Characterization of potential spermatogonia biomarker genes in the European eel (Anguilla anguilla).

Identification of specific molecular markers for spermatogonial stem cells in teleost is crucial for enhancing the efficacy of reproductive biotechnologies in aquaculture, such as transplantation and surrogate production in fishes. Since it is not yet possible to distinguish spermatogonial stem cells of European eel (Anguilla anguilla) using specific molecular markers, we isolated spermatogonial cells from immature European eels to find these potential markers. We attempted this by studying three candidate genes: vasa, nanos2, and dnd1. Two vasa (vasa1 and vasa2) genes, nanos2, and dnd1 were identified, characterized, and studied in the muscle, testis, and isolated spermatogonia. Our results showed that vasa1 and vasa2 had the highest levels of expression when measured by qPCR. In situ hybridization and immunochemistry assays showed that the four genes were localized explicitly in type A spermatogonia. However, vasa1 and vasa2 exhibited stronger signals in the immature testicular tissue than the other two potential markers. According to this, vasa1 and vasa2 were found to be the most effective markers for spermatogonial cells in the European eel.

Collagen Anchoring Protein-Nucleic Acid Chimeric Probe for In Situ In Vivo Mapping of a Tumor-Specific Protease.

In situ analysis of biomarkers in the tumor microenvironment (TME) is important to reveal their potential roles in tumor progression and early diagnosis of tumors but remains a challenge. In this work, a bottom-up modular assembly strategy was proposed for a multifunctional protein-nucleic chimeric probe (PNCP) for in situ mapping of cancer-specific proteases. PNCP, containing a collagen anchoring module and a target proteolysis-responsive isothermal amplification sensor module, can be anchored in the collagen-rich TME and respond to the target protease in situ and generate amplified signals through rolling cycle amplification of tandem fluorescent RNAs. Taking matrix metalloproteinase 2 (MMP-2), a tumor-associated protease, as the model, the feasibility of PNCP was demonstrated for the in situ detection of MMP-2 activity in 3D tumor spheroids. Moreover, in situ in vivo mapping of MMP-2 activity was also achieved in a metastatic solid tumor model with high sensitivity, providing a useful tool for evaluating tumor metastasis and distinguishing highly aggressive forms of tumors.

Rapid intraoperative multi-molecular diagnosis of glioma with ultrasound radio frequency signals and deep learning.

BACKGROUND: Molecular diagnosis is crucial for biomarker-assisted glioma resection and management. However, some limitations of current molecular diagnostic techniques prevent their widespread use intraoperatively. With the unique advantages of ultrasound, this study developed a rapid intraoperative molecular diagnostic method based on ultrasound radio-frequency signals. METHODS: We built a brain tumor ultrasound bank with 169 cases enrolled since July 2020, of which 43483 RF signal patches from 67 cases with a pathological diagnosis of glioma were a retrospective cohort for model training and validation. IDH1 and TERT promoter (TERTp) mutations and 1p/19q co-deletion were detected by next-generation sequencing. We designed a spatial-temporal integration model (STIM) to diagnose the three molecular biomarkers, thus establishing a rapid intraoperative molecular diagnostic system for glioma, and further analysed its consistency with the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5). We tested STIM in 16-case prospective cohorts, which contained a total of 10384 RF signal patches. Two other RF-based classical models were used for comparison. Further, we included 20 cases additional prospective data for robustness test (ClinicalTrials.govNCT05656053). FINDINGS: In the retrospective cohort, STIM achieved a mean accuracy and AUC of 0.9190 and 0.9650 (95% CI, 0.94-0.99) respectively for the three molecular biomarkers, with a total time of 3 s and a 96% match to WHO CNS5. In the prospective cohort, the diagnostic accuracy of STIM is 0.85 ± 0.04 (mean ± SD) for IDH1, 0.84 ± 0.05 for TERTp, and 0.88 ± 0.04 for 1p/19q. The AUC is 0.89 ± 0.02 (95% CI, 0.84-0.94) for IDH1, 0.80 ± 0.04 (95% CI, 0.71-0.89) for TERTp, and 0.85 ± 0.06 (95% CI, 0.73-0.98) for 1p/19q. Compared to the second best available method based on RF signal, the diagnostic accuracy of STIM is improved by 16.70% and the AUC is improved by 19.23% on average. INTERPRETATION: STIM is a rapid, cost-effective, and easy-to-manipulate AI method to perform real-time intraoperative molecular diagnosis. In the future, it may help neurosurgeons designate personalized surgical plans and predict survival outcomes. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation.

