Impact of Molecular Weight Variations in Dendrobium officinale Polysaccharides on Antioxidant Activity and Anti-Obesity in Caenorhabditis elegans.

This research investigates the impact of Dendrobium officinale polysaccharides (DOP) with different molecular weights on antioxidant effects, lifespan enhancement, and obesity reduction, utilizing both in vitro analyses and the Caenorhabditis elegans (C. elegans) model. Through a series of experiments-ranging from the extraction and modification of polysaccharides, Gel Permeation Chromatography (GPC), and analysis of composition to the evaluation of antioxidant capabilities, this study thoroughly examines DOP and its derivatives (DOP5, DOP15, DOP25) produced via H2O2-Fe2+ degradation. The results reveal a direct relationship between the molecular weight of polysaccharides and their bioactivity. Notably, DOP5, with its intermediate molecular weight, demonstrated superior antioxidant properties, significantly extended the lifespan, and improved the health of C. elegans. Furthermore, DOP15 appeared to regulate lipid metabolism by affecting crucial lipid metabolism genes, including fat-4, fat-5, fat-6, sbp-1, and acs-2. These findings highlight the potential application of DOP derivatives as natural antioxidants and agents against obesity, contributing to the development of functional foods and dietary supplements.

Terpenoids derived from Semen Ziziphi Spinosae oil enhance sleep by modulating neurotransmitter signaling in mice.

Semen Ziziphi Spinosae oil (SZSO) is a natural vegetable oil extracted from Semen Ziziphi Spinosae, a traditional Chinese medicine renowned for its sleep-promoting properties, while the mechanisms are still unclear. Our findings revealed that the terpenoids present in SZSO (T-SZSO) were identified as the active components responsible for promoting sleep. Network pharmacological analysis suggested that T-SZSO targeted different sleep-aid pathways to varying degrees and exhibited potential for preventing central nervous system diseases. Notably, lupeol and betulinicaldehyde exhibited more pronounced effects. Additionally, T-SZSO significantly elevated serotonin levels, enhanced gamma-aminobutyric acid (GABA) synthesis, promoted GABA A receptor expression, and decreased glutamate and norepinephrine expression levels. Moreover, T-SZSO was found to downregulate IL-1ß expression while upregulating superoxide dismutase and inducible nitric oxide synthase levels. In conclusion, this study presents the first investigation into the pharmacological basis of SZSO in promoting sleep and highlights the potential of nature food in improving suboptimal health conditions.

Effect of stearoyl-coenzyme a desaturase 1 (SCD1) on the function of mast cells.

Background: The prevalence of childhood asthma and obesity is increasing, while obesity increases the risk and severity of asthma. Lipid metabolism has been considered as an important factor in the pathogenesis of obesity-associated asthma. Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that catalyzes the production of monounsaturated fatty acids (MUFA).Methods: In the present study, the microarray data retrieved from the Gene Expression Comprehensive Database (GEO) was analyzed to further clarify the impact of SCD1 on Mast cell activation related lipid mediators and the correlation between SCD1 and obesity asthma in the population.Results: SCD1 was highly expressed in IgE-activated bone marrow-derived mast cells (BMMCs). Meanwhile, SCD1 was also verified expressed highly in dinitrophenyl human serum albumin (DNP-HAS) stimulated RBL-2H3 cells. The expression of SCD1 was up-regulated in peripheral blood leukocytes of asthmatic children, and was positively correlated with skinfold thickness of upper arm, abdominal skinfold and body mass index (BMI). Inhibition of SCD1 expression significantly suppressed the degranulation, lipid mediator production, as well as the migration ability in DNP-HAS-stimulated RBL-2H3 cells.Conclusion: SCD1 is involved in obese-related asthma through regulating mast cells.

Characterization of antigen presentation capability for neoantigen-based products using targeted LC-MS/MS method.

