuse pediatric-type high-grade gliomas (pedHGG), H3-wildtype and IDH-wildtype, encompass three main methylome-based subclasses: pedHGG-MYCN, -RTK1A/B/C, and -RTK2A/B. Since their first description in 2017, tumors of pedHGG-RTK2A/B have not been further characterized and their clinical significance is unknown. METHODS A not yet published cases series on pedHGG with a gliomatosis cerebri (GC) growth pattern showed an increased incidence of pedHGG-RTK2A/B (n=18/40). We assembled a cohort of 14 additional methylation-based pedHGG-RTK2A/B tumors and pooled them with the GC tumors providing centrally reviewed radiological, histological, and molecular characterization. RESULTS Our cohort of 32 pedHGG-RTK2A/B tumors consisted of 25 RTK2A (78%) and seven RTK2B (22%) cases. The median age was 11.6 years (4-17) with an overall survival of 15.9 months (interquartile range 12.1-25.8). Of the additional unselected cases with available imaging (10 of 14), seven showed a GC phenotype at diagnosis or follow-up. In addition, pedHGG-RTK2B tumors exhibited bithalamic involvement (6/7, 86%). Histopathology confirmed a diffuse glial neoplasm in all cases with prominent angiocentric features in both subclasses. Most tumors (24/29, 83%) diffusely expressed EGFR, notably with a focal perivascular enhancement. Cells of pedHGG-RTK2A lacked Olig2 expression, whereas 43% (3/7) of pedHGG-RTK2B expressed Olig2. Loss of ATRX expression occurred in four pedHGG-RTK2B samples (57%). In sequencing analyses (RTK2A: n=18, RTK2B: n=5), EGFR alterations (n=15/23, 65%; predominantly point mutations) were commonly found in both subclasses. Mutations in BCOR (n=14/18, 78%), SETD2 (n=7/18, 39%), and TERT promoter (n=6/18, 33%) occurred exclusively in pedHGG-RTK2A tumors, while pedHGG-RTK2B tumors were enriched for TP53 mutations (4/5, 80%). CONCLUSIONS In conclusion, genotype-phenotype correlations in a multicenter series of pedHGG-RTK2A/B tumors revealed a highly diffuse-infiltrating tumor frequently exhibiting a GC phenotype. The two subclasses share particular histomolecular features (EGFR alterations, angiocentric pattern), whereas they differ in specific characteristics (pedHGG-RTK2A: Olig2 negativity, BCOR and SETD2 mutations; pedHGG-RTK2B: ATRX and TP53 alterations).

Associations of dietary flavonoid intake with the risk of all-cause and cardiovascular mortality in adults

Background and AimsFlavonoids are widely distributed polyphenolic compounds in the diet that possess various health-promoting effects. This study aimed to investigate the association between dietary flavonoid intake and all-cause and cardiovascular mortality in adults. Methods and ResultsThe data on the six main subclasses of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the 2007-2010 National Health and Nutrition Examination Survey (NHANES) dataset of adults. The participants were followed up until December 30, 2019. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary flavonoid intake and mortality. The study included a total of 8,758 adults (mean age 44.00 years; 47.40% men). A median follow-up of 10.7 years yielded 1,113 all-cause deaths and 261 cardiovascular deaths were recorded. In comparison to category 1, category 4 of flavan-3-ols, flavonols, and total flavonoids were associated with lower risks of all-cause mortality, with multivariable-adjusted HRs of 0.71 (95% CI: 0.55–0.92, Ptrend=0.021), 0.58 (95% CI: 0.45–0.74, Ptrend<0.001), and 0.63 (95% CI: 0.50–0.80, Ptrend=0.010), respectively. Similarly, higher intake of category 4 flavonoids was associated with a reduced risk of cardiovascular mortality, with HRs of 0.68 (95% CI: 0.29–0.89, Ptrend=0.035) for flavones, 0.41 (95% CI: 0.22–0.78, Ptrend=0.001) for flavonols, and 0.54 (95% CI: 0.36–0.80, Ptrend=0.021) for total flavonoids. ConclusionDietary flavonoid intake is associated with all-cause and cardiovascular mortality. Increasing dietary flavonoid intake may reduce the risk of death in adults.

Agranular frontal cortical microcircuit underlying cognitive control in macaques.

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas. In this minireview, we outline a tentative microcircuit model underlying cognitive control in the agranular frontal cortex of primates. The model incorporates the main GABAergic interneuron subclasses with specific laminar arrangements and target regions on pyramidal cells. We emphasize the role of layer 5 pyramidal cells in error and conflict detection. We offer several specific questions necessary for creating a specific intrinsic microcircuit model of the agranular frontal cortex.

Lipidomic and transcriptomic analysis of the increase in eicosapentaenoic acid under cobalamin deficiency of Schizochytrium sp.