Obesity, a worldwide epidemic in recent years, is mainly due to the uncontrolled development of adipose tissues, which includes adipocyte hypertrophy and hyperplasia. Adipocyte differentiation is a process involving multiple transcription factor cascades, and the exact mechanism has not yet been defined. As a bHLH transcription factor, Twist1 exerts its activity by forming homo- or heterodimers with other factors. In this study, we showed Twist1 restricts adipogenesis through PPARγ. Expression of various differentiation markers (including PPARγ and adiponectin) and triglyceride-containing lipid droplets were decreased with overexpression of Twist1. Pathway enrichment analysis of RNA-seq data showed that differentially expressed genes (DEGs) caused by Twist1 overexpression were significantly related to lipolysis and PPARγ signaling. This implicates that Twist1 plays important regulatory roles in these processes. ChIP and dual luciferase assays showed that Twist1 could bind either PPARγ or adiponectin promoter to repress their respective transcription or directly to PPARγ protein to regulate its transcriptional activity. Furthermore, Twist1 directly interacted RXRα, which usually forms heterodimer with PPARγ to regulate adipogenesis. Taken together, our results suggest that Twist1 is an inhibitory modulator of adipogenesis and its function is likely through direct interaction with PPARγ protein or its gene promoter.

Study of radiochemotherapy decision-making for young high-risk low-grade glioma patients using a macroscopic and microscopic combined radiomics model.

OBJECTIVES: As a few types of glioma, young high-risk low-grade gliomas (HRLGGs) have higher requirements for postoperative quality of life. Although adjuvant chemotherapy with delayed radiotherapy is the first treatment strategy for HRLGGs, not all HRLGGs benefit from it. Accurate assessment of chemosensitivity in HRLGGs is vital for making treatment choices. This study developed a multimodal fusion radiomics (MFR) model to support radiochemotherapy decision-making for HRLGGs. METHODS: A MFR model combining macroscopic MRI and microscopic pathological images was proposed. Multiscale features including macroscopic tumor structure and microscopic histological layer and nuclear information were grabbed by unique paradigm, respectively. Then, these features were adaptively incorporated into the MFR model through attention mechanism to predict the chemosensitivity of temozolomide (TMZ) by means of objective response rate and progression free survival (PFS). RESULTS: Macroscopic tumor texture complexity and microscopic nuclear size showed significant statistical differences (p < 0.001) between sensitivity and insensitivity groups. The MFR model achieved stable prediction results, with an area under the curve of 0.950 (95% CI: 0.942-0.958), sensitivity of 0.833 (95% CI: 0.780-0.848), specificity of 0.929 (95% CI: 0.914-0.936), positive predictive value of 0.833 (95% CI: 0.811-0.860), and negative predictive value of 0.929 (95% CI: 0.914-0.934). The predictive efficacy of MFR was significantly higher than that of the reported molecular markers (p < 0.001). MFR was also demonstrated to be a predictor of PFS. CONCLUSIONS: A MFR model including radiomics and pathological features predicts accurately the response postoperative TMZ treatment. CLINICAL RELEVANCE STATEMENT: Our MFR model could identify young high-risk low-grade glioma patients who can have the most benefit from postoperative upfront temozolomide (TMZ) treatment. KEY POINTS: • Multimodal radiomics is proposed to support the radiochemotherapy of glioma. • Some macro and micro image markers related to tumor chemotherapy sensitivity are revealed. • The proposed model surpasses reported molecular markers, with a promising area under the curve (AUC) of 0.95.

Dominance vs epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles.