The generation of an immune response in neoantigen-based products relies on antigen presentation, which is closely analyzed by bioassays for T-cell functions such as tetramer or cytokine release. Mass spectrometry (MS) has the potential to directly assess the antigen-presenting capability of antigen-presenting cells (APCs), offering advantages such as speed, multi-target analysis, robustness, and ease of transferability. However, it has not been used for quality control of these products due to challenges in sensitivity, including the number of cells and peptide diversity. In this study, we describe the development and validation of an improved targeted LC-MS/MS method with high sensitivity for characterizing antigen presentation, which could be applied in the quality control of neoantigen-based products. The parameters for the extraction were carefully optimized by different short peptides. Highly sensitive targeted triple quadrupole mass spectrometry combined with ultra-high performance liquid chromatography (UHPLC) was employed using a selective ion monitoring mode (Multiple Reaction Monitoring, MRM). Besides, we successfully implemented robust quality control peptides to ensure the reliability and consistency of this method, which proved invaluable for different APCs. With reference to the guidelines from ICH Q2 (R2), M10, as well as considering the specific attributes of the product itself, we validated the method for selectivity, specificity, sensitivity, limit of detection (LOD), recovery rate, matrix effect, repeatability, and application in dendritic cells (DCs) associated with neoantigen-based products. The validation process yields satisfactory results. Combining this approach with T cell assays will comprehensively assess cell product quality attributes from physicochemical and biological perspectives.

Single-cell and spatial transcriptomics reveal POSTN+ cancer-associated fibroblasts correlated with immune suppression and tumour progression in non-small cell lung cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, the influence of CAF subpopulations on the progression of lung cancer is still unclear, which impedes the translational advances in targeting CAFs. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on tumour, paired tumour-adjacent, and normal samples from 16 non-small cell lung cancer (NSCLC) patients. CAF subpopulations were analyzed after integration with published NSCLC scRNA-seq data. SpaTial enhanced resolution omics-sequencing (Stereo-seq) was applied in tumour and tumour-adjacent samples from seven NSCLC patients to map the architecture of major cell populations in tumour microenvironment (TME). Immunohistochemistry (IHC) and multiplexed IHC (mIHC) were used to validate marker gene expression and the association of CAFs with immune infiltration in TME. RESULTS: A subcluster of myofibroblastic CAFs, POSTN+ CAFs, were significantly enriched in advanced tumours and presented gene expression signatures related to extracellular matrix remodeling, tumour invasion pathways and immune suppression. Stereo-seq and mIHC demonstrated that POSTN+ CAFs were in close localization with SPP1+ macrophages and were associated with the exhausted phenotype and lower infiltration of T cells. POSTN expression or the abundance of POSTN+ CAFs were associated with poor prognosis of NSCLC. CONCLUSIONS: Our study identified a myofibroblastic CAF subpopulation, POSTN+ CAFs, which might associate with SPP1+ macrophages to promote the formation of desmoplastic architecture and participate in immune suppression. Furthermore, we showed that POSTN+ CAFs associated with cancer progression and poor clinical outcomes and may provide new insights on the treatment of NSCLC.

Simple One-Step Molten Salt Method for Synthesizing Highly Efficient MXene-Supported Pt Nanoalloy Electrocatalysts.

MXene-supported noble metal alloy catalysts exhibit remarkable electrocatalytic activity in various applications. However, there is no facile one-step method for synthesizing these catalysts, because the synthesis of MXenes requires a strongly oxidizing environment and the preparation of platinum nanoalloys requires a strongly reducing environment and high temperatures. Hence, achieving coupling in one step is extremely challenging. In this paper, a straightforward one-step molten salt method for preparing MXene-supported platinum nanoalloy catalysts is proposed. The molten salt acts as the reaction medium to dissolve the transition metals and platinum ions at high temperatures. Transition metal ions oxidize the A-site element from its MAX precursor at high temperatures, and the resulting transition metals further reduce platinum ions to form alloys. By coupling Al oxidation and platinum ion reduction using a molten salt solvent, this method directly converts Ti3 AlC2 to a Pt-M@Ti3 C2 Tx catalyst (where M denotes the transition metal). It further offers the possibility of extending the Pt-M phase to binary, ternary, or quaternary platinum-containing nanoalloys and converting the Al-containing MAX phase to Ti2 AlC and Ti3 AlCN. Due to the strong interfacial interaction, the as-prepared Pt-Co@Ti3 C2 Tx is superior to commercial Pt/C (20 wt.%) in the hydrogen evolution reaction.

