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Mass spectrometry-based lipidomics is the primary tool for the structural analysis of lipids but the effective localization of carbon–carbon double bonds (C=C) in unsaturated lipids to distinguish C=C location isomers remains challenging. Here, we develop a large-scale lipid analysis platform by coupling online C=C derivatization through the Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry. This provides rich information on lipid C=C location isomers, revealing C=C locations for more than 200 unsaturated glycerophospholipids in bovine liver among which we identify 55 groups of C=C location isomers. By analyzing tissue samples of patients with breast cancer and type 2 diabetes plasma samples, we find that the ratios of C=C isomers are much less affected by interpersonal variations than their individual abundances, suggesting that isomer ratios may be used for the discovery of lipid biomarkers. Mass spectrometry is widely used for large-scale lipid profiling but distinguishing unsaturated lipid isomers is still challenging. Here, the authors present an analytical platform for high-throughput identification of lipid C=C location isomers in clinical samples, showing that isomer ratios may guide biomarker discovery.

Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices. Implantation-caused foreign-body response is a commonly encountered issue and can result in failure of implants. Here, the authors demonstrate that a highly water soluble, biocompatible, and easily accessible poly-DL-serine hydrogel can mitigate foreign-body response.

Glycosphingolipids (GSLs) are essential components of cell membranes, particularly enriched in the nervous system. Altered molecular distributions of GSLs are increasingly associated with human diseases, emphasizing the significance of lipidomic profiling. Traditional GSL analysis methods are hampered by matrix effect from phospholipids and the difficulty in distinguishing structural isomers. Herein, we introduce a highly sensitive workflow that harnesses magnetic TiO 2 nanoparticle-based selective enrichment, charge-tagging Paternò–Büchi reaction, and liquid chromatography-tandem mass spectrometry. This approach enables mapping over 300 distinct GSLs in brain tissues by defining sugar types, long chain bases, N-acyl chains, and the locations of desaturation and hydroxylation. Relative quantitation of GSLs across multiple structural levels provides evidence of dysregulated gene and protein expressions of FA2H and CerS2 in human glioma tissue. Based on the structural features of GSLs, our method accurately differentiates human glioma with/without isocitrate dehydrogenase genetic mutation, and normal brain tissue. The molecular profiling of glycosphingolipids (GSLs) is hindered by the coexistence of abundant phospholipids and diverse isomers. The authors introduce a highly sensitive workflow that maps out the structural atlas of neutral GSLs, previously deemed a “dark space” within the lipidome.

Cell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic amphiphilic β-amino acid polymers that are stable upon proteolysis and easily prepared in large scale at low cost. The optimal polymer strongly promotes cell adhesion, using preosteoblast cell as a model, by following dual mechanisms that are independent of sequence and chirality of the statistic copolymer. Our strategy opens avenues in designing the next-generation cell-adhesive materials and may guide future studies and applications. Cell adhesion peptides like RGD are important to biomedical applications but suffer from proteolysis as well as processing and cost issues. Here, the authors report on the development of cationic-hydrophobic amphiphilic β-amino acid polymers which function as cell adhesion motifs but are resistant to proteolysis.

To enhance the operational efficiency of emergency shelters in disaster management, this study focuses on flood disasters and identifies four critical indicators. These include the hazard posed by disaster-inducing factors, the sensitivity of the disaster-prone environment, the vulnerability of the carrying capacity, and the capability for disaster prevention and mitigation. The Random Forest algorithm is employed to assess the spatial distribution of flood risk, and the resulting risk values are incorporated as weights to address latent threats. The method simultaneously considers the minimization of weighted evacuation distance and accessibility inequality. It addresses multiple objectives-such as equity, efficiency, and balance-within a multi-objective optimization model for shelter location. The model utilizes an enhanced Non-dominated Sorting Genetic Algorithm II (NSGA-II), validated through a case study of shelter allocation in Zhengzhou. The results show that, compared to the current shelter configuration, the optimized plan reduces total evacuation distance, uncovered risk value, and accessibility inequality by 31.46%, 10.73%, and 28.80%, respectively.