Schizochytrium sp. is a heterotrophic microorganism capable of accumulating polyunsaturated fatty acids and has achieved industrial production of docosahexaenoic acid (DHA). It also has the potential for eicosapentaenoic acid (EPA) production. In this study, it was found that the cell growth, lipid synthesis and fatty acid composition of Schizochytrium sp. were significantly affected by the level of cobalamin in the medium, especially with regard to the content of EPA in the fatty acids. The content of EPA in the fatty acids increased 17.91 times, reaching 12.00%, but cell growth and lipid synthesis were significantly inhibited under cobalamin deficiency. The response mechanism for this phenomenon was revealed through combined lipidomic and transcriptomic analysis. Although cell growth was inhibited under cobalamin deficiency, the genes encoding key enzymes in central carbon metabolism were still up-regulated to provide precursors (Acetyl-CoA) and reducing power (NADPH) for the synthesis and accumulation of fatty acids. Moreover, the main lipid subclasses observed during cobalamin deficiency were glycerolipids (including glycerophospholipids), with EPA primarily distributed in them. The genes involved in the biosynthesis of these lipid subclasses were significantly up-regulated, such as the key enzymes in the Kennedy pathway for the synthesis of triglycerides. Thus, this study provided insights into the specific response of Schizochytrium sp. to cobalamin deficiency and identified a subset of new genes that can be engineered for modification.

Lipidomic analysis of facial skin surface lipids in acne in young women.

Alterations in the secretion and composition of skin surface lipids (SSL) are closely associated with the development of acne. Lipidomics is a useful tool to analyse the SSL of different types of acne. Our previous study found that phosphatidylserine and triacylglycerols dominate SSL changes in male acne and infantile acne, respectively. However, skin surface lipids as well as specific lipids in female acne patients remain to be investigated. To analyse and compare the SSL profile of acne women and healthy women and to discuss the involvement of differential lipids in acne development. Systematic lipidomics approach (high-throughput UPLC-QTOF-MS technology in combination with multivariate data analysis methods) was used to analyse the variations of SSL between acne and healthy groups. Analysis revealed significant differences in lipid content and composition between the two groups. Further analysis showed that levels of 13 individual lipids were significantly different and followed the same trend as the main class and subclasses. The largest individual contributor to the subgroup was triglycerides (TG) and phosphatidylinositol (PI). In addition, female acne patients exhibited reduced ceramide chain length (CCL) and increased levels of unsaturated fatty acids (UFAs), The changes of CCL in female acne are identical to male acne. There was a significantly higher level of TG and PI in the SSL of female acne patients. A reduction in CCL and an increase in UFAs content might contribute to the reduced skin barrier function in acne patients. The results suggest that female acne may have different pathogenesis than male acne.

Effect of sphingosine and phytosphingosine ceramide ratio on lipid arrangement and barrier function in skin lipid models

The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main subclasses in the SC lipid matrix are ceramides (CER), cholesterol, and free fatty acids. In inflammatory skin diseases, such as atopic dermatitis and psoriasis, the SC lipid composition is modulated compared to the composition in healthy SC. One of the main alterations is the molar ratio between the concentration of CER N-(tetracosanoyl)-sphingosine (CER NS) and CER N-(tetracosanoyl)-phytosphingosine (CER NP), which correlated with an impaired skin barrier function. In the present study, we investigated the impact of varying the CER NS:CER NP ratios on the lipid organization, lipid arrangement, and barrier functionality in SC lipid model systems. The results indicate that a higher CER NS:CER NP ratio as observed in diseased skin did not alter the lipid organization or lipid arrangement in the long periodicity phase encountered in SC. The trans-epidermal water loss, an indication of the barrier functionality, was significantly higher for the CER NS:CER NP 2:1 model (mimicking the ratio in inflammatory skin diseases) compared to the CER NS:CER NP 1:2 ratio (in healthy skin). These findings provide a more detailed insight into the lipid organization in both healthy and diseased skin and suggest that in vivo the molar ratio between CER NS:CER NP contributes to barrier impairment as well but might not be the main factor.

A study of land suitability for developing corn in West Sumatra: an approach of GIS-based multi-criteria and legacy soil data

In 2020 Indonesia imported 911,194 tons of corn. Therefore, each region needs to optimize their land-use. One of the potential areas for corn development is in West Sumatra. Therefore, this research was conducted with the objectives of a) assessing land suitability for corn and b) analyzing limiting factors and alternatives for land improvements. The geodatabase analysis used an approach of GIS-based multi-criteria and legacy soil data. Land suitability was analyzed using the Matching method with classes highly suitable (S1), moderately suitable (S2), marginally suitable (S3), and not suitable (N). The results showed that 33.9% of the land in West Sumatra was suitable for corn cultivation (1,210,592.9 ha). The suitability class consisted of an S1 of 169.5 ha, an S2 class of 143,761.2 ha, and an S3 class of 1,066,662.2 ha. As much as 66% of the land was not suitable for corn cultivation due to slope factors and rooting media. The S2 and S3 classes had main subclasses S2.tc.wa.eh widely distributed in Dharmasraya and Sijunjung, S3.wa.oa in Pesisir Selatan, and S3.wa in West Pasaman. The limiting factors of subclasses S2 and S3 of corn in West Sumatra were due to high rainfall, steep slopes, and poor drainage.