A scATAC-seq atlas of chromatin accessibility in axolotl brain regions.

Axolotl (Ambystoma mexicanum) is an excellent model for investigating regeneration, the interaction between regenerative and developmental processes, comparative genomics, and evolution. The brain, which serves as the material basis of consciousness, learning, memory, and behavior, is the most complex and advanced organ in axolotl. The modulation of transcription factors is a crucial aspect in determining the function of diverse regions within the brain. There is, however, no comprehensive understanding of the gene regulatory network of axolotl brain regions. Here, we utilized single-cell ATAC sequencing to generate the chromatin accessibility landscapes of 81,199 cells from the olfactory bulb, telencephalon, diencephalon and mesencephalon, hypothalamus and pituitary, and the rhombencephalon. Based on these data, we identified key transcription factors specific to distinct cell types and compared cell type functions across brain regions. Our results provide a foundation for comprehensive analysis of gene regulatory programs, which are valuable for future studies of axolotl brain development, regeneration, and evolution, as well as on the mechanisms underlying cell-type diversity in vertebrate brains.

Single-nucleus chromatin landscapes during zebrafish early embryogenesis.

Vertebrate embryogenesis is a remarkable process, during which numerous cell types of different lineages arise within a short time frame. An overwhelming challenge to understand this process is the lack of dynamic chromatin accessibility information to correlate cis-regulatory elements (CREs) and gene expression within the hierarchy of cell fate decisions. Here, we employed single-nucleus ATAC-seq to generate a chromatin accessibility dataset on the first day of zebrafish embryogenesis, including 3.3 hpf, 5.25 hpf, 6 hpf, 10 hpf, 12 hpf, 18 hpf and 24 hpf, obtained 51,620 high-quality nuclei and 23 clusters. Furthermore, by integrating snATAC-seq data with single-cell RNA-seq data, we described the dynamics of chromatin accessibility and gene expression across developmental time points, which validates the accuracy of the chromatin landscape data. Together, our data could serve as a fundamental resource for revealing the epigenetic regulatory mechanisms of zebrafish embryogenesis.

Advances of neuroimaging in chemotherapy related cognitive impairment (CRCI) of patients with breast cancer.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) has seriously affected the quality of life (QOL) of patients with breast cancer (BCs), thus the neurobiological mechanism of CRCI attracted widespread attention. Previous studies have found that chemotherapy causes CRCI through affecting brain structure, function, metabolism, and blood perfusion. FINDINGS: A variety of neuroimaging techniques such as functional magnetic resonance imaging (fMRI), event-related potential (ERP), near-infrared spectroscopy (NIRS) have been widely applied to explore the neurobiological mechanism of CRCI. CONCLUSION: This review summarized the progress of neuroimaging research in BCs with CRCI, which provides a theoretical basis for further exploration of CRCI mechanism, disease diagnosis and symptom intervention in the future. Multiple neuroimaging techniques for CRCI research.