An important challenge in genetics, evolution and biotechnology is to understand and predict how mutations combine to alter phenotypes, including molecular activities, fitness and disease. In diploids, mutations in a gene can combine on the same chromosome or on different chromosomes as a "heteroallelic combination". However, a direct comparison of the extent, sign, and stability of the genetic interactions between variants within and between alleles is lacking. Here we use thermodynamic models of protein folding and ligand-binding to show that interactions between mutations within and between alleles are expected in even very simple biophysical systems. Protein folding alone generates within-allele interactions and a single molecular interaction is sufficient to cause between-allele interactions and dominance. These interactions change differently, quantitatively and qualitatively as a system becomes more complex. Altering the concentration of a ligand can, for example, switch alleles from dominant to recessive. Our results show that intra-molecular epistasis and dominance should be widely expected in even the simplest biological systems but also reinforce the view that they are plastic system properties and so a formidable challenge to predict. Accurate prediction of both intra-molecular epistasis and dominance will require either detailed mechanistic understanding and experimental parameterization or brute-force measurement and learning.

Robust dimethyl-based multiplex-DIA doubles single-cell proteome depth via a reference channel.

Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput, and robustness, which we address here by a streamlined multiplexed workflow using data-independent acquisition (mDIA). We demonstrate automated and complete dimethyl labeling of bulk or single-cell samples, without losing proteomic depth. Lys-N digestion enables five-plex quantification at MS1 and MS2 level. Because the multiplexed channels are quantitatively isolated from each other, mDIA accommodates a reference channel that does not interfere with the target channels. Our algorithm RefQuant takes advantage of this and confidently quantifies twice as many proteins per single cell compared to our previous work (Brunner et al, PMID 35226415), while our workflow currently allows routine analysis of 80 single cells per day. Finally, we combined mDIA with spatial proteomics to increase the throughput of Deep Visual Proteomics seven-fold for microdissection and four-fold for MS analysis. Applying this to primary cutaneous melanoma, we discovered proteomic signatures of cells within distinct tumor microenvironments, showcasing its potential for precision oncology.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Farmland Soil and Crops in the Suburbs of Urumqi].

In order to understand the occurrence of PAHs in soil and crops, the enrichment capacity of different crops for PAHs, and the distribution characteristics of PAHs in different parts of crops, the crops and soil planted in the farmland around Urumqi were studied as examples. Samples were collected in the farmland gathering area in the suburb of Urumqi in July 2021. A total of 100 crop samples were collected, including 21 crop species and 45 surface soil samples. The results showed that 16 types of PAHs were detected in the soil and crops. The total concentration of PAHs in farmland soil ranged from 19.06 to 1870.86 µg·kg-1, and the average concentration was 127.40 µg·kg-1. Seven carcinogenic PAHs accounted for 42.85%-79.20% of the 16 types of PAHs, among which BaP was the main pollutant in the soil. Through the characteristic ratio method, it was found that the main sources of PAHs in the soil were biomass and coal combustion. Total PAHs in crops ranged from 1.86 µg·kg-1 to 974.05 µg·kg-1, with an average of 303.30 µg·kg-1. Different crops had different enrichment capacities for PAHs. Among the 21 crops sampled, the accumulative content of PAHs in pumpkin was the highest (431.75 µg·kg-1). In leaf vegetable crops, the content of PAHs in leaves was higher than that in roots and fruits. In fruit and vegetable crops, the PAH content in fruit was higher than that in the root or leaf. There was a significant correlation between high cyclic PAHs in soil and PAHs in plant leaves. The health risk assessment of PAHs in crops showed that dietary intake had potential carcinogenic risk and even had high carcinogenic risk in adult male and female groups, which requires further attention.

Extrusion Modification of Wheat Bran and Its Effects on Structural and Rheological Properties of Wheat Flour Dough.

The study investigated the extrusion modification of wheat bran and its effects on structural and rheological properties of wheat flour dough. Extruded bran showed better solubility of dietary fiber and structural porosity, leading to higher hydration and swelling power. Addition of extruded bran to dough caused water redistribution as an intensive aggregation of bound water to gluten matrix with reduced mobility. The bran-gluten interaction influenced by water sequestering caused partial gluten dehydration and conversion of ß-turn into ß-sheet, which demonstrated the formation of a more polymerized and stable gluten network. Farinographic data confirmed the promotion of dough stability with extruded bran addition at lower gluten content, while viscoelastic data suggested improved dough elasticity at all gluten contents by increasing elastic moduli and decreasing loss tangent. This study would be useful for interpreting the modification effect and mechanism of extrusion on cereal brans and provide valuable guidance for applying it as an effective modification technology on the commercial production of cereal bran and its flour products.