The primary cilium is elongated from the mother centriole and has diverse signaling roles during development and disease. The CP110-CEP97 complex functions as a negative regulator of ciliogenesis, although the mechanisms regulating its mother centriole localization are poorly understood. Here we show that M-Phase Phosphoprotein 9 (MPP9) is recruited by Kinesin Family Member 24 (KIF24) to the distal end of mother centriole where it forms a ring-like structure and recruits CP110-CEP97 by directly binding CEP97. Loss of MPP9 causes abnormal primary cilia formation in growing cells and mouse kidneys. After phosphorylation by Tau Tubulin Kinase 2 (TTBK2) at the beginning of ciliogenesis, MPP9 is targeted for degradation via the ubiquitin-proteasome system, which facilitates the removal of CP110 and CEP97 from the distal end of the mother centriole. Thus, MPP9 acts as a regulator of ciliogenesis by regulating the localization of CP110-CEP97 at the mother centriole. Ciliogenesis is negatively regulated by the CP110-CEP97 complex, although the mechanism controlling mother centriole localization is poorly understood. Here, Huang et al. show that KIF24 recruits MMP9 to the mother centriole, where it regulates ciliogenesis by controlling CP110-CEP97 recruitment.

Disulfidptosis, a newly discovered form of regulated cell death, is involved in multiple disease processes. This study applied computational methods to identify disulfidptosis‐related genes in myocardial infarction (MI). Differentially expressed genes (DEGs) from GSE66360 dataset were screened using the limma package and intersected with genes in weighted gene coexpression network analysis (WGCNA) modules to obtain candidate genes. Biomarkers were selected via support vector machine‐recursive feature elimination (SVM‐RFE) and least absolute shrinkage and selection operator (LASSO), and validated by quantitative real‐time (qRT)‐PCR, CCK‐8, and flow cytometry. Enrichment and immune infiltration analyses were performed using clusterProfiler and CIBERSORT tools. Potential drugs were predicted via the Coremine database and visualized with Cytoscape. Seurat and CellChat packages were employed to perform single‐cell transcriptomic analysis and develop cell–cell communication network, respectively. The genes in the lightgreen module that had the highest correlation with immune scores were selected. Next, we identified 10 biomarkers ( THBD , IRAK3 , NFIL3 , IL1R2 , THBS1 , MAP3K8 , JDP2 , FCGR2A , CCL20 , and EREG ), all of which showed significantly higher mRNA levels in AC16‐oxygen–glucose deprivation (OGD) cells compared to controls. Silencing MAP3K8 and NFIL3 enhanced cell viability and reduced apoptosis in AC16‐OGD cells. Immune infiltration analysis suggested that NFIL3 and MAP3K8 modulated T cell function, contributing to MI pathogenesis. Drug analysis predicted 15 candidate drugs targeting both NFIL3 and MAP3K8 . Single‐cell analysis showed that distinguished six cell types in MI, with adipocytes serving as a communication hub interacting closely with cardiomyocytes, fibroblasts, endothelial cells, and macrophages. These findings highlighted the potential of the identified biomarkers as novel therapeutic targets for MI.

A lipidome comprises thousands of lipid species, many of which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating lipid isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities of hydrophilic interaction liquid chromatography (HILIC) and trapped ion mobility spectrometry (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, which enable pinpointing double bond locations in phospholipids and sn -positions in phosphatidylcholine. This system profiles phospholipids at multiple structural levels with short analysis time (<10 min per LC run), high sensitivity (nM detection limit), and wide coverage, while data analysis is streamlined using a home-developed software, LipidNovelist. Notably, compared to our previous report, the system doubles the coverage of phospholipids in bovine liver and reveals uncanonical desaturation pathways in RAW 264.7 macrophages. Relative quantitation of the double bond location isomers of phospholipids and the sn -position isomers of phosphatidylcholine enables the phenotyping of human bladder cancer tissue relative to normal control, which would be otherwise indistinguishable by traditional profiling methods. Our research offers a comprehensive solution for lipidomic profiling and highlights the critical role of isomer analysis in studying lipid metabolism in both healthy and diseased states. The existence of large number of isomers poses challenges for lipidomic analysis. The authors integrate hydrophilic interaction liquid chromatography, trapped ion mobility, and isomer-resolved MS/MS into a single system, enabling deep profiling of phospholipidomes at fast speed and wide coverage.

Hydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications. Functionalisation of hydrogels can be difficult to achieve and often requires modification of polymers before gelation. Here, the authors report on a sandcastle worm inspired adhesive tripeptide for the post gelation functionalisation of wet hydrogels, demonstrating the addition of different functionality.

Adult stem cells are excellent cell resource for cell therapy and regenerative medicine. Dental pulp stem cells (DPSCs) have been discovered and well known in various application. Here, we reviewed the history of dental pulp stem cell study and the detail experimental method including isolation, culture, cryopreservation, and the differentiation strategy to different cell lineage. Moreover, we discussed the future potential application of the combination of tissue engineering and of DPSC differentiation. This review will help the new learner to quickly get into the DPSC filed.