A comprehensive computational analysis to explore the importance of SIGLECs in HCC biology.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive, malignant cancer with a complex pathogenesis. However, effective therapeutic targets and prognostic biomarkers are limited. Sorafenib provides delaying cancer progression and survival improvement in advanced HCC. But despite 10 years of research on the clinical application of sorafenib, predictive markers for its therapeutic effect are lacking. METHODS: The clinical significance and molecular functions of SIGLEC family members were assessed by a comprehensive bioinformatic analysis. The datasets included in this study (ICGC-LIRI-JP, GSE22058 and GSE14520) are mainly based on patients with HBV infections or HBV-related liver cirrhosis. The TCGA, GEO, and HCCDB databases were used to explore the expression of SIGLEC family genes in HCC. The Kaplan-Meier Plotter database was used to evaluate relationships between the expression levels of SIGLEC family genes and prognosis. Associations between differentially expressed genes in the SIGLEC family and tumour-associated immune cells were evaluated using TIMER. RESULTS: The mRNA levels of most SIGLEC family genes were significantly lower in HCC than in normal tissues. Low protein and mRNA expression levels of SIGLECs were strongly correlated with tumour grade and clinical cancer stage in patients with HCC. Tumour-related SIGLEC family genes were associated with tumour immune infiltrating cells. High SIGLEC expression was significantly related to a better prognosis in patients with advanced HCC treated with sorafenib. CONCLUSIONS: SIGLEC family genes have potential prognostic value in HCC and may contribute to the regulation of cancer progression and immune cell infiltration. More importantly, our results revealed that SIGLEC family gene expression may be used as a prognostic marker for HCC patients treated with sorafenib.

Lignin Promotes Mycelial Growth and Accumulation of Polyphenols and Ergosterol in Lentinula edodes.

It has been demonstrated that lignin was efficiently degraded by Lentinula edodes (L. edodes). However, the process of lignin degradation and utilization by L. edodes has not been discussed in detail. Therefore, the effects of lignin on L. edodes mycelium growth, chemical compositions, and phenolic profiles were investigated herein. It has been revealed that 0.10% lignin acted as the most effective concentration to accelerate mycelia growth, which yielded the highest biomass of 5.32 ± 0.07 g/L. Furthermore, a 0.10% concentration of lignin promoted the accumulation of phenolic compounds, especially protocatechuic acid, with peak value of 48.5 ± 1.2 µg/g. In contrast, the higher concentration of lignin (0.20%) exerted an inhibitory effect on the growth of L. edodes. Overall, the application of lignin at the optimal concentration of 0.10% could not only enhance the mycelial growth but also accumulate the phenolic acids and raise the nutritional and medical values of L. edodes.

Evaluating the Effects of Storage Conditions on Multiple Cell-Free RNAs in Plasma by High-Throughput Sequencing.

Background: Plasma cell-free RNAs (cfRNAs) can serve as noninvasive biomarkers for the diagnosis and monitoring of diseases. However, the delay in blood processing may lead to unreliable results. Therefore, an unbiased evaluation based on the whole transcriptome under different storage conditions is needed. Methods: Here, blood samples were collected in ethylenediaminetetraacetic acid tubes and processed immediately (0 hour), or stored at room temperature (RT) or 4°C for different time intervals (2, 6, and 24 hours) before plasma separation. High-throughput sequencing was applied to assess the effects of storage conditions on the transcript profiles and fragment characteristics of plasma cell-free mRNA, long noncoding RNA (lncRNA), and small RNAs. Results: More genes changed their expression levels with time when blood was stored at RT compared with those at 4°C. Cell-free mRNA and lncRNA were relatively stable in blood preserved at 4°C for 6 hours, while cell-free microRNA (miRNA) and piwi-interacting RNA (piRNA) remained stable at 4°C for 24 hours. After 24 hours, more contamination of the leukocyte-derived RNAs occurred at RT, possibly due to apoptosis. Meanwhile, significant changes were also observed regarding the characteristics of the RNA fragments, including fragment size, the proportion of intron, and the pyrimidine frequency of the fragmented 3' end. Fifteen tissue-enriched genes were detected in the plasma but not expressed in leukocytes. The expression level and fragment length of these genes gradually decreased during storage, suggesting the degradation of the cfRNA and the dilution of leukocyte-derived RNA with other tissue-derived cfRNA. Conclusions: Our results suggest that the contamination of leukocyte-derived RNA and the degradation of original cfRNA contribute to the changes in the cfRNA expression profiles and the fragment characteristics during short-term storage. The storage of blood at 4°C for 6 hours allows plasma cfRNA to remain relatively stable, which will be useful for further studies or clinical applications where adequate quantification or the fragment signature of cfRNA is required.