Intratumoral microbiome impacts immune infiltrates in tumor microenvironment and predicts prognosis in esophageal squamous cell carcinoma patients.

Background: Different intratumoral microbiotaexist in different tumors and play a crucial function in carcinogenesis. However, whether they impact clinical outcomes in esophageal squamous cell carcinoma (ESCC) and their mechanism remain unclear. Methods: 16S rDNA amplicon sequencing was performed on surgically resected samples from 98 ESCC patients to analyze intratumoral microbiome abundance and composition. Multiplex fluorescent immunohistochemistry staining was used to profile the phenotypes of immune infiltrates in the tumor microenvironment (TME). Results: Patients with higher intratumoral Shannon index had significantly worse surgical outcomes. When patients were divided into short-term survivors and long-term survivors based on the median survival time, both intratumoral alpha-diversity and beta-diversity were found to be significantly inconsistent, and the relative abundance of Lactobacillus and Leptotrichia emerged as the two microorganisms that probably influenced the survival of ESCC patients. Only Lactobacillus in ESCC was validated to significantly worsen patients' prognoses and to be positively correlated with the Shannon index. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus, and the pathologic tumor-node-metastasis (pTNM) stage were independently associated with patients' overall survival. Furthermore, the relative abundance of both Lactobacillus and Shannon index was positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs). The Shannon index was negatively correlated with the proportions of natural killer (NK) cells in the TME. Conclusions: A high abundance of intratumoral Lactobacillus and bacterial alpha-diversity was associated with the formation of the immunosuppressive TME and predicted poor long-term survival in ESCC patients.

A propensity score-matched analysis of neoadjuvant chemoimmunotherapy versus surgery alone for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to evaluate the safety, efficacy, and oncologic outcomes of neoadjuvant immunotherapy combined with chemotherapy (NICT) group and surgery alone group in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A series of 232 consecutive patients who underwent surgery with or without NICT from June 2019 to August 2022 were evaluated. We performed propensity score matching between the NICT and surgery alone groups on the basis of estimated propensity scores for each patient. RESULTS: After propensity score matching, data of 137 patients with clinical stages II-IV ESCC, including 85 receiving surgery alone and 52 receiving NICT, were analyzed. Compared with the surgery alone group (301.7 ± 94.4 min), the operation time was significantly longer in the NICT group (333.4 ± 79.7 min). However, there was no significant difference between the two groups in the postoperative complications, intraoperative blood loss, thoracic fluid volume, chest tube duration, lengths of intensive care unit stay and postoperative hospitalization. Additionally, 90-day mortality rate and 30-day readmission were similar in both groups. CONCLUSIONS: Overall, NICT followed by esophagectomy appears to be safe and feasible for locally advanced ESCC. However, further multicenter prospective clinical trials are needed to validate our results.

Controllable synthesis of MoS2@TiO2 nanocomposites for visual detection of dopamine secretion with highly-efficient enzymatic activity.

Dopamine (DA) plays an essential role in dopaminergic neuronal behavior and disease. However, current detection methods for discriminating the secretion of DA are hampered by the limitations of the requirement for bulky instrumentation and non-intuitive signals. Herein, we have controllably and proportionately integrated molybdenum disulfide (MoS2) with titanium dioxide (TiO2) to prepare MoS2@TiO2 nanocomposites (MoS2@TiO2 NCs) via a facile synthesis method. MoS2@TiO2 NCs with a certain reactant mass ratio have shown a significant enhancement in peroxidase-like activity with superiority of the nanocomposite structure compared to single MoS2 or natural enzyme. The method for catalyzing the decomposition of H2O2 by MoS2@TiO2 NCs and competition for hydroxyl radicals (˙OH) between the chromogenic agent and DA enable a sensitive, specific, and colorimetric DA analysis with a low detection limit of 0.194 µM and a wide linear detection range (0.8 to 100 µM). Because of the favorable detection performance, we were encouraged to explore and finally realize the visual detection of cellular DA secretion that is stimulated in a High-K+ neurocyte environment. Collectively, this method will provide a promising strategy for basic research in neuroscience with its portable, sensitive, and naked-eye detectable performance.