Pharmacogenetic substantiation of personalized prescription of oral anticoagulants in clinical practice

Thromboembolic diseases are of great clinical concern because of their high prevalence and consequences, which are often fatal. Despite significant progress in the prevention and treatment of thrombotic events, patients remain at risk of life-threatening bleeding episodes and other side effects arising from anticoagulant therapy, so the issue of personalizing prescriptions taking into account the genetic characteristics of patients has become urgent. The purpose of the study is to substantiate the need for patient genotype analysis in order to increase the effectiveness and safety of individual pharmacotherapy. The article has a conceptual nature, therefore the following research methods were chosen: systematization and generalization; analysis and specification; abstract and logical. For the search, we used PubMed, PubMedCentral, Google Scholar, dbSNP, Elsevier, Springer from September 2000 to November 2022. The review included studies written in English and Ukrainian. There were analyzed literature data on two main subclasses of oral antithrombotic agents, including oral anticoagulants and antiplatelet agents, namely warfarin, apixaban, rivaroxaban, and clopidogrel. Prognostically significant for evaluating the effectiveness and safety of anticoagulant use, as well as the most studied in this aspect, are CYP2C9 (rs1799853, rs1057910), CYP2C19 (rs4244285, rs4986893, rs12248560), VKORC1 (rs9923231, rs7294, rs9934438), MDR1 (rs4148738, rs2032582, rs1045642), FGB (rs1800787), PAI-1 (rs1799889) genes. The results of CYP2B6, CYP3A4/5 (rs776746), CYP4F2 (rs2108622) genes analysis indicate a certain influence on the anticoagulants metabolism and require further detailed study. Factors such as age, race, sex, smoking, diet, and other medications are known to influence the effectiveness of antithrombotic therapy, but the most influential factor is genetics, which accounts a significant percentage of interindividual variability. Future research should focus on the study of known and novel genetic variants that influence drug metabolism, as well as the molecular mechanisms that contribute to changes in plasma anticoagulant levels. The article provides a brief overview of action mechanisms, pharmacogenetics, and interactions between drugs and the genes responsible for their metabolism. The results indicate the need for studies of gene variants considered in this review before starting anticoagulant therapy, and attention should also be paid to the possibility of inhibitors and inductors influence on components of the metabolic pathway of anticoagulants and gene expression products that participate in their metabolism. The totality of these measures will ensure an increase in the efficiency and safety of individual pharmacotherapy and allow optimizing the choice and dosage of anticoagulants.

Perturbation of arachidonic acid and glycerolipid metabolism promoted particulate matter-induced inflammatory responses in human bronchial epithelial cells

Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage.

Chemical Composition of Hazelnut Skin Food Waste and Protective Role against Advanced Glycation End-Products (AGEs) Damage in THP-1-Derived Macrophages.

Glycation and the accumulation of advanced glycation end-products (AGEs) are known to occur during aging, diabetes and neurodegenerative diseases. Increased glucose or methylglyoxal (MGO) levels in the blood of diabetic patients result in increased AGEs. A diet rich in bioactive food compounds, like polyphenols, has a protective effect. The aim of this work is to evaluate the capacity of hazelnut skin polyphenolic extract to protect THP-1-macrophages from damage induced by AGEs. The main polyphenolic subclass was identified and quantified by means of HPLC/MS and the Folin-Ciocalteu method. AGEs derived from incubation of bovine serum albumin (BSA) and MGO were characterized by fluorescence. Cell viability measurement was performed to evaluate the cytotoxic effect of the polyphenolic extract in macrophages. Reactive oxygen species' (ROS) production was assessed by the H2-DCF-DA assay, the inflammatory response by real-time PCR for gene expression, and the ELISA assay for protein quantification. We have shown that the polyphenolic extract protected cell viability from damage induced by AGEs. After treatment with AGEs, macrophages expressed high levels of pro-inflammatory cytokines and ROS, whereas in co-treatment with polyphenol extract there was a reduction in either case. Our study suggests that hazelnut skin polyphenol-rich extracts have positive effects and could be further investigated for nutraceutical applications.