Research on Spheroidization of Tungsten Powder from Three Different Raw Materials.

In this work, three kinds of tungsten powders with different particle sizes were spheroidized by radio-frequency (RF) inductively coupled plasma spheroidization. The spheroidization behavior of these tungsten powders was investigated and compared. The spheroidization effects of irregular tungsten powder improves with the decrease in degree of agglomeration and increases with primary particle size. Spherical tungsten powder from irregular powder with a primary particle size of 19.9 µm and an agglomeration coefficient of 1.59 had the best spheroidization effect; its apparent density, hall flow time, and spheroidization ratio are 9.36 g/cm3, 6.28 s/50 g, and 98%, respectively. The results show that irregular feedstock tungsten powder with a smaller primary particle size and higher agglomeration degree has a poor spheroidization effect because it is easily affected by the gas flow and deviates from the high temperature zone. On the contrary, irregular feedstock tungsten powder with larger primary particle sizes and lower agglomeration degrees has better spheroidization effects.

Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer's disease.

Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer's disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment.

Infiltration Patterns of Cervical Epithelial Microenvironment Cells During Carcinogenesis.

Background: Local cellular microenvironment plays a crucial role in the HPV-induced cervical malignant transformation. Characterization of the dynamic infiltration changes of microenvironment cells during cervical carcinogenesis would contribute to a better understanding of involved mechanisms. Methods: Three public gene expression datasets of cervical squamous epithelium samples were collected and combined. We applied seven up-to-date computational methods for infiltrating estimation and compared their results (CD4+ and CD8+ T cells) to the known fraction. After benchmarking the applied methods, the cell filtration patterns were determined and clustered through fuzzy c-means algorithm. Results: Most methods displayed better performance in predicting the abundance of CD4+ T cell than that of CD8+ T cell. The infiltration patterns of 33 microenvironment cell types (including 31 immune cells and 2 non-immune cells) were determined, and five immune cell clusters with distinct features were then derived. Meanwhile, opposite changes in abundance were observed between the activated and resting state of some immune cells from the progression perspective. Conclusions: Based on characteristics and evaluation performance of different methods, as well as previous findings, for the first time we provide a comprehensive overview of the infiltration patterns of microenvironment cells throughout cervical cancer progression.

Potential association factors for developing effective peptide-based cancer vaccines.

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

Plasma Exo-miRNAs Correlated with AD-Related Factors of Chinese Individuals Involved in Aß Accumulation and Cognition Decline.

Numerous studies have investigated the risk factors of Alzheimer's disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aß), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aß generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

Association of PTPRT Mutations with Cancer Metastasis in Multiple Cancer Types.

Metastasis is one of the characteristics of advanced cancer and the primary cause of cancer-related deaths from cancer, but the mechanism underlying metastasis is unclear, and there is a lack of metastasis markers. PTPRT is a protein-coding gene involved in both signal transduction and cellular adhesion. It is also known as a tumor suppressor gene that inhibits cell malignant proliferation by inhibiting the STAT3 pathway. Recent studies have reported that PTPRT is involved in the early metastatic seeding of colorectal cancer; however, the correlation between PTPRT and metastasis in other types of cancer has not been revealed. A combined analysis using a dataset from the genomics evidence neoplasia information exchange (GENIE) and cBioPortal revealed that PTPRT mutation is associated with poor prognosis in pan-cancer and non-small-cell lung cancer. The mutations of PTPRT or "gene modules" containing PTPRT are significantly enriched in patients with metastatic cancer in multiple cancers, suggesting that the PTPRT mutations serve as potential biomarkers of cancer metastasis.