Alleviating Zn Dendrites by Growth of Ultrafine ZnO Nanowire Arrays through Horizontal Anodizing for High-Capacity, Long-Life Zn Ion Capacitors.

Zn ion capacitors (ZICs) composed of a carbon-based cathode and a Zn anode are one of the most promising energy storage devices due to their inherent safety and high-power output. However, their poor cycling stability originating from the Zn dendrites' formation and low energy density limited by insufficient activated carbon properties remain major challenges for development of high-performance ZICs. Hence, we constructed a facile and effective strategy to alleviate "edge effects" and suppress Zn dendrites by growing ZnO nanowire arrays on Zn foil (ZnO@Zn) using a horizontally potentiostatic anodizing technique. The electrochemical characterizations and in situ optical microscopy observation revealed that the introduction of ZnO nanowire arrays can significantly suppress the growth of Zn dendrites and enhance the cycling stability of the Zn anode. The superfine and interlaced ZnO nanowire arrays provide uniform nucleation sites and high electrical conductivity for the Zn metal anode, reducing the local current density and promoting the rapid diffusion and migration of Zn ions on the Zn anode surface. As a result, the ZnO@Zn electrode has a very low nucleation overpotential and excellent cycle stability, far superior to the bare Zn anode. Furthermore, a ZnO@Zn//NPHC ZIC assembled with an N, P-codoped hard carbon (NPHC) cathode delivers a high specific capacity of 110.3 mAh g-1 at 0.1 A g-1 and achieves outstanding cycling stability with 90% capacity retention together with ∼100% Coulombic efficiency after 20000 cycles.

PINK1-Mediated Mitophagy Promotes Oxidative Phosphorylation and Redox Homeostasis to Induce Drug-Tolerant Persister Cancer Cells.

The drug-tolerant persister (DTP) state enables cancer cells to evade cytotoxic stress from anticancer therapy. However, the mechanisms governing DTP generation remain poorly understood. Here, we observed that lung adenocarcinoma (LUAD) cells and organoids entered a quiescent DTP state to survive MAPK inhibitor treatment. DTP cells following MAPK inhibition underwent a metabolic switch from glycolysis to oxidative phosphorylation (OXPHOS). PTEN-induced kinase 1 (PINK1), a serine/threonine kinase that initiates mitophagy, was upregulated to maintain mitochondrial homeostasis during DTP generation. PINK1-mediated mitophagy supported DTP cell survival and contributed to poor prognosis. Mechanistically, MAPK pathway inhibition resulted in MYC-dependent transcriptional upregulation of PINK1, leading to mitophagy activation. Mitophagy inhibition using either clinically applicable chloroquine or depletion of PINK1 eradicated drug tolerance and allowed complete response to MAPK inhibitors. This study uncovers PINK1-mediated mitophagy as a novel tumor protective mechanism for DTP generation, providing a therapeutic opportunity to eradicate DTP and achieve complete responses. SIGNIFICANCE: DTP cancer cells that cause relapse after anticancer therapy critically depend on PINK1-mediated mitophagy and metabolic reprogramming, providing a therapeutic opportunity to eradicate persister cells to prolong treatment efficacy.

Vitrification of the ovarian tissue in sturgeons.