Gene expression variability across cells and species shapes the relationship between renal resident macrophages and infiltrated macrophages

BackgroundTwo main subclasses of macrophages are found in almost all solid tissues: embryo-derived resident tissue macrophages and bone marrow-derived infiltrated macrophages. These macrophage subtypes show transcriptional and functional divergence, and the programs that have shaped the evolution of renal macrophages and related signaling pathways remain poorly understood. To clarify these processes, we performed data analysis based on single-cell transcriptional profiling of renal tissue-resident and infiltrated macrophages in human, mouse and rat.ResultsIn this study, we (i) characterized the transcriptional divergence among species and (ii) illustrated variability in expression among cells of each subtype and (iii) compared the gene regulation network and (iv) ligand-receptor pairs in human and mouse. Using single-cell transcriptomics, we mapped the promoter architecture during homeostasis.ConclusionsTranscriptionally divergent genes, such as the differentially TF-encoding genes expressed in resident and infiltrated macrophages across the three species, vary among cells and include distinct promoter structures. The gene regulatory network in infiltrated macrophages shows comparatively better species-wide consistency than resident macrophages. The conserved transcriptional gene regulatory network in infiltrated macrophages among species is uniquely enriched in pathways related to kinases, and TFs associated with largely conserved regulons among species are uniquely enriched in kinase-related pathways.

Theranostic Applications of Glycosaminoglycans in Metastatic Renal Cell Carcinoma.

Renal cell carcinoma (RCC) makes up the majority of kidney cancers, with a poor prognosis for metastatic RCC (mRCC). Challenges faced in the management of mRCC, include a lack of reliable prognostic markers and biomarkers for precise monitoring of disease treatment, together with the potential risk of toxicity associated with more recent therapeutic options. Glycosaminoglycans (GAGs) are a class of carbohydrates that can be categorized into four main subclasses, viz., chondroitin sulfate, hyaluronic acid, heparan sulfate and keratan sulfate. GAGs are known to be closely associated with cancer progression and modulation of metastasis by modification of the tumor microenvironment. Alterations of expression, composition and spatiotemporal distribution of GAGs in the extracellular matrix (ECM), dysregulate ECM functions and drive cancer invasion. In this review, we focus on the clinical utility of GAGs as biomarkers for mRCC (which is important for risk stratification and strategizing effective treatment protocols), as well as potential therapeutic targets that could benefit patients afflicted with advanced RCC. Besides GAG-targeted therapies that holds promise in mRCC, other potential strategies include utilizing GAGs as drug carriers and their mimetics to counter cancer progression, and enhance immunotherapy through binding and transducing signals for immune mediators.

FriendlyClearMap: an optimized toolkit for mouse brain mapping and analysis.

Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratory's use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2's CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline. For more precise alignment, we add a landmark-based atlas registration to ClearMap's functions as well as include young mouse reference atlases for developmental studies. We provide an alternative cell segmentation method besides ClearMap's threshold-based approach: Ilastik's Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3-dimensional visualization of the annotated cells. As a proof of principle, we use FriendlyClearMap to quantify the distribution of the 3 main GABAergic interneuron subclasses (parvalbumin+ [PV+], somatostatin+, and vasoactive intestinal peptide+) in the mouse forebrain and midbrain. For PV+ neurons, we provide an additional dataset with adolescent vs. adult PV+ neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.

Evolutionary analyses and expression patterns of TCP genes in Ranunculales.

TCP transcription factors play a role in a large number of developmental processes and are at the crossroads of numerous hormonal biosynthetic and signaling pathways. The complete repertoire of TCP genes has already been characterized in several plant species, but not in any species of early diverging eudicots. We focused on the order Ranunculales because of its phylogenetic position as sister group to all other eudicots and its important morphological diversity. Results show that all the TCP genes expressed in the floral transcriptome of Nigella damascena (Ranunculaceae) are the orthologs of the TCP genes previously identified from the fully sequenced genome ofAquilegia coerulea. Phylogenetic analyses combined with the identification of conserved amino acid motifs suggest that six paralogous genes of class I TCP transcription factors were present in the common ancestor of angiosperms. We highlight independent duplications in core eudicots and Ranunculales within the class I and class II subfamilies, resulting in different numbers of paralogs within the main subclasses of TCP genes. This has most probably major consequences on the functional diversification of these genes in different plant clades. The expression patterns of TCP genes in Nigella damascena were consistent with the general suggestion that CIN and class I TCP genes may have redundant roles or take part in same pathways, while CYC/TB1 genes have more specific actions. Our findings open the way for future studies at the tissue level, and for investigating redundancy and subfunctionalisation in TCP genes and their role in the evolution of morphological novelties.

Clinical features of Guillain-Barré syndrome with anti-neurofascin 155 antibody.

Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p=.010), higher modified Erasmus GBS outcome score (p=.022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p=.002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p=.040), and poorer therapeutic effect (p=.017). Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.