Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Periodic Lamellae-Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis.

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) are developed by surface-directed epitaxial crystallization. The in vitro result shows that the PLN can precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhance the migration and osteogenic differentiation of Bone marrow stromal cells, Scanning electron microscopy. Notably, results suggest that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicate that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. The authors' findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis.

Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.

Mesenchymal stem cells (MSCs) possess the ability to self-renew and differentiate into multiple cell types, making them highly suitable for use as seed cells in tissue engineering. These can be derived from various sources and have been found to play crucial roles in several physiological processes, such as tissue repair, immune regulation, and intercellular communication. However, the limited capacity for cell proliferation and the secretion of senescence-associated secreted phenotypes (SASPs) pose challenges for the clinical application of MSCs. In this review, we provide a comprehensive summary of the senescence characteristics of MSCs and examine the different features of cellular microenvironments studied thus far. Additionally, we discuss the mechanisms by which cellular microenvironments regulate the senescence process of MSCs, offering insights into preserving their functionality and enhancing their effectiveness.

Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of interest in identifying UTUC patients with high risk and poor prognosis. We also identify a ten-protein classifier and establish a progression clock predicting progression-free survival of UTUC patients. Finally, we further validate the signature proteins by parallel reaction monitoring assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of a UTUC cohort and provides a valuable resource for further biological and diagnostic research in UTUC.

Scalable Fabrication of Polymeric Composite Microspheres to Inhibit Oral Pathogens and Promote Osteogenic Differentiation of Periodontal Membrane Stem Cells.

Periodontitis is a worldwide bacterial infectious disease, resulting in the resorption of tooth-supporting structures. Biodegradable polymeric microspheres are emerging as an appealing local therapy candidate for periodontal defect regeneration but suffer from tedious procedures and low yields. Herein, we developed a facile yet scalable approach to prepare polylactide composite microspheres with outstanding drug-loading capability. It was realized by blending equimolar polylactide enantiomers at the temperature between the melting point of homocrystallites and stereocomplex (sc) crystallites, enabling the precipitation of sc crystallites in the form of microspheres. Meanwhile, epigallocatechin gallate (EGCG) and nano-hydroxyapatite were encapsulated in the microspheres in the designated amount. Such an assembly allowed the fast and sustained release of EGCG and Ca2+ ions. The resultant hybrid composite microspheres not only exhibited strong antimicrobial activity against typical oral pathogens (Porphyromonas gingivalis and Enterococcus faecalis), but also directly promoted osteogenic differentiation of periodontal ligament stem cells with good cytocompatibility. These dual-functional composite microspheres offer a desired drug delivery platform to address the practical needs for periodontitis treatment.

Toward Excellent Energy Storage Performance via Well-Aligned and Isolated Interfaces in Multicomponent Polypropylene-Based All-Organic Polymer Dielectric Films.

Polypropylene (PP) serves as an excellent commercialized polymer dielectric film owing to its high breakdown strength, excellent self-healing ability, and flexibility. However, its low dielectric constant causes the large volume of the capacitor. Constructing multicomponent polypropylene-based all-organic polymer dielectric films is a facile strategy for achieving high energy density and efficiency simultaneously. Thereinto, the interfaces between the components become the key factors that determine the energy storage performance of the dielectric films. In this work, we propose to fabricate high-performance polyamide 513 (PA513)/PP all-organic polymer dielectric films via the construction of abundant well-aligned and isolated nanofibrillar interfaces. Laudably, a significant enhancement in the breakdown strength is achieved from 573.1 MV/m of pure PP to 692.3 MV/m with 5 wt % of PA513 nanofibrils. Besides, a maximum discharge energy density of about 4.4 J/cm2 is realized with 20 wt % of PA513 nanofibrils, which is about 1.6-folds higher than pure PP. Simultaneously, the energy efficiency of samples with modulated interfaces maintains higher than 80% up to 600 MV/m, which is much higher than pure PP of about 40.7% at 550 MV/m. This work provides a new strategy to fabricate high-performance multicomponent all-organic polymer dielectric films on an industrial scale.

Environmental DNA metabarcoding revealed the impacts of anthropogenic activities on phytoplankton diversity in Dianchi Lake and its three inflow rivers.