The aim of this study was to test whether vitrification of sterlet Acipenser ruthenus and Russian sturgeon Acipenser gueldenstaedtii ovarian tissue through needle-immersed vitrification (NIV) is an efficient strategy for the preservation of oogonia (OOG) in order to supplement the current conservation efforts for these endangered fish species. Histological analyses of the gonads displayed that the ovaries of both species were immature and contained predominantly OOG and primary oocytes. The germline origin of these cells was verified by localization of the vasa protein through immunocytochemistry. NIV protocol was optimized by testing different equilibration (ES) and vitrification solutions (VS) containing various concentrations of dimethyl sulfoxide (Me2SO), propylene glycol (PG) or methanol (MeOH). In sterlet, the highest average viability (55.7 ± 11.5%) was obtained by using a combination of 1.5 M PG and 1.5 M Me2SO in the ES, and 1.5 M MeOH and 5.5 M Me2SO in the VS. In Russian sturgeon, the highest average viability (49.4 ± 17.1%) was obtained by using a combination of 1.5 M MeOH and 1.5 M Me2SO in the ES, and 3 M PG and 3 M Me2SO in the VS. To test whether vitrified/warmed OOG are functional, we have conducted an intra-specific transplantation assay to verify whether transplanted sterlet OOG will colonize the gonads of recipient fish. Fluorescently labelled cells were detected within recipient gonads at 2 and 3 months post-fertilization (mpf). Colonization rates of vitrified/warmed OOG (70% at 2 mpf and 61% at 3 mpf) were similar to those of fresh OOG (80% at 2 mpf and 70% at 3 mpf). This study has demonstrated that vitrification of ovarian tissue is an effective method for the preservation of OOG, and that the vitrified/warmed cells are functional and are able to colonize recipient gonads after transplantation similarly to the fresh cells. Since the vitrification procedure displayed in this study is simple and does not require complex and expensive laboratory equipment, it can be readily applied in field conditions, and therefore it can be invaluable for the conservation efforts of the critically endangered sturgeon species. However, care needs to be taken that despite the research conducted so far, donor-derived progeny was not yet obtained in sturgeons.

Comparison of the physical stabilities and oxidation of lipids and proteins in natural and polyphenol-modified soybean protein isolate-stabilized emulsions.

Oil-in-water emulsions are widely used in the food industry; however, lipids are often easily oxidized, which may adversely affect food quality. Herein, we investigated the effects of alkali treatment, free radical induction, and carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS)-mediated synthetic methods on the structures and antioxidant properties of soy protein isolate (SPI)-gallic acid (GA) conjugates and the physical stabilities and protein-lipid co-oxidation properties of the resulting emulsions. These three methods are well established; however, their effects on the same protein-phenolic compound system have not been directly compared. Additionally, the co-oxidation of proteins and oils in emulsions remains unexplored. Alkali treatment yielded superior antioxidant properties compared to those obtained using free radicals or EDC/NHS, as this method was more likely to yield CS bonds and resulted in an increased quantity of grafted GA. Spectroscopic analysis showed that alkali treatment promoted GA oxidation and thereby increased GA-protein interactions and the quenching of tryptophan fluorescence. Correspondingly, EDC/NHS-mediated conjugation retained the activity of the hydroxyl groups of GA to the largest extent. Moreover, the grafting of GA improved the physical and oxidative stabilities of the emulsions. In particular, EDC/NHS-mediated conjugation produced an emulsion with optimal oxidative stability owing to its effective inhibition of lipid and protein oxidation. Conversely, the conjugates synthesized via alkali treatment and free radical induction displayed less inhibition of lipid oxidation and promoted protein oxidation. In conclusion, optimized protein-phenolic compound conjugates for use in developing nutritional fortification products with longer shelf lives can be obtained by using appropriate synthetic methods.

The role of preoperative inflammatory markers in patients with central nervous system tumors, focus on glioma.

Background: CNS tumors, particularly gliomas, are associated with a high rate of disability and lethality, and are typically diagnosed with histopathology and immunohistochemistry. Our research aims to develop a minimally invasive method for diagnosing, grading and molecular typing glioma. Methods: We collected patients who underwent surgery for glioma, Trigeminal neuralgia/Hemifacial spasm, schwannoma, pituitary adenomas and meningioma at our hospital from June 2019 to June 2021. Preoperative WBCs, neutrophils, lymphocytes, monocytes, platelet counts and albumin levels were collected. Preoperative NLR, dNLR, PLR, LMR and PNI were calculated, and the correlation between them and glioma diagnosis as well as grading was analyzed. We also evaluated the diagnostic significance of NLR, dNLR, PLR, LMR, PNI and their combinations for gliomas, particularly GBM, as well as the diagnostic significance of IDH molecular typing of gliomas. Results: There were 182 healthy samples and 3101 diseased samples in our study. Compared with other groups, glioma patients had significantly higher preoperative NLR, dNLR and PLR values, but lower LMR and PNI values. Further analysis showed that NLR, dNLR, and PLR were positively correlated with glioma grading, while LMR and PNI were negatively correlated with glioma grading. For the diagnosis of glioma, NLR showed a maximum AUC value of 0.8099 (0.7823-0.8374). For GBM, NLR showed a maximum AUC value of 0.9585 (0.9467-0.9703). In the combination, NLR+dNLR showed the highest AUC value of 0.8070(0.7849-0.8291). NLR showed significant statistical significance in all grades of glioma IDH molecular typing, while PLR did not show statistical significance. Conclusions: NLR has the greatest value for the diagnosis, differential diagnosis, grading and molecular typing of gliomas. The NLR+dNLR combination also showed high sensitivity and specificity. We believe that inflammatory parameters may serve as economical and specific markers for glioma diagnosis, grading, molecular typing, and progression.

m6A-modified lincRNA Dubr is required for neuronal development by stabilizing YTHDF1/3 and facilitating mRNA translation.

Long intergenic noncoding RNAs (lincRNAs) are crucial regulators in numerous biological processes. However, the functions and mechanisms of m6A-modified lincRNAs in neuronal development remain unclear. Here, we report an m6A-modified lincRNA, Dppa2 upstream binding RNA (Dubr), abundantly expressed at the early developmental stage of dorsal root ganglion (DRG) and cerebral cortex. Silencing Dubr impairs axon elongation of DRG neurons and axon projection and migration of cortical neurons, whereas lacking m6A modification of Dubr fully loses its functions. Mechanically, Dubr interacts with m6A-binding proteins, the YTHDF1/3 complex, through its m6A motifs to protect YTHDF1/3 from degradation via the proteasome pathway. Furthermore, Tau and Calmodulin are regulated by YTHDF1/3 and m6A-modified Dubr. Overexpression of YTHDF1/3 not only rescues the reduced Tau and Calmodulin but also restores axon elongation of DRG neurons by Dubr knockdown. This study uncovers a critical role of m6A-modified lincRNA in neuronal development by regulating the degradation of RNA-binding protein.

AlphaPeptDeep: a modular deep learning framework to predict peptide properties for proteomics.

Machine learning and in particular deep learning (DL) are increasingly important in mass spectrometry (MS)-based proteomics. Recent DL models can predict the retention time, ion mobility and fragment intensities of a peptide just from the amino acid sequence with good accuracy. However, DL is a very rapidly developing field with new neural network architectures frequently appearing, which are challenging to incorporate for proteomics researchers. Here we introduce AlphaPeptDeep, a modular Python framework built on the PyTorch DL library that learns and predicts the properties of peptides ( https://github.com/MannLabs/alphapeptdeep ). It features a model shop that enables non-specialists to create models in just a few lines of code. AlphaPeptDeep represents post-translational modifications in a generic manner, even if only the chemical composition is known. Extensive use of transfer learning obviates the need for large data sets to refine models for particular experimental conditions. The AlphaPeptDeep models for predicting retention time, collisional cross sections and fragment intensities are at least on par with existing tools. Additional sequence-based properties can also be predicted by AlphaPeptDeep, as demonstrated with a HLA peptide prediction model to improve HLA peptide identification for data-independent acquisition ( https://github.com/MannLabs/PeptDeep-HLA ).

Optimization of in vitro culture conditions of common carp germ cells for purpose of surrogate production.

Common carp (Cyprinus carpio) is the fourth most-produced fish species in aquaculture and frequently used model species with significant effort invested in development of biotechnological applications. In present study, we attempted to establish an in vitro germ cell culture condition for short term cell culture, which could facilitate further applications such as surrogacy or gene manipulation. Basal media and different types of feeder cells were investigated to optimize carp germ cell culture condition to favor maintenance of mitotic proliferation. Results indicated that germ cells cultured with hESC media and RTG2 cell line as feeder possessed significantly higher proliferation and survival rate compared to that cultured with StemPro media and Sertoli cell line as feeder. In addition, we compared two dissection strategies to compare risk of cell culture contamination and body cavity was open from dorsal part or from ventral part. As a result, carp open from the dorsal side can minimize the risk of contamination. In summary, this is the first study to optimize the cultivation of germ cells in common carp. This opens up new opportunities for the application of specific techniques in the breeding of those species with high commercial value and frequent use as a model fish. Results obtained in this study are important for implementation of new strategies in common carp breeding, conservation of genetic resources, restoration of lines or development of clonal and isogenic carp lines.