Phytoplankton diversity is closely related to environmental variables and has been widely used in ecological health assessment of rivers and lakes. Combining advantages of DNA-based identification and high-throughput sequencing technology, environmental DNA (eDNA) metabarcoding permits a new measurement for biodiversity monitoring in aquatic ecosystems. However, it had rarely been used to explore the variability and similarity of phytoplankton diversity between lake and its inflow rivers and the effects of environmental variables on phytoplankton. This study utilized eDNA metabarcoding to investigate the spatial distribution of phytoplankton and the impacts of environmental variables on the phytoplankton diversity in Dianchi Lake (one of the most polluted urban lakes in China) and its main inflow rivers (Panlong River, Baoxiang River, and Chai River). A total of 243 distinct phytoplankton taxa were detected, covering 9 phyla, 30 classes, 84 orders, and 132 families, and the taxonomic richness of rivers was higher than that of Dianchi Lake. Distinct biodiversity patterns (e.g., community structure, dominant taxon, ɑ-diversity) were exhibited among Dianchi Lake and its three inflow rivers, but similar biodiversity patterns were also observed in Dianchi Lake and the estuarine sites. The patterns of phytoplankton diversity were closely related to environmental variables, which were associated with pollution sources from different anthropogenic activities (e.g., urbanization, water diversion, industrial and agricultural activities). The primary environmental variables correlated with phytoplankton diversity varied in different habitats. The total phosphorus (TP) and chemical oxygen demand (COD) positively correlated with the phytoplankton community structures in Dianchi Lake, whereas negatively correlated in Panlong River and Baoxiang River. The total nitrogen (TN) positively correlated with the phytoplankton community structures in Baoxiang River and Chai River but negatively correlated in Dianchi Lake. Overall, this study provides insights on the phytoplankton diversity monitoring and the conservation of its diversity and healthy management of Dianchi Lake.

Comparison of Pairwise Venous and Fingertip Plasma Using Quantitative Proteomics Based on Data-Independent Acquisition.

Blood contains a great deal of health-related information and can be used to monitor human health status. Clinically, venous or fingertip blood is usually used for blood tests. However, the clinical application settings of the two sources of blood are unclear. In this study, the proteomes of pairwise venous plasma (VP) and fingertip plasma (FP) were analyzed, and the levels of 3797 proteins were compared between VP and FP. The Spearman's correlation coefficient for the relationship between protein levels of VP and FP ranges from 0.64 to 0.78 (p < 0.0001). The common pathways of VP and FP are related to cell-cell adhesion, protein stabilization, innate immune response, and complement activation, the classical pathway. The VP-overrepresented pathway is related to actin filament organization, while the FP-overrepresented pathway is related to the hydrogen peroxide catabolic process. ADAMTSL4, ADIPOQ, HIBADH, and XPO5 both in VP and FP are potential gender-related proteins. Notably, the VP proteome has a higher interpretation on age than the FP proteome, and CD14 is a potential age-related protein in VP but not in FP. Our study mapped the different proteomes between VP and FP, which can provide value for the standardization of clinical blood tests.

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.

A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1-3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.

Protective roles of mesenchymal stem cells on skin photoaging: A narrative review.

Skin is a natural barrier of human body and a visual indicator of aging process. Exposure to ultraviolet (UV) radiation in the sunlight may injure the skin tissues and cause local damage. Besides, it is reported that repetitive or long-term exposure to UV radiation may reduce the collagen production, change the normal skin structure and cause premature skin aging. This is termed "photoaging". The classical symptoms of photoaging include increased roughness, wrinkle formation, mottled pigmentation or even precancerous changes. Mesenchymal stem cells (MSCs) are a kind of cells with the ability of self-renewal and multidirectional differentiation into many types of cells, like adipocytes, osteoblasts and chondrocytes. Researchers have explored diverse pharmacological actions of MSCs because of their migratory activity, paracrine actions and immunoregulation effects. In recent years, the huge potential of MSCs in preventing skin from photoaging has gained wide attention. MSCs exert their beneficial effects on skin photoaging via antioxidant effect, anti-apoptotic/anti-inflammatory effect, reduction of matrix metalloproteinases (MMPs) and activation of dermal fibroblasts proliferation. MSCs and MSC related products have demonstrated huge potential in the treatment of skin photoaging. This narrative review concisely sums up the recent research developments on the roles of MSCs in protection against photoaging and highlights the enormous potential of MSCs in skin photoaging treatment.

Mechanism of psychoactive substance-induced cognitive disorders: does tau protein play a role?

Psychoactive substances are a class of chemical substances which could cause public health threats. Cognitive disorders are a category of mental health disorders that primarily affect cognitive abilities. Tau protein could maintain neuronal cytoskeleton stabilization. Post-translational modification of tau, especially phosphorylation, is an important way to regulate the structure and function of tau and phosphorylated tau is closely related to cognitive function. Lots of studies have reported the phenomenon that psychoactive substances can cause cognitive function impairment. We reviewed recent related studies and discussed them by drug classification. We mainly focused on cognitive disorders caused by acute or chronic exposure of each drugs, animal experiments and the mechanisms associated with tau phosphorylation, then compared the similarities and differences among them, trying to find out the common rules. The results suggested that tau phosphorylation is involved in psychoactive substance-induced cognitive disorder and different psychoactive substances may act by affecting amount or activity of different kinases and phosphatases in the metabolic pathway of tau. We demonstrated that tau protein is a potential target for psychoactive substances induced cognitive disorder treatments.

Deep Dive on the Proteome of Human Body Fluids: A Valuable Data Resource for Biomarker Discovery.

BACKGROUND/AIM: Body fluids are considered to be a rich source of disease biomarkers. Proteins in many body fluids have potential clinical applications for disease diagnostic and prognostic purposes. The aim of this study was to establish an in-depth multi-body fluid proteome. MATERIALS AND METHODS: Ten body fluids associated with 8 types of cancers collected from 23 patients involved in 19 common diseases underwent liquid chromatography tandem mass spectrometry (MS) analysis after gel-based protein separation (SDS-PAGE) or peptide-based fractionations. Bioinformatic analysis, including principal component analysis (PCA), consensus clustering, and hierarchical clustering analysis were also performed. The biological function was determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We profiled the proteome of ten body fluids, including ascites, bile, cerebrospinal fluid (CSF), hydrothorax, knee joint fluid (KJF), plasma, saliva, serum, tears, and urine. A total of 3,396 nonredundant proteins were identified, of which 304 were shared among ten body fluids, with common functions in focal adhesion and complement/coagulation cascades. A total of 41.5% (1,409) of the proteins were detected in only one body fluid and were closely related to their adjacent tissues by function. The functional analysis of the remaining 1,683 proteins showed that similar functions might be shared among different body fluids, which further highlighted the close connection of body fluids in the human body. CONCLUSION: A deep proteome of multi-body fluids originated from patients diagnosed with 19 common diseases provides a valuable data resource, and might indicate the potential application of body fluids for biomarker discovery.

Highly Thermally Conductive Graphene-Based Thermal Interface Materials with a Bilayer Structure for Central Processing Unit Cooling.

Innovations of transistors toward miniaturization and integration aggravate heat accumulation of central processing units (CPUs). Thermal interface materials (TIMs) are critical to remove the generated heat and to guarantee the device reliability. Herein, maltose-assisted mechanochemical exfoliation was proposed to prepare maltose-g-graphene as a structural motif of TIMs. Then, maltose-g-graphene/gelatin composite films with a bilayer structure were prepared by two-step vacuum filtration to construct effective thermally conductive pathways consisting of the directionally arranged and tightly packed maltose-g-graphene. The bilayer composite film exhibited a remarkable in-plane thermal conductivity (30.8 W m-1 K-1) and strong anisotropic ratio (∼8325%) at 40 wt % maltose-g-graphene addition. More intriguingly, the cooling effect on CPUs was significantly better for the bilayer composite films than commercial thermal pads as TIMs. The outstanding thermally conductive stability in resistance to instantaneous and prolonged thermal shocks as well as fatigue stability was gathered. Our work offers a valuable reference to design and fabricate high-performance TIMs for CPU cooling to surmount harsh application scenarios.

Sanguinarine caused larval lethality and growth inhibition by suppressing energy metabolism in silkworms, Bombyx mori.

Sanguinarine (Sang) is a natural alkaloid and distributed in several plants of Papaveraceae. The antitumor, antioxidant, antimicrobial and anti-inflammatory effects of Sang were extensively reported, but its speciality and mechanism against Lepidoptera insects were still unknown. In this study, detailed toxicological parameters of Sang against silkworms, Bombyx mori (B. mori), were determined by a toxicological test. Then, a nuclear magnetic resonance-based (NMR) metabolomics method was adopted to analyze the changes in hemolymph metabolites of silkworms after feeding Sang. The growth of fourth-instar larvae was significantly ceased by the oral administration of 0.05-0.3% Sang and vast deaths appeared in 0.3% Sang group on Day 4 and Day 5. The quantitative analysis of metabolites indicated that trehalose and citrate levels in hemolymph were increased after 24 h of feeding 0.3% Sang, whereas the concentrations of pyruvate, succinate, malate and fumarate were decreased. In addition, the enzymatic determination and reverse transcription quantitative PCR (RT-qPCR) showed that the trehalase (THL) activity and the transcriptional level of one gene coding THL were uniformly weakened by 0.3% Sang. One of the important mechanisms of Sang against silkworms might be interpreted as follows. Sang impaired trehalose hydrolysis, reduced THL activity and transcription, and led to the inhibition of energy metabolism, consequent antigrowth and high lethality in larvae of B. mori. Our findings offered new insights into the insecticidal effect of Sang from the perspective of energy metabolism and provided the basis for the application of Sang in the control of Lepidoptera